Safety of Vaginal Estrogens: a Systematic Review Supplemental

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Safety of Vaginal Estrogens: A Systematic Review

Supplemental Tables Page # Supplemental Table 1. National Library of Medicine’s DAILYMED Repository 2 Search Results Supplemental Table 2. Contraindications to vaginal estrogens approved by the U.S. 3 Food and Drug Administration Supplemental Table 3. Excluded articles and reasons for exclusion 4 Supplemental Table 4. Study design characteristics of clinical trials of vaginal 30 estrogen in postmenopausal women Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and 45 manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women Supplemental Table 6. Endometrial biopsy results in clinical trials of vaginal estrogen 52 in postmenopausal women Supplemental Table 7a. Summary of Heterogeneity of Level 1 Studies with 55 Endometrial Biopsy Outcomes Supplemental Table 7b. Summary of Heterogeneity of Level 2 Studies with 55 Endometrial Biopsy Outcomes Supplemental Table 7c. Summary of Heterogeneity of Level 1 Studies with 56 Endometrial Thickness Outcomes Supplemental Table 7d. Summary of Heterogeneity of Level 2 Studies with 57 Endometrial Thickness Outcomes Bibliography 58

Supplemental Table 1. National Library of Medicine’s DAILYMED Repository Search Resultsa Retrieved result for non-injectable preparation of Vaginal route confirmed after estrogen alone (without other hormones) review of label Alora estradiol transdermal system patch No Climara estradiol patch No Divigel estradiol gel No Dotti estradiol patch extended release No Elestrin estradiol gel No Estra-50 estradiol pellet, implantable No Estrace estradiol cream 0.01% Yes Estrace estradiol tablet No Estraderm estradiol patch No Estradiol cream 0.01% Yes Estradiol film, extended release No Estradiol insert, 10mcg estradiol per insert Yes Estradiol patch No Estradiol tablet No Estradiol transdermal system estradiol patch No Estradiol vaginal cream 0.01% Yes Estradiol vaginal inserts estradiol tablet film-coated, 10mcg Yes estradiol Estring estradiol ring 2 mg releasing 7.5 mcg/d Yes Estrogel estradiol gel No Evamist estradiol spray No Femring estradiol acetate ring Yes Imvexxy estradiol insert 10mcg estradiol per insert Yes Menostar estradiol patch No Minivelle estradiol film No Premarin conjugated estrogens tablet No Premarin vaginal conjugated estrogens cream Yes Vagifem estradiol insert, film-coated, 10mcg or 25 mcg Yes estradiol per insert Vivelle dot estradiol patch No Yuvafem estradiol tablet 10mcg estradiol per tablet Yes

a Note: To ensure that the list of estrogen preparations used as search terms was inclusive of all U.S. FDA-approved vaginal estrogen preparations, we performed a search of the U.S. National Library of Medicine’s DAILYMED webpage (https://dailymed.nlm.nih.gov/dailymed/index.cfm) “estrogen” drug class on 3/8/2019. The search revealed vaginal estrogens in the form of estradiol cream, estradiol insert (also known as estradiol vaginal tablet), estradiol ring, and conjugated equine estrogens cream.

Supplemental Table 2. Contraindications to vaginal estrogens approved by the U.S. Food and Drug Administration Preparation Contraindications Vaginal conjugated estrogens • Undiagnosed abnormal genital bleeding, cream, estradiol cream, vaginal • known, suspected, or history of breast cancer estradiol insert (tablet) • known or suspected estrogen-dependent neoplasia • active deep vein thrombosis, pulmonary embolism, or a history of these conditions • active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions • known liver dysfunction or disease • known protein C, protein S, or antithrombin deficiency or other known thrombophilic disordersa • known or suspected pregnancyb

a known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders is not listed as a contraindication of the estradiol vaginal ring (Estring) b Known or suspected pregnancy is not listed as a contraindication of Imvexxy vaginal estradiol insert.

Supplemental Table 3. Excluded Articles and Reasons for Exclusion Ref. Author, year Reason for Reason for exclusion after full-text # exclusion after search title/abstract search 1 1972 Eur J Cancer Not VE 2 1989 Contraception Special pop 3 1991 Fertil Steril Not VE 4 1993 Int J Fertil Menopausal Not VE Stud 5 Abate 1999 Clin Exp Obstet Not VE Gynecol 6 Abdalla 1992 Contraception Special pop 7 Abdel-Aleem 2005 Not VE Contraception 8 Abdelbary 2015 Urology Excluded after full- No AE text search 9 Abdullah 2005 J Coll Not VE Physicians Surg Pak 10 Abraham 2014 Maturitas Not VE 11 Achiron 1995 Fertil Steril Not VE 12 Adler 2005 Gynecol Obstet Not VE Invest 13 Affinito 1998 Ultrasound Not VE Obstet Gynecol 14 Agarwal 2016 J Obstet Special pop Gynaecol 15 Aguirre 2010 Gynecol Not VE Endocrinol 16 Ahlstrom 1990 Gynecol Obstet Not FDA app prep Invest 17 AinMelk 1996 Fertil Steril Not VE 18 Akrivis 2003 Clin Exp Obstet I Gynecol 19 Al-Azzawi 2003 Climacteric Hi dose VE 20 Al-Azzawi 2005 Menopause Excluded after full- Not VE Alone text search 21 Albert 2002 Obstet Gynecol Not VE 22 Albertazzi 1999 Obstet Gynecol Not VE 23 Algorta 2017 Eur J Contracept Special pop Reprod Health Care 24 Al-Saqi 2015 Post Reprod Not VE Health 25 Alvarez 1996 Contraception Not VE 26 Alvarez-Sanchez 1992 Special pop Contraception 27 Anderson 2003 JAMA Not VE 28 Andersson 2000 Maturitas Not VE

29 Andreen 2003 Eur J Endocrinol Not VE 30 Andreen 2005 Not VE Psychoneuroendocrinology 31 Apperloo 2006 J Sex Med Not VE 32 Apter 1990 Contraception Special 33 Apter 2016 Contraception Not VE 34 Archer 2017 Menopause I 35 Archer 2001 Fertil Steril Not VE 36 Archer 2007 J Clin Not VE Endocrinol Metab 37 Archer 2018 J Womens Excluded after full- Not FDA app prep Health (Larchmt) text search 38 Archer 2012 Menopause Not VE 39 Archer 2014 Menopause Not VE 40 Archer 2016 Contraception Special 41 Artini 1995 J Endocrinol Special Invest 42 Artymuk 2010 Int J Gynaecol Special Obstet 43 Ata 2010 J Reprod Med Special 44 Atmaca 2005 Tohoku J Exp Med Not VE Alone 45 Aylward 1974 Curr Med Res Not VE Opin 46 Aylward 1978 Postgrad Med J Not VE 47 Ayton 1996 Br J Obstet I Gynaecol 48 Bachmann 2010 Climacteric Not VE 49 Bachmann 2009 Menopause I 50 Bachmann 2011 Menopause Not VE 51 Bachmann 2008 Obstet Gynecol I 52 Bachmann 2010 Menopause Not VE 53 Bachmann 2009 Menopause Not VE 54 Back 1987 Contraception Special 55 Baerug 1998 Climacteric Not VE 56 Bahamondes 1995 Hum Reprod Not VE 57 Bahamondes 2000 Not VE Contraception 58 Bai 2007 Maturitas Not VE 59 Baird 1995 J Clin Endocrinol Not VE Metab 60 Baird 1996 J Clin Epidemiol Not VE 61 Baker 1995 J Assist Reprod Not VE Genet 62 Baker 1998 J Clin Endocrinol Not VE Metab 63 Balasch 1982 Fertil Steril Not VE

64 Balk 2002 J Soc Gynecol Not VE Investig 65 Ballagh 1994 Contraception Special 66 Ballagh 1994 Contraception Special 67 Baracat 2001 Clin Exp Obstet Not VE Gynecol 68 Barbosa 2009 Gynecol Not VE Endocrinol 69 Barentsen 1997 Eur J Obstet I Gynecol Reprod Biol 70 Barnabei 2005 Obstet Gynecol Not VE 71 Barnabei 2002 Obstet Gynecol Not VE 72 Barton 2018 Support Care Not VE Cance 73 Barton 2018 Support Care Not VE Cance 74 Bassol 2005 Maturitas Not VE 75 Basson 2003 BJOG Not VE 76 Bateson 2009 Menopause Excluded after full- No AE text search 77 Battaglia 2009 J Sex Med Not VE 78 Baysoy 2006 Reprod Biomed Not VE Online 79 Beardsworth 1999 Br J Obstet Not VE Gynaecol 80 Beaton 1967 Br J Clin Pract Not VE 81 Behilovic 1987 Contraception Not VE 82 Behre 2001 J Int Med Res Not VE 83 Bellantoni 1991 J Gerontol Not VE 84 Bellina 1983 Lasers Surg Med Not VE 85 Belsey 1988 Contraception Special 86 Ben-Chetrit 1996 Fertil Steril Not VE 87 Ben-Chetrit 2005 Isr Med Assoc Not FDA app prep J 88 Benjamin 1971 J Reprod Med Not VE 89 Benson 1996 Am J Obstet Not VE Gynecol 90 Berger 1979 Contraception Not VE 91 Berning 2000 Maturitas Not VE 92 Bhamra 2011 Menopause Not FDA app prep 93 Bishop 1992 Cancer Chemother Not VE Pharmacol 94 Bishun 1977 J Surg Oncol Not VE 95 Bjarnadottir 2002 Am J Obstet Special Gynecol 96 Blakely 2004 Clin Cancer Res Not VE 97 Bolaji 1996 Gynecol Endocrinol Not VE

98 Bolognese 2009 J Clin Not VE Endocrinol Metab 99 Bonneterre 2001 Cancer Not VE 100 Bonneterre 2000 J Clin Oncol Not VE 101 Boon 2003 Maturitas Not VE 102 Botsis 1997 Maturitas I 103 Bottiglione 1995 Maturitas Not FDA app prep 104 Bouchard 2015 Climacteric Not VE 105 Bouchard 2016 Horm Mol Biol Not VE Clin Investig 106 Brache 2007 Contraception Not VE 107 Brache 2000 Contraception Not VE 108 Brache 2001 Contraception Not VE 109 Breast International Group 2005 Not VE N Engl J Med 110 Brenner 1988 Obstet Gynecol Not Original 111 Brezina 2012 Reprod Biol Special Endocrinol 112 Brinsmead 1989 J In Vitro Fert Special Embryo Transf 113 Bronstein 1967 Int J Fertil Not VE 114 Brown 2001 Obstet Gynecol Not VE 115 Bruce 2004 Climacteric Not VE 116 Bruhat 2001 Maturitas Not VE 117 Bruni 2008 Eur J Obstet Not VE Gynecol Reprod Biol 118 Brunner 2010 Menopause Not VE 119 Bruyniks 2016 Climacteric Not VE 120 Brys 2009 Sao Paulo Med J Not FDA app prep 121 Brzyski 1992 Am J Obstet Not VE Gynecol 122 Buckler 2003 BJOG Hi Dose VE 123 Burch 1995 Br J Obstet Not VE Gynaecol 124 Buzdar 2001 J Clin Oncol Not VE 125 Bygdeman 1996 Maturitas Not FDA app prep 126 Cagnacci 1992 Life Sci Not VE 127 Cagnacci 1999 Maturitas Not FDA app prep 128 Campbell 1977 Clin Obstet Not VE Gynaecol 129 Cano 2012 Menopause Not FDA app prep 130 Cano 1999 Fertil Steril Not VE 131 Carmignani 2010 Maturitas Not VE 132 Carmignani 2015 Menopause Not VE 133 Carr 1995 J Clin Endocrinol Not VE Metab 134 Carranza-Lira 2007 Int J Fertil Not VE Womens Med

135 Carranza-Lira 2004 Int J Fertil Not VE Womens Med 136 Caruso 2004 Contraception Not VE 137 Caruso 2017 Menopause Not FDA app prep 138 Caruso 2000 Fertil Steril Not VE 139 Casanas-Roux 1996 Hum Not VE Reprod 140 Casanova 2015 Climacteric Not VE 141 Casanova 2009 Fertil Steril Not VE 142 Casanova 2012 Lipids Health Not VE Dis 143 Casper 1999 Int Urogynecol J I Pelvic Floor Dysfunct 144 Castellani 2015 Urol Int Not FDA app prep 145 Cayan 2008 J Sex Med Excluded after full- No AE text search 146 Ceyhan 2008 Fertil Steril Not VE 147 Chaikittisilpa 2011 J Med Assoc Not VE Thai 148 Checa 2005 Maturitas Not VE 149 Check 2004 Clin Exp Obstet Special Gynecol 150 Chen 2013 J Sex Med Not FDA app prep 151 Chen 2019 J Coll Physicians Not FDA app prep Surg Pak 152 Chiechi 2003 Maturitas Not VE 153 Chlebowski 2004 N Engl J Med Not VE 154 Choavaratana 2004 J Med Not VE Assoc Thai 155 Choktanasiri 1996 Int J Not VE Gynaecol Obstet 156 Chollet 2009 Menopause Not FDA app prep 157 Chompootaweep 1998 Clin Excluded after full- No AE Pharmacol Ther. text search 158 Christensen 1982 Am J Obstet Not VE Gynecol 159 Chughtai 2016 Post Reprod Excluded after full- Not VE Alone Health text search 160 Chung 2007 Yonsei Med J Not VE 161 Cicinelli 1996 Fertil Steril Not VE 162 Cicinelli 2004 Fertil Steril Excluded after full- No AE text search 163 Cicinelli 2003 Am J Obstet I Gynecol 164 Cicinelli 1993 Maturitas Not VE 165 Cicinelli 2007 Fertil Steril Not VE 166 Civelli 2007 Br J Clin Not VE Pharmacol

167 Clisham 1992 Obstet Gynecol Not VE 168 Coates 2007 J Clin Oncol Not VE 169 Cobo 1999 Hum Reprod Not VE 170 Cochrane 1997 Hum Reprod Not VE 171 Coelingh 2016 Maturitas Not FDA app prep 172 Colli 2012 J Med Food Not VE 173 Colodner 2003 Isr Med Assoc J. Not VE 174 Combs 2014 Am J Perinatol Not VE 175 Conner 2001 Climacteric Hi dose 176 Constantine 2014 J Sex Med Not VE 177 Constantine 2015 Climacteric Not VE 178 Constantine 2017 J Womens I Health (Larchmt) 179 Constantine 2015 Menopause Not VE 180 Constantine 2017 Menopause Excluded after full- No AE text search 181 Coope 1976 Postgrad Med J Not VE 182 Coope 1975 Br Med J Not VE 183 Corenthal 1994 Fertil Steril Not VE 184 Costantino 2008 Eur Rev Med Not VE Pharmacol Sci 185 Coutinho 1984 Fertil Steril Special 186 Coutinho 1993 Clin Pharmacol Special Ther 187 Coutinho 1993 Clin Pharmacol Special Ther 188 Coutinho 1995 Contraception Special 189 Couzinet 1992 J Clin Not VE Endocrinol Metab 190 Crisafulli 2004 Menopause Not VE 191 Croxatto 2006 Contraception Special 192 Crucitti 2018 PLoS One Special 193 Cruz 2018 Menopause Not FDA app prep 194 Cullberg 1984 Contraception Not VE 195 Cummings 2002 Menopause Not VE 196 Cuong 1996 Contraception Special 197 Dahiya 2016 Eur J Obstet Not VE alone Gynecol Reprod Biol 198 Dalais 1998 Climacteric Not VE 199 Darney 1992 Fertil Steril Not VE 200 Davies 1999 Obstet Gynecol Not VE 201 Davies 1999 Menopause Not VE 202 Day 2001 Ann N Y Acad Sci Not VE 203 de Ziegler 1992 J Clin Not VE Endocrinol Metab 204 de Ziegler 2000 Hum Reprod Not VE

205 Dehbashi 2003 Int J Gynaecol Not VE Obstet 206 Del Pup 2012 Maturitas Not FDA app prep 207 Delmanto 2008 Eur J Obstet Not VE Gynecol Reprod Biol 208 Delmas 1996 Eur J Obstet Not VE Gynecol Reprod Biol 209 Delmas 1997 N Engl J Med Not VE 210 Dempsey 2010 Contraception Special 211 Dennerstein 1980 Maturitas Not VE 212 Deshmane 2007 J Clin Oncol Not VE 213 Devenport 1989 Br J Clin Not VE Pharmacol 214 Devoto 1997 Hum Reprod Not VE 215 Di Carlo 2005 Menopause Not VE 216 Di Carlo 2010 Climacteric Not VE 217 Diaz 1999 Hum Reprod Special 218 Dickerson 1979 Clin Pharmacol I Ther 219 Dickey 1995 Hum Reprod Not VE 220 Dieben 2002 Obstet Gynecol Special 221 Diem 2006 Menopause Not VE 222 Dietz 2013 Int Urogynecol J Not VE 223 Ditkoff 1991 Am J Obstet Not VE Gynecol 224 Dogterom 2005 Clin Special Pharmacokinet 225 Donders 2014 Breast Cancer Not FDA app prep Res Treat 226 Donnez 2003 Fertil Steril Not VE 227 Doren 1999 Menopause Not VE 228 Dorr 2010 Fertil Steril I 229 Dragonas 2007 Eur J Med Res Not VE 230 Duffy 1995 Fertil Steril Not VE 231 Dugal 2000 Acta Obstet Gynecol I Scand 232 Duijkers 2004 Eur J Contracept Special Reprod Health Care 233 Duijkers 2018 Eur J Contracept Special Reprod Health Care 234 Duijkers 2004 Hum Reprod Special 235 Duijkers 1993 Hum Reprod Not VE 236 Duijkers 2004 Hum Reprod Special 237 Duncan 1999 J Clin Endocrinol Not VE Metab 238 Dyer 1982 Br Med J (Clin Res Excluded after full- No AE Ed) text search

239 Eagleson 2000 J Clin Not VE Endocrinol Metab 240 Egarter 1996 Maturitas Not VE 241 Egarter 1995 Contraception Special 242 Ekin 2011 Arch Gynecol Obstet Excluded after full- No AE text search 243 el-Damarawy 1977 Not VE Prostaglandins 244 Elfituri 2005 Maturitas Not VE 245 el-Habashy 1970 Obstet Not VE Gynecol 246 Elkind-Hirsch 2005 Curr Med Not VE Res Opin 247 Elkind-Hirsch 2007 Special Contraception 248 Elkind-Hirsch 2002 Hum Special Reprod 249 Ellington 2016 Female Pelvic I Med Reconstr Surg 250 Ellmen 2003 Breast Cancer Res Not VE Treat 251 Elomaa 2001 Hum Reprod Special 252 Engmann 2008 Fertil Steril Special 253 Epstein 2001 Ultrasound Obstet Not VE Gynecol 254 Eriksen 1999 Am J Obstet I Gynecol 255 Eriksen 1992 Eur J Obstet Excluded after full- No AE Gynecol Reprod Biol text search 256 Ettinger 1997 Am J Obstet Not VE Gynecol 257 Ettinger 1999 JAMA Not VE 258 Ettinger 2008 Obstet Gynecol Not VE 259 Ettinger 2001 Obstet Gynecol Not VE 260 Eugster 2003 J Pediatr Not VE 261 Eugster-Hausmann 2010 I Climacteric 262 Exton 1999 Psychosom Med Not VE 263 Fahy 19995 Hum Reprod Not VE 264 Fallowfield 2012 Br J Cancer Not VE 265 Fanchin 1997 Obstet Gynecol Not VE 266 Fanchin 2001 Fertil Steril Not VE 267 Fanchin 2001 Fertil Steril Special 268 Fantl 1996 Am J Obstet Gynecol Not VE 269 Farag 2002 Am J Obstet Not VE Gynecol 270 Fatemi 2007 Hum Reprod Not VE 271 Fatemi 2007 Fertil Steril Not VE

272 Fatemi 2006 Hum Reprod Not VE 273 Faundes 1998 Hum Reprod Special 274 Fedele 1993 Fertil Steril Not VE 275 Felding 1992 Maturitas I 276 Fernandes 2016 Menopause I 277 Fernandes 2014 J Sex Med Excluded after full- No AE text search 278 Ferrero 2002 Minerva Ginecol Not VE 279 Ferrero 2013 Arch Gynecol Not VE Obstet 280 Feuillan 2007 J Clin Endocrinol Not VE Metab 281 Ficicioglu 2004 Gynecol Not VE Endocrinol 282 Florio 2012 Steroids Not VE 283 Foster 1999 Obstet Gynecol Excluded after full- No AE text search 284 Franke 2006 Gynecol Not VE Endocrinol 285 Fraser 1989 Maturitas Not VE 286 Fraser 1995 Maturitas Excluded after full- Not Original text search 287 Fraser 2000 Contraception Special 288 Fraser 2005 Contraception Special 289 Fredricsson 1989 Gynecol Not VE Obstet Invest 290 Freedman 2009 Menopause Not FDA app prep 291 Friedler 2006 Reprod Biomed Not VE Online 292 Friedler 1999 Hum Reprod Special 293 Friedrich 1998 Eur J Gynaecol Not VE Oncol 294 Frigo 1995 Maturitas Not VE 295 Fuertes-de 1973 J Reprod Med Special 296 Gabrielsson 1996 Acta Obstet Excluded after full- Not Original Gynecol Scand Suppl text search 297 Galhardo 2006 Clin Exp Obstet Excluded after full- Not VE Gynecol text search 298 Galuppi 2011 Int J Gynecol Not VE Cancer 299 Ganz 2000 J Natl Cancer Inst Not VE 300 Garcia 1968 Int J Fertil Not VE 301 Gass 2004 Maturitas Not VE 302 Gass 2018 Menopause Not VE 303 Gast 2009 Menopause Excluded after full- Not VE Alone text search 304 Gazvani 2012 Trials Not VE 305 Gerber 2000 J Clin Oncol Not VE

306 Gerhard 1987 Biol Res Not VE Pregnancy Perinatol 307 Gerhard 1992 Clin Ther Not VE 308 Gerhard 1998 Circulation Not VE 309 Gilboa 2005 Reprod Biomed Not VE Online 310 Ginsburg 1995 Maturitas Not VE 311 Glaser 2008 Gynecol Obstet Not VE Alone Invest 312 Glasier 2002 Fertil Steril Not VE 313 Glazener 1985 Br J Obstet Not VE Gynaecol 314 Glock 1995 Obstet Gynecol Not VE 315 Gocmen 2002 Clin Exp Obstet Not VE Gynecol 316 Goetsch 2014 Obstet Gynecol Not VE 317 Goetsch 2015 J Clin Oncol Not VE 318 Goldstein 2012 Menopause Not VE 319 Goldstein 2002 Am J Obstet Not VE Gynecol 320 Goldstein 2011 Menopause Not VE 321 Goldzieher 1975 Am J Obstet Special Gynecol 322 Goni 1994 Hum Reprod Not VE 323 Good 1996 Clin Ther Not VE 324 Good 1999 Climacteric Not VE 325 Gorkemli 2004 Gynecol Obstet Not VE Invest 326 Goss 1995 Clin Cancer Res Not VE 327 Goss 2003 N Engl J Med Not VE 328 Granese 2007 Ginecol Not VE 329 Graser 2000 Climacteric Not VE 330 Grigoryan 2008 Gynecol Special Endocrinol 331 Grimes 1994 Obstet Gynecol Not VE 332 Grodnitskaya 2010 Gynecol Special Endocrinol 333 Grubb 1989 Fertil Steril Not VE 334 Guerriero 2001 Menopause Not VE 335 Guida 2005 Hum Reprod Special 336 Gupta 2008 Menopause I 337 Haas 1988 Obstet Gynecol Not VE 338 Haimov-Kochman 2006 Not VE Menopause 339 Haines 2009 Climacteric Not VE 340 Hall 2002 Fertil Steril Excluded after full- Hi dose VE text search 341 Halmesmaki 2007 BJOG Not VE

342 Hamilton 1993 Fertil Steril Not VE 343 Hamm 1991 J Clin Oncol Not VE 344 Hammar 1998 Br J Obstet Not VE Gynaecol 345 Hammar 2007 BJOG Not VE 346 Hammond 1979 Am J Obstet Not VE Gynecol 347 Hampton 2005 Hum Reprod Not VE 348 Hanifi-Moghaddam 2007 J Mol Not VE Med (Berl) 349 Hanifi-Moghaddam 2008 Hum Not VE Reprod 350 Haring 2003 Contraception Special 351 Hedrick 2009 Menopause Not VE 352 Heimer 1992 Maturitas Not FDA app prep 353 Henderson 2016 Neurology Not VE 354 Henriksson 1994 Am J Obstet I Gynecol 355 Henriksson 1996 Am J Obstet I Gynecol 356 Herbst 1980 J Reprod Med Not VE 357 Hernandez-Torres 1970 Am J Not VE Obstet Gynecol 358 Hickey 2016 Breast Cancer Res Not VE Treat 359 Hickok 1993 Obstet Gynecol Not VE 360 Hilbert 2001 Obstet Gynecol Not VE 361 Hilton 1983 Br J Obstet I Gynaecol 362 Hirata 1997 Fertil Steril Not VE 363 Hirvonen 2000 Climacteric Not VE 364 Hodis 2016 N Engl J Med Not VE 365 Holli 2000 J Clin Oncol Not VE 366 Holmgren 1989 Maturitas I 367 Homesley 1993 Am J Clin Not VE Oncol 368 Honjo 2009 Climacteric Not VE 369 Honkanen 2005 Acta Obstet Not VE Gynecol Scand 370 Hovik 1989 Maturitas Not VE 371 Howell 1996 Br J Cancer Not VE 372 Huang 2008 Am J Obstet Not VE Gynecol 373 Huang 2008 Arch Intern Med Not VE 374 Huber 2002 BJOG Not VE 375 Hudita 2003 Eur Rev Med Not VE Pharmacol Sci 376 Humaidan 2005 Hum Reprod Not VE

377 Hundley 2005 Am J Obstet Not VE Gynecol 378 Hupperets 1993 Ann Oncol Not VE 379 Hurd 1996 Fertil Steril Not VE 380 Hurst 2008 J Reprod Med I 381 Illston 2015 Maturitas I 382 Ismail 2016 Hum Fertil (Camb) Not VE 383 Ito 2006 J Sex Marital Ther Not VE 384 Iwase 2013 Br J Cancer Not VE 385 Jackson 1989 Contraception Special 386 Jackson 2002 BJOG Not VE 387 Jain 1999 Contraception Not VE 388 Jaisamrarn 2001 J Med Assoc Not VE Thai 389 Jaschevatzky 1979 Acta Obstet Not VE Gynecol Scand 390 Jensen 1987 Br J Obstet Not VE Gynaecol 391 Jensen 187 Br J Obstet Not VE Gynaecol 392 Jensen 1989 Maturitas Not VE 393 Jewelewicz 1971 J Clin Not VE Endocrinol Metab 394 Jiang 2016 Menopause Not VE alone 395 Johannisson 1988 Maturitas Not VE 396 Johnson 2005 Not VE 397 Jolly 2003 Menopause Not VE 398 Jonasson 2011 Menopause Not VE 399 Judd 1987 Am J Obstet Gynecol Not VE 400 Kaari 2006 Maturitas Not VE 401 Kagan 2018 Postgrad Med Not VE 402 Kagan 2010 Menopause Not VE 403 Kalogeropoulos 2004 Gynecol Not VE Endocrinol 404 Kalogirou 1996 Int J Fertil Not VE alone Menopausal Stud 405 Karp 2012 Female Pelvic Med Special Reconstr Surg 406 Kauppila 1988 Gynecol Obstet Not VE Invest 407 Kazerooni 2004 Gynecol Not VE Endocrinol 408 Ke 2015 Horm Mol Biol Clin Not VE Investig 409 Ke 2015 J Steroid Biochem Not VE Mol Biol 410 Kedzia 2000 Eur J Gynaecol Not VE Oncol

411 Keskin 2012 J Minim Invasive Not VE Gynecol 412 Kessel 2003 Climacteric Excluded after full- Not VE Alone text search 413 Kestelyn 2018 PLoS One Special 414 Killick 1998 Am J Obstet Not VE Gynecol 415 Kingsberg 2016 J Sex Med Excluded after full- No AE text search 416 Kingsberg 2017 Menopause Excluded after full- No AE text search 417 Kives 2005 Contraception Special 418 Knight 1999 Climacteric Not VE 419 Knight 2001 Climacteric Not VE 420 Kobata 2008 Maturitas Excluded after full- No AE text search 421 Koetsawang 1990 Contraception Special 422 Kohler 1990 Breast Cancer Res Not VE Treat 423 Kokcu 2000 Maturitas Not VE 424 Kolibianakis 2005 Hum Reprod Not VE 425 Komi 2006 J Bone Miner Metab Not VE 426 Komi 2005 Menopause Not VE 427 Kornafel 1992 South Med J Not VE 428 Koskimies 2013 Int J Clin Not VE Pharmacol Ther 429 Koss 1995 J Cell Biochem Suppl Not VE 430 Kotsopoulos 2000 Climacteric Not VE 431 Kresanov 1994 Ann Chir Not VE Gynaecol Suppl 432 Kroiss 2005 BJOG Not VE 433 Kroll 2018 Menopause Not FDA app. prep. 434 Kunz 2007 Reprod Biomed Not VE Online 435 Kutlusoy 2014 Gynecol Not VE Endocrinol 436 Laan 2008 J Sex Med Not VE 437 Labrie 2009 Menopause Not VE 438 Labrie 2009 Menopause Not VE 439 Labrie 2010 Gynecol Endocrinol Not VE 440 Labrie 2009 Menopause Not VE 441 Labrie 2014 J Sex Med Not VE 442 Labrie 2011 Climacteric Not VE 443 Labrie 2008 J Steroid Biochem Not VE Mol Biol 444 Labrie 2009 Menopause I 445 Labrie 2017 Horm Mol Biol Clin Not VE Investig

446 Labrie 2013 J Steroid Biochem Not VE Mol Biol 447 Lahti 1994 Gynecol Oncol Not VE 448 Lan 2008 Reprod Biomed Online Not VE 449 Landgren 1994 Contraception Not VE 450 Landgren 1985 Contraception Not VE 451 Landgren 1995 Contraception Not VE 452 Landgren 2002 BJOG Not VE 453 Landgren 2005 Maturitas Not VE 454 Langer 2006 Am J Obstet Not VE Gynecol 455 Langrish 2009 Hypertension Not VE 456 Lara 2014 Tissue Cell Not VE 457 Larmo 2014 Maturitas Not VE 458 Larmon 2002 J Matern Fetal Special Neonatal Med 459 Ledee-Bataille 2002 Hum Special Reprod 460 Lee 2007 Maturitas Not VE 461 Lee 2013 Hum Reprod Not VE 462 Lee 2012 Ultrasound Obstet Not VE Gynecol 463 Lee 2017 Hum Reprod Not VE 464 Leeton 1973 Aust N Z J Obstet Not VE Gynaecol 465 Legro 2008 J Clin Endocrinol Not VE Metab 466 Lemay 1988 Am J Obstet Not VE Gynecol 467 Leone 2014 Acta Obstet Gynecol Special Scand 468 Leonetti 2005 Altern Ther Not VE Health Med 469 Leslie 2007 Appl Not VE Immunohistochem Mol Morphol 470 Lete 1997 Eur J Contracept Not VE Reprod Health Care 471 Leung 2005 Clin Pediatr (Phila) Special 472 Levis 2010 Contemp Clin Trials Not VE 473 Levis 2011 Arch Intern Med Not VE 474 Lewin 2002 Gynecol Endocrinol Not VE 475 Liang 2006 J Huazhong Univ Not VE Sci Technolog Med Sci 476 Liapis 2010 Maturitas Special 477 Lightman 1999 Hum Reprod Not VE 478 Lima 2014 Maturitas Not VE 479 Lima 2013 Maturitas I 480 Lin 2011 Climacteric Not VE

481 Lin 1973 Obstet Gynecol Excluded after full- Not VE text search 482 Lind 1979 Br J Obstet Gynaecol Not VE 483 Lindgren 1992 Maturitas Not VE 484 Lindsay 2002 JAMA Not VE 485 Lippuner 1997 J Bone Miner Not VE Res 486 Liske 2002 J Womens Health Not VE Gend Based Med 487 Liu 2009 J Altern Complement Not VE Med 488 Lobo 2009 Fertil Steril Not VE 489 Long 2006 Fertil Steril I 490 Long 2006 Menopause I 491 Loprinzi 1997 J Clin Oncol Not VE 492 Lose 2000 BJOG I 493 Ludwig 2001 Acta Obstet Not VE Gynecol Scand 494 Luisi 2009 Fertil Steril Not VE 495 MacDonald 1972 Obstet Special Gynecol 496 MacLennan 1981 Obstet Special Gynecol 497 Maenpaa 1990 J Steroid Not VE Biochem 498 Magann 1995 Am J Obstet Special Gynecol 499 Magnusdottir 2004 Special Contraception 500 Mainini 2005 Clin Exp Obstet I Gynecol 501 Makkar 2014 Gynecol Obstet Special Invest 502 Malik 2016 Arch Gynecol Obstet Not VE 503 Manonai 2004 Eur J Obstet Excluded after full- Not VE Gynecol Reprod Biol text search 504 Manonai 2006 Eur J Obstet I Gynecol Reprod Biol 505 Manonai 2001 J Obstet I Gynaecol Res 506 Mansel 2007 Breast Cancer Res Not VE Treat 507 Manuck 2016 Am J Obstet Not VE Gynecol 508 Marsden 2000 Fertil Steril Not VE 509 Martin 1998 Contraception Not VE 510 Martinez 2006 Hum Reprod Special 511 Martinez 2000 Gynecol Not VE Endocrinol

512 Martinez 1998 Contraception Not VE 513 Marttunen 2001 Br J Cancer Not VE 514 Marx 2004 Maturitas Not FDA app prep 515 Massai 2005 Hum Reprod Special 516 Massaro 2010 Contraception Special 517 Matorras 2002 Hum Reprod Not VE 518 Matorras 2000 Hum Reprod Not VE 519 Mattsson 1989 Maturitas I 520 McArthur 1993 Acta Endocrinol Not VE (Copenh) 521 Melis 1995 Fertil Steril Not VE 522 Melis 1992 J Endocrinol Invest Not VE 523 Melisko 2017 JAMA Oncol Special 524 Mercuro 1999 Am J Cardiol Not VE 525 Merz 2010 Am Heart J Not VE 526 Mettler 1991 Maturitas I 527 Meyer 1995 S Afr Med J Not VE 528 Michael 1970 J Gerontol Excluded after full- No AE text search 529 Mikkelsen 1995 Gynecol Obstet Special Invest 530 Mikkelsen 2000 Hum Reprod Not VE 531 Miller 2005 Obstet Gynecol Special 532 Mirkin 2013 Climacteric Not VE 533 Mirkin 2016 J Womens Health Not VE (Larchmt) 534 Mishell 1998 Contraception Not VE 535 Mitchell 2018 JAMA Intern I Med 536 Mitchell 2017 Menopause Not VE 537 Mochtar 1996 Hum Reprod Not VE 538 Mochtar 2006 Hum Reprod Not VE 539 Moghissi 1998 Fertil Steril Not VE 540 Molander 1993 Acta Obstet Not VE Gynecol Scand Suppl 541 Molander 1990 Maturitas Not VE 542 Morales 2004 Anticancer Drugs Not VE 543 Morales 2009 Breast Cancer Res Not VE Treat 544 Morali 2006 Not VE Arzneimittelforschung 545 Morgan 2007 Maturitas Not VE 546 Mortimer 1999 J Clin Oncol Not VE 547 Mozzanega 2007 Gynecol Not VE Endocrinol 548 Mulders 2001 Fertil Steril Special 549 Mulders 2002 Hum Reprod Special

550 Murina 2016 Eur J Obstet Not FDA app prep Gynecol Reprod Biol 551 Murkies 1995 Maturitas Not VE 552 Nabholtz 2003 Eur J Cancer Not VE 553 Nabholtz 2000 J Clin Oncol Not VE 554 Nachtigall 1994 Fertil Steril I 555 Nachtigall 1995 Maturitas I 556 Naessen 1997 Am J Obstet I Gynecol 557 Naessen 2002 Am J Obstet I Gynecol 558 Naessen 2001 J Clin Endocrinol I Metab 559 Nand 1998 Climacteric Not VE 560 Nand 1998 Obstet Gynecol Not VE 561 Nand 1995 Aust N Z J Obstet Not VE Gynaecol 562 Nankin 1986 Fertil Steril Not VE 563 Nappi 2006 Maturitas Not VE 564 Nappi 2015 Climacteric Not VE 565 Narvekar 2007 Contraception Not VE 566 Nash 1999 Am J Obstet Gynecol Hi dose VE 567 Nathorst-Boos 1993 Acta Obstet Not VE Gynecol Scand 568 Navarro 2003 Maturitas Not VE 569 Nelken 2011 Menopause I 570 Neven 2003 BJOG Not VE 571 Ng 2007 Eur J Obstet Gynecol Not VE Reprod Biol 572 Nijland 2009 Climacteric Not VE 573 Nijland 2007 Maturitas Not VE 574 Nikander 2005 Fertil Steril Not VE 575 Nilsson 1992 Maturitas I 576 Noe 2010 Climacteric Not VE 577 Noh 2016 J Med Food Not VE 578 Norman 2011 Reprod Sci Not VE 579 Notelovitz 1995 Maturitas Not VE 580 Notelovitz 2002 Obstet Gynecol I 581 Notelovitz 2000 Menopause Not VE 582 Novak 2003 Contraception Special 583 Nummi 1978 Curr Med Res Not VE Opin 584 Nunes 2011 Climacteric Not VE 585 O'Brien 1996 Br J Cancer Not VE 586 O'Connell 2005 Contraception Special 587 Odabasi 2007 J Postgrad Med Not VE 588 Oddsson 2005 Hum Reprod Special

589 O'Donnell 2012 Hum Reprod Not VE 590 Oppegaard 2008 BJOG Special 591 Oppegaard 2010 BJOG Special 592 Osmanagaoglu 2006 Climacteric Not VE 593 Ouslander 1999 J Am Geriatr I Soc 594 Ouslander 2001 J Am Geriatr Not VE Soc 595 Padayachi 1989 S Afr Med J Not VE 596 Padwick 1986 Br J Obstet Not VE Gynaecol 597 Pafumi 2002 Minerva Ginecol Not VE 598 Palacios 2016 Climacteric Not VE 599 Palacios 2005 Maturitas Excluded after full- Not VE Alone text search 600 Palva 2013 Eur J Cancer Not VE 601 Panay 2007 Climacteric Not VE 602 Parker 1994 Pediatr Res Not VE 603 Parker 1980 Contraception Not VE 604 Parkinson 2011 Parkinsonism Not VE Relat Disord 605 Parsons 2003 Obstet Gynecol Excluded after full- Not VE Alone text search 606 Pasquale 1997 Fertil Steril Not VE 607 Pattison 1989 Aust N Z J Obstet Not VE Gynaecol 608 Peethambaram 1999 Breast Not VE Cancer Res Treat 609 Pentikis 2017 Adv Ther Not VE 610 Perovic 1975 Not FDA app prep Arzneimittelforschung 611 Petri 2004 Maturitas Not VE 612 Petta 1998 Fertil Steril Not VE 613 Petta 2001 Fertil Steril Not VE 614 Pfeiler 2011 Climacteric Not FDA app prep 615 Piccoli 2008 Eur J Obstet Special Gynecol Reprod Biol 616 Pickar 2016 Climacteric I 617 Pickar 2016 Menopause I 618 Pinelli 1996 Gynecol Oncol Not VE 619 Pinkerton 2016 Menopause Not VE 620 Pinkerton 2017 Menopause Not VE 621 Pinkerton 2017 Maturitas Not VE 622 Pinkerton 2016 Menopause Not VE 623 Pinkerton 2003 Menopause I 624 Pirard 2006 Hum Reprod Not VE 625 Piya-Anant 1998 Contraception Not VE

626 Ploch 1987 Gynecol Oncol Not VE 627 Portman 2014 Maturitas Not VE 628 Portman 2013 Menopause Not VE 629 Portman 2015 Menopause Not VE 630 Powles 1994 Breast Cancer Res Not VE Treat 631 Prata 2018 Theriogenology Not VE 632 Preston 2015 Am J Ther Not VE 633 Preston 2007 Menopause Not VE 634 Prince 1991 N Engl J Med Not VE 635 Propst 2001 Fertil Steril Not VE 636 Quaranta2014 Minerva Ginecol Not VE 637 Rad 2006 Am J Obstet Gynecol Special 638 Raghunandan 2010 J Sex Med I 639 Ragni 1999 Gynecol Obstet Not VE Invest 640 Rahn 2014 J Clin Endocrinol Special Metab 641 Raudaskoski 2002 BJOG Not VE 642 Raymundo 2004 Climacteric I 643 Raz 1993 N Engl J Med Non FDA app prep 644 Rebar 2000 Climacteric Not VE 645 Reed 2014 Obstet Gynecol Not VE 646 Reed 2008 Menopause Not VE 647 Reindollar 2002 Fertil Steril Not VE 648 Rice 1996 Hum Reprod Not VE 649 Riman 2002 J Natl Cancer Inst Not VE 650 Rioux 2000 Menopause I 651 Ronnberg 1989 Acta Obstet Not VE Gynecol Scand 652 Ross 1997 Am J Obstet Gynecol Not VE 653 Ross 1997 Maturitas Not VE 654 Rotem 2007 Gynecol Endocrinol Not VE 655 Roumen 2006 Fertil Steril Special 656 Roux 2002 Osteoporos Not VE 657 Rovati 1999 Not VE Arzneimittelforschung 658 Roy 1980 Am J Obstet Gynecol Special 659 Rozenberg 2009 Hum Reprod Not VE 660 Rozenberg 1997 Int J Fertil Not VE Womens Med 661 Roztocil 1998 Ceska Gynekol Special 662 Rufford 2003 Int Urogynecol J Excluded after full- Not VE Pelvic Floor Dysfunct text search 663 Rungruxsirivorn 2006 J Med Not VE Assoc Thai 664 Russo 2003 Acta Biomed Not VE

665 Rutanen 2003 Menopause Not VE 666 Rymer 1994 Br J Obstet Not VE Gynaecol 667 Saano 1995 Clin Pharmacol Not VE Ther 668 Sabatini 2006 Contraception Special 669 Sagsoz 2005 Eur J Obstet Not VE Gynecol Reprod Biol 670 Said 1996 Hum Reprod Not VE 671 Saleh 1993 Am J Obstet Gynecol Not VE 672 Salminen 2007 Maturitas Excluded after full- Not VE alone text search 673 Sammour 1970 Fertil Steril Special 674 Samsioe 2007 Maturitas Not VE 675 Sang 1995 Contraception Not VE 676 Santen 2002 Menopause Excluded after full- Not FDA app prep -Note: Goal was text search to use FDA-approved preparation to determine lowest effective dose that is lower than FDA-approved dose 677 Sarrel 1998 Int J Impot Res Not VE 678 Sarrel 1997 Fertil Steril Not VE 679 Sator 2001 Maturitas Not VE 680 Saunders 1990 Br J Obstet Not VE Gynaecol 681 Saure 1995 Am J Obstet Gynecol Excluded after full- Not Original text search 682 Saure 2000 Maturitas Not VE 683 Sawaya 2000 Ann Intern Med Not VE 684 Scambia 2000 Menopause Not VE 685 Schmidt 1994 Gynecol Obstet I Invest 686 Schug 2012 Int J Clin Not VE Pharmacol Ther 687 Schwartz 2002 Obstet Gynecol Not VE 688 Schwarz 1992 Int J Fertil Not VE 689 Seckin 2014 J Reprod Med Not VE 690 Seely 1999 Hypertension Not VE 691 Segal 1992 Fertil Steril Not VE 692 Shaaban 1991 J Steroid Biochem Not VE Mol Biol 693 Shapiro 1993 Fertil Steril Not VE 694 Sho 2017 Climacteric Not VE 695 Shulman 2002 Menopause Not VE 696 Siddle 1990 Br J Obstet Not VE Gynaecol 697 Silverman 1966 J Oral Ther Not VE Pharmacol

698 Simmons 2012 Clin Oncol (R Special Coll Radiol) 699 Simon 1998 Hum Reprod Not VE 700 Simon 2005 Hum Reprod Not VE 701 Simon 2008 Obstet Gynecol I 702 Simon 2010 Obstet Gynecol I 703 Simon 2014 Maturitas Not VE 704 Simon 2018 J Womens Health Not VE (Larchmt) 705 Simon 2017 Menopause Not VE 706 Simon 2007 Obstet Gynecol Not VE 707 Simon 2013 Menopause Not VE 708 Simon 2003 Am J Obstet Not VE Gynecol 709 Simon 2008 Fertil Steril Not FDA app prep 710 Simunic 2003 Int J Gynaecol I Obstet 711 Sinofsky 1998 Am J Obstet Not VE Gynecol 712 Siseles 1995 Maturitas Not VE 713 Sismondi 2011 Maturitas Not VE 714 Sit 2004 Cancer Epidemiol Not VE Biomarkers Prev 715 Sitruk-Ware 2007 J Clin Not FDA app prep Endocrinol Metab 716 Sitruk-Ware 2007 Contraception Special 717 Sivin 1981 Contraception Special 718 Smith 2000 J Wound Ostomy Not VE Continence Nurs 719 Smith 2014 J Clin Endocrinol Not VE Metab 720 Smitz 1993 Hum Reprod Not VE 721 Smitz 1992 Hum Reprod Not VE 722 Sonnendecker 1990 S Afr Med J Not VE 723 Sonntag 2013 Gynecol Not VE Endocrinol 724 Souka 1985 Contraception Special 725 Speroff 2003 Obstet Gynecol Hi Dose 726 Speroff 2006 Menopause Not VE 727 Spicer 1993 Contraception Not VE 728 Spiryda 2003 Biol Blood Special Marrow Transplant 729 Spritzer 2003 Exp Clin Not VE Endocrinol Diabetes 730 Stachenfeld 2001 Am J Physiol Not VE Regul Integr Comp Physiol 731 Stark 1978 Am J Obstet Gynecol Excluded after full- No AE text search

732 Steer 1995 Fertil Steril Not VE 733 Stephenson 2000 Fertil Steril Not VE 734 Stomati 1997 Maturitas Not VE 735 Stone 1975 Obstet Gynecol Not VE 736 Stratton 2000 Hum Reprod Not VE 737 Streuli 2008 Fertil Steril Special 738 Sulak 1999 Int J Fertil Womens Not VE Med 739 Sulak 2008 Obstet Gynecol Special 740 Sun 2016 Menopause Special 741 Surrey 1992 J Clin Endocrinol Not VE Metab 742 Surrey 195 Fertil Steril Not VE 743 Suvanto-Luukkonen 1999 Fertil Not VE Steril 744 Suwanvesh 2017 Menopause I 745 Swanson 2006 Menopause Not VE 746 Symons 2000 Obstet Gynecol Not VE 747 Taechakraichana 1997 J Med I Assoc Thai 748 Tahara 2006 Fertil Steril Not VE 749 Takahashi 2000 Hum Reprod Not VE 750 Tan 2005 Maturitas Not VE 751 Tang 1999 Hum Reprod Not VE 752 Tanko 2002 Biomarkers Not VE 753 Tarkkila 1977 Curr Med Res Not VE Opin 754 Taskin 1997 Fertil Steril Not VE 755 Tay 2003 Med J Malaysia Not VE 756 Tedeschi 2012 Gynecol Not VE Endocrinol 757 Teichmann 2009 Contraception Not VE 758 Teter 1972 Acta Cytol Not VE 759 Thatcher 1988 Fertil Steril Not VE 760 Thijssen 1984 J Steroid Biochem Not FDA app prep 761 Thong 1993 Br J Obstet Not VE Gynaecol 762 Timmer 2000 Clin Special Pharmacokinet 763 Timmer 2002 Br J Clin Not VE Pharmacol 764 Tinelli 2007 Gynecol Endocrinol Not FDA app prep 765 Toner 2000 Hum Reprod Not VE 766 Tontivuthikul 2016 J Med Assoc I Thai 767 Torella 2016 Eur J Obstet Excluded after full- Not FDA app prep Gynecol Reprod Biol text search 768 Torky 2018 Climacteric Not VE

769 Tourgeman 2001 Fertil Steril Special 770 Tourgeman 1999 Am J Obstet Special Gynecol 771 Tourgeman 2001 Fertil Steril Special 772 Traina 2008 Breast Cancer Res Not VE Treat 773 Tregon 2003 Menopause Not VE 774 Tromans 1981 Br Med J (Clin Special Res Ed) 775 Trotter 2002 Am J Obstet Not VE Gynecol 776 Tsai 2001 Osteoporos Int Not VE 777 Tsang 2000 Neurology Not VE 778 Tseng 2009 Neurourol Urodyn Not VE alone 779 Tuppurainen 2004 Special Contraception 780 Uesugi 2003 Endocr J Not VE 781 Ulrich 2010 Climacteric I 782 Unfer 2004 Reprod Biomed Not VE Online 783 Unkila 2013 J Steroid Biochem Not VE Mol Biol 784 Utian 1973 Br Med J Not VE 785 Utian 1989 Minerva Endocrinol Not VE 786 Utian 2004 Menopause Not VE 787 Utian 2001 Fertil Steril Not VE 788 Utian 2005 Menopause Not VE 789 Uygur 2005 Gynecol Endocrinol Not VE 790 Vaccaro 2013 Female Pelvic Special Med Reconstr Surg 791 Valiati 2009 Maturitas Not VE 792 van de Vijver 2017 Gynecol Not VE Endocrinol 793 van de Vijver 2016 Hum Reprod Not VE 794 van de Weijer 1999 Obstet Not VE Gynecol 795 van de Weijer 1998 Maturitas Not VE 796 van de Weijer 1992 Climacteric Not VE 797 van den Heuvel 2005 Special Contraception 798 van der Laak 2002 J Clin Pathol Not VE 799 van der Linden 1993 Eur J Not FDA app prep Obstet Gynecol Reprod Biol 800 van Haaften 1989 J Steroid I Biochem 801 van Haaften 1997 Gynecol I Endocrinol

802 Van Leusden 1993 Int J Fertil Not VE Menopausal Stud 803 Var 2011 Fertil Steril Not VE 804 Vardy 2003 Am J Obstet Not VE Gynecol 805 Vartiainen 1993 Maturitas Hi Dose 806 Veerus 2008 BMC Womens Not VE Health 807 Vercellini 2005 Fertil Steril Not VE 808 Veres 2004 Obstet Gynecol Special 809 Verheul 2007 Reprod Sci Not VE 810 Verhoeven 2004 Contraception Special 811 Verhoeven 2004 Contraception Special 812 Veronesi 2007 J Natl Cancer Not VE Inst 813 Vestergaard 2003 Maturitas Not VE 814 Victor 1984 Ups J Med Sci Special 815 Victor 2006 Am J Ther Special 816 Vilodre 2003 Gynecol Not VE Endocrinol 817 Voipio 2002 Maturitas Not VE 818 von Holst 2000 Maturitas Not VE 819 Wang 2015 PLoS One Not VE 820 Warming 2003 Maturitas Not VE 821 Warming 2005 Maturitas Not VE 822 Warren 1999 Am J Obstet Not VE Gynecol 823 Watts 1995 Obstet Gynecol Not VE 824 Webb 1992 BMJ Not VE 825 Weeks 1999 Am J Obstet Not VE Gynecol 826 Weidner 2013 Int Urogynecol J Special 827 Weinstein 1987 Obstet Gynecol Not VE 828 Weisberg 2005 Climacteric I 829 Weisberg 2005 Contraception Special 830 Weisberg 1997 Contraception Special 831 Weisberg 1995 Contraception Special 832 Weisberg 1999 Contraception Special 833 Welton 2008 BMJ Not VE 834 Werther 1990 J Paediatr Child Not VE Health 835 Westergaard 1996 Hum Reprod Not VE 836 Westhoff 2005 Obstet Gynecol Special 837 Widholm 1974 Ann Chir Excluded after full- Not FDA app prep Gynaecol Fenn text search 838 Wihlback 2007 Gynecol Not VE Endocrinol

839 Wihlback 2005 Not VE Psychoneuroendocrinology 840 Wiklund 1999 Int J Clin Not VE Pharmacol Res 841 Wilcox 1990 BMJ Not VE 842 Wildemeersch 2000 Maturitas Not VE 843 Williams 1994 Obstet Gynecol Not VE 844 Williams 2001 Fertil Steril Not VE 845 Williams 1990 Am J Obstet Not VE Gynecol 846 Wilson 2007 Int J STD AIDS Not VE 847 Wilson 1987 Br J Obstet Not VE Gynaecol 848 Wishart 1991 Australas J Not VE Dermatol 849 Witherby 2011 Oncologist Not VE 850 Wolfe 1999 Maturitas Not VE 851 Wolfe 1994 Maturitas Not VE 852 Wolff 2013 Fertil Steril Not VE 853 Wolff 1982 Maturitas Not FDA app prep 854 Wright 2006 Reprod Biomed Special Online 855 Wu 2001 Climacteric Not VE 856 Wuttke 2006 Menopause Excluded after full- Not VE text search 857 Wuttke 2003 Maturitas Excluded after full- Not VE text search 858 Xiao 1995 Contraception Not VE 859 Xiao 1985 Contraception Not VE 860 Xing 2003 Chin Med J (Engl) Not VE 861 Xu 1994 Adv Contracept Not VE 862 Yagel 1992 Fertil Steril Not VE 863 Yang 2003 Neurourol Urodyn Not VE 864 Yang 1999 Zhonghua Yi Xue Za Not VE Zhi (Taipei) 865 Yanushpolsky 2011 Fertil Steril Not VE 866 Yasmeen 2006 Obstet Gynecol Not VE 867 Yasui 2001 Horm Res Not VE 868 Yasui 2005 Maturitas Not VE 869 Yildirim 2006 Arch Gynecol Not VE Obstet 870 Young 1992 Am J Obstet Not VE Gynecol 871 Young 2001 Am J Obstet Not VE Gynecol 872 Yu 2015 Arch Gynecol Obstet Special 873 Yumru 2009 J Int Med Res I 874 Yung 2016 Contraception Not VE

875 Zahradnik 1998 Contraception Not VE 876 Zalanyi 2001 Eur J Obstet Not VE Gynecol Reprod Biol 877 Zegers-Hochschild 2000 Hum Not VE Reprod 878 Zervoudis 2009 Rev Med Chir Not VE Soc Med Nat Iasi 879 Zeyneloglu 2007 Fertil Steril Not VE 880 Zheng 2013 Chin Med J (Engl) Not VE 881 Zhou 2007 Explore (NY) Not VE 882 Ziaei 2002 Contraception Special 883 Zinaman 1995 J Clin Endocrinol Not VE Metab 884 Zucchini 2015 Eur J Cancer Not VE 885 Zullo 2005 Menopause Not VE Alone

Abbreviations Not VE did not examine a vaginal estrogen intervention. Special pop Specific population with underlying disease and/or for purpose other than FDA-approved purpose (e.g. for cervical ripening, contraception, fertility) Not FDA app prep Not FDA-approved vaginal estrogen preparation I included Hi dose VE High-dose vaginal estrogen (used for relieve of vasomotor symptoms, or daily [high-dose] use of low-dose vaginal estrogen ring) Not VE Alone Did not include a group that received vaginal estrogen alone Not Original Literature review or not original study (e.g. abstract of study that was later published in full) No AE Did not include safety or adverse effect information

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Akrivis 200318 91 postmenopausal women with vaginal 12 weeks 2 dryness, vaginal itching, and dyspareunia, mean age 59 years Single-arm study vaginal estradiol (Vagifem) tablet 25 mcg/d daily for 2 weeks then twice a week, details regarding blinding of participants and investigators not provided Archer 201734 72 postmenopausal women with dyspareunia 12 weeks 1 and VVA, substudy of REJOICE trial, mean ages 59 years (placebo), 57 years (4 mcg), 59 years (10 mcg), 59 years (25 mcg) Double-blind RCT, randomized separately from the parent trial; placebo vs. 4 mcg vs. 10 mcg vs. 25 mcg vaginal estradiol softgel capsule daily for 2 weeks followed by twice weekly for 10 weeks Ayton 199647 194 postmenopausal women with signs and 12 weeks 1 symptoms of urogenital atrophy, mean age 59 years (vaginal ring group) and 60 years (vaginal cream group) Open-label RCT, vaginal estradiol ring 7.5 mcg (Estring) single ring vs. vaginal CEE cream (Premarin) 0.625 mg nightly for 3 weeks followed by 1 week off cyclically Bachmann 423 postmenopausal women with moderate-to- 52 weeks 1 200949 severe vaginal atrophy, mean age 58 years (active group) and 59 years (placebo group) Double-blind RCT followed by open-label phase, vaginal CEE cream (Premarin) 0.3mg vs. placebo given cyclically (21 days treatment followed by 7 days without treatment) versus vaginal CEE cream 0.3 mg twice weekly for 12 weeks, followed by open-label extension for 40 weeks Bachmann 230 postmenopausal women with moderate-to- 52 weeks 1 200851 severe vaginal dryness and soreness, mean 58 years old Double-blind RCT, vaginal estradiol tablets 25 mcg or 10 mcg (Vagifem) or placebo daily for 2

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions weeks, then twice weekly for 10 weeks followed by open-label treatment with 25 mcg twice weekly up to week 52 Barentsen 199769 165 postmenopausal women with signs and 12 weeks + 1 symptoms of vaginal atrophy, mean age 58 12 weeks years (ring to cream group) and 59 years (cream to ring group) RCT open-label with crossover, vaginal estradiol ring 7.5 mcg (Estring) single ring vs. estradiol cream 1 mg/gram (not FDA-approved) 0.5 mg/d for 2 weeks followed by twice weekly for 10 weeks. After 12 weeks, crossover to the alternative therapy. Botsis 1997102 72 postmenopausal women with atrophic 6 months 1 vaginitis symptoms (dryness, dyspareunia, dysuria, urinary urgency, burning, tightness) and objective signs (pallor, petechiae, dryness), mean age 54 years RCT, details regarding blinding of participants and investigators not provided (but outcomes assessment was blinded), vaginal CEE cream 0.625 mg/d vs. tibolone 2.5mg/d Carlstrom 7 postmenopausal women with highly atrophic 14 days 1 1982886 vaginal mucosa, mean age 82 years Single-arm, details regarding blinding of participants and investigators not provided, CEE vaginal cream 0.625mg/d Casper 1999143 219 postmenopausal women with signs Study 1: 12 1 (petechiae, friability, or vaginal dryness) or weeks symptoms (pruritic vulvae, dyspareunia, Study 2: 24 dysuria, urinary urgency) of atrophic vaginitis weeks in open label-study; 84 postmenopausal women in the double-blind placebo-controlled study. Mean age of participants not specified. RCT open-label study and separate double- blind placebo-controlled study. Open label study was vaginal estradiol ring 7.5 mcg (Estring) vs. estriol pessary (not FDA- approved), for 12 weeks. Double-blind placebo-controlled study was vaginal estradiol ring vs. placebo ring for 24 weeks, unclear

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions whether the vaginal estradiol ring was replaced after 12 weeks. Cicinelli 2003163 10 healthy postmenopausal women, mean age 3 hours + 3 1 56 years hours RCT open-label with cross-over, estradiol vaginal tablet 10 mcg (Vagifem) in outer 1/3rd of vagina versus in inner 1/3rd of vagina, single dose, with assessment at baseline and 3 hours later. Subsequent washout followed by crossover to alternative intervention. Constantine 764 postmenopausal women with bothersome 12 weeks 1 2017180 dyspareunia, mean age 59 years (placebo group, 10 mcg group, 25 mcg group) and 60 years (4 mcg group) RCT double-blind, REJOICE trial, placebo vs. 4 mcg vs. 10 mcg vs. 25 mcg vaginal estradiol softgel capsules daily for 2 weeks followed by twice weekly for 10 weeks Deutsch 1981887 46 postmenopausal women with “vasomotor 7 days 2 symptoms or vaginal problems”, mean age and age range not provided details regarding blinding of participants and investigators and randomization not provided, vaginal CEE cream 0.3mg, 0.625mg, or 1.25mg daily versus oral CEE 0.3mg, 0.625mg, or 1.25 mg/d for 7 days Dickerson 29 postmenopausal women with vasomotor or 14 days 1 1979218 vaginal symptoms of estrogen deficiency, mean 55 years (estradiol group) and 54 years (CEE group) RCT double-blind, intravaginal CEE cream (2 gm, 1.25mg CEE) vs. estradiol cream 0.01% (0.2 mg estradiol) daily for 14 days, assessment 12 hours after final dose (on day 15) Dorr 2010228 24 postmenopausal women with signs and 7 days 1 symptoms of moderate to severe atrophic vaginitis, mean age 58 years RCT open-label crossover, oral CEE 0.3 mg/d vs. CEE vaginal cream 0.3 mg/d i.e. 0.5 g of 0.625 mg/g cream) X 7 days

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Dugal 2000231 96 postmenopausal women with symptoms of 24 weeks 1 atrophic vaginitis, mean age 58 years in estradiol tablet group and 59 years in estriol vagitories group RCT single-blind, vaginal estradiol tablet 25 mcg vs. estriol vagitory 0.5 mg (not FDA- approved), each daily for 2 weeks followed by twice weekly for total 24 weeks Ellington 2016249 58 postmenopausal women with urinary 12 weeks 1 frequency, urgency, nocturia, and/or urgency urinary incontinence, mean age 64 years (tolterodine) and 60 (estradiol cream group) RCT open-label, tolterodine extended release 4mg oral daily vs. intravaginal estradiol cream (Estrace) 0.5 mg nightly for 6 weeks followed by twice weekly Englund 1978888 5 postmenopausal women without vaginal Single dose 2 atrophy signs or symptoms, mean age not provided, range 52-65 years. details regarding blinding of participants and investigators not provided, single arm study oral CEE 1.25 mg (Premarin) single dose followed by vaginal CEE cream (Premarin) 1.25 mg one month later with blood sampling during the 48 hours after each dose Eriksen 1999254 108 postmenopausal women with recurrent UTI 36 weeks 1 confirmed, mean age 67 years (ring group) and 69 years (control group) RCT open-label, estradiol vaginal ring 7.5 mcg (Estring) every 12 weeks vs. control (no estrogen) Eugster- 58 postmenopausal women with vaginal 12 weeks 1 Haumann atrophy, mean age 65 years 2010261 RCT, details regarding blinding of participants and investigators not provided, vaginal estradiol tablet daily 10 mcg vs. 25 mcg for 2 weeks then twice weekly for 10 weeks Felding 1992275 48 postmenopausal women with genital 3 weeks 1 prolapse scheduled for surgery, mean age 64 in each group

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions RCT double-blind, vaginal estradiol tablet 25 mcg (Vagifem) vs. placebo Fernandes 80 postmenopausal women with vaginal 12 weeks 1 2016276 atrophy, mean age 56 years (estrogen group), 58 years (polyacrylic acid group), 56 years (testosterone group), 58 years lubricant group RCT, details regarding blinding of participants and investigators not provided, vaginal CEE cream (Premarin) 0.625 mg/d vs. polyacrylic acid (Vagidrat) 3 grams/d vs. testosterone vaginal cream 300 mcg/d (not FDA-approved) vs. vaginal lubricant (K-Y Jelly) 3g/d, each given three times per week Furuhjelm 5 postmenopausal women, no symptom criteria Single dose 2 1980889 noted, range 44-84 years mean age not provided details regarding blinding of participants and investigators not provided, single arm study, single dose CEE vaginal cream (Premarin) 0.625 mg Gabrielsson 1995 15 postmenopausal women, no symptom 4 weeks 2 890 criteria noted, age and age range not noted details regarding blinding of participants and investigators not provided, single-arm study, vaginal estradiol ring 7.5 mcg/d Gupta 2008336 24 healthy postmenopausal women mean age 12 weeks 1 57 years in transdermal group and 56 years in vaginal estradiol ring group RCT transdermal estradiol patch 14 mcg/d vs. vaginal estradiol ring 7.5 mcg/d (Estring), details regarding blinding of participants and investigators not provided Handa 1994891 20 postmenopausal women with symptoms, 6 months 2 signs, and cytologic evidence of atrophic vaginitis, mean age 65 years details regarding blinding of participants and investigators not provided, single-arm study vaginal CEE cream (Premarin) 0.3 mg/d for 2 weeks, then thrice weekly for 24 weeks Henrikkson 136 postmenopausal women with symptoms 1 year 1 1996355 and signs of atrophic vaginitis, mean 59 years

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions old (estradiol ring) and 61 years (estradiol pessary group) RCT, open-label, continuation of 1994 RCT by same authors in same journal354. Vaginal estradiol ring (Estring) 7.5 mcg vs. vaginal estradiol pessary 0.5 mg daily for 3 weeks followed by twice weekly for 12 weeks for the initial RCT, then open-label extension in which all participants received vaginal estradiol ring replaced every 12 weeks Henriksson 146 postmenopausal women with symptoms 12 weeks 1 1994354 and signs of atrophic vaginitis, mean age 59 years (vaginal ring group) and 60 years (vaginal pessary group) RCT open-label, vaginal estradiol ring (Estring) 7.5 mcg vs. estradiol vaginal pessary 0.5 mg daily for 3 weeks followed by twice weekly for 12 weeks. Hilton 1983361 10 postmenopausal women with atrophic 4 weeks 2 vaginal changes and symptoms of stress incontinence, mean age 60 years Single-arm, open-label, vaginal CEE cream (Premarin), 2 g nightly (i.e. 1.25 mg/d) Holmgren 24 postmenopausal women with symptoms of 12 weeks 2 1989366 urogenital atrophy, mean age 61 years in 5-10 mcg/d group and mean age 56 years in 20-30 mcg/d group Single-arm, efficacy assessments were blinded but other details regarding blinding of participants and investigators not provided, vaginal estradiol ring containing 2mg E2 with release rate of 5-10 mcg/d vs. ring containing 5 mg E2 with release rate of 20-30 mcg/d Hurst 2008380 10 postmenopausal sexually active women, 12 hours 1 mean age 55 years RCT, double-blind crossover study, vaginal estradiol cream (1 g/night, strength of cream per g not specified) vs. placebo for 1 night followed by intercourse 2 hours later, then crossover following washout period of 7-14 days. Subsequently 7-14 days later, all participants

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions used vaginal estradiol cream at night and abstained from intercourse. Illston 2015381 17 postmenopausal women with signs of 16 weeks 2 vaginal atrophy (symptoms of atrophic vaginitis were not required), mean age 72 years. Single-arm study, investigators blinded, no description regarding participant blinding, vaginal E2 0.01% cream 0.5g nightly for 8 weeks, then twice weekly for 8 weeks Labrie 2009444 20 postmenopausal women with moderate to 7 days 1 severe symptoms (vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, dyspareunia, vaginaleeding with sexual activity) and/or signs of vaginal atrophy, mean age 61 years RCT vaginal estradiol tablet 25 mcg (Vagifem) vs. vaginal CEE cream 1 g (0.625 mg)(Premarin) daily for 7 days Lima 2013479 90 postmenopausal women with vaginal 12 weeks 1 dryness, pruritus, pain, burning, or dyspareunia, mean age 57 years (placebo group) , 57 years (isoflavone group), 56 years (CEE group) RCT double-blind, isoflavone vaginal gel 4% 1 gm/d vs. CEE vaginal cream 0.3mg/d (Premarin) vs. placebo Long 2006a490 57 postmenopausal women with hysterectomy 3 months 1 not selected for symptoms, mean age 53 years (oral CEE group) and 54 years (vaginal CEE group) RCT, details regarding blinding of participants and investigators not provided, oral CEE 0.625/d vs. vaginal CEE cream 0.625 mg/d Long 2006b489 57 postmenopausal women with previous 3 months 1 hysterectomy, mean age 55 years in oral CEE group and 55 years in vaginal CEE cream group RCT, investigator assessment blinded but unclear details regarding blinding of participants and investigators not provided, oral CEE 0.625 mg/d (Premarin) vs. vaginal CEE cream 1gm (0.625 mg) daily

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Lose 2000492 251 postmenopausal women with at least one 24 weeks 1 bothersome lower urinary tract symptom mean age 66 years RCT open-label, vaginal estradiol ring 7.5 mcg/d (Estring) replaced every 12 weeks vs. estriol pessaries 0.5 mg every other day (not FDA-approved) Luisi 1980892 14 postmenopausal women with vaginal 3 weeks 1 atrophy, mean age not reported, range 53-65 years Open RCT, vaginal estradiol cream (Ovestin) 0.5 mg/d vs. vaginal CEE cream (Premarin) 1.25 mg/d Mainini 2005500 325 postmenopausal women with atrophic 24 weeks 2 vaginitis, mean age not specified Single-arm study, details regarding blinding of participants and investigators not provided, vaginal estradiol tablet 25 mcg (Vagifem) daily for 2 weeks then twice weekly for 22 weeks Mandel 1983893 20 postmenopausal women and 20 4 weeks 2 premenopausal women, symptom criteria for inclusion were not stated, mean age or age range not stated Details regarding blinding of participants and investigators and whether or not there was randomization were not provided, dosing progressed from lower to higher doses (0.3 mg, 0.625 mg, 1.25 mg, and 2.5 mg/d) of vaginal CEE cream in 10 participants, and progressed from higher to lower doses in the other 10 participants. Each dose was administered for 4 weeks, with a 1-week interval between each dose level. Manonai 2006504 53 postmenopausal women, mean age 55 years 12-weeks 1 in estrogen group, 55 years in control group RCT open-label, vaginal estradiol tablet 25 mcg or vaginal CEE cream 1g daily for 2 weeks, then twice a week for 10 weeks versus control group receiving no hormonal therapy

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Manonai 2001505 53 postmenopausal women with urogenital 12 weeks 1 symptoms, mean 55 years (vaginal estradiol tablet) and mean 56 years (vaginal CEE cream) RCT open-label, vaginal estradiol tablet 25 mcg/d vs. vaginal CEE cream 0.625 mg/d daily for 2 weeks then twice weekly for 10 weeks Martin 1979894 30 postmenopausal patients with vaginal 15 days 2 atrophy, mean age and age range not provided details regarding blinding of participants and investigators and whether there was randomization not provided, 10 participants assigned a daily dose of 1.25 mg of vaginal CEE cream (Premarin) and 20 were assigned vaginal estradiol cream (Estrace) 0.2 mg daily for 15 days Mattsson 1989519 20 postmenopausal women with “atrophy- 9 weeks 1 related symptoms caused by estrogen deficiency), mean age 62 years RCT, double-blind cross-over, vaginal estradiol pessary 25 vs. 50 mcg/d for 3 weeks, followed by twice weekly for 6 weeks, followed by crossover after 4–week washout Mettler 1991526 51 postmenopausal women with symptoms of 1 year 1 estrogen deficiency-derived atrophic vaginitis, mean age not provided Open RCT, vaginal estradiol tablets 25 mcg/d (Vagifem) once versus twice weekly for 52 weeks (9 participants continued for 2 years total) Mitchell 2018535 302 postmenopausal women with moderate to 12 weeks 1 severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration, mean age 61 years in each group RCT, double-blind, vaginal estradiol tablet 10 mcg (daily for 2 weeks, then twice weekly) + placebo gel (3 times/week) vs. placebo vaginal tablet + vaginal moisturizer (Replens) every 3 days vs. dual placebo Nachtigall 196 postmenopausal women with symptoms 12 weeks 1 1995555 and signs of atrophic vaginitis, mean age not described

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions RCT open-label with blinded cytological evaluation, vaginal estradiol ring 7.5 mcg/d single dose removed vs. CEE vaginal cream 2 gm thrice weekly for 12 weeks followed by 3 weeks of follow-up. Note: The publication contains a statement that an FDA-approved preparation was used as reference intervention, and the only such preparation at time of study publication was Premarin 1.25 mg/d (i.e. 2 g of cream containing 0.625 mg/g) Nachtigall 30 postmenopausal women, mean age not stated 12 weeks 1 1994554 RCT open-label Replens thrice weekly vs. vaginal CEE cream (Premarin) 2 g daily Naessen 2002557 60 postmenopausal women, mean age 67 years 12 months 1 in vaginal ring group, 68 years in untreated group RCT, details regarding blinding of participants and investigators not provided (ultrasound assessments not blinded), vaginal estradiol ring 7.5 mcg/d (Estring) replaced every 3 months vs. no treatment Naessen 2001558 70 postmenopausal women, mean age 67 12 months 1 vaginal estradiol group, 69 years in untreated group RCT, details regarding blinding of participants and investigators not provided, vaginal estradiol ring 7.5 mcg/d (Estring) replaced every 3 months or no treatment Naessen 1997556 30 healthy postmenopausal women without 6 months 1 conditions affecting bone, mean forearm bone density at baseline 0.367 gm/cm2 in vaginal estradiol group, 0.378 gm/cm2 in untreated group mean age 67 years in estradiol ring group, 68 years in no-treatment group RCT, details regarding blinding of participants and investigators not provided, vaginal estradiol ring 7.5 mcg/d (Estring) replaced every 3 months vs. no treatment (2:1 randomization)

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Nelken 2011569 54 postmenopausal women with overactive 12 weeks 1 bladder, mean age 59 in oxybutynin group and 58 years in the estradiol ring group RCT unblinded (only pathologist blinded), oxybutynin 5 mg bid vs. estradiol vaginal ring 7.5 mcg/d (Estring) Nilsson 1992575 24 postmenopausal women with vaginal 2 weeks 1 atrophy due to estrogen deficiency, mean participant age 56 years RCT, double-blind with cross-over, vaginal estradiol tablets (Vagifem) 10 mcg/d or 25 mcg/d for 2 weeks, then cross-over Nilsson 1995895 6 postmenopausal women with severe vaginal 12 weeks 2 atrophy, mean age 60 years Single-arm., details regarding blinding of participants and investigators not provided, vaginal E2 tablet (Vagifem) 25 mcg daily for 2 weeks then twice weekly for another 10 weeks Notelovitz 58 healthy postmenopausal women with serum 12 weeks 1 2002580 E2 concentrations below 20 pg/ml at baseline, mean age 52 years in 25 mcg group and 55 years 10 mcg group RCT double-blind single-center, estradiol vaginal tablet (Vagifem) 10 mcg or 25 mcg daily for 2 weeks then twice per week for 10 weeks Ouslander 9 consecutive ambulatory older women with 12 weeks 2 1999593 urinary incontinence, mean age 84 years Single-arm open-label, vaginal estradiol ring (Estring), dosage not specified Pickar 71 healthy postmenopausal women, no Single dose 1 Climacteric description of particular symptoms required for 2016a616 enrollment, mean age 50 years in the 10 mcg and the 25 mcg groups 2 RCTs single-dose with two-way cross-over. Study 1: vaginal estradiol softgel capsule (Vagicap) 10 mcg vs. vaginal estradiol tablet (Vagifem) 10 mcg single dose followed by crossover. Study 2: vaginal estradiol softgel capsule 25 mcg dose vs. vaginal estradiol tablet

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions (Vagifem) 25 mcg single dose followed by crossover. Pickar 50 postmenopausal women with moderate-to- 14 days 1 Menopause severe vulvovaginal atrophy, mean age 62 years 2016b617 (vaginal estradiol group) and 63 years (placebo group) RCT double-blind, vaginal estradiol capsule (Vagicap) 10 mcg/d vs. placebo daily for 14 days Pinkerton 91 postmenopausal women with at least 2 signs 6 months 1 2003623 of vaginal atrophy, mean age 58 years RCT, double-blind with regard to oral study drug, open-label with regard to vaginal ring, vaginal estradiol ring 7.5 mcg/d (Estring) replaced after 3 months + placebo tablet vs. estradiol ring + raloxifene 60 mg/d Raghunandan 75 postmenopausal women with symptoms of 12 weeks 1 2010638 urogenital and sexual dysfunction, mean age 53 years in vaginal CEE group, 51 years in vaginal CEE + testosterone cream group, and 52 years in nonhormone lubricant group RCT vaginal CEE 0.625 mg (Premarin cream) vs. vaginal CEE cream + testosterone 2% cream 0.5 gm (equivalent to testosterone 1 mg) vs. nonhormone lubricant KY gel once daily for 2 weeks followed by twice weekly for 10 weeks Raymundo 150 postmenopausal women with atrophic 56 days 2 2004642 vaginitis, mean age 56 years Open-label single-arm, vaginal CEE cream (Premarin) 0.625 mg/d on days 1-21 of two 28- day cycles Rigg 1978896 6 estrogen-deficient women, mean age not Single dose 2 described details regarding blinding of participants and investigators and whether there was randomization not provided, vaginal CEE cream (Premarin) 1.25 mg vs. vaginal estradiol cream (Estrace) 2 mg or 0.2 mg Rioux 2000650 159 postmenopausal women with moderate-to- 24 weeks 1 sever vaginal dryness, soreness, or irritation,

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions mean age 57 years (estradiol tablet group) and 57 years (vaginal cream group) RCT open-label, vaginal estradiol tablet (Vagifem) 25 mcg/d for 2 weeks then twice weekly vs. vaginal CEE cream (Premarin) 1.25 mg/d cyclically (daily for 21 days followed by 7 days without therapy) for 24 weeks total Schmidt 1994685 14 postmenopausal women with signs of 16 weeks 2 estrogen deficiency, atrophic vaginitis (atrophic change, petechiae; friability, and vaginal dryness), mean age not stated, range 55-72 years Single-arm, details regarding blinding of participants and investigators not provided, vaginal estradiol ring 7.5 mcg/d (Estring) worn continuously for 12 weeks, replaced with a second ring for a further 4 weeks Simon 2010702 Postmenopausal women with vaginal atrophy 52 weeks 1 (at least 3 genitourinary symptoms, one of which is moderate-to-sever). Two studies were pooled. N = 205 for study 1; N = 336 for Study 2. Mean age 59 years (estradiol group) and 58 years (placebo group) Pooled analysis of active therapy groups of 2 placebo-controlled RCTs to examine endometrial safety of vaginal estradiol tablet 10 mcg vs. placebo vaginal tablet daily for 2 weeks then twice weekly for 52 weeks total. (Study 1 was double-blind and Study 2 was open-label). Simon 2008701 309 postmenopausal women with at least three 12 weeks 1 urogenital symptoms (vaginal dryness, vaginal and/r or vulvar irritation/itching, vaginal soreness, dysuria, or dyspareunia, and vaginal bleeding with sexual activity), one of which was moderate to severe in intensity, mean age 58 years in the placebo group and 58 years in the vaginal estradiol tablet group RCT, double-blind, estradiol vaginal tablet 10 mcg (Vagifem) vs. placebo tablet daily for 14 days, subsequently one tablet twice per week

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Simunic 2003710 1612 postmenopausal women with urogenital 12 months 1 complaints, mean age 58 years (estradiol group) and 60 years (placebo group) RCT double-blind, vaginal estradiol tablet (Vagifem) 25 mcg vs. placebo once daily for 2 weeks then twice-weekly, total 12 months Smith 1993897 222 postmenopausal women with symptomatic 54 weeks 2 atrophic vaginitis (vaginal dryness or dyspareunia) and signs (pallor, petechiae, friability, vaginal dryness), mean age 57 years details regarding blinding of participants and investigators not provided, single arm vaginal E2 ring 5-10 mcg/d removed after 24 weeks, followed by 3-week washout and progestogen challenge followed by offer of two further 12- week treatment periods and progestogen challenge test. Suwanvesh 82 postmenopausal women with at least 1 12 weeks 1 2017744 symptom of dryness, soreness, irritation, dyspareunia, or soreness, mean age 56 years in each treatment group. RCT non-inferiority, vaginal CEE cream 0.5 g (strength and brand of cream not specified) vs. Pueraria mirifica vaginal gel daily for 2 weeks followed by thrice weekly for 10 weeks Taechakraichana 32 women with oophorectomy, mean age 48 12 weeks 2 1997747 years Single-arm clinical trial, no comparison group, vaginal CEE cream (Premarin) 1.25 mg/d for 12 weeks Tontivuthikul 40 postmenopausal women with pelvic organ 24 weeks 1 2016766 prolapse who had already used a pessary and vaginal CEE cream (Premarin 0.625 mg/g, 0.5 g daily for 2 weeks followed by twice weekly) for 6 weeks prior to enrollment, mean age 67 years (control group) and 66 years (estrogen group) RCT without placebo group but included “no treatment” comparison group, details regarding blinding of participants and investigators not provided, vaginal CEE cream 0.5g (Premarin, 0.625 mg/g) once weekly vs. no treatment

Supplemental Table 4. Study design characteristics of clinical trials of vaginal estrogen in postmenopausal women First author & N/population/age of participants at baseline Duration of Quality year reference # intervention rating Study design/blinding/interventions Ulrich 2010781 336 postmenopausal women with at least 1 52 weeks 2 moderate-to-severe urogenital symptom (vaginal soreness, dryness, dysuria, dyspareunia, bleeding with sexual activity), mean age 60 years Single-arm open-label, vaginal estradiol tablet 10 mcg once/d for 2 weeks then twice weekly for 50 weeks, total 52 weeks. Van Haaften 29 postmenopausal women who underwent 3 weeks 2 1997801 hysterectomy for uterine prolapse or uterine myomata, mean age not provided, range between 49 and 82 years No details provided about whether study was blinded or about whether treatment was randomly assigned, vaginal estriol 0.5 mg/d insert (“ovula”) vs. vaginal estradiol 0.05 mg/d insert (“ovula”) for 3 weeks prior to hysterectomy vs. untreated control group Van Haaften 29 postmenopausal women who underwent 3 weeks 2 1989800 hysterectomy (not for oncological reasons), mean age not provided, range between 49 and 82 years No details provided about whether study was blinded or about whether treatment was randomly assigned, estriol 0.5 mg/d vaginal insert vs. estradiol 0.05 mg/d vaginal insert vs. untreated control Weisberg 185 postmenopausal women with significant 48 weeks 1 2005828 symptoms or signs of urogenital atrophy (dryness, dyspareunia, dysuria, pruritus, urinary urgency, frequency, or nocturia), mean age 58 years in each treatment arm RCT open-label, vaginal estradiol ring 7.5 mcg (Estring) with new ring every 12 weeks vs. vaginal estradiol tablet (Vagifem) 25 mcg/d for 2 weeks then twice weekly, total 48 weeks followed by 3 weeks follow-up for progestogen challenge. Yumru 2009873 35 postmenopausal women with symptoms of 12 weeks 2 vaginal atrophy, mean age 58 years.

Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women First author E1 E2 FSH LH RC LLD & year T of reference # estroge n assays specifi ed Akrivis N/A RIA RIA RIA No No 200318 Archer GC/MS/MS, GC/MS/MS, LLD 2 N/A N/A Yes Yes 201734 LLD 5pg/mL pg/mL Bachmann Quest Quest diagnostics N/A N/A Yes No 200851 diagnostics (Madison, NJ) (Madison, NJ) Carlstrom RIA method RIA method of RIA method of RIA method of No No 1982886 of Furuhelm Furuhelm Int J Furuhelm Int J Furuhelm Int J Int J Gynecol Gynecol Obstet 1980 Gynecol Obstet Gynecol Obstet Obstet 1980 1980 1980 Cicinelli N/A RIA (DI RIA-ESTR; N/A Yes Yes 2003163 Sorin Biomedics, Saluggia, Italy), LLD 10 pg/mL Deutsch 1981 N/A RIA for “total N/A N/A No No 887 estrogens” Dickerson RIA method RIA method of RIA RIA Yes No 1979218 of DeVane DeVane Am J Obstet Am J Obstet Gynecol 1975 and Gynecol Longcope Endocrinol 1975 and Metab 1971 Longcope Endocrinol Metab 1971 Dorr 2010228 GC/MS/MS GC/MS/MS N/A N/A Yes Yes Dugal N/A no assay details no assay details N/A Yes No 2000231 provided provided Englund RIA method RIA modified method Method of Wide Method of Acta No No 1978888 of Axelsson of Edqvist and Acta Endocrinologica Acta Johansson Acta Endocrinologica 1973 endocrinologi endocrinologica 1972 1973 ca 1978 Eugster- GC/MS GC/MS N/A N/A Yes No Haumann 2010261 Felding N/A RIA RIA N/A Yes No 1992275 Fernandes N/A no assay details N/A N/A Yes No 2016276 provided Furuhjelm RIA after N/A RIA using DASP RIA using DASP No No 1980889 method of separation separation Carlstrom et (Organon NV, (Organon NV, al J steroid Oss, Holland). Oss, Holland).

Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women First author E1 E2 FSH LH RC LLD & year T of reference # estroge n assays specifi ed Biochem Antisera against Antisera against 1977. Intra- FSH and purified LH and purified assay and hormones for 125I hormones for 125I interassay labeling were labeling were variations from KABI AB, from KABI AB, were 7.0% Stockholm, Stockholm, and 8.9% Sweden. Intra- Sweden. Intra- assay and assay and interassay interassay variations were variations 8.7% 8.0% and 10.5%. and 8.7% for LH. Gabrielsson N/A Assay details N/A N/A No No 1995890 incomplete. Lower limit of quantification (20 pmol/l Gupta RIA with RIA with preceding Direct RIA Direct RIA Yes Yes 2008336 preceding ethyl acetate:hexane ethyl (3:2) extraction and acetate:hexan celite column e (3:2) partition extraction chromatography, and celite method of Stanczyk column Am J Obstet Gynecol partition 1988, LLD 3 pg/mL chromatograp hy, method of Stanczyk Am J Obstet Gynecol 1988, LLD 4 pg/mL Handa RIA RIA Hazelton N/A N/A No Yes 1994891 Hazelton Washington, Vienna, Washington, VA method of Vienna, VA DeVane Am J Obstet method of Gynecol 1975. DeVane Am Sensitivity of the RIA J Obstet was 5.38 pg/mL, LLD Gynecol 5.38 pg/mL 1975, LLD not provided Holmgren N/A RIA, Nunez Acta RIA (Farmos N/A No Yes 1989366 Endocrinol 1977, Diagnostica, LLD 45 pmol/L Turku, Finland) Hurst 2008380 N/A Electrochemiluminesc N/A N/A Yes Yes ence, LLD 5 pg/mL

Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women First author E1 E2 FSH LH RC LLD & year T of reference # estroge n assays specifi ed Illston N/A RIA, LLD 2.2 pg/mL N/A N/A No Yes 2015381 Labrie GC/MS, 8 GC/MS, LLD 2.0 N/A N/A Yes Yes 2009444 pg/mL pg/mL Lima 2013479 N/A Chemiluminescence Chemiluminesce N/A Yes Yes (Chiron), LLD 5 nce (ACS-180 pg/mL Chiron) Long 2006490 N/A no assay details N/A N/A Yes No provided Long N/A No assay details N/A N/A Yes No 2006b489 provided Luisi 1980 892 RIA by the RIA by the method of Radioimmunosor Radioimmunosor Yes No method of Emment Acta bent method of bent method of Emment Acta Endocrinol 1972 Wide et al Acta Wide et al Acta Endocrinol using test kits from Endocrinol 1973 Endocrinol 1973 1972 using Biodata using Biodata using Biodata test kits from test kits using test kits using Medical regents from regents from Systems Medical Medical Systems. Systems. Mainini N/A no assay details N/A N/A No No 2005500 provided Mandel RIA using RIA using the method Double antibody Double antibody No No 1983893 the method of of De Vane et al Am J RIA using RIA using De Vane et al Obstet Gynecol 1975 reagents by the reagents by the Am J Obstet National National Gynecol Pituitary Agency. Pituitary Agency. 1975 Manonai N/A Enzymun-Test ES N/A N/A Yes Yes 2001505 300, LLD <5 pg/mL Martin RIA RIA N/A N/A No No 1979894 Mettler N/A Biermann I131 RIA Enzyme- Amersham Yes No 1991526 immuno- Buchler Double- fluorescence antibody RIA Nachtigall no assay no assay details N/A N/A Yes No 1995555 details provided provided Naessen N/A Extraction followed N/A N/A Yes Yes 2002557 by RIA (Estradiol Double Antibody; Diagnostic Products, Los Angeles, CA), LLD 6 pmol/L Naessen N/A Extraction followed Auto-Delfia N/A Yes Yes 2001558 by RIA (Estradiol human FSH

Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women First author E1 E2 FSH LH RC LLD & year T of reference # estroge n assays specifi ed Double Antibody; (Pharmacia- Diagnostic Products, Wallac, Inc, Los Angeles, CA) Turku, Finland) with modifications, LLD 6 pmol/L Naessen N/A Extraction followed No assay details N/A Yes Yes 1997556 by RIA (Estradiol provided Double Antibody kit; Diagnostic Products, Los Angeles), LLD 5 pmol/L Nilsson RIA, method RIA, method of Fluoroimmunoas Fluoroimmunoas Yes Yes 1992575 of Axelsson Axelsson Acta say kit (Delfia, say kit (Delfia, Acta Endocrinol 1978 and Wallac OY, Wallac OY, Endocrinol Lindberg Acta Obstet Turku, Finland) Turku, Finland) 1978 and Gynecol Scand 1974, Lindberg LLD 19 pmol/L Acta Obstet Gynecol Scand 1974, LLD 19 pmol/L Nilsson RIA method RIA method of Commercial Commercial No Yes 1995895 of Axelsson Axelsson Acta fluoroimmunoass fluoroimmunoass Acta Endocrinol 1978 and ay kit (Delfia, ay kit (Delfia, Endocrinol Lindberg Acta Obstet Wallac OY, Wallac OY, 1978 and Gynecol Scand 1974), Turku, Fiknland) Turku, Fiknland) Lindberg detection limit 19 Acta Obstet pmol/l Gynecol Scand 1974), detection limit 19 pmol/l Notelovitz N/A RIA (Nichols Chemiluminesce N/A Yes No 2002580 Institute, San Juan nce (Nichols Capistrano, CA) Institute, San Juan Capistrano, CA) Pickar LC/MS LC/MS (Esoterix N/A N/A Yes Yes Climacteric (Esoterix Endocrinology, 2016a616 Endocrinolog Calabasas, CA),, LLD y, Calabasas, 1 pg/mL CA), LLD 2.5 pg/mL

Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women First author E1 E2 FSH LH RC LLD & year T of reference # estroge n assays specifi ed Pickar N/A Assay details N/A N/A Yes Yes Menopause incomplete, LLD 10 2016b617 pg/mL Raghunandan N/A no assay details N/A N/A Yes No 2010638 provided Rigg 1978896 RIA, method RIA, method of RIA, method of RIA, method of No No of DeVane DeVane Am J Obstet Yen J Clin Yen J Clin Am J Obstet Gynecol 1975, Endocrinol Endocrinol Gynecol Metab 1970 Metab 1968 1975, Rioux N/A no assay details no assay details N/A Yes No 2000650 provided provided Schmidt Competitive Competitive RIA N/A N/A No Yes 1994685 RIA, LLD 50 double-antibody, LLD pmol/L 4 pmol/L Simunic N/A Immunochemical E2 N/A N/A Yes No 2003710 assay (Ortho-Clinical Diagnostics) Smith Competitive Double-antibody 125- N/A N/A No Yes 1993897 RIA, method I RIA LLD 20 pmol/l of Carlstrom J Steroid Biochem 1977, LLD 100 pmol/L Taechakraich N/A Fluoroimmunoassay, Fluoroimmunoas N/A No Yes ana 1997747 LLD 20 pmol/L say Ulrich N/A RIA (Diagnostic Chemiluminesce N/A No Yes 2010781 Products Corporation, nce USA), LLD 5 pg/mL immunoassay (Bayer Diagnostics, USA) Van Haaften RIA RIA RIA, reagents RIA, reagents No No 1989800 from Byk- from Byk- Mallinckrodt Mallinckrodt (Dietzenbach, (Dietzenbach, FRG) FRG) Weisberg Details not RIA (Diagnostic N/A N/A Yes Yes 2005828 described, Products Corporation, LLD 30 USA), LLD 5 pmol/L pmol/L Yumru N/A Details not described Details not Details not No No 2009873 described described LC: liquid chromatography GC: gas chromatography

Supplemental Table 5. Serum sex steroid, and/or gonadotropin assay methods (and manufacturer if stated) in clinical trials of vaginal estrogen in postmenopausal women First author E1 E2 FSH LH RC LLD & year T of reference # estroge n assays specifi ed E1: estrone E2: estradiol FSH: follicle-stimulating hormone LH: luteinizing hormone LLD: lower limit of assay detection MS: mass spectrometry N/A: not applicable (not measured) RCT: randomized controlled trial RIA: radioimmunoassay

Supplemental Table 6. Endometrial biopsy results in clinical trials of vaginal estrogen in postmenopausal women a First author Preparations tested Results Time point & year of reference # assessment Bachmann Vaginal CEE cream twice Endometrial assessments were made in 82 52 weeks 200949 weekly, vaginal CEE participants receiving vaginal CEE cream cyclically cream cyclically (21 days and 73 participants receiving CEE vaginal cream on then 7 days off) vs. twice weekly; endometrial assessments were not placebo made (due to refusal, loss to follow-up, etc) in 91 women in the cyclical group and 71 women in the twice weekly group. No endometrial hyperplasia or cancer in 82 participants receiving vaginal CEE cream cyclically and 73 participants receiving CEE vaginal cream twice weekly. Proliferative endometrium in six participants in each group. Bachmann Vaginal estradiol tablet No participants had hyperplasia or malignancy. 52 weeks 200851 (Vagifem) 25 mcg or 10 EMB was performed in the 42 women with intact mcg or placebo daily for 2 uteri who finished the 52-week treatment (15 in the weeks, then twice weekly former 25 mcg estradiol group, 18 in the former 10 for 10 weeks, followed by mcg estradiol group, and 9 in the former placebo open-label 25 mcg group). Constantine Vaginal estradiol softgel No endometrial hyperplasia or malignancy at week 12 weeks 2017180 capsules 4 mcg, 10 mcg, 12. Unclear how many women underwent EMB or 25 mcg or placebo daily but initial numbers of participants assigned to for 2 weeks, then twice treatment were 186 (4 mcg dose), 188 (10 mcg weekly dose), 186 (25 mcg dose) and 187 (placebo). Handa 1994 Vaginal CEE cream After treatment, 17 (85%) of biopsies showed 6 months 891 (Premarin) 0.3 mg daily atrophy, 1 (5%) showed proliferation, and biopsies for 2 weeks, then thrice were unable to be obtained in 2 (10%). After weekly for 6 months treatment, one endometrial specimen demonstrated proliferation, and the participant had a pretreatment biopsy showing atrophy. Endometrial thickness increased from 3.5 to 3.8 mm. Her post- treatment E1 level was 50 pg/mL and her post- treatment serum E2 was undetectable. Luisi 1980892 Vaginal estradiol cream Specimens were obtained from 2 patients in each 3 weeks (Ovestin)0.5 mg/d vs. treatment group at baseline and at day 15. No vaginal CEE cream mention of how those particular participants were (Premarin) 1.25 mg/d selected. In the two participants of the vaginal estradiol cream group, samples were atrophic at baseline and after treatment. In the two participants of the vaginal CEE cream group, specimens were atrophic at baseline but showed moderate proliferation at day 15. Mattsson Vaginal estradiol pessary EMB obtained from 18 women (out of 20 women). 9 weeks 1989519 25 vs. 50 mcg/d for 3 After 3 weeks of treatment, weak proliferation in weeks then twice weekly one participant in 50 mcg group; after 9 weeks, no for 6 weeks, followed by proliferation in either group. Most samples were washout and crossover atrophic in both groups at 3 weeks and at 9 weeks. Mettler vaginal estradiol tablets 25 EMB obtained from the 45 patients who completed 52 weeks 1991526 mcg/d (Vagifem) once the 1-year study period. There were no cases of hyperplasia. a Includes studies that routinely performed EMB in all participants as part of study protocol.

Supplemental Table 6. Endometrial biopsy results in clinical trials of vaginal estrogen in postmenopausal women a First author Preparations tested Results Time point & year of reference # assessment weekly versus twice weekly for 52 weeks Nachtigall Vaginal estradiol ring 7.5 Two (5%) of participants in vaginal estradiol ring 12 weeks 1995555 mcg/d (single ring) vs. group had moderate endometrial proliferation or vaginal CEE cream 1.25 hyperplasia vs. three (10%) of participants in mg thrice weekly vaginal CEE cream group. Unclear how many participants underwent EMB, but 159 participants (105 in ring group, 54 in cream group) were included in the per-protocol analysis. Pinkerton vaginal estradiol ring 7.5 No hyperplasia, carcinoma, or clinically significant 6 months 2003623 mcg/d (Estring) + placebo endometrial proliferation in either group. No tablet vs. estradiol ring + further details provided. raloxifene 60 mg/d Rioux Vaginal estradiol tablet 25 EMB was performed 60/80 women assigned to 24 weeks 2000650 mcg (Vagifem) daily for 2 vaginal tablets and 59/79 women assigned to weeks then twice weekly vaginal cream. Proliferative endometrium was vs. vaginal CEE cream found in 1 participant in the tablet group and 7 1.25 mg cyclically participants of the cream group. Endometrial hyperplasia was seen in 2 participants in the cream group and no participants in the tablet group. Tissue was insufficient in 14/49 participants of the tablet group and 21/49 participants in the cream group. Simon estradiol vaginal tablet 10 Simon and colleagues 2010702 (see row above) 12 weeks 701 2008 mcg (Vagifem) vs. presents the extension of this study. Methods placebo daily for 2 weeks section states that EMB was performed but specific then twice weekly results of EMB are not provided. There was one case of endometrial cancer (stage II, grade 2) in a participant of the estradiol vaginal tablet treatment group but it is uncertain whether the event was treatment-related because she did not undergo baseline biopsy. Simon Vaginal estradiol tablet 10 Numbers of participants who underwent EMB at 52 weeks 2010702 mcg vs. placebo, daily for week 52 was 443 (100%) in vaginal estradiol tablet 2 weeks, then twice group and 79 (100%) in the placebo group. Tissue weekly. was insufficient for diagnosis in 17 (25%) of placebo group and 126 (28%) of estradiol tablet group. Complex hyperplasia was present in no participants of either group. Carcinoma was present in 1 (0.2%) of the estradiol group and none of the placebo group. Ulrich Vaginal estradiol tablet 10 EMB results were available for all 284 participants 52 weeks 2010781 mcg/d for 2 weeks then who completed the study. There was no tissue in twice weekly 21 (7%), insufficient tissue for diagnosis in 85 (30%), weakly proliferative endometrial in 1 (0.4%). There were no cases of hyperplasia or carcinoma. Van Haaften vaginal estriol 0.5 mg/d Endometria from the control were all atrophic. All 3 weeks 1997801 insert (“ovula”) vs. 17 endometria from the estriol-treated and estradiol-treated groups showed estrogenic

Supplemental Table 6. Endometrial biopsy results in clinical trials of vaginal estrogen in postmenopausal women a First author Preparations tested Results Time point & year of reference # assessment vaginal estradiol 0.05 stimulation. In the estriol group four endometria mg/d insert (“ovula”) were under moderate estrogenic influence and four scored 2 (defined as significant proliferative changes of epithelium with hyperplasia of endometrial glands and/or crowding and/or architectural changes in the glands), with a mean score of 1.5. In the estradiol group, three endometria scored 1 (defined as proliferative changes of the epithelium without hyperplasia and/or crowding of endometrial glands) and six scored 2, with a mean score of 1.7. Yumru estradiol vaginal tablet 25 EMB was not performed systematically, only in 12 weeks 2009873 mcg/d for 14 days, then participants with endometrial thickness ≥5 mm. twice weekly for 10 weeks Two participants had endometrial thickness ≥ 5mm before treatment (which remained ≥5mm after treatment), and subsequent EMB showed proliferative endometrium both before and after treatment. Two participants had endometrial thickness <5 mm before treatment but ≥5 mm after treatment. In those participants, EMB showed atrophic endometrium. Abbreviations: CEE, conjugated equine estrogen; EMB, endometrial biopsy

Supplemental Table 7a. Summary of Heterogeneity of Level 1 Studies with Endometrial Biopsy Outcomes

Preparation and dose Comparator (active, Number of Study Duration(s) placebo, control) studies Vaginal CEE cream 0.3 Vaginal CEE cream 0.3 mg 1 52 weeks mg cyclically twice weekly Vaginal CEE cream Vaginal estradiol cream 0.5 1 3 weeks 1.25 mg daily mg/day Vaginal CEE cream Vaginal estradiol ring 7.5 1 12 weeks 1.25 mg thrice weekly mcg/d Vaginal CEE cream Vaginal estradiol tablet 25 1 24 weeks 1.25 mg cyclically mcg twice weekly Vaginal estradiol tablet Vaginal estradiol tablet 10 1 12 weeks 4 mcg twice weekly mcg twice weekly Vaginal estradiol tablet Vaginal estradiol tablet 25 1 12 weeks 4 mcg twice weekly mcg twice weekly Vaginal estradiol tablet Placebo 1 12 weeks 4 mcg twice weekly Vaginal estradiol tablet Placebo 4 12 weeks (3 studies), 10 mcg twice weekly 52 weeks (1 study) Vaginal estradiol tablet Vaginal estradiol tablet 25 2 12 weeks, 52 weeks 10 mcg twice weekly mcg twice weekly Vaginal estradiol tablet Placebo 2 12 weeks, 52 weeks 25 mcg twice weekly Vaginal estradiol tablet Vaginal estradiol tablet 50 1 9 weeks 25 mcg twice weekly mcg twice weekly Vaginal estradiol tablet Vaginal estradiol tablet 25 1 52 weeks 25 mcg only weekly mcg twice weekly Vaginal estradiol ring Vaginal estradiol ring 7.5 1 6 months 7.5 mcg/d mcg/d plus raloxifene daily (oral) CEE: conjugated equine estrogen

Supplemental Table 7b. Summary of Heterogeneity of Level 2 Studies with Endometrial Biopsy Outcomes Preparation and dose Number of Studies Study Duration(s) Vaginal CEE cream 0.3 mg thrice weekly 1 6 months Vaginal estradiol tablet 10 mcg twice weekly 1 52 weeks Vaginal estradiol tablet 0.05 mg daily 1 3 weeks Vaginal estradiol tablet 25 mcg daily 1 12 weeks Abbreviations. CEE: conjugated equine estrogen

Supplemental Table 7c. Summary of Heterogeneity of Level 1 Studies with Endometrial Thickness Outcomes

Preparation and dose Comparator (active, placebo, Number of Study control)a studies Duration(s) Vaginal CEE cream 0.3 Isoflavone vaginal gel 1 12 weeks mg daily Vaginal CEE cream 0.3 placebo 1 12 weeks mg daily Vaginal CEE cream 0.3 Vaginal CEE cream 0.3 mg twice 1 52 weeks mg cyclically weekly Vaginal CEE cream Tibolone oral 1 6 months 0.625 mg daily Vaginal CEE cream Polyacrylic acid 1 12 weeks 0.625 mg thrice weekly Vaginal CEE cream Testosterone vaginal cream 1 12 weeks 0.625 mg thrice weekly Vaginal CEE cream K-Y vaginal lubricant 1 12 weeks 0.625 mg thrice weekly Vaginal CEE cream K-Y jelly 1 12 weeks 0.625 mg twice weekly Vaginal CEE cream Vaginal CEE cream 0.625 mg 1 12 weeks 0.625 mg twice weekly twice weekly plus testosterone cream 2% Vaginal CEE cream No treatment (control) 1 24 weeks 0.625 mg weekly Vaginal CEE cream 1 Vaginal estradiol tablet 25 mcg 2 12 weeks (both gram twice weekly twice weekly studies) Vaginal CEE cream Vaginal estradiol ring 7.5 mcg/d 1 12 weeks 1.25 mg thrice weekly Vaginal CEE cream Pueraria mirifica vaginal gel 1 12 weeks dose not specified Vaginal estradiol ring Placebo 1 24 weeks 7.5 mcg/d Vaginal estradiol ring No treatment (control) 1 12 months 7.5 mcg/d Vaginal estradiol ring Vaginal estradiol ring 7.5 mcg/d 1 6 months 7.5 mcg/d plus raloxifene (oral) Vaginal estradiol tablet Placebo 1 52 weeks 10 mcg twice weekly Vaginal estradiol tablet Placebo 1 52 weeks 25 mcg twice weekly CEE: conjugated equine estrogen

a Note that not all comparators are approved by the U.S. Food and Drug Administration

Supplemental Table 7d. Summary of Heterogeneity of Level 2 Studies with Endometrial Thickness Outcomes

Preparation and dose Number of Study Duration(s) Studies Vaginal CEE cream 0.3 mg thrice weekly 1 6 months Vaginal estradiol tablet 25 mcg twice weekly 3 12 weeks, 24 weeks, 52 weeks Estradiol ring 5-10 mcg/d removed after 24 weeks, 1 54 weeks then replaced every 12 weeks Abbreviations. CEE: conjugated equine estrogen

References

1. Clinical trial of nafoxidine, an oestrogen antagonist in advanced breast cancer. Eur J Cancer. 1972;8(4):387-9. 2. A multicentred phase III comparative study of two hormonal contraceptive preparations given once-a-month by intramuscular injection. II. The comparison of bleeding patterns. World Health Organization Task Force on Long-Acting Systemic Agents for Fertility Regulation. Contraception. 1989;40(5):531-51. 3. Pregnancy termination with mifepristone and gemeprost: a multicenter comparison between repeated doses and a single dose of mifepristone. World Health Organization. Fertil Steril. 1991;56(1):32-40. 4. A randomized study to compare the effectiveness, tolerability, and acceptability of two different transdermal estradiol replacement therapies. The Transdermal HRT Investigators Group. International journal of fertility and menopausal studies. 1993;38(1):5-11. 5. Abate A, Perino M, Abate FG, Brigandi A, Costabile L, Manti F. Intramuscular versus vaginal administration of progesterone for luteal phase support after in vitro fertilization and embryo transfer. A comparative randomized study. Clinical and experimental obstetrics & gynecology. 1999;26(3-4):203-6. 6. Abdalla KA, Shabaan MM, Stanczyk FZ. Interrelationship of serum levonorgestrel and sex hormone-binding globulin levels following vaginal and oral administration of combined steroid contraceptive tablets. Contraception. 1992;45(2):111-8. 7. Abdel-Aleem H, Shaaban OM, Amin AF, Abdel-Aleem AM. Tamoxifen treatment of bleeding irregularities associated with Norplant use. Contraception. 2005;72(6):432-7. 8. Abdelbary AM, El-Dessoukey AA, Massoud AM, et al. Combined Vaginal Pelvic Floor Electrical Stimulation (PFS) and Local Vaginal Estrogen for Treatment of Overactive Bladder (OAB) in Perimenopausal Females. Randomized Controlled Trial (RCT). Urology. 2015;86(3):482-6. 9. Abdullah KN, Raoof A, Raoof M. Effectiveness and safety of raloxifene in postmenopausal females. J Coll Physicians Surg Pak. 2005;15(5):266-9. 10. Abraham L, Pinkerton JV, Messig M, Ryan KA, Komm BS, Mirkin S. Menopause- specific quality of life across varying menopausal populations with conjugated estrogens/bazedoxifene. Maturitas. 2014;78(3):212-8. 11. Achiron R, Levran D, Sivan E, Lipitz S, Dor J, Mashiach S. Endometrial blood flow response to hormone replacement therapy in women with premature ovarian failure: a transvaginal Doppler study. Fertil Steril. 1995;63(3):550-4. 12. Adler G, Young D, Galant R, Quinn L, Witchger MS, Maki KC. A multicenter, open- label study to evaluate satisfaction and menopausal quality of life in women using transdermal estradiol/norethindrone acetate therapy for the management of menopausal signs and symptoms. Gynecol Obstet Invest. 2005;59(4):212-9. 13. Affinito P, Palomba S, Pellicano M, et al. Ultrasonographic measurement of endometrial thickness during hormonal replacement therapy in postmenopausal women. Ultrasound Obstet Gynecol. 1998;11(5):343-6. 14. Agarwal N, Gupta M, Kriplani A, Bhatla N, Singh N. Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study. J Obstet Gynaecol. 2016;36(1):71-5.

15. Aguirre W, Chedraui P, Mendoza J, Ruilova I. Gabapentin vs. low-dose transdermal estradiol for treating post-menopausal women with moderate to very severe hot flushes. Gynecol Endocrinol. 2010;26(5):333-7. 16. Ahlstrom K, Sandahl B, Sjoberg B, Ulmsten U, Stormby N, Lindskog M. Effect of combined treatment with phenylpropanolamine and estriol, compared with estriol treatment alone, in postmenopausal women with stress urinary incontinence. Gynecol Obstet Invest. 1990;30(1):37-43. 17. AinMelk Y. Comparison of two continuous combined estrogen progestogen regimens in postmenopausal women: a randomized trial. Fertil Steril. 1996;66(6):962-8. 18. Akrivis C, Varras M, Thodos A, Hadjopoulos G, Bellou A, Antoniou N. Action of 25 microg 17beta-oestradiol vaginal tablets in the treatment of vaginal atrophy in Greek postmenopausal women; clinical study. Clinical and experimental obstetrics & gynecology. 2003;30(4):229-34. 19. Al-Azzawi F, Buckler HM, United Kingdom Vaginal Ring Investigator G. Comparison of a novel vaginal ring delivering estradiol acetate versus oral estradiol for relief of vasomotor menopausal symptoms. Climacteric. 2003;6(2):118-27. 20. Al-Azzawi F, Lees B, Thompson J, Stevenson JC. Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate. Menopause. 2005;12(3):331-9. 21. Albert A, Altabre C, Baro F, et al. Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial. Phytomedicine. 2002;9(2):85-92. 22. Albertazzi P, Pansini F, Bottazzi M, Bonaccorsi G, De Aloysio D, Morton MS. Dietary soy supplementation and phytoestrogen levels. Obstet Gynecol. 1999;94(2):229-31. 23. Algorta J, Diaz M, de Benito R, et al. Pharmacokinetic bioequivalence, safety and acceptability of Ornibel((R)), a new polymer composition contraceptive vaginal ring (etonogestrel/ethinylestradiol 11.00/3.474 mg) compared with Nuvaring((R)) (etonogestrel/ethinylestradiol 11.7/2.7 mg). Eur J Contracept Reprod Health Care. 2017;22(6):429-38. 24. Al-Saqi SH, Uvnas-Moberg K, Jonasson AF. Intravaginally applied oxytocin improves post-menopausal vaginal atrophy. Post Reprod Health. 2015;21(3):88-97. 25. Alvarez F, Brache V, Faundes A, Tejada AS, Thevenin F. Ultrasonographic and endocrine evaluation of ovarian function among Norplant implants users with regular menses. Contraception. 1996;54(5):275-9. 26. Alvarez-Sanchez F, Brache V, Jackanicz T, Faundes A. Evaluation of four different contraceptive vaginal rings: steroid serum levels, luteal activity, bleeding control and lipid profiles. Contraception. 1992;46(4):387-98. 27. Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA. 2003;290(13):1739-48. 28. Andersson TL, Stehle B, Davidsson B, Hoglund P. Bioavailability of estradiol from two matrix transdermal delivery systems: Menorest and Climara. Maturitas. 2000;34(1):57-64. 29. Andreen L, Bixo M, Nyberg S, Sundstrom-Poromaa I, Backstrom T. Progesterone effects during sequential hormone replacement therapy. Eur J Endocrinol. 2003;148(5):571-7. 30. Andreen L, Sundstrom-Poromaa I, Bixo M, Andersson A, Nyberg S, Backstrom T. Relationship between allopregnanolone and negative mood in postmenopausal women taking

sequential hormone replacement therapy with vaginal progesterone. Psychoneuroendocrinology. 2005;30(2):212-24. 31. Apperloo M, Midden M, van der Stege J, Wouda J, Hoek A, Weijmar Schultz W. Vaginal application of testosterone: A study on pharmacokinetics and the sexual response in healthy volunteers. J Sex Med. 2006;3(3):541-9. 32. Apter D, Cacciatore B, Stenman UH, Alapiessa U, Assendorp R. Clinical performance and endocrine profiles of contraceptive vaginal rings releasing 3-keto-desogestrel and ethinylestradiol. Contraception. 1990;42(3):285-95. 33. Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose- finding study (FIESTA). Contraception. 2016;94(4):366-73. 34. Archer DF, Constantine GD, Simon JA, et al. TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol. Menopause. 2017;24(5):510-6. 35. Archer DF, Dorin M, Lewis V, Schneider DL, Pickar JH. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding. Fertil Steril. 2001;75(6):1080-7. 36. Archer DF, Hendrix S, Gallagher JC, et al. Endometrial effects of tibolone. J Clin Endocrinol Metab. 2007;92(3):911-8. 37. Archer DF, Kimble TD, Lin FDY, Battucci S, Sniukiene V, Liu JH. A Randomized, Multicenter, Double-Blind, Study to Evaluate the Safety and Efficacy of Estradiol Vaginal Cream 0.003% in Postmenopausal Women with Vaginal Dryness as the Most Bothersome Symptom. J Womens Health (Larchmt). 2018;27(3):231-7. 38. Archer DF, Pickar JH, MacAllister DC, Warren MP. Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. Menopause. 2012;19(6):622-9. 39. Archer DF, Schmelter T, Schaefers M, Gerlinger C, Gude K. A randomized, double- blind, placebo-controlled study of the lowest effective dose of drospirenone with 17beta-estradiol for moderate to severe vasomotor symptoms in postmenopausal women. Menopause. 2014;21(3):227-35. 40. Archer DF, Thomas MA, Conard J, et al. Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone(R) and ethinyl estradiol. Contraception. 2016;93(1):58-64. 41. Artini PG, Volpe A, Angioni S, Galassi MC, Battaglia C, Genazzani AR. A comparative, randomized study of three different progesterone support of the luteal phase following IVF/ET program. Journal of endocrinological investigation. 1995;18(1):51-6. 42. Artymuk NV, Kira EF, Kondratieva TA. Intravaginal gel prepared from Dead Sea peloid for treating luteal-phase defect. Int J Gynaecol Obstet. 2010;108(1):72-3. 43. Ata B, Kucuk M, Seyhan A, Urman B. Effect of high-dose estrogen in luteal phase support on live birth rates after assisted reproduction treatment cycles. J Reprod Med. 2010;55(11-12):485-90. 44. Atmaca R, Kafkasli A, Burak F, Germen AT. Priming effect of misoprostol on estrogen pretreated cervix in postmenopausal women. Tohoku J Exp Med. 2005;206(3):237-41. 45. Aylward M, Holly F, Parker RJ. An evaluation of clinical response to piperazine oestrone sulphate ('Harmogen') in menopause patients. Curr Med Res Opin. 1974;2(7):417-23. 46. Aylward M, Maddock J, Parker A, Protheroe DA, Ward A. Endometrial factors under treatment with oestrogen and oestrogen/progestogen combinations. Postgrad Med J. 1978;54 Suppl 2:74-81.

47. Ayton RA, Darling GM, Murkies AL, et al. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. British journal of obstetrics and gynaecology. 1996;103(4):351-8. 48. Bachmann G, Bobula J, Mirkin S. Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy. Climacteric. 2010;13(2):132-40. 49. Bachmann G, Bouchard C, Hoppe D, et al. Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally. Menopause. 2009;16(4):719-27. 50. Bachmann G, Crosby U, Feldman RA, Ronkin S, Constantine GD. Effects of bazedoxifene in nonflushing postmenopausal women: a randomized phase 2 trial. Menopause. 2011;18(5):508-14. 51. Bachmann G, Lobo RA, Gut R, Nachtigall L, Notelovitz M. Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Obstet Gynecol. 2008;111(1):67-76. 52. Bachmann GA, Komi JO, Ospemifene Study G. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010;17(3):480-6. 53. Bachmann GA, Schaefers M, Uddin A, Utian WH. Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women. Menopause. 2009;16(5):877-82. 54. Back DJ, Grimmer SF, Rogers S, Stevenson PJ, Orme ML. Comparative pharmacokinetics of levonorgestrel and ethinyloestradiol following intravenous, oral and vaginal administration. Contraception. 1987;36(4):471-9. 55. Baerug U, Winge T, Nordland G, et al. Do combinations of 1 mg estradiol and low doses of NETA effectively control menopausal symptoms? Climacteric. 1998;1(3):219-28. 56. Bahamondes L, Faundes D, Marchi N, Ramos M, Perrotti M, Cristofoletti ML. The influence of human chorionic gonadotrophin administration upon the next ovarian cycle. Hum Reprod. 1995;10(3):533-5. 57. Bahamondes L, Trevisan M, Andrade L, et al. The effect upon the human vaginal histology of the long-term use of the injectable contraceptive Depo-Provera. Contraception. 2000;62(1):23-7. 58. Bai W, Henneicke-von Zepelin HH, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas. 2007;58(1):31-41. 59. Baird DD, Umbach DM, Lansdell L, et al. Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab. 1995;80(5):1685-90. 60. Baird DD, Wilcox AJ, Herbst AL. Self-reported allergy, infection, and autoimmune diseases among men and women exposed in utero to diethylstilbestrol. Journal of clinical epidemiology. 1996;49(2):263-6. 61. Baker ER, Best RG, Manfredi RL, Demers LM, Wolf GC. Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual syndrome. J Assist Reprod Genet. 1995;12(3):205-9.

62. Baker VL, Draper M, Paul S, et al. Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles. J Clin Endocrinol Metab. 1998;83(1):6-13. 63. Balasch J, Vanrell JA, Marquez M, Burzaco I, Gonzalez-Merlo J. Dehydrogesterone versus vaginal progesterone in the treatment of the endometrial luteal phase deficiency. Fertil Steril. 1982;37(6):751-4. 64. Balk JL, Whiteside DA, Naus G, DeFerrari E, Roberts JM. A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium. J Soc Gynecol Investig. 2002;9(4):238-42. 65. Ballagh SA, Mishell DR, Jr., Jackanicz TM, Lacarra M, Eggena P. Dose-finding study of a contraceptive ring releasing norethindrone acetate/ethinyl estradiol. Contraception. 1994;50(6):535-49. 66. Ballagh SA, Mishell DR, Jr., Lacarra M, Shoupe D, Jackanicz TM, Eggena P. A contraceptive vaginal ring releasing norethindrone acetate and ethinyl estradiol. Contraception. 1994;50(6):517-33. 67. Baracat EC, Simoes MJ, Soares JM, Jr., Haidar MA, Rodrigues de Lima G. Ultrastructural aspects of the postmenopausal endometrium after oral or transdermal estrogen administration. Clinical and experimental obstetrics & gynecology. 2001;28(1):26-30. 68. Barbosa IC, Coutinho EM, Oladapo L, et al. An open-label study of subdermal implants of estradiol-only versus subdermal implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid profile and tolerability. Gynecol Endocrinol. 2009;25(4):269-75. 69. Barentsen R, van de Weijer PH, Schram JH. Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. European journal of obstetrics, gynecology, and reproductive biology. 1997;71(1):73-80. 70. Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and treatment- related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol. 2005;105(5 Pt 1):1063-73. 71. Barnabei VM, Grady D, Stovall DW, et al. Menopausal symptoms in older women and the effects of treatment with hormone therapy. Obstet Gynecol. 2002;100(6):1209-18. 72. Barton DL, Shuster LT, Dockter T, et al. Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance). Support Care Cancer. 2018;26(4):1335-43. 73. Barton DL, Sloan JA, Shuster LT, et al. Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance). Support Care Cancer. 2018;26(2):643-50. 74. Bassol S, Carranza-Lira S, Celis-Gonzalez C, et al. The impact of a monophasic continuous estro-progestogenic treatment on Latin American menopausal women. Maturitas. 2005;50(3):189-95. 75. Basson R, Brotto LA. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial. BJOG. 2003;110(11):1014-24. 76. Bateson DJ, Weisberg E. An open-label randomized trial to determine the most effective regimen of vaginal estrogen to reduce the prevalence of atrophic changes reported in postmenopausal cervical smears. Menopause. 2009;16(4):765-9.

77. Battaglia C, Cianciosi A, Mancini F, et al. Genistein supplements might not induce clitoral modifications in postmenopausal women: a prospective, pilot study. J Sex Med. 2009;6(11):3132-8. 78. Baysoy A, Serdaroglu H, Jamal H, Karatekeli E, Ozornek H, Attar E. Letrozole versus human menopausal gonadotrophin in women undergoing intrauterine insemination. Reprod Biomed Online. 2006;13(2):208-12. 79. Beardsworth SA, Kearney CE, Purdie DW. Prevention of postmenopausal bone loss at lumbar spine and upper femur with tibolone: a two-year randomised controlled trial. British journal of obstetrics and gynaecology. 1999;106(7):678-83. 80. Beaton D. A comparative trial of quinestradol and ethinyl oestradiol. Br J Clin Pract. 1967;21(5):241-3. 81. Behilovic B, Rowan AJ. A comparative study of Norinyl 1/35 versus Norinyl 1/50 in Belgrade, Yugoslavia. Contraception. 1987;36(5):515-26. 82. Behre HM. Trial protocol and sample result of a study comparing the Clearplan Easy Fertility Monitor with serum hormone and vaginal ultrasound measurements in the determination of ovulation. J Int Med Res. 2001;29 Suppl 1:21A-7A. 83. Bellantoni MF, Harman SM, Cullins VE, Engelhardt SM, Blackman MR. Transdermal estradiol with oral progestin: biological and clinical effects in younger and older postmenopausal women. J Gerontol. 1991;46(6):M216-22. 84. Bellina JH, Ross LF, Hemmings R, Voros JI, Moorehead M. Carbon dioxide laser treatment of vaginal adenosis in DES-exposed offspring: a prospective study. Lasers Surg Med. 1983;3(1):23-8. 85. Belsey EM. Vaginal bleeding patterns among women using one natural and eight hormonal methods of contraception. Contraception. 1988;38(2):181-206. 86. Ben-Chetrit A, Gotlieb L, Wong PY, Casper RF. Ovarian response to recombinant human follicle-stimulating hormone in luteinizing hormone-depleted women: examination of the two cell, two gonadotropin theory. Fertil Steril. 1996;65(4):711-7. 87. Ben-Chetrit A, Hochner-Celnikier D, Lindenberg T, et al. Vaginal ring delivering estradiol and progesterone: a possible alternative to relieve climacteric symptoms. Isr Med Assoc J. 2005;7(5):302-6. 88. Benjamin F, Kolodny HD, Schwartz ED. The comparative effects of the administration of cortisone, estrogen-progestin, and placebo on the clinical manifestations of the polycystic ovary (Stein-Leventhal) syndrome. J Reprod Med. 1971;6(6):266-9. 89. Benson JT, Lucente V, McClellan E. Vaginal versus abdominal reconstructive surgery for the treatment of pelvic support defects: a prospective randomized study with long-term outcome evaluation. Am J Obstet Gynecol. 1996;175(6):1418-21; discussion 21-2. 90. Berger GS, Edelman DA, Talwar PP. The probability of side effects with ovral, norinyl 1/50 and norlestrin. Contraception. 1979;20(5):447-53. 91. Berning B, van Kuijk C, Bennink HJ, Fauser BC. Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women. Maturitas. 2000;35(1):81-8. 92. Bhamra RK, Margolis MB, Liu JH, Hendy CH, Jenkins RG, DiLiberti CE. A randomized, multiple-dose parallel study to compare the pharmacokinetic parameters of synthetic conjugated estrogens, A, administered as oral tablet or vaginal cream. Menopause. 2011;18(4):393-9.

93. Bishop J, Murray R, Webster L, et al. Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. Cancer Chemother Pharmacol. 1992;30(3):174-8. 94. Bishun NP, Smith NS, Williams DC, Raven RW. Carcinogenic and possible mutagenic effects of stilboestrol in offspring exposed in utero. J Surg Oncol. 1977;9(3):293-300. 95. Bjarnadottir RI, Tuppurainen M, Killick SR. Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol. Am J Obstet Gynecol. 2002;186(3):389-95. 96. Blakely LJ, Buzdar A, Chang HY, et al. A phase I and pharmacokinetic study of TAS- 108 in postmenopausal female patients with locally advanced, locally recurrent inoperable, or progressive metastatic breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004;10(16):5425-31. 97. Bolaji, II, Mortimer G, Grimes H, Tallon DF, O'Dwyer E, Fottrell PF. Clinical evaluation of near-continuous oral micronized progesterone therapy in estrogenized postmenopausal women. Gynecol Endocrinol. 1996;10(1):41-7. 98. Bolognese M, Krege JH, Utian WH, et al. Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass. J Clin Endocrinol Metab. 2009;94(7):2284-9. 99. Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole is superior to tamoxifen as first- line therapy in hormone receptor positive advanced breast carcinoma. Cancer. 2001;92(9):2247- 58. 100. Bonneterre J, Thurlimann B, Robertson JF, et al. Anastrozole versus tamoxifen as first- line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(22):3748-57. 101. Boon J, Scholten PC, Oldenhave A, Heintz AP. Continuous intrauterine compared with cyclic oral progestin administration in perimenopausal HRT. Maturitas. 2003;46(1):69-77. 102. Botsis D, Kassanos D, Kalogirou D, Antoniou G, Vitoratos N, Karakitsos P. Vaginal ultrasound of the endometrium in postmenopausal women with symptoms of urogenital atrophy on low-dose estrogen or tibolone treatment: a comparison. Maturitas. 1997;26(1):57-62. 103. Bottiglione F, Volpe A, Esposito G, Aloysio DD. Transvaginal estriol administration in postmenopausal women: a double blind comparative study of two different doses. Maturitas. 1995;22(3):227-32. 104. Bouchard C, Labrie F, Archer DF, et al. Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy. Climacteric. 2015;18(4):590-607. 105. Bouchard C, Labrie F, Derogatis L, et al. Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study. Horm Mol Biol Clin Investig. 2016;25(3):181-90. 106. Brache V, Croxatto H, Sitruk-Ware R, et al. Effect of a single vaginal administration of levonorgestrel in Carraguard gel on the ovulatory process: a potential candidate for "dual protection" emergency contraception. Contraception. 2007;76(2):111-6. 107. Brache V, Massai R, Mishell DR, et al. Ovarian function during use of Nestorone(R) subdermal implants. Contraception. 2000;61(3):199-204. 108. Brache V, Mishell DR, Lahteenmaki P, et al. Ovarian function during use of vaginal rings delivering three different doses of Nestorone. Contraception. 2001;63(5):257-61.

109. Breast International Group 1-98 Collaborative G, Thurlimann B, Keshaviah A, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353(26):2747-57. 110. Brenner PF. The menopausal syndrome. Obstet Gynecol. 1988;72(5 Suppl):6S-11S. 111. Brezina PR, Vlahos NF, Lai TH, Garcia JE, Wallach EE, Zhao Y. The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial. Reprod Biol Endocrinol. 2012;10:16. 112. Brinsmead M, Stanger J, Oliver M, Shumack J, Raymond S, Clark L. A randomized trial of laparoscopy and transvaginal ultrasound-directed oocyte pickup for in vitro fertilization. J In Vitro Fert Embryo Transf. 1989;6(3):149-54. 113. Bronstein SB, Stough A. Response of human vaginal epithelium to single high dose or daily lower dose of oral quinesteol. Int J Fertil. 1967;12(2):170-5. 114. Brown JS, Vittinghoff E, Kanaya AM, et al. Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Obstet Gynecol. 2001;98(6):1045-52. 115. Bruce D, Robinson J, Rymer J. Long-term effects of tibolone on the endometrium as assessed by bleeding episodes, transvaginal scan and endometrial biopsy. Climacteric. 2004;7(3):261-6. 116. Bruhat M, Rudolf K, Vaheri R, Kainulainen P, Timonen U, Viitanen A. Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: a randomized comparative dose-ranging study. Maturitas. 2001;40(3):259- 71. 117. Bruni V, Pontello V, Luisi S, Petraglia F. An open-label, multicentre trial to evaluate the vaginal bleeding pattern of the combined contraceptive vaginal ring NuvaRing. European journal of obstetrics, gynecology, and reproductive biology. 2008;139(1):65-71. 118. Brunner RL, Aragaki A, Barnabei V, et al. Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial. Menopause. 2010;17(5):946-54. 119. Bruyniks N, Nappi RE, Castelo-Branco C, de Villiers TJ, Simon J. Effect of ospemifene on moderate or severe symptoms of vulvar and vaginal atrophy. Climacteric. 2016;19(1):60-5. 120. Brys M, Szyllo K, Romanowicz-Makowska H, Dobrowolski Z, Maslowska I, Krajewska W. Expression of estrogen and progesterone receptor genes in endometrium, myometrium and vagina of postmenopausal women treated with estriol. Sao Paulo Med J. 2009;127(3):128-33. 121. Brzyski RG, Viniegra A, Archer DF. Effects of chronic nocturnal opiate antagonism on the menstrual cycle. Am J Obstet Gynecol. 1992;167(6):1780-4. 122. Buckler H, Al-Azzawi F, Group UVMT. The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women. BJOG. 2003;110(8):753- 9. 123. Burch DJ, Spowart KJ, Jesinger DK, Randall S, Smith SK. A dose-ranging study of the use of cyclical dydrogesterone with continuous 17 beta oestradiol. British journal of obstetrics and gynaecology. 1995;102(3):243-8. 124. Buzdar A, Douma J, Davidson N, et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001;19(14):3357-66. 125. Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996;23(3):259-63.

126. Cagnacci A, Melis GB, Soldani R, Paoletti AM, Fioretti P. Effect of sex steroids on body temperature in postmenopausal women. Role of endogenous opioids. Life Sci. 1992;50(7):515- 21. 127. Cagnacci A, Neri I, Tarabusi M, Volpe A, Facchinetti F. Effect of long-term local or systemic hormone replacement therapy on post-menopausal mood disturbances. Influences of socio-economic and personality factors. Maturitas. 1999;31(2):111-6. 128. Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol. 1977;4(1):31-47. 129. Cano A, Estevez J, Usandizaga R, et al. The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study. Menopause. 2012;19(10):1130-9. 130. Cano A, Tarin JJ, Duenas JL. Two-year prospective, randomized trial comparing an innovative twice-a-week progestin regimen with a continuous combined regimen as postmenopausal hormone therapy. Fertil Steril. 1999;71(1):129-36. 131. Carmignani LO, Pedro AO, Costa-Paiva LH, Pinto-Neto AM. The effect of dietary soy supplementation compared to estrogen and placebo on menopausal symptoms: a randomized controlled trial. Maturitas. 2010;67(3):262-9. 132. Carmignani LO, Pedro AO, Montemor EB, Arias VA, Costa-Paiva LH, Pinto-Neto AM. Effects of a soy-based dietary supplement compared with low-dose hormone therapy on the urogenital system: a randomized, double-blind, controlled clinical trial. Menopause. 2015;22(7):741-9. 133. Carr BR, Breslau NA, Givens C, Byrd W, Barnett-Hamm C, Marshburn PB. Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study. J Clin Endocrinol Metab. 1995;80(4):1169-78. 134. Carranza-Lira S, Gooch AL, Saldivar N, Osterwalder MS. Climacteric symptom control after the addition of low-dose esterified conjugated estrogens to raloxifene standard doses. Int J Fertil Womens Med. 2007;52(2-3):93-6. 135. Carranza-Lira S, MacGregor-Gooch AL. Differences in vaginal dryness according to hormone therapy schedule using pH test strip in two groups of postmenopausal women. Int J Fertil Womens Med. 2004;49(2):88-90. 136. Caruso S, Agnello C, Intelisano G, Farina M, Di Mari L, Cianci A. Sexual behavior of women taking low-dose oral contraceptive containing 15 microg ethinylestradiol/60 microg gestodene. Contraception. 2004;69(3):237-40. 137. Caruso S, Cianci S, Vitale SG, Matarazzo MG, Amore FF, Cianci A. Effects of ultralow topical estriol dose on vaginal health and quality of life in postmenopausal women who underwent surgical treatment for pelvic organ prolapse. Menopause. 2017;24(8):900-7. 138. Caruso S, Roccasalva L, Sapienza G, Zappala M, Nuciforo G, Biondi S. Laryngeal cytological aspects in women with surgically induced menopause who were treated with transdermal estrogen replacement therapy. Fertil Steril. 2000;74(6):1073-9. 139. Casanas-Roux F, Nisolle M, Marbaix E, Smets M, Bassil S, Donnez J. Morphometric, immunohistological and three-dimensional evaluation of the endometrium of menopausal women treated by oestrogen and Crinone, a new slow-release vaginal progesterone. Hum Reprod. 1996;11(2):357-63.

140. Casanova G, dos Reis AM, Spritzer PM. Low-dose oral or non-oral hormone therapy: effects on C-reactive protein and atrial natriuretic peptide in menopause. Climacteric. 2015;18(1):86-93. 141. Casanova G, Radavelli S, Lhullier F, Spritzer PM. Effects of nonoral estradiol- micronized progesterone or low-dose oral estradiol-drospirenone therapy on metabolic variables and markers of endothelial function in early postmenopause. Fertil Steril. 2009;92(2):605-12. 142. Casanova G, Spritzer PM. Effects of micronized progesterone added to non-oral estradiol on lipids and cardiovascular risk factors in early postmenopause: a clinical trial. Lipids Health Dis. 2012;11:133. 143. Casper F, Petri E. Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study. Vaginal Ring Study Group. Int Urogynecol J Pelvic Floor Dysfunct. 1999;10(3):171-6. 144. Castellani D, Saldutto P, Galica V, et al. Low-Dose Intravaginal Estriol and Pelvic Floor Rehabilitation in Post-Menopausal Stress Urinary Incontinence. Urol Int. 2015;95(4):417-21. 145. Cayan F, Dilek U, Pata O, Dilek S. Comparison of the effects of hormone therapy regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. J Sex Med. 2008;5(1):132-8. 146. Ceyhan ST, Basaran M, Kemal Duru N, Yilmaz A, Goktolga U, Baser I. Use of luteal estrogen supplementation in normal responder patients treated with fixed multidose GnRH antagonist: a prospective randomized controlled study. Fertil Steril. 2008;89(6):1827-30. 147. Chaikittisilpa S, Angsuwathana S, Chaovisitsaree S, et al. Clinical responses to the combination of estradiol and drospirenone in symptomatic postmenopausal Thai women. J Med Assoc Thai. 2011;94(9):1019-25. 148. Checa MA, Garrido A, Prat M, Conangla M, Rueda C, Carreras R. A comparison of raloxifene and calcium plus vitamin D on vaginal atrophy after discontinuation of long-standing postmenopausal hormone therapy in osteoporotic women. A randomized, masked-evaluator, one- year, prospective study. Maturitas. 2005;52(1):70-7. 149. Check JH, Graziano V, Lee G, Nazari A, Choe JK, Dietterich C. Neither sildenafil nor vaginal estradiol improves endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages. Clinical and experimental obstetrics & gynecology. 2004;31(2):99-102. 150. Chen J, Geng L, Song X, Li H, Giordan N, Liao Q. Evaluation of the efficacy and safety of hyaluronic acid vaginal gel to ease vaginal dryness: a multicenter, randomized, controlled, open-label, parallel-group, clinical trial. J Sex Med. 2013;10(6):1575-84. 151. Chen X, Guo H. Comparison of Chlorquinaldol-Promestriene Vaginal Tablets and Opin Suppositories Effect on Inflammatory Factors and Immune Function in Chronic HPV Cervicitis. J Coll Physicians Surg Pak. 2019;29(2):115-8. 152. Chiechi LM, Putignano G, Guerra V, Schiavelli MP, Cisternino AM, Carriero C. The effect of a soy rich diet on the vaginal epithelium in postmenopause: a randomized double blind trial. Maturitas. 2003;45(4):241-6. 153. Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med. 2004;350(10):991-1004. 154. Choavaratana R, Manoch D. Efficacy of oral micronized progesterone when applied via vaginal route. J Med Assoc Thai. 2004;87(5):455-8. 155. Choktanasiri W, Boonkasemsanti W, Sittisomwong T, et al. Long-acting triptorelin for the treatment of endometriosis. Int J Gynaecol Obstet. 1996;54(3):237-43.

156. Chollet JA, Carter G, Meyn LA, Mermelstein F, Balk JL. Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic vaginitis. Menopause. 2009;16(5):978-83. 157. Chompootaweep S, Nunthapisud P, Trivijitsilp P, Sentrakul P, Dusitsin N. The use of two estrogen preparations (a combined contraceptive pill versus conjugated estrogen cream) intravaginally to treat urogenital symptoms in postmenopausal Thai women: a comparative study. Clin Pharmacol Ther. 1998;64(2):204-10. 158. Christensen MS, Hagen C, Christiansen C, Transbol I. Dose-response evaluation of cyclic estrogen/gestagen in postmenopausal women: placebo-controlled trial of its gynecologic and metabolic actions. Am J Obstet Gynecol. 1982;144(8):873-9. 159. Chughtai B, Forde JC, Buck J, et al. The concomitant use of fesoterodine and topical vaginal estrogen in the management of overactive bladder and sexual dysfunction in postmenopausal women. Post Reprod Health. 2016;22(1):34-40. 160. Chung DJ, Kim HY, Park KH, et al. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J. 2007;48(2):289-94. 161. Cicinelli E, Borraccino V, Petruzzi D, Mazzotta N, Cerundolo ML, Schonauer LM. Pharmacokinetics and endometrial effects of the vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women. Fertil Steril. 1996;65(4):860-2. 162. Cicinelli E, De Ziegler D, Morgese S, Bulletti C, Luisi D, Schonauer LM. "First uterine pass effect" is observed when estradiol is placed in the upper but not lower third of the vagina. Fertil Steril. 2004;81(5):1414-6. 163. Cicinelli E, Di Naro E, De Ziegler D, et al. Placement of the vaginal 17beta-estradiol tablets in the inner or outer one third of the vagina affects the preferential delivery of 17beta- estradiol toward the uterus or periurethral areas, thereby modifying efficacy and endometrial safety. Am J Obstet Gynecol. 2003;189(1):55-8. 164. Cicinelli E, Petruzzi D, Scorcia P, Resta L. Effects of progesterone administered by nasal spray on the human postmenopausal endometrium. Maturitas. 1993;18(1):65-72. 165. Cicinelli E, Pinto V, Tinelli R, Saliani N, De Leo V, Cianci A. Rapid endometrial preparation for hysteroscopic surgery with oral desogestrel plus vaginal raloxifene: a prospective, randomized pilot study. Fertil Steril. 2007;88(3):698-701. 166. Civelli M, Preti AP, Cenacchi V, et al. Single and multiple ascending dose studies of a novel tissue-selective oestrogen receptor modulator, CHF 4227, in healthy postmenopausal women. Br J Clin Pharmacol. 2007;64(3):304-16. 167. Clisham PR, Cedars MI, Greendale G, Fu YS, Gambone J, Judd HL. Long-term transdermal estradiol therapy: effects on endometrial histology and bleeding patterns. Obstet Gynecol. 1992;79(2):196-201. 168. Coates AS, Keshaviah A, Thurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007;25(5):486-92. 169. Cobo AC, Requena A, Neuspiller F, et al. Maturation in vitro of human oocytes from unstimulated cycles: selection of the optimal day for ovum retrieval based on follicular size. Hum Reprod. 1999;14(7):1864-8. 170. Cochrane R, Regan L. Undetected gynaecological disorders in women with renal disease. Hum Reprod. 1997;12(4):667-70.

171. Coelingh Bennink HJ, Verhoeven C, Zimmerman Y, Visser M, Foidart JM, Gemzell- Danielsson K. Clinical effects of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Maturitas. 2016;91:93-100. 172. Colli MC, Bracht A, Soares AA, et al. Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms. J Med Food. 2012;15(9):840-5. 173. Colodner R, Edelstein H, Chazan B, Raz R. Vaginal colonization by orally administered Lactobacillus rhamnosus GG. Isr Med Assoc J. 2003;5(11):767-9. 174. Combs CA, Garite TJ, Maurel K, Das A, Obstetrix Collaborative Research N. Fetal fibronectin versus cervical length as predictors of preterm birth in twin pregnancy with or without 17-hydroxyprogesterone caproate. Am J Perinatol. 2014;31(12):1023-30. 175. Conner P, Skoog L, Soderqvist G. Breast epithelial proliferation in postmenopausal women evaluated through fine-needle-aspiration cytology. Climacteric. 2001;4(1):7-12. 176. Constantine G, Graham S, Koltun WD, Kingsberg SA. Assessment of ospemifene or lubricants on clinical signs of VVA. J Sex Med. 2014;11(4):1033-41. 177. Constantine G, Graham S, Portman DJ, Rosen RC, Kingsberg SA. Female sexual function improved with ospemifene in postmenopausal women with vulvar and vaginal atrophy: results of a randomized, placebo-controlled trial. Climacteric. 2015;18(2):226-32. 178. Constantine GD, Bouchard C, Pickar JH, et al. Consistency of Effect with a Low-Dose, Estradiol Vaginal Capsule (TX-004HR): Evaluating Improvement in Vaginal Physiology and Moderate-to-Severe Dyspareunia in Subgroups of Postmenopausal Women. J Womens Health (Larchmt). 2017;26(6):616-23. 179. Constantine GD, Goldstein SR, Archer DF. Endometrial safety of ospemifene: results of the phase 2/3 clinical development program. Menopause. 2015;22(1):36-43. 180. Constantine GD, Simon JA, Pickar JH, et al. The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic vulvar and vaginal atrophy. Menopause. 2017;24(4):409-16. 181. Coope J. The effect of 'natural' oestrogen replacement therapy on menopausal symptoms. Postgrad Med J. 1976;52 Suppl 6:27. 182. Coope J, Thomson JM, Poller L. Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting. Br Med J. 1975;4(5989):139-43. 183. Corenthal L, Von Hagen S, Larkins D, Ibrahim J, Santoro N. Benefits of continuous physiological pulsatile gonadotropin-releasing hormone therapy in women with polycystic ovarian syndrome. Fertil Steril. 1994;61(6):1027-33. 184. Costantino D, Guaraldi C. Effectiveness and safety of vaginal suppositories for the treatment of the vaginal atrophy in postmenopausal women: an open, non-controlled clinical trial. Eur Rev Med Pharmacol Sci. 2008;12(6):411-6. 185. Coutinho EM, da Silva AR, Carreira C, Rodrigues V, Goncalves MT. Conception control by vaginal administration of pills containing ethinyl estradiol and dl-norgestrel. Fertil Steril. 1984;42(3):478-81. 186. Coutinho EM, de Souza JC, da Silva AR, et al. Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial. Clin Pharmacol Ther. 1993;53(1):65-75. 187. Coutinho EM, Mascarenhas I, de Acosta OM, et al. Comparative study on the efficacy, acceptability, and side effects of a contraceptive pill administered by the oral and the vaginal route: an international multicenter clinical trial. Clin Pharmacol Ther. 1993;54(5):540-5.

188. Coutinho EM, O'Dwyer E, Barbosa IC, et al. Comparative study on intermittent versus continuous use of a contraceptive pill administered by vaginal route. Contraception. 1995;51(6):355-8. 189. Couzinet B, Brailly S, Bouchard P, Schaison G. Progesterone stimulates luteinizing hormone secretion by acting directly on the pituitary. J Clin Endocrinol Metab. 1992;74(2):374- 8. 190. Crisafulli A, Marini H, Bitto A, et al. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause. 2004;11(4):400-4. 191. Croxatto HB, Brache V, Massai R, et al. Feasibility study of Nestorone-ethinylestradiol vaginal contraceptive ring for emergency contraception. Contraception. 2006;73(1):46-52. 192. Crucitti T, Hardy L, van de Wijgert J, et al. Contraceptive rings promote vaginal lactobacilli in a high bacterial vaginosis prevalence population: A randomised, open-label longitudinal study in Rwandan women. PLoS One. 2018;13(7):e0201003. 193. Cruz VL, Steiner ML, Pompei LM, et al. Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women. Menopause. 2018;25(1):21-8. 194. Cullberg G. Androgenic, anabolic, estrogenic and antiestrogenic effects of desogestrel and lynestrenol: effects on serum proteins and vaginal cytology. Contraception. 1984;30(1):73-9. 195. Cummings JA, Brizendine L. Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women. Menopause. 2002;9(4):253-63. 196. Cuong DT, My Huong NT. Comparative phase III clinical trial of two injectable contraceptive preparations, depot-medroxyprogesterone acetate and Cyclofem, in Vietnamese women. Contraception. 1996;54(3):169-79. 197. Dahiya P, Dalal M, Yadav A, Dahiya K, Jain S, Silan V. Efficacy of combined hormonal vaginal ring in comparison to combined hormonal pills in heavy menstrual bleeding. European journal of obstetrics, gynecology, and reproductive biology. 2016;203:147-51. 198. Dalais FS, Rice GE, Wahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric. 1998;1(2):124-9. 199. Darney PD, Klaisle CM, Monroe SE, Cook CE, Phillips NR, Schindler A. Evaluation of a 1-year levonorgestrel-releasing contraceptive implant: side effects, release rates, and biodegradability. Fertil Steril. 1992;58(1):137-43. 200. Davies GC, Huster WJ, Lu Y, Plouffe L, Jr., Lakshmanan M. Adverse events reported by postmenopausal women in controlled trials with raloxifene. Obstet Gynecol. 1999;93(4):558-65. 201. Davies GC, Huster WJ, Shen W, et al. Endometrial response to raloxifene compared with placebo, cyclical hormone replacement therapy, and unopposed estrogen in postmenopausal women. Menopause. 1999;6(3):188-95. 202. Day R, National Surgical Adjuvant B, Bowel Projet Ps. Quality of life and tamoxifen in a breast cancer prevention trial: a summary of findings from the NSABP P-1 study. National Surgical Adjuvant Breast and Bowel Project. Ann N Y Acad Sci. 2001;949:143-50. 203. de Ziegler D, Bergeron C, Cornel C, et al. Effects of luteal estradiol on the secretory transformation of human endometrium and plasma gonadotropins. J Clin Endocrinol Metab. 1992;74(2):322-31. 204. de Ziegler D, Ferriani R, Moraes LA, Bulletti C. Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined regimens. Hum Reprod. 2000;15 Suppl 1:149-58.

205. Dehbashi S, Parsanezhad ME, Alborzi S, Zarei A. Effect of clomiphene citrate on endometrium thickness and echogenic patterns. Int J Gynaecol Obstet. 2003;80(1):49-53. 206. Del Pup L, Postruznik D, Corona G. Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: a pilot study. Maturitas. 2012;72(1):93-4. 207. Delmanto A, Nahas-Neto J, Nahas EA, de Oliveira ML, Fernandes CE, Traiman P. Effect of raloxifene on the vaginal epithelium of postmenopausal women. European journal of obstetrics, gynecology, and reproductive biology. 2008;139(2):187-92. 208. Delmas P, Gimona A. Osteoporosis prevention clinical study program. European journal of obstetrics, gynecology, and reproductive biology. 1996;64 Suppl:S39-45. 209. Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337(23):1641-7. 210. Dempsey A, Roca C, Westhoff C. Vaginal estrogen supplementation during Depo- Provera initiation: a randomized controlled trial. Contraception. 2010;82(3):250-5. 211. Dennerstein L, Burrows GD, Hyman GJ, Sharpe K. Some clinical effects of oestrogen- progestogen therapy in surgically castrated women. Maturitas. 1980;2(1):19-28. 212. Deshmane V, Krishnamurthy S, Melemed AS, Peterson P, Buzdar AU. Phase III double- blind trial of arzoxifene compared with tamoxifen for locally advanced or metastatic breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007;25(31):4967-73. 213. Devenport MH, Crook D, Wynn V, Lees LJ. Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives. Br J Clin Pharmacol. 1989;27(6):851-9. 214. Devoto L, Kohen P, Barnhart K, et al. Hormonal profile, endometrial histology and ovarian ultrasound assessment during 1 year of nomegestrol acetate implant (Uniplant). Hum Reprod. 1997;12(4):708-13. 215. Di Carlo C, Sammartino A, Di Spiezio Sardo A, et al. Bleeding patterns during continuous estradiol with different sequential progestogens therapy. Menopause. 2005;12(5):520-5. 216. Di Carlo C, Tommaselli GA, Gargano V, Savoia F, Bifulco G, Nappi C. Transdermal estradiol and oral or vaginal natural progesterone: bleeding patterns. Climacteric. 2010;13(5):442-6. 217. Diaz S, Reyes MV, Zepeda A, et al. Norplant((R)) implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod. 1999;14(10):2499-505. 218. Dickerson J, Bressler R, Christian CD, Hermann HW. Efficacy of estradiol vaginal cream in postmenopausal women. Clin Pharmacol Ther. 1979;26(4):502-7. 219. Dickey RP, Hower JF. Effect of ovulation induction on uterine blood flow and oestradiol and progesterone concentrations in early pregnancy. Hum Reprod. 1995;10(11):2875-9. 220. Dieben TO, Roumen FJ, Apter D. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol. 2002;100(3):585-93. 221. Diem S, Grady D, Quan J, et al. Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years. Menopause. 2006;13(1):130-8. 222. Dietz HP, Shek KL, Daly O, Korda A. Can levator avulsion be repaired surgically? A prospective surgical pilot study. Int Urogynecol J. 2013;24(6):1011-5.

223. Ditkoff EC, Cassidenti DL, Paulson RJ, et al. The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women. Am J Obstet Gynecol. 1991;165(6 Pt 1):1811-7. 224. Dogterom P, van den Heuvel MW, Thomsen T. Absence of pharmacokinetic interactions of the combined contraceptive vaginal ring NuvaRing with oral amoxicillin or doxycycline in two randomised trials. Clin Pharmacokinet. 2005;44(4):429-38. 225. Donders G, Neven P, Moegele M, et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. 2014;145(2):371-9. 226. Donnez J, Hervais Vivancos B, Kudela M, Audebert A, Jadoul P. A randomized, placebo-controlled, dose-ranging trial comparing fulvestrant with goserelin in premenopausal patients with uterine fibroids awaiting hysterectomy. Fertil Steril. 2003;79(6):1380-9. 227. Doren M, Rubig A, Coelingh Bennink HJ, Holzgreve W. Impact on uterine bleeding and endometrial thickness: tibolone compared with continuous combined estradiol and norethisterone acetate replacement therapy. Menopause. 1999;6(4):299-306. 228. Dorr MB, Nelson AL, Mayer PR, et al. Plasma estrogen concentrations after oral and vaginal estrogen administration in women with atrophic vaginitis. Fertil Steril. 2010;94(6):2365- 8. 229. Dragonas C, Maltaris T, Binder H, et al. Progesterone bioavailability with a progesterone-releasing silicone vaginal ring in IVF candidates. Eur J Med Res. 2007;12(6):264- 7. 230. Duffy DM, Lindheim SR, Vijod MA, Chang L, Nakamura RM, Lobo RA. Low-dose growth hormone-releasing factor may enhance folliculogenesis in regularly menstruating women: a preliminary study. Fertil Steril. 1995;63(4):756-60. 231. Dugal R, Hesla K, Sordal T, Aase KH, Lilleeidet O, Wickstrom E. Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy. Acta Obstet Gynecol Scand. 2000;79(4):293-7. 232. Duijkers I, Killick S, Bigrigg A, Dieben TO. A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function. Eur J Contracept Reprod Health Care. 2004;9(3):131-40. 233. Duijkers I, Klipping C, Heger-Mahn D, et al. Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17beta-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing. Eur J Contracept Reprod Health Care. 2018;23(4):245-54. 234. Duijkers IJ, Klipping C, Verhoeven CH, Dieben TO. Ovarian function with the contraceptive vaginal ring or an oral contraceptive: a randomized study. Hum Reprod. 2004;19(11):2668-73. 235. Duijkers IJ, Vemer HM, Hollanders JM, et al. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation. Hum Reprod. 1993;8(9):1387-91. 236. Duijkers IJ, Verhoeven CH, Dieben TO, Klipping C. Follicular growth during contraceptive pill or vaginal ring treatment depends on the day of ovulation in the pretreatment cycle. Hum Reprod. 2004;19(11):2674-9. 237. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab. 1999;84(10):3479-84.

238. Dyer GI, Young O, Townsend PT, Collins WP, Whitehead MI, Jelowitz J. Dose-related changes in vaginal cytology after topical conjugated equine oestrogens. Br Med J (Clin Res Ed). 1982;284(6318):789. 239. Eagleson CA, Gingrich MB, Pastor CL, et al. Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab. 2000;85(11):4047-52. 240. Egarter C, Huber J, Leikermoser R, et al. Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints. Maturitas. 1996;23(1):55-62. 241. Egarter C, Putz M, Strohmer H, Speiser P, Wenzl R, Huber J. Ovarian function during low-dose oral contraceptive use. Contraception. 1995;51(6):329-33. 242. Ekin M, Yasar L, Savan K, et al. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Arch Gynecol Obstet. 2011;283(3):539-43. 243. el-Damarawy H, el-Sahwi S, Toppozada M. Management of missed abortion and fetal death in utero. Prostaglandins. 1977;14(3):583-90. 244. Elfituri A, Sherif F, Elmahaishi M, Chrystyn H. Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women. Maturitas. 2005;52(1):52-9. 245. el-Habashy MA, Mishell DR, Jr., Moyer DL. Effect of supplementary oral estrogen on long-acting injectable progestogen contraception. Obstet Gynecol. 1970;35(1):51-4. 246. Elkind-Hirsch KE, Darensbourg C, Creasy G, Gipe D. Conception rates in clomiphene citrate cycles with and without hormone supplementation: a pilot study. Curr Med Res Opin. 2005;21(7):1035-40. 247. Elkind-Hirsch KE, Darensbourg C, Ogden B, Ogden LF, Hindelang P. Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive. Contraception. 2007;76(5):348-56. 248. Elkind-Hirsch KE, Phillips K, Bello SM, McNicho M, de Ziegler D. Sequential hormonal supplementation with vaginal estradiol and progesterone gel corrects the effect of clomiphene on the endometrium in oligo-ovulatory women. Hum Reprod. 2002;17(2):295-8. 249. Ellington DR, Szychowski JM, Malek JM, Gerten KA, Burgio KL, Richter HE. Combined Tolterodine and Vaginal Estradiol Cream for Overactive Bladder Symptoms After Randomized Single-Therapy Treatment. Female Pelvic Med Reconstr Surg. 2016;22(4):254-60. 250. Ellmen J, Hakulinen P, Partanen A, Hayes DF. Estrogenic effects of toremifene and tamoxifen in postmenopausal breast cancer patients. Breast Cancer Res Treat. 2003;82(2):103- 11. 251. Elomaa K, Ranta S, Tuominen J, Lahteenmaki P. Charcoal treatment and risk of escape ovulation in oral contraceptive users. Hum Reprod. 2001;16(1):76-81. 252. Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008;89(3):554-61. 253. Epstein E, Valentin L. Rebleeding and endometrial growth in women with postmenopausal bleeding and endometrial thickness < 5 mm managed by dilatation and curettage or ultrasound follow-up: a randomized controlled study. Ultrasound Obstet Gynecol. 2001;18(5):499-504. 254. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999;180(5):1072-9.

255. Eriksen PS, Rasmussen H. Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. European journal of obstetrics, gynecology, and reproductive biology. 1992;44(2):137-44. 256. Ettinger B, Bainton L, Upmalis DH, Citron JT, VanGessel A. Comparison of endometrial growth produced by unopposed conjugated estrogens or by micronized estradiol in postmenopausal women. Am J Obstet Gynecol. 1997;176(1 Pt 1):112-7. 257. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 1999;282(7):637-45. 258. Ettinger B, Kenemans P, Johnson SR, et al. Endometrial effects of tibolone in elderly, osteoporotic women. Obstet Gynecol. 2008;112(3):653-9. 259. Ettinger B, Pressman A, Van Gessel A. Low-dosage esterified estrogens opposed by progestin at 6-month intervals. Obstet Gynecol. 2001;98(2):205-11. 260. Eugster EA, Rubin SD, Reiter EO, et al. Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial. J Pediatr. 2003;143(1):60-6. 261. Eugster-Hausmann M, Waitzinger J, Lehnick D. Minimized estradiol absorption with ultra-low-dose 10 microg 17beta-estradiol vaginal tablets. Climacteric. 2010;13(3):219-27. 262. Exton MS, Bindert A, Kruger T, Scheller F, Hartmann U, Schedlowski M. Cardiovascular and endocrine alterations after masturbation-induced orgasm in women. Psychosom Med. 1999;61(3):280-9. 263. Fahy UM, Cahill DJ, Wardle PG, Hull MG. In-vitro fertilization in completely natural cycles. Hum Reprod. 1995;10(3):572-5. 264. Fallowfield LJ, Kilburn LS, Langridge C, et al. Long-term assessment of quality of life in the Intergroup Exemestane Study: 5 years post-randomisation. Br J Cancer. 2012;106(6):1062-7. 265. Fanchin R, De Ziegler D, Bergeron C, Righini C, Torrisi C, Frydman R. Transvaginal administration of progesterone. Obstet Gynecol. 1997;90(3):396-401. 266. Fanchin R, Righini C, de Ziegler D, Olivennes F, Ledee N, Frydman R. Effects of vaginal progesterone administration on uterine contractility at the time of embryo transfer. Fertil Steril. 2001;75(6):1136-40. 267. Fanchin R, Righini C, Schonauer LM, Olivennes F, Cunha Filho JS, Frydman R. Vaginal versus oral E(2) administration: effects on endometrial thickness, uterine perfusion, and contractility. Fertil Steril. 2001;76(5):994-8. 268. Fantl JA, Bump RC, Robinson D, McClish DK, Wyman JF. Efficacy of estrogen supplementation in the treatment of urinary incontinence. The Continence Program for Women Research Group. Obstet Gynecol. 1996;88(5):745-9. 269. Farag NH, Nelesen RA, Parry BL, Loredo JS, Dimsdale JE, Mills PJ. Autonomic and cardiovascular function in postmenopausal women: the effects of estrogen versus combination therapy. Am J Obstet Gynecol. 2002;186(5):954-61. 270. Fatemi HM, Bourgain C, Donoso P, et al. Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept. Hum Reprod. 2007;22(5):1260-3. 271. Fatemi HM, Camus M, Kolibianakis EM, et al. The luteal phase of recombinant follicle- stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization cycles

during supplementation with progesterone or progesterone and estradiol. Fertil Steril. 2007;87(3):504-8. 272. Fatemi HM, Kolibianakis EM, Camus M, et al. Addition of estradiol to progesterone for luteal supplementation in patients stimulated with GnRH antagonist/rFSH for IVF: a randomized controlled trial. Hum Reprod. 2006;21(10):2628-32. 273. Faundes A, Alvarez F, Brache V, Cochon L. Endometrial thickness and oestradiol concentration in women with bleeding complaints during use of Norplant implants. Hum Reprod. 1998;13(1):188-91. 274. Fedele L, Marchini M, Bianchi S, Baglioni A, Zanotti F. Vaginal patterns during danazol and buserelin acetate therapy for endometriosis: structural and ultrastructural study. Fertil Steril. 1993;59(6):1191-5. 275. Felding C, Mikkelsen AL, Clausen HV, Loft A, Larsen LG. Preoperative treatment with oestradiol in women scheduled for vaginal operation for genital prolapse. A randomised, double- blind trial. Maturitas. 1992;15(3):241-9. 276. Fernandes T, Costa-Paiva LH, Pedro AO, Baccaro LF, Pinto-Neto AM. Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on vaginal atrophy: a randomized controlled trial. Menopause. 2016;23(7):792-8. 277. Fernandes T, Costa-Paiva LH, Pinto-Neto AM. Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on sexual function in postmenopausal women: a randomized controlled trial. J Sex Med. 2014;11(5):1262-70. 278. Ferrero S, Gerbaldo D, Fulcheri E, Cristoforoni P. Vaginal micronized progesterone in continuous hormone replacement therapy. A prospective randomized study. Minerva Ginecol. 2002;54(6):519-30. 279. Ferrero S, Leone Roberti Maggiore U, Scala C, Di Luca M, Venturini PL, Remorgida V. Changes in the size of rectovaginal endometriotic nodules infiltrating the rectum during hormonal therapies. Arch Gynecol Obstet. 2013;287(3):447-53. 280. Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study. J Clin Endocrinol Metab. 2007;92(6):2100-6. 281. Ficicioglu C, Gurbuz B, Tasdemir S, Yalti S, Canova H. High local endometrial effect of vaginal progesterone gel. Gynecol Endocrinol. 2004;18(5):240-3. 282. Florio P, Filippeschi M, Imperatore A, et al. The practicability and surgeons' subjective experiences with vaginal danazol before an operative hysteroscopy. Steroids. 2012;77(5):528-33. 283. Foster DC, Palmer M, Marks J. Effect of vulvovaginal estrogen on sensorimotor response of the lower genital tract: a randomized controlled trial. Obstet Gynecol. 1999;94(2):232-7. 284. Franke HR, Snaaijer FF, Houben PW, van der Mooren MJ. Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial. Gynecol Endocrinol. 2006;22(12):692-7. 285. Fraser DI, Padwick ML, Whitehead MI, White J, Ryder TA, Pryse-Davies J. The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy. Maturitas. 1989;11(1):21-34. 286. Fraser IS, Ayton R, Farrell E, Weisberg E, Darling G, Murkies A. A multicentre Australian trial of low dose estradiol therapy for symptoms of vaginal atrophy using a vaginal ring as delivery system. Maturitas. 1995;22 Suppl:S41.

287. Fraser IS, Lacarra M, Mishell DR, et al. Vaginal epithelial surface appearances in women using vaginal rings for contraception. Contraception. 2000;61(2):131-8. 288. Fraser IS, Weisberg E, Brache V, et al. Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen. Contraception. 2005;72(1):40-5. 289. Fredricsson B, Englund K, Weintraub L, Olund A, Nord CE. Bacterial vaginosis is not a simple ecological disorder. Gynecol Obstet Invest. 1989;28(3):156-60. 290. Freedman M, Kaunitz AM, Reape KZ, Hait H, Shu H. Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy. Menopause. 2009;16(4):735-41. 291. Friedler S, Gilboa S, Schachter M, Raziel A, Strassburger D, Ron El R. Luteal phase characteristics following GnRH antagonist or agonist treatment - a comparative study. Reprod Biomed Online. 2006;12(1):27-32. 292. Friedler S, Raziel A, Schachter M, Strassburger D, Bukovsky I, Ron-El R. Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. Hum Reprod. 1999;14(8):1944-8. 293. Friedrich M, Villena-Heinsen C, Mink D, Endres V, Reitnauer K, Schmidt W. Ultrasonography of the endometrium and endometrial pathology under tamoxifen treatment. Eur J Gynaecol Oncol. 1998;19(6):536-40. 294. Frigo P, Eppel W, Asseryanis E, et al. The effects of hormone substitution in depot form on the uterus in a group of 50 perimenopausal women--a vaginosonographic study. Maturitas. 1995;21(3):221-5. 295. Fuertes-de la Haba A, Pelegrina I, Bangdiwala IS, Hernandez-Cibes JJ. Changing patterns in cervical cytology among oral and non-oral contraceptive users. J Reprod Med. 1973;10(1):3-10. 296. Gabrielsson J, Wallenbeck I, Birgerson L. Pharmacokinetic data on estradiol in light of the estring concept. Estradiol and estring pharmacokinetics. Acta Obstet Gynecol Scand Suppl. 1996;163:26-31; discussion 2-4. 297. Galhardo CL, Soares JM, Jr., Simoes RS, Haidar MA, Rodrigues de Lima G, Baracat EC. Estrogen effects on the vaginal pH, flora and cytology in late postmenopause after a long period without hormone therapy. Clinical and experimental obstetrics & gynecology. 2006;33(2):85-9. 298. Galuppi A, Perrone AM, La Macchia M, et al. Local alpha-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors. Int J Gynecol Cancer. 2011;21(9):1708-11. 299. Ganz PA, Greendale GA, Petersen L, Zibecchi L, Kahn B, Belin TR. Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. J Natl Cancer Inst. 2000;92(13):1054-64. 300. Garcia CR, David A. Long-term effects of oral contraceptives on the ovary and pituitary. Int J Fertil. 1968;13(4):287-96. 301. Gass MS, Rebar RW, Cuffie-Jackson C, et al. A short study in the treatment of hot flashes with buccal administration of 17-beta estradiol. Maturitas. 2004;49(2):140-7. 302. Gass M, Larson J, Cochrane B, et al. Sexual activity and vaginal symptoms in the postintervention phase of the Women's Health Initiative Hormone Therapy Trials. Menopause. 2018;25(3):252-64.

303. Gast MJ, Freedman MA, Vieweg AJ, et al. A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women. Menopause. 2009;16(2):247-56. 304. Gazvani R, Russell R, Sajjad Y, Alfirevic Z. Duration of luteal support (DOLS) with progesterone pessaries to improve the success rates in assisted conception: study protocol for a randomized controlled trial. Trials. 2012;13:118. 305. Gerber B, Krause A, Muller H, et al. Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(20):3464-70. 306. Gerhard I, Gwinner B, Eggert-Kruse W, Runnebaum B. Double-blind controlled trial of progesterone substitution in threatened abortion. Biol Res Pregnancy Perinatol. 1987;8(1 1ST Half):26-34. 307. Gerhard I, Schindler AE, Buhler K, et al. Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study. Clinical therapeutics. 1992;14 Suppl A:3-16. 308. Gerhard M, Walsh BW, Tawakol A, et al. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation. 1998;98(12):1158-63. 309. Gilboa Y, Bar-Hava I, Fisch B, et al. Does intravaginal probiotic supplementation increase the pregnancy rate in IVF-embryo transfer cycles? Reprod Biomed Online. 2005;11(1):71-5. 310. Ginsburg J, Prelevic G, Butler D, Okolo S. Clinical experience with tibolone (Livial) over 8 years. Maturitas. 1995;21(1):71-6. 311. Glaser RL, Zava DT, Wurtzbacher D. Pilot study: absorption and efficacy of multiple hormones delivered in a single cream applied to the mucous membranes of the labia and vagina. Gynecol Obstet Invest. 2008;66(2):111-8. 312. Glasier AF, Wang H, Davie JE, Kelly RW, Critchley HO. Administration of an antiprogesterone up-regulates estrogen receptors in the endometrium of women using Norplant: a pilot study. Fertil Steril. 2002;77(2):366-72. 313. Glazener CM, Bailey I, Hull MG. Effectiveness of vaginal administration of progesterone. British journal of obstetrics and gynaecology. 1985;92(4):364-8. 314. Glock JL, Blackman JA, Badger GJ, Brumsted JR. Prognostic significance of morphologic changes of the corpus luteum by transvaginal ultrasound in early pregnancy monitoring. Obstet Gynecol. 1995;85(1):37-41. 315. Gocmen A, Kara IH, Karaca M. The effects of add-back therapy with tibolone on myoma uteri. Clinical and experimental obstetrics & gynecology. 2002;29(3):222-4. 316. Goetsch MF, Lim JY, Caughey AB. Locating pain in breast cancer survivors experiencing dyspareunia: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1231-6. 317. Goetsch MF, Lim JY, Caughey AB. A Practical Solution for Dyspareunia in Breast Cancer Survivors: A Randomized Controlled Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;33(30):3394-400. 318. Goldstein SR, Bhattoa HP, Neven P, et al. Gynecologic effects of arzoxifene in postmenopausal women with osteoporosis or low bone mass. Menopause. 2012;19(1):41-7. 319. Goldstein SR, Nanavati N. Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Am J Obstet Gynecol. 2002;187(3):521-7.

320. Goldstein SR, Neven P, Cummings S, et al. Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18(1):17-22. 321. Goldzieher JW, Dozier TS. Oral contraceptives and thromboembolism: a reassessment. Am J Obstet Gynecol. 1975;123(8):878-914. 322. Goni M, Markussis V, Tolis G. Efficacy of chronic therapy with the gonadotrophin releasing hormone agonist decapeptyl in patients with polycystic ovary syndrome. Hum Reprod. 1994;9(6):1048-52. 323. Good WR, John VA, Ramirez M, Higgins JE. Double-masked, multicenter study of an estradiol matrix transdermal delivery system (Alora) versus placebo in postmenopausal women experiencing menopausal symptoms. Alora Study Group. Clinical therapeutics. 1996;18(6):1093-105. 324. Good WR, John VA, Ramirez M, Higgins JE. Comparison of Alora estradiol matrix transdermal delivery system with oral conjugated equine estrogen therapy in relieving menopausal symptoms. Alora Study Group. Climacteric. 1999;2(1):29-36. 325. Gorkemli H, Ak D, Akyurek C, Aktan M, Duman S. Comparison of pregnancy outcomes of progesterone or progesterone + estradiol for luteal phase support in ICSI-ET cycles. Gynecol Obstet Invest. 2004;58(3):140-4. 326. Goss PE, Clark RM, Ambus U, et al. Phase II study of vorozole (R83842), a new aromatase inhibitor, in postmenopausal women with advanced breast cancer in progression on tamoxifen. Clinical cancer research : an official journal of the American Association for Cancer Research. 1995;1(3):287-94. 327. Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349(19):1793-802. 328. Granese R, Adile B. Tension-free cystocele repair: an analysis after a follow-up of 24 months. Minerva Ginecol. 2007;59(4):369-76. 329. Graser T, Koytchev R, Muller A, Oettel M. Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women. Climacteric. 2000;3(2):109-18. 330. Grigoryan OR, Grodnitskaya EE, Andreeva EN, Chebotnikova TV, Melnichenko GA. Use of the NuvaRing hormone-releasing system in late reproductive-age women with type 1 diabetes mellitus. Gynecol Endocrinol. 2008;24(2):99-104. 331. Grimes DA, Godwin AJ, Rubin A, Smith JA, Lacarra M. Ovulation and follicular development associated with three low-dose oral contraceptives: a randomized controlled trial. Obstet Gynecol. 1994;83(1):29-34. 332. Grodnitskaya EE, Grigoryan OR, Klinyshkova EV, Andreeva EN, Melnichenko GA, Dedov, II. Effect on carbohydrate metabolism and analysis of acceptability (menstrual cycle control) of extended regimens of the vaginally inserted hormone-releasing system 'NuvaRing' as compared with the standard 21/7 regime in reproductive-age women with type 1 diabetes mellitus. Gynecol Endocrinol. 2010;26(9):663-8. 333. Grubb GS, Welch JD, Cole L, Goldsmith A, Rivera R. A comparative evaluation of the safety and contraceptive effectiveness of 65 mg and 100 mg of 90-day norethindrone (NET) injectable microspheres: a multicenter study. Fertil Steril. 1989;51(5):803-10. 334. Guerriero S, Paoletti AM, Ajossa S, et al. Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy. Menopause. 2001;8(6):424-8.

335. Guida M, Di Spiezio Sardo A, Bramante S, et al. Effects of two types of hormonal contraception--oral versus intravaginal--on the sexual life of women and their partners. Hum Reprod. 2005;20(4):1100-6. 336. Gupta P, Ozel B, Stanczyk FZ, Felix JC, Mishell DR, Jr. The effect of transdermal and vaginal estrogen therapy on markers of postmenopausal estrogen status. Menopause. 2008;15(1):94-7. 337. Haas S, Walsh B, Evans S, Krache M, Ravnikar V, Schiff I. The effect of transdermal estradiol on hormone and metabolic dynamics over a six-week period. Obstet Gynecol. 1988;71(5):671-6. 338. Haimov-Kochman R, Barak-Glantz E, Arbel R, et al. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Menopause. 2006;13(3):370-6. 339. Haines C, Yu SL, Hiemeyer F, Schaefers M. Micro-dose transdermal estradiol for relief of hot flushes in postmenopausal Asian women: a randomized controlled trial. Climacteric. 2009;12(5):419-26. 340. Hall G, Blomback M, Landgren BM, Bremme K. Effects of vaginally administered high estradiol doses on hormonal pharmacokinetics and hemostasis in postmenopausal women. Fertil Steril. 2002;78(6):1172-7. 341. Halmesmaki K, Hurskainen R, Teperi J, et al. The effect of hysterectomy or levonorgestrel-releasing intrauterine system on sexual functioning among women with menorrhagia: a 5-year randomised controlled trial. BJOG. 2007;114(5):563-8. 342. Hamilton CJ, Jaroudi KA, Sieck UV. The value of luteal support with progesterone in gonadotropin-induced cycles. Fertil Steril. 1993;60(5):786-90. 343. Hamm JT, Tormey DC, Kohler PC, Haller D, Green M, Shemano I. Phase I study of toremifene in patients with advanced cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1991;9(11):2036-41. 344. Hammar M, Christau S, Nathorst-Boos J, Rud T, Garre K. A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms. British journal of obstetrics and gynaecology. 1998;105(8):904-11. 345. Hammar ML, van de Weijer P, Franke HR, et al. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. BJOG. 2007;114(12):1522-9. 346. Hammond CB, Wiebe RH, Haney AF, Yancy SG. Ovulation induction with luteinizing hormone--releasing hormone in amenorrheic, infertile women. Am J Obstet Gynecol. 1979;135(7):924-39. 347. Hampton NR, Rees MC, Lowe DG, Rauramo I, Barlow D, Guillebaud J. Levonorgestrel intrauterine system (LNG-IUS) with conjugated oral equine estrogen: a successful regimen for HRT in perimenopausal women. Hum Reprod. 2005;20(9):2653-60. 348. Hanifi-Moghaddam P, Boers-Sijmons B, Klaassens AH, et al. Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling. J Mol Med (Berl). 2007;85(5):471-80. 349. Hanifi-Moghaddam P, Boers-Sijmons B, Klaassens AH, et al. Difference in signalling between various hormone therapies in endometrium, myometrium and upper part of the vagina. Hum Reprod. 2008;23(2):298-305.

350. Haring T, Mulders TM. The combined contraceptive ring NuvaRing and spermicide co- medication. Contraception. 2003;67(4):271-2. 351. Hedrick RE, Ackerman RT, Koltun WD, Halvorsen MB, Lambrecht LJ. Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women. Menopause. 2009;16(1):132-40. 352. Heimer GM, Englund DE. Effects of vaginally-administered oestriol on post-menopausal urogenital disorders: a cytohormonal study. Maturitas. 1992;14(3):171-9. 353. Henderson VW, St John JA, Hodis HN, et al. Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology. 2016;87(7):699-708. 354. Henriksson L, Stjernquist M, Boquist L, Alander U, Selinus I. A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy. Am J Obstet Gynecol. 1994;171(3):624-32. 355. Henriksson L, Stjernquist M, Boquist L, Cedergren I, Selinus I. A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging. Am J Obstet Gynecol. 1996;174(1 Pt 1):85-92. 356. Herbst AL, Hubby MM, Blough RR, Azizi F. A comparison of pregnancy experience in DES-exposed and DES-unexposed daughters. J Reprod Med. 1980;24(2):62-9. 357. Hernandez-Torres A, Satterthwaite AP. Norgestrel-ethinyl estradiol--an oral contraceptive. A clinical study of 725 patients. Am J Obstet Gynecol. 1970;108(2):183-7. 358. Hickey M, Marino JL, Braat S, Wong S. A randomized, double-blind, crossover trial comparing a silicone- versus water-based lubricant for sexual discomfort after breast cancer. Breast Cancer Res Treat. 2016;158(1):79-90. 359. Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. Obstet Gynecol. 1993;82(6):919-24. 360. Hilbert J, Messig M, Kuye O, Friedman H. Evaluation of interaction between fluconazole and an oral contraceptive in healthy women. Obstet Gynecol. 2001;98(2):218-23. 361. Hilton P, Stanton SL. The use of intravaginal oestrogen cream in genuine stress incontinence. British journal of obstetrics and gynaecology. 1983;90(10):940-4. 362. Hirata JD, Swiersz LM, Zell B, Small R, Ettinger B. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril. 1997;68(6):981-6. 363. Hirvonen E, Crona N, Wahlstrom T, Backstrom AC. Effect of an estradiol gel with monthly or quarterly progestogen on menopausal symptoms and bleeding. Climacteric. 2000;3(4):262-70. 364. Hodis HN, Mack WJ, Henderson VW, et al. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016;374(13):1221-31. 365. Holli K, Valavaara R, Blanco G, et al. Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer. Finnish Breast Cancer Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(20):3487-94. 366. Holmgren PA, Lindskog M, von Schoultz B. Vaginal rings for continuous low-dose release of oestradiol in the treatment of urogenital atrophy. Maturitas. 1989;11(1):55-63.

367. Homesley HD, Shemano I, Gams RA, et al. Antiestrogenic potency of toremifene and tamoxifen in postmenopausal women. Am J Clin Oncol. 1993;16(2):117-22. 368. Honjo H, Taketani Y. Low-dose estradiol for climacteric symptoms in Japanese women: a randomized, controlled trial. Climacteric. 2009;12(4):319-28. 369. Honkanen H, Ranta S, Ylikorkala O, Heikinheimo O. Effect of antiprogesterone mifepristone followed by misoprostol on circulating leptin in early pregnancy. Acta Obstet Gynecol Scand. 2005;84(2):134-9. 370. Hovik P, Sundsbak HP, Gaasemyr M, Sandvik L. Comparison of continuous and sequential oestrogen-progestogen treatment in women with climacteric symptoms. Maturitas. 1989;11(1):75-82. 371. Howell A, DeFriend DJ, Robertson JF, et al. Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. Br J Cancer. 1996;74(2):300-8. 372. Huang A, Yaffe K, Vittinghoff E, et al. The effect of ultralow-dose transdermal estradiol on sexual function in postmenopausal women. Am J Obstet Gynecol. 2008;198(3):265 e1-7. 373. Huang AJ, Grady D, Jacoby VL, Blackwell TL, Bauer DC, Sawaya GF. Persistent hot flushes in older postmenopausal women. Arch Intern Med. 2008;168(8):840-6. 374. Huber J, Palacios S, Berglund L, et al. Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women. BJOG. 2002;109(8):886-93. 375. Hudita D, Posea C, Ceausu I, Rusu M. Efficacy and safety of oral tibolone 1.25 or 2.5 mg/day vs. placebo in postmenopausal women. Eur Rev Med Pharmacol Sci. 2003;7(5):117-25. 376. Humaidan P, Bredkjaer HE, Bungum L, et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005;20(5):1213-20. 377. Hundley AF, Wu JM, Visco AG. A comparison of perineometer to brink score for assessment of pelvic floor muscle strength. Am J Obstet Gynecol. 2005;192(5):1583-91. 378. Hupperets PS, Wils J, Volovics L, et al. Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients. Ann Oncol. 1993;4(4):295-301. 379. Hurd WW, Randolph JF, Jr., Christman GM, Ansbacher R, Menge AC, Gell JS. Luteal support with both estradiol and progesterone after clomiphene citrate stimulation for in vitro fertilization. Fertil Steril. 1996;66(4):587-92. 380. Hurst BS, Jones AI, Elliot M, Marshburn PB, Matthews ML. Absorption of vaginal estrogen cream during sexual intercourse: a prospective, randomized, controlled trial. J Reprod Med. 2008;53(1):29-32. 381. Illston JD, Wheeler TL, Parker CR, et al. Low-dose 17-beta-estradiol cream for vaginal atrophy in a cohort without prolapse: Serum levels and vaginal response including tissue biomarkers associated with tissue remodeling. Maturitas. 2015;81(4):475-9. 382. Ismail Madkour WA, Noah B, Abdel Hamid AM, et al. Luteal phase support with estradiol and progesterone versus progesterone alone in GnRH antagonist ICSI cycles: a randomized controlled study. Hum Fertil (Camb). 2016;19(2):142-9. 383. Ito TY, Polan ML, Whipple B, Trant AS. The enhancement of female sexual function with ArginMax, a nutritional supplement, among women differing in menopausal status. J Sex Marital Ther. 2006;32(5):369-78.

384. Iwase H, Yamamoto Y, Yamamoto-Ibusuki M, et al. Ethinylestradiol is beneficial for postmenopausal patients with heavily pre-treated metastatic breast cancer after prior aromatase inhibitor treatment: a prospective study. Br J Cancer. 2013;109(6):1537-42. 385. Jackson R, Newton JR. Pharmacodynamics of a contraceptive vaginal ring releasing 3- keto-desogestrel. Contraception. 1989;39(6):653-64. 386. Jackson S, James M, Abrams P. The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence. BJOG. 2002;109(3):339-44. 387. Jain JK, Meckstroth KR, Park M, Mishell DR, Jr. A comparison of tamoxifen and misoprostol to misoprostol alone for early pregnancy termination. Contraception. 1999;60(6):353-6. 388. Jaisamrarn U, Reinprayoon D, Virutamasen P. Clinical study of a monophasic pill containing 20 microg ethinylestradiol and 150 microg desogestrel in Thai women. J Med Assoc Thai. 2001;84 Suppl 1:S377-83. 389. Jaschevatzky OE, Anderman S, Shalit A, Kampf D, Grunstein S. The treatment of postmenopausal syndrome by monthly oral doses of quinestrol. Acta Obstet Gynecol Scand. 1979;58(2):175-8. 390. Jensen J, Riis BJ, Christiansen C. Cyproterone acetate, an alternative progestogen in postmenopausal hormone replacement therapy? Effects on serum lipids and lipoproteins. British journal of obstetrics and gynaecology. 1987;94(2):136-41. 391. Jensen J, Riis BJ, Strom V, Christiansen C. Continuous oestrogen-progestogen treatment and serum lipoproteins in postmenopausal women. British journal of obstetrics and gynaecology. 1987;94(2):130-5. 392. Jensen J, Riis BJ, Strom V, Christiansen C. Long-term and withdrawal effects of two different oestrogen-progestogen combinations on lipid and lipoprotein profiles in postmenopausal women. Maturitas. 1989;11(2):117-28. 393. Jewelewicz R, Warren M, Dyrenfurth I, Vande Wiele RL. Physiological studies with purified human pituitary FSH (HP-FSH). J Clin Endocrinol Metab. 1971;32(5):688-91. 394. Jiang F, Zhu L, Xu T, et al. Efficacy and safety of solifenacin succinate tablets versus solifenacin succinate tablets with local estrogen for the treatment of overactive bladder in postmenopausal women--a multicenter, randomized, open-label, controlled comparison study. Menopause. 2016;23(4):451-7. 395. Johannisson E, Landgren BM, Diczfalusy E. Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes. Maturitas. 1988;10(3):181-92. 396. Johnson SR, Ettinger B, Macer JL, Ensrud KE, Quan J, Grady D. Uterine and vaginal effects of unopposed ultralow-dose transdermal estradiol. Obstet Gynecol. 2005;105(4):779-87. 397. Jolly EE, Bjarnason NH, Neven P, et al. Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years. Menopause. 2003;10(4):337-44. 398. Jonasson AF, Edwall L, Uvnas-Moberg K. Topical oxytocin reverses vaginal atrophy in postmenopausal women: a double-blind randomized pilot study. Menopause Int. 2011;17(4):120- 5. 399. Judd H. Efficacy of transdermal estradiol. Am J Obstet Gynecol. 1987;156(5):1326-31. 400. Kaari C, Haidar MA, Junior JM, et al. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Maturitas. 2006;53(1):49-58.

401. Kagan R, Abreu P, Andrews E. Vaginal bleeding/spotting with conjugated estrogens/bazedoxifene, conjugated estrogens/medroxyprogesterone acetate, and placebo. Postgrad Med. 2018;130(8):687-93. 402. Kagan R, Williams RS, Pan K, Mirkin S, Pickar JH. A randomized, placebo- and active- controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause. 2010;17(2):281-9. 403. Kalogeropoulos S, Petrogiannopoulos C, Gagos S, Kampas N, Kalogeropoulos G. The influence of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia. Gynecol Endocrinol. 2004;18(4):227-32. 404. Kalogirou D, Antoniou G, Karakitsos P, Kalogirou O, Antoniou D, Giannikos L. A comparative study of the effects of an estradiol-releasing vaginal ring combined with an oral gestagen versus transdermal estrogen combined with a levonorgestrel-releasing IUD: clinical findings and endometrial response. International journal of fertility and menopausal studies. 1996;41(6):522-7. 405. Karp DR, Jean-Michel M, Johnston Y, Suciu G, Aguilar VC, Davila GW. A randomized clinical trial of the impact of local estrogen on postoperative tissue quality after vaginal reconstructive surgery. Female Pelvic Med Reconstr Surg. 2012;18(4):211-5. 406. Kauppila A, Kivinen S, Stenback F, Vihko R, Vuopala S. Tamoxifen and natural progesterone as supplements to low-dose postmenopausal estrogen therapy. Gynecol Obstet Invest. 1988;25(1):58-65. 407. Kazerooni T, Zolghadri J. The comparison of bleeding patterns with high-dose and low- dose hormone replacement therapy in postmenopausal women. Gynecol Endocrinol. 2004;19(2):64-8. 408. Ke Y, Gonthier R, Simard JN, et al. Serum steroids remain within the same normal postmenopausal values during 12-month intravaginal 0.50% DHEA. Horm Mol Biol Clin Investig. 2015;24(3):117-29. 409. Ke Y, Labrie F, Gonthier R, et al. Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration. J Steroid Biochem Mol Biol. 2015;154:186-96. 410. Kedzia W, Gozdzicka-Jozefiak A, Kwasniewska A, Schmidt M, Miturski R, Spaczynski M. Relationship between HPV infection of the cervix and blood serum levels of steroid hormones among pre- and postmenopausal women. Eur J Gynaecol Oncol. 2000;21(2):177-9. 411. Keskin AE, Onaran Y, Duvan IC, Simavli S, Kafali H. Topical anesthetic (lidocaine- prilocaine) cream application before speculum examination in postmenopausal women. J Minim Invasive Gynecol. 2012;19(3):350-5. 412. Kessel B, Nachtigall L, Plouffe L, Siddhanti S, Rosen A, Parsons A. Effect of raloxifene on sexual function in postmenopausal women. Climacteric. 2003;6(3):248-56. 413. Kestelyn E, Agaba S, Van Nuil JI, et al. A randomised trial of a contraceptive vaginal ring in women at risk of HIV infection in Rwanda: Safety of intermittent and continuous use. PLoS One. 2018;13(6):e0197572. 414. Killick SR, Fitzgerald C, Davis A. Ovarian activity in women taking an oral contraceptive containing 20 microg ethinyl estradiol and 150 microg desogestrel: effects of low estrogen doses during the hormone-free interval. Am J Obstet Gynecol. 1998;179(1):S18-24. 415. Kingsberg SA, Derogatis L, Simon JA, et al. TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial. J Sex Med. 2016;13(12):1930-7.

416. Kingsberg SA, Kroll R, Goldstein I, et al. Patient acceptability and satisfaction with a low-dose solubilized vaginal estradiol softgel capsule, TX-004HR. Menopause. 2017;24(8):894- 9. 417. Kives S, Hahn PM, White E, Stanczyk FZ, Reid RL. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration. Contraception. 2005;71(3):197-201. 418. Knight DC, Howes JB, Eden JA. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric. 1999;2(2):79-84. 419. Knight DC, Howes JB, Eden JA, Howes LG. Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric. 2001;4(1):13-8. 420. Kobata SA, Girao MJ, Baracat EC, et al. Estrogen therapy influence on periurethral vessels in postmenopausal incontinent women using Dopplervelocimetry analysis. Maturitas. 2008;61(3):243-7. 421. Koetsawang S, Ji G, Krishna U, et al. Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation. Contraception. 1990;41(2):105-24. 422. Kohler PC, Hamm JT, Wiebe VJ, DeGregorio MW, Shemano I, Tormey DC. Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. Breast Cancer Res Treat. 1990;16 Suppl:S19-26. 423. Kokcu A, Cetinkaya MB, Yanik F, Alper T, Malatyalioglu E. The comparison of effects of tibolone and conjugated estrogen-medroxyprogesterone acetate therapy on sexual performance in postmenopausal women. Maturitas. 2000;36(1):75-80. 424. Kolibianakis EM, Schultze-Mosgau A, Schroer A, et al. A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists. Hum Reprod. 2005;20(10):2887-92. 425. Komi J, Lankinen KS, DeGregorio M, et al. Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women. J Bone Miner Metab. 2006;24(4):314-8. 426. Komi J, Lankinen KS, Harkonen P, et al. Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women. Menopause. 2005;12(2):202-9. 427. Kornafel KL, March CM. Estradiol gel in the treatment of menopausal symptoms: a placebo-controlled double-blind case study of efficacy and safety. Southern medical journal. 1992;85(3):270-3. 428. Koskimies P, Turunen J, Lammintausta R, Scheinin M. Single-dose and steady-state pharmacokinetics of ospemifene, a selective estrogen receptor modulator, in postmenopausal women. Int J Clin Pharmacol Ther. 2013;51(11):861-7. 429. Koss LG. Detection of occult endometrial carcinoma. J Cell Biochem Suppl. 1995;23:165-73. 430. Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede HJ. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric. 2000;3(3):161-7.

431. Kresanov I, Nikkanen V, Klemi P. Disturbances of the endometrium in the luteal phase of cycles stimulated for in vitro fertilization and of normal cycles treated with vaginal progesterone. Ann Chir Gynaecol Suppl. 1994;208:33-9. 432. Kroiss R, Fentiman IS, Helmond FA, et al. The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo- controlled trial. BJOG. 2005;112(2):228-33. 433. Kroll R, Archer DF, Lin Y, Sniukiene V, Liu JH. A randomized, multicenter, double- blind study to evaluate the safety and efficacy of estradiol vaginal cream 0.003% in postmenopausal women with dyspareunia as the most bothersome symptom. Menopause. 2018;25(2):133-8. 434. Kunz G, Beil D, Huppert P, Leyendecker G. Oxytocin--a stimulator of directed sperm transport in humans. Reprod Biomed Online. 2007;14(1):32-9. 435. Kutlusoy F, Guler I, Erdem M, et al. Luteal phase support with estrogen in addition to progesterone increases pregnancy rates in in vitro fertilization cycles with poor response to gonadotropins. Gynecol Endocrinol. 2014;30(5):363-6. 436. Laan E, van Driel EM, van Lunsen RH. Genital responsiveness in healthy women with and without sexual arousal disorder. J Sex Med. 2008;5(6):1424-35. 437. Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause. 2009;16(5):907- 22. 438. Labrie F, Archer D, Bouchard C, et al. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause. 2009;16(5):923-31. 439. Labrie F, Archer D, Bouchard C, et al. High internal consistency and efficacy of intravaginal DHEA for vaginal atrophy. Gynecol Endocrinol. 2010;26(7):524-32. 440. Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause. 2009;16(5):897-906. 441. Labrie F, Archer D, Bouchard C, et al. Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women. J Sex Med. 2014;11(7):1766-85. 442. Labrie F, Archer DF, Bouchard C, et al. Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia. Climacteric. 2011;14(2):282-8. 443. Labrie F, Cusan L, Gomez JL, et al. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol. 2008;111(3- 5):178-94. 444. Labrie F, Cusan L, Gomez JL, et al. Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause. 2009;16(1):30-6. 445. Labrie F, Martel C. A low dose (6.5 mg) of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens as well as their metabolites within normal values. Horm Mol Biol Clin Investig. 2017;29(2):39-60. 446. Labrie F, Martel C, Berube R, et al. Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol. 2013;138:359-67. 447. Lahti E, Vuopala S, Kauppila A, Blanco G, Ruokonen A, Laatikainen T. Maturation of vaginal and endometrial epithelium in postmenopausal breast cancer patients receiving long-term tamoxifen. Gynecol Oncol. 1994;55(3 Pt 1):410-4.

448. Lan VT, Tuan PH, Canh LT, Tuong HM, Howles CM. Progesterone supplementation during cryopreserved embryo transfer cycles: efficacy and convenience of two vaginal formulations. Reprod Biomed Online. 2008;17(3):318-23. 449. Landgren BM, Aedo AR, Johannisson E, Cekan SZ. Studies on a vaginal ring releasing levonorgestrel at an initial rate of 27 micrograms/24 h when used alone or in combination with transdermal systems releasing estradiol. Contraception. 1994;50(1):87-100. 450. Landgren BM, Johannisson E, Xing S, Aedo AR, Diczfalusy E. A clinical pharmacological study of a new type of vaginal delivery system for levonorgestrel. Contraception. 1985;32(6):581-601. 451. Landgren BM, Jonsson B, Cekan SZ. The effect of small doses of progesterone released from two types of vaginal rings on ovarian activity and bleeding patterns during the first postpartum year. Contraception. 1995;51(4):255-60. 452. Landgren MB, Bennink HJ, Helmond FA, Engelen S. Dose-response analysis of effects of tibolone on climacteric symptoms. BJOG. 2002;109(10):1109-14. 453. Landgren MB, Helmond FA, Engelen S. Tibolone relieves climacteric symptoms in highly symptomatic women with at least seven hot flushes and sweats per day. Maturitas. 2005;50(3):222-30. 454. Langer RD, Landgren BM, Rymer J, Helmond FA, Investigators O. Effects of tibolone and continuous combined conjugated equine estrogen/medroxyprogesterone acetate on the endometrium and vaginal bleeding: results of the OPAL study. Am J Obstet Gynecol. 2006;195(5):1320-7. 455. Langrish JP, Mills NL, Bath LE, et al. Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. Hypertension. 2009;53(5):805-11. 456. Lara LA, Ribeiro da Silva A, Rosa-e-Silva JC, Silva-de-Sa MF, Rosa-e-Silva AC. Estrogen receptor expression and vessel density in the vagina wall in postmenopausal women with prolapse. Tissue Cell. 2014;46(2):159-64. 457. Larmo PS, Yang B, Hyssala J, Kallio HP, Erkkola R. Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: a randomized, double-blind, placebo-controlled study. Maturitas. 2014;79(3):316-21. 458. Larmon JE, Magann EF, Dickerson GA, Morrison JC. Outpatient cervical ripening with prostaglandin E2 and estradiol. J Matern Fetal Neonatal Med. 2002;11(2):113-7. 459. Ledee-Bataille N, Olivennes F, Lefaix JL, Chaouat G, Frydman R, Delanian S. Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme. Hum Reprod. 2002;17(5):1249-53. 460. Lee BS, Kang BM, Yoon BK, Choi H, Park HM, Kim JG. Efficacy and tolerability of estradiol 1 mg and drospirenone 2 mg in postmenopausal Korean women: a double-blind, randomized, placebo-controlled, multicenter study. Maturitas. 2007;57(4):361-9. 461. Lee VC, Gao J, Lee KF, Ng EH, Yeung WS, Ho PC. The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta. Hum Reprod. 2013;28(11):2912-9. 462. Lee VC, Yeung TW, Tang OS, Ng EH, Yeung WS, Ho PC. Effect of letrozole on uterine artery Doppler flow indices prior to first-trimester termination of pregnancy: a randomized controlled trial. Ultrasound Obstet Gynecol. 2012;40(4):392-7.

463. Lee VCY, Li RHW, Yeung WSB, Pak Chung HO, Ng EHY. A randomized double- blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer. Hum Reprod. 2017;32(5):1130-7. 464. Leeton J. The relationship of oral contraception to depressive symptoms. Aust N Z J Obstet Gynaecol. 1973;13(2):115-20. 465. Legro RS, Pauli JG, Kunselman AR, et al. Effects of continuous versus cyclical oral contraception: a randomized controlled trial. J Clin Endocrinol Metab. 2008;93(2):420-9. 466. Lemay A, Maheux R, Huot C, Blanchet J, Faure N. Efficacy of intranasal or subcutaneous luteinizing hormone-releasing hormone agonist inhibition of ovarian function in the treatment of endometriosis. Am J Obstet Gynecol. 1988;158(2):233-6. 467. Leone Roberti Maggiore U, Remorgida V, Scala C, Tafi E, Venturini PL, Ferrero S. Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study. Acta Obstet Gynecol Scand. 2014;93(3):239-47. 468. Leonetti HB, Landes J, Steinberg D, Anasti JN. Transdermal progesterone cream as an alternative progestin in hormone therapy. Altern Ther Health Med. 2005;11(6):36-8. 469. Leslie KK, Walter SA, Torkko K, Stephens JK, Thompson C, Singh M. Effect of tamoxifen on endometrial histology, hormone receptors, and cervical cytology: a prospective study with follow-up. Appl Immunohistochem Mol Morphol. 2007;15(3):284-93. 470. Lete I, Morales P. Inhibition of follicular growth by two different oral contraceptives (monophasic and triphasic) containing ethinylestradiol and gestodene. Eur J Contracept Reprod Health Care. 1997;2(3):187-91. 471. Leung AK, Robson WL, Kao CP, Liu EK, Fong JH. Treatment of labial fusion with topical estrogen therapy. Clin Pediatr (Phila). 2005;44(3):245-7. 472. Levis S, Strickman-Stein N, Doerge DR, Krischer J. Design and baseline characteristics of the soy phytoestrogens as replacement estrogen (SPARE) study--a clinical trial of the effects of soy isoflavones in menopausal women. Contemp Clin Trials. 2010;31(4):293-302. 473. Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Arch Intern Med. 2011;171(15):1363-9. 474. Lewin A, Pisov G, Turgeman R, et al. Simplified artificial endometrial preparation, using oral estradiol and novel vaginal progesterone tablets: a prospective randomized study. Gynecol Endocrinol. 2002;16(2):131-6. 475. Liang Y, Wei H, Zhang J, Hou L, Luo X. Efficacy of subcutaneous administration of gonadotropin-releasing hormone agonist on idiopathic central precocious puberty. J Huazhong Univ Sci Technolog Med Sci. 2006;26(5):558-61. 476. Liapis A, Bakas P, Georgantopoulou C, Creatsas G. The use of oestradiol therapy in postmenopausal women after TVT-O anti-incontinence surgery. Maturitas. 2010;66(1):101-6. 477. Lightman A, Kol S, Itskovitz-Eldor J. A prospective randomized study comparing intramuscular with intravaginal natural progesterone in programmed thaw cycles. Hum Reprod. 1999;14(10):2596-9. 478. Lima SM, Bernardo BF, Yamada SS, Reis BF, da Silva GM, Galvao MA. Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium morphology and estrogen receptor expression in postmenopausal women: a 12-week, randomized, double-blind, placebo- controlled trial. Maturitas. 2014;78(3):205-11.

479. Lima SM, Yamada SS, Reis BF, Postigo S, Galvao da Silva MA, Aoki T. Effective treatment of vaginal atrophy with isoflavone vaginal gel. Maturitas. 2013;74(3):252-8. 480. Lin SQ, Sun LZ, Lin JF, et al. Estradiol 1 mg and drospirenone 2 mg as hormone replacement therapy in postmenopausal Chinese women. Climacteric. 2011;14(4):472-81. 481. Lin TJ, So-Bosita JL, Brar HK, Roblete BV. Clinical and cytologic responses of postmenopausal women to estrogen. Obstet Gynecol. 1973;41(1):97-107. 482. Lind T, Cameron EC, Hunter WM, et al. A prospective, controlled trial of six forms of hormone replacement therapy given to postmenopausal women. British journal of obstetrics and gynaecology. 1979;86 Suppl 3:1-29. 483. Lindgren R, Risberg B, Hammar M, Berg G, Pryse-Davies J. Endometrial effects of transdermal estradiol/norethisterone acetate. Maturitas. 1992;15(1):71-8. 484. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA. 2002;287(20):2668-76. 485. Lippuner K, Haenggi W, Birkhaeuser MH, Casez JP, Jaeger P. Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone. J Bone Miner Res. 1997;12(5):806-12. 486. Liske E, Hanggi W, Henneicke-von Zepelin HH, Boblitz N, Wustenberg P, Rahlfs VW. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Womens Health Gend Based Med. 2002;11(2):163-74. 487. Liu D, Lu Y, Ma H, et al. A pilot observational study to assess the safety and efficacy of Menoprogen for the management of menopausal symptoms in Chinese women. J Altern Complement Med. 2009;15(1):79-85. 488. Lobo RA, Pinkerton JV, Gass ML, et al. Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril. 2009;92(3):1025-38. 489. Long CY, Liu CM, Hsu SC, Chen YH, Wu CH, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the lower urinary tract of hysterectomized postmenopausal women. Fertil Steril. 2006;85(1):155-60. 490. Long CY, Liu CM, Hsu SC, Wu CH, Wang CL, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause. 2006;13(5):737-43. 491. Loprinzi CL, Abu-Ghazaleh S, Sloan JA, et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1997;15(3):969-73. 492. Lose G, Englev E. Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. BJOG. 2000;107(8):1029-34. 493. Ludwig M, Finas A, Katalinic A, et al. Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support. Acta Obstet Gynecol Scand. 2001;80(6):574-82. 494. Luisi S, Razzi S, Lazzeri L, Bocchi C, Severi FM, Petraglia F. Efficacy of vaginal danazol treatment in women with menorrhagia during fertile age. Fertil Steril. 2009;92(4):1351- 4.

495. MacDonald RR, Goulden R, Oakey RE. Cervical mucus, vaginal cytology and steroid excretion in recurrent abortion. Obstet Gynecol. 1972;40(3):394-402. 496. MacLennan AH, Green RC, Bryant-Greenwood GD, Greenwood FC, Seamark RF. Cervical ripening with combinations of vaginal prostaglandin F2-alpha estradiol, and relaxin. Obstet Gynecol. 1981;58(5):601-4. 497. Maenpaa J, Soderstrom KO, Gronroos M, Taina E, Hajba A, Kangas L. Effect of toremifene on estrogen primed vaginal mucosa in postmenopausal women. J Steroid Biochem. 1990;36(3):221-3. 498. Magann EF, Perry KG, Jr., Dockery JR, Jr., Bass JD, Chauhan SP, Morrison JC. Cervical ripening before medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin. Am J Obstet Gynecol. 1995;172(6):1702-6; discussion 4-8. 499. Magnusdottir EM, Bjarnadottir RI, Onundarson PT, et al. The contraceptive vaginal ring (NuvaRing) and hemostasis: a comparative study. Contraception. 2004;69(6):461-7. 500. Mainini G, Scaffa C, Rotondi M, Messalli EM, Quirino L, Ragucci A. Local estrogen replacement therapy in postmenopausal atrophic vaginitis: efficacy and safety of low dose 17beta-estradiol vaginal tablets. Clinical and experimental obstetrics & gynecology. 2005;32(2):111-3. 501. Makkar B, Batra S, Gandhi G, Zutshi V, Goswami D. Vaginal misoprostol versus vaginal estradiol in overcoming unsatisfactory colposcopy. Gynecol Obstet Invest. 2014;77(3):176-9. 502. Malik S, Pannu D, Prateek S, Sinha R, Gaikwad H. Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial. Arch Gynecol Obstet. 2016;293(6):1325- 33. 503. Manonai J, Chittacharoen A, Theppisai U. Effect of estradiol valerate and levonorgestrel on vaginal health. European journal of obstetrics, gynecology, and reproductive biology. 2004;115(2):190-3. 504. Manonai J, Chittacharoen A, Theppisai U. Transvaginal color Doppler sonographic assessment of uterus and ovaries in postmenopausal women: the effect of local estrogen treatment. European journal of obstetrics, gynecology, and reproductive biology. 2006;127(2):222-6. 505. Manonai J, Theppisai U, Suthutvoravut S, Udomsubpayakul U, Chittacharoen A. The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: a comparative study. J Obstet Gynaecol Res. 2001;27(5):255-60. 506. Mansel R, Goyal A, Nestour EL, Masini-Eteve V, O'Connell K, Afimoxifene Breast Pain Research G. A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. Breast Cancer Res Treat. 2007;106(3):389-97. 507. Manuck TA, Stoddard GJ, Fry RC, Esplin MS, Varner MW. Nonresponse to 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention: clinical prediction and generation of a risk scoring system. Am J Obstet Gynecol. 2016;215(5):622 e1- e8. 508. Marsden J, Whitehead M, A'Hern R, Baum M, Sacks N. Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible? Fertil Steril. 2000;73(2):292-9. 509. Martin CW, Brown AH, Baird DT. A pilot study of the effect of methotrexate or combined oral contraceptive on bleeding patterns after induction of abortion with mifepristone and a prostaglandin pessary. Contraception. 1998;58(2):99-103.

510. Martinez F, Boada M, Coroleu B, et al. A prospective trial comparing oocyte donor ovarian response and recipient pregnancy rates between suppression with gonadotrophin- releasing hormone agonist (GnRHa) alone and dual suppression with a contraceptive vaginal ring and GnRH. Hum Reprod. 2006;21(8):2121-5. 511. Martinez F, Coroleu B, Parera N, et al. Human chorionic gonadotropin and intravaginal natural progesterone are equally effective for luteal phase support in IVF. Gynecol Endocrinol. 2000;14(5):316-20. 512. Martinez GH, Castaneda A, Correa JE. Vaginal bleeding patterns in users of Perlutal, a once-a-month injectable contraceptive consisting of 10 mg estradiol enanthate combined with 150 mg dihydroxyprogesterone acetophenide. A trial of 5462 woman-months. Contraception. 1998;58(1):21-7. 513. Marttunen MB, Cacciatore B, Hietanen P, et al. Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women. Br J Cancer. 2001;84(7):897-902. 514. Marx P, Schade G, Wilbourn S, Blank S, Moyer DL, Nett R. Low-dose (0.3 mg) synthetic conjugated estrogens A is effective for managing atrophic vaginitis. Maturitas. 2004;47(1):47-54. 515. Massai R, Makarainen L, Kuukankorpi A, Klipping C, Duijkers I, Dieben T. The combined contraceptive vaginal ring and bone mineral density in healthy pre-menopausal women. Hum Reprod. 2005;20(10):2764-8. 516. Massaro M, Di Carlo C, Gargano V, Formisano C, Bifulco G, Nappi C. Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study. Contraception. 2010;81(3):209-14. 517. Matorras R, Diaz T, Corcostegui B, Ramon O, Pijoan JI, Rodriguez-Escudero FJ. Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH. Hum Reprod. 2002;17(8):2107-11. 518. Matorras R, Recio V, Corcostegui B, Rodriguez-Escudero FJ. Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa. Hum Reprod. 2000;15(6):1231-4. 519. Mattsson LA, Cullberg G, Eriksson O, Knutsson F. Vaginal administration of low-dose oestradiol--effects on the endometrium and vaginal cytology. Maturitas. 1989;11(3):217-22. 520. McArthur JW, Turnbull BA, Pehrson J, et al. Nalmefene enhances LH secretion in a proportion of oligo-amenorrheic athletes. Acta Endocrinol (Copenh). 1993;128(4):325-33. 521. Melis GB, Paoletti AM, Ajossa S, Guerriero S, Depau GF, Mais V. Ovulation induction with gonadotropins as sole treatment in infertile couples with open tubes: a randomized prospective comparison between intrauterine insemination and timed vaginal intercourse. Fertil Steril. 1995;64(6):1088-93. 522. Melis GB, Paoletti AM, Cagnacci A, et al. Lack of any estrogenic effect of ipriflavone in postmenopausal women. Journal of endocrinological investigation. 1992;15(10):755-61. 523. Melisko ME, Goldman ME, Hwang J, et al. Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2017;3(3):313-9.

524. Mercuro G, Pitzalis L, Podda A, et al. Effects of acute administration of natural progesterone on peripheral vascular responsiveness in healthy postmenopausal women. Am J Cardiol. 1999;84(2):214-8. 525. Merz CN, Olson MB, McClure C, et al. A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE). Am Heart J. 2010;159(6):987 e1-7. 526. Mettler L, Olsen PG. Long-term treatment of atrophic vaginitis with low-dose oestradiol vaginal tablets. Maturitas. 1991;14(1):23-31. 527. Meyer BH, Muller FO, de la Rey N, Luus HG, Rosenkranz B. The effects of buserelin microparticles on ovarian function in healthy women. S Afr Med J. 1995;85(8):766-7. 528. Michael CM, Kantor HI, Shore H. Further psychometric evaluation of older women--the effect of estrogen administration. J Gerontol. 1970;25(4):337-41. 529. Mikkelsen AL, Felding C, Clausen HV. Clinical effects of preoperative oestradiol treatment before vaginal repair operation. A double-blind, randomized trial. Gynecol Obstet Invest. 1995;40(2):125-8. 530. Mikkelsen AL, Smith S, Lindenberg S. Possible factors affecting the development of oocytes in in-vitro maturation. Hum Reprod. 2000;15 Suppl 5:11-7. 531. Miller L, Verhoeven CH, Hout J. Extended regimens of the contraceptive vaginal ring: a randomized trial. Obstet Gynecol. 2005;106(3):473-82. 532. Mirkin S, Komm BS, Pan K, Chines AA. Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women. Climacteric. 2013;16(3):338-46. 533. Mirkin S, Pinkerton JV, Kagan R, et al. Gynecologic Safety of Conjugated Estrogens Plus Bazedoxifene: Pooled Analysis of Five Phase 3 Trials. J Womens Health (Larchmt). 2016;25(5):431-42. 534. Mishell DR, Jr., Jain JK, Byrne JD, Lacarra MD. A medical method of early pregnancy termination using tamoxifen and misoprostol. Contraception. 1998;58(1):1-6. 535. Mitchell CM, Reed SD, Diem S, et al. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018;178(5):681-90. 536. Mitchell CM, Srinivasan S, Zhan X, et al. Vaginal microbiota and genitourinary menopausal symptoms: a cross-sectional analysis. Menopause. 2017;24(10):1160-6. 537. Mochtar MH, Hogerzeil HV, Mol BW. Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial. Hum Reprod. 1996;11(8):1602-5. 538. Mochtar MH, Van Wely M, Van der Veen F. Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles. Hum Reprod. 2006;21(4):905-8. 539. Moghissi KS, Schlaff WD, Olive DL, Skinner MA, Yin H. Goserelin acetate (Zoladex) with or without hormone replacement therapy for the treatment of endometriosis. Fertil Steril. 1998;69(6):1056-62. 540. Molander U. Urinary incontinence and related urogenital symptoms in elderly women. Acta Obstet Gynecol Scand Suppl. 1993;158:1-22. 541. Molander U, Milsom I, Ekelund P, Mellstrom D, Eriksson O. Effect of oral oestriol on vaginal flora and cytology and urogenital symptoms in the post-menopause. Maturitas. 1990;12(2):113-20.

542. Morales L, Neven P, Timmerman D, et al. Acute effects of tamoxifen and third- generation aromatase inhibitors on menopausal symptoms of breast cancer patients. Anticancer Drugs. 2004;15(8):753-60. 543. Morales L, Neven P, Timmerman D, et al. Prospective assessment of the endometrium in postmenopausal breast cancer patients treated with fulvestrant. Breast Cancer Res Treat. 2009;117(1):77-81. 544. Morali G, Polatti F, Metelitsa EN, Mascarucci P, Magnani P, Marre GB. Open, non- controlled clinical studies to assess the efficacy and safety of a medical device in form of gel topically and intravaginally used in postmenopausal women with genital atrophy. Arzneimittel- Forschung. 2006;56(3):230-8. 545. Morgan ML, Cook IA, Rapkin AJ, Leuchter AF. Neurophysiologic changes during estrogen augmentation in perimenopausal depression. Maturitas. 2007;56(1):54-60. 546. Mortimer JE, Boucher L, Baty J, Knapp DL, Ryan E, Rowland JH. Effect of tamoxifen on sexual functioning in patients with breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999;17(5):1488-92. 547. Mozzanega B, Babbo GL, Salmaso L, et al. Oral 17beta-estradiol and sequential progesterone in menopause: effects on insulin-like growth factors and their binding proteins. Gynecol Endocrinol. 2007;23(1):50-7. 548. Mulders TM, Dieben TO. Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition. Fertil Steril. 2001;75(5):865-70. 549. Mulders TM, Dieben TO, Bennink HJ. Ovarian function with a novel combined contraceptive vaginal ring. Hum Reprod. 2002;17(10):2594-9. 550. Murina F, Graziottin A, Felice R, Di Francesco S. Coital pain in the elderly: could a low dose estriol gel thrill the vulvar vestibule? European journal of obstetrics, gynecology, and reproductive biology. 2016;207:121-4. 551. Murkies AL, Lombard C, Strauss BJ, Wilcox G, Burger HG, Morton MS. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas. 1995;21(3):189-95. 552. Nabholtz JM, Bonneterre J, Buzdar A, Robertson JF, Thurlimann B. Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. Eur J Cancer. 2003;39(12):1684-9. 553. Nabholtz JM, Buzdar A, Pollak M, et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(22):3758-67. 554. Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril. 1994;61(1):178-80. 555. Nachtigall LE. Clinical trial of the estradiol vaginal ring in the U.S. Maturitas. 1995;22 Suppl:S43-7. 556. Naessen T, Berglund L, Ulmsten U. Bone loss in elderly women prevented by ultralow doses of parenteral 17beta-estradiol. Am J Obstet Gynecol. 1997;177(1):115-9. 557. Naessen T, Rodriguez-Macias K. Endometrial thickness and uterine diameter not affected by ultralow doses of 17beta-estradiol in elderly women. Am J Obstet Gynecol. 2002;186(5):944- 7. 558. Naessen T, Rodriguez-Macias K, Lithell H. Serum lipid profile improved by ultra-low doses of 17 beta-estradiol in elderly women. J Clin Endocrinol Metab. 2001;86(6):2757-62.

559. Nand SL, Webster MA, Baber R, Heller GZ. Menopausal symptom control and side- effects on continuous estrone sulfate and three doses of medroxyprogesterone acetate. Ogen/Provera Study Group. Climacteric. 1998;1(3):211-8. 560. Nand SL, Webster MA, Baber R, O'Connor V. Bleeding pattern and endometrial changes during continuous combined hormone replacement therapy. The Ogen/Provera Study Group. Obstet Gynecol. 1998;91(5 Pt 1):678-84. 561. Nand SL, Webster MA, Wren BG. Continuous combined piperazine oestrone sulphate and medroxyprogesterone acetate hormone replacement therapy--a study of bleeding pattern, endometrial response, serum lipid and bone density changes. Aust N Z J Obstet Gynaecol. 1995;35(1):92-6. 562. Nankin HR, Lin T, Osterman J. Chronic testosterone cypionate therapy in men with secondary impotence. Fertil Steril. 1986;46(2):300-7. 563. Nappi RE, Ferdeghini F, Sampaolo P, et al. Clitoral circulation in postmenopausal women with sexual dysfunction: a pilot randomized study with hormone therapy. Maturitas. 2006;55(3):288-95. 564. Nappi RE, Panay N, Bruyniks N, Castelo-Branco C, De Villiers TJ, Simon JA. The clinical relevance of the effect of ospemifene on symptoms of vulvar and vaginal atrophy. Climacteric. 2015;18(2):233-40. 565. Narvekar N, Lakha F, Critchley HO, et al. Changes in vaginal morphology, steroid receptor and natural antimicrobial content following treatment with low-dose mifepristone. Contraception. 2007;75(4):271-80. 566. Nash HA, Alvarez-Sanchez F, Mishell DR, Jr., Fraser IS, Maruo T, Harmon TM. Estradiol-delivering vaginal rings for hormone replacement therapy. Am J Obstet Gynecol. 1999;181(6):1400-6. 567. Nathorst-Boos J, Wiklund I, Mattsson LA, Sandin K, von Schoultz B. Is sexual life influenced by transdermal estrogen therapy? A double blind placebo controlled study in postmenopausal women. Acta Obstet Gynecol Scand. 1993;72(8):656-60. 568. Navarro PA, Kaddouz D, de Ziegler D, Silva de Sa MF, Ferriani RA. Vaginal administration of allopregnanolone to postmenopausal women undergoing estrogen replacement therapy: preliminary results. Maturitas. 2003;46(2):147-52. 569. Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell DR, Jr. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause. 2011;18(9):962-6. 570. Neven P, Lunde T, Benedetti-Panici P, et al. A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate. BJOG. 2003;110(2):157-67. 571. Ng EH, Chan CC, Tang OS, Ho PC. A randomized comparison of side effects and patient convenience between Cyclogest suppositories and Endometrin tablets used for luteal phase support in IVF treatment. European journal of obstetrics, gynecology, and reproductive biology. 2007;131(2):182-8. 572. Nijland EA, Nathorst-Boos J, Palacios S, et al. Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA treatment in postmenopausal women with female sexual dysfunction. Climacteric. 2009;12(2):114-21. 573. Nijland EA, Weijmar Schultz WC, Davis SR. Effects of tibolone and raloxifene on health-related quality of life and sexual function. Maturitas. 2007;58(2):164-73.

574. Nikander E, Rutanen EM, Nieminen P, Wahlstrom T, Ylikorkala O, Tiitinen A. Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women. Fertil Steril. 2005;83(1):137-42. 575. Nilsson K, Heimer G. Low-dose oestradiol in the treatment of urogenital oestrogen deficiency--a pharmacokinetic and pharmacodynamic study. Maturitas. 1992;15(2):121-7. 576. Noe G, Sitruk-Ware R, Zegers-Hochschild F, et al. Endometrial effect of progesterone delivered by vaginal rings in estrogen-treated postmenopausal women. Climacteric. 2010;13(5):433-41. 577. Noh YH, Kim DH, Lee SA, et al. The Natural Substance MS-10 Improves and Prevents Menopausal Symptoms, Including Colpoxerosis, in Clinical Research. J Med Food. 2016;19(3):228-37. 578. Norman JE, Yuan M, Anderson L, et al. Effect of prolonged in vivo administration of progesterone in pregnancy on myometrial gene expression, peripheral blood leukocyte activation, and circulating steroid hormone levels. Reprod Sci. 2011;18(5):435-46. 579. Notelovitz M. Estrogen therapy in the management of problems associated with urogenital ageing: a simple diagnostic test and the effect of the route of hormone administration. Maturitas. 1995;22 Suppl:S31-3. 580. Notelovitz M, Funk S, Nanavati N, Mazzeo M. Estradiol absorption from vaginal tablets in postmenopausal women. Obstet Gynecol. 2002;99(4):556-62. 581. Notelovitz M, Mattox JH. Suppression of vasomotor and vulvovaginal symptoms with continuous oral 17beta-estradiol. Menopause. 2000;7(5):310-7. 582. Novak A, de la Loge C, Abetz L, van der Meulen EA. The combined contraceptive vaginal ring, NuvaRing: an international study of user acceptability. Contraception. 2003;67(3):187-94. 583. Nummi S. 'Patient failure' as a reliability model for the 'minipill': a clinical study. Curr Med Res Opin. 1978;5(5):406-11. 584. Nunes JM, Feldner PC, Jr., Castro RA, Nader HB, Sartori MG, Girao MJ. Uterine prolapse: evaluation of glycosaminoglycans in postmenopausal women after estrogen therapy. Climacteric. 2011;14(1):121-5. 585. O'Brien M, Montes A, Powles TJ. Hormone replacement therapy as treatment of breast cancer--a phase II study of Org OD 14 (tibilone). Br J Cancer. 1996;73(9):1086-8. 586. O'Connell KJ, Osborne LM, Westhoff C. Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive. Contraception. 2005;72(5):323-7. 587. Odabasi AR, Yuksel H, Demircan SS, Kacar DF, Culhaci N, Ozkara EE. A prospective randomized comparative study of the effects of intranasal and transdermal 17 beta-estradiol on postmenopausal symptoms and vaginal cytology. J Postgrad Med. 2007;53(4):221-7. 588. Oddsson K, Leifels-Fischer B, Wiel-Masson D, et al. Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel: a randomized trial. Hum Reprod. 2005;20(2):557-62. 589. O'Donnell RL, Warner P, Lee RJ, et al. Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Hum Reprod. 2012;27(4):1130-8. 590. Oppegaard KS, Lieng M, Berg A, Istre O, Qvigstad E, Nesheim BI. Does self- administered vaginal misoprostol result in cervical ripening in postmenopausal women after 14

94 days of pre-treatment with estradiol? Trial protocol for a randomised, placebo-controlled sequential trial. BJOG. 2008;115(7):917-e10. 591. Oppegaard KS, Lieng M, Berg A, Istre O, Qvigstad E, Nesheim BI. A combination of misoprostol and estradiol for preoperative cervical ripening in postmenopausal women: a randomised controlled trial. BJOG. 2010;117(1):53-61. 592. Osmanagaoglu MA, Atasaral T, Baltaci D, Bozkaya H. Effect of different preparations of hormone therapy on sexual dysfunction in naturally postmenopausal women. Climacteric. 2006;9(6):464-72. 593. Ouslander JG, Cooper E, Godley D. Estrogen treatment for incontinence in frail older women. J Am Geriatr Soc. 1999;47(11):1383-4. 594. Ouslander JG, Greendale GA, Uman G, Lee C, Paul W, Schnelle J. Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents. J Am Geriatr Soc. 2001;49(6):803-7. 595. Padayachi T, Moodley J, Norman RJ, Heyns A. Termination of pregnancy with mifepristone after intra-uterine death. Clinical and hormonal effects. S Afr Med J. 1989;75(11):540-2. 596. Padwick ML, Siddle NC, Lane G, et al. Oestriol with oestradiol verses oestradiol alone: a comparison of endometrial, symptomatic and psychological effects. British journal of obstetrics and gynaecology. 1986;93(6):606-12. 597. Pafumi C, Ciotta L, Farina M, et al. Uterine bleeding pattern during low dosage Noretisterone acetate and 17-b-Estradiol treatment in postmenopausal patients. Minerva Ginecol. 2002;54(6):513-8. 598. Palacios S, Arias L, Lavenberg J, Pan K, Mirkin S, Komm BS. Evaluation of efficacy and safety of conjugated estrogens/bazedoxifene in a Latin American population. Climacteric. 2016;19(3):261-7. 599. Palacios S, Castelo-Branco C, Cancelo MJ, Vazquez F. Low-dose, vaginally administered estrogens may enhance local benefits of systemic therapy in the treatment of urogenital atrophy in postmenopausal women on hormone therapy. Maturitas. 2005;50(2):98- 104. 600. Palva T, Ranta H, Koivisto AM, Pylkkanen L, Cuzick J, Holli K. A double-blind placebo-controlled study to evaluate endometrial safety and gynaecological symptoms in women treated for up to 5 years with tamoxifen or placebo - a substudy for IBIS I Breast Cancer Prevention Trial. Eur J Cancer. 2013;49(1):45-51. 601. Panay N, Ylikorkala O, Archer DF, Gut R, Lang E. Ultra-low-dose estradiol and norethisterone acetate: effective menopausal symptom relief. Climacteric. 2007;10(2):120-31. 602. Parker CR, Jr., Buchina ES, Barefoot TK. Abnormal adrenal steroidogenesis in growth- retarded newborn infants. Pediatr Res. 1994;35(6):633-6. 603. Parker RA, McDaniel EB. The use of quinesterol for the control of vaginal bleeding irregularities caused by DMPA. Contraception. 1980;22(1):1-7. 604. Parkinson Study Group PI. A randomized pilot trial of estrogen replacement therapy in post-menopausal women with Parkinson's disease. Parkinsonism Relat Disord. 2011;17(10):757- 60. 605. Parsons A, Merritt D, Rosen A, et al. Effect of raloxifene on the response to conjugated estrogen vaginal cream or nonhormonal moisturizers in postmenopausal vaginal atrophy. Obstet Gynecol. 2003;101(2):346-52.

606. Pasquale SA, Foldesy RG, Levine JP, Bachmann GA, Blackwell RE. Peripheral progesterone (P) levels and endometrial response to various dosages of vaginally administered P in estrogen-primed women. Fertil Steril. 1997;68(5):810-5. 607. Pattison NS, Uptin T, Knox B, France J. Transdermal oestrogen for postmenopausal women: a double blind crossover comparative study with ethinyl oestradiol. Aust N Z J Obstet Gynaecol. 1989;29(1):62-5. 608. Peethambaram PP, Ingle JN, Suman VJ, Hartmann LC, Loprinzi CL. Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis. Breast Cancer Res Treat. 1999;54(2):117-22. 609. Pentikis HS, Adetoro N, Braun CJ. Lack of a Pharmacokinetic Interaction Between SYM-1219 Granules Containing 2 Grams of Secnidazole and a Combined Oral Contraceptive in a Phase 1, Randomized, Open-Label Study in Healthy Female Volunteers. Adv Ther. 2017;33(12):2229-41. 610. Perovic D, Kopajtic B, Stankovic T. Treatment of climacteric complaints with oestriol. Arzneimittel-Forschung. 1975;25(6):962-4. 611. Petri Nahas E, Nahas Neto J, De Luca L, Traiman P, Pontes A, Dalben I. Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. Maturitas. 2004;48(4):372-80. 612. Petta CA, Faundes A, Dunson TR, et al. Timing of onset of contraceptive effectiveness in Depo-Provera users. II. Effects on ovarian function. Fertil Steril. 1998;70(5):817-20. 613. Petta CA, Hays M, Brache V, et al. Delayed first injection of the once-a-month injectable contraceptive containing 25 mg of medroxyprogesterone acetate and 5 mg of E(2)-cypionate: effects on ovarian function. Fertil Steril. 2001;75(4):744-8. 614. Pfeiler G, Glatz C, Konigsberg R, et al. Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients. Climacteric. 2011;14(3):339-44. 615. Piccoli R, Mandato VD, Lavitola G, et al. Atypical squamous cells and low squamous intraepithelial lesions in postmenopausal women: implications for management. European journal of obstetrics, gynecology, and reproductive biology. 2008;140(2):269-74. 616. Pickar JH, Amadio JM, Bernick BA, Mirkin S. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule. Climacteric. 2016;19(2):181-7. 617. Pickar JH, Amadio JM, Hill JM, Bernick BA, Mirkin S. A randomized, double-blind, placebo-controlled phase 2 pilot trial evaluating a novel, vaginal softgel capsule containing solubilized estradiol. Menopause. 2016;23(5):506-10. 618. Pinelli DM, Fiorica JV, Roberts WS, Hoffman MS, Nicosia SV, Cavanagh D. Chemotherapy plus sequential hormonal therapy for advanced and recurrent endometrial carcinoma: a phase II study. Gynecol Oncol. 1996;60(3):462-7. 619. Pinkerton JV, Bushmakin AG, Abraham L, Cappelleri JC, Komm BS. Most bothersome symptom in women with genitourinary syndrome of menopause as a moderator of treatment effects. Menopause. 2016;23(10):1092-101. 620. Pinkerton JV, Bushmakin AG, Bobula J, Lavenberg J, Komm BS, Abraham L. Time to first occurrence of breast pain and vaginal bleeding in phase 3 trials of CE/BZA. Menopause. 2017;24(12):1372-7. 621. Pinkerton JV, Bushmakin AG, Komm BS, Abraham L. Relationship between changes in vulvar-vaginal atrophy and changes in sexual functioning. Maturitas. 2017;100:57-63.

622. Pinkerton JV, Pickar JH, Ryan KA, Yu CR, Mirkin S, Komm BS. Conjugated estrogens and bazedoxifene in minority populations: pooled analysis of four phase 3 trials. Menopause. 2016;23(6):611-20. 623. Pinkerton JV, Shifren JL, La Valleur J, Rosen A, Roesinger M, Siddhanti S. Influence of raloxifene on the efficacy of an estradiol-releasing ring for treating vaginal atrophy in postmenopausal women. Menopause. 2003;10(1):45-52. 624. Pirard C, Donnez J, Loumaye E. GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study. Hum Reprod. 2006;21(7):1894-900. 625. Piya-Anant M, Koetsawang S, Patrasupapong N, et al. Effectiveness of Cyclofem in the treatment of depot medroxyprogesterone acetate induced amenorrhea. Contraception. 1998;57(1):23-8. 626. Ploch E. Hormonal replacement therapy in patients after cervical cancer treatment. Gynecol Oncol. 1987;26(2):169-77. 627. Portman D, Palacios S, Nappi RE, Mueck AO. Ospemifene, a non-oestrogen selective oestrogen receptor modulator for the treatment of vaginal dryness associated with postmenopausal vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial. Maturitas. 2014;78(2):91-8. 628. Portman DJ, Bachmann GA, Simon JA, Ospemifene Study G. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623-30. 629. Portman DJ, Labrie F, Archer DF, et al. Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Menopause. 2015;22(12):1289-95. 630. Powles TJ, Jones AL, Ashley SE, et al. The Royal Marsden Hospital pilot tamoxifen chemoprevention trial. Breast Cancer Res Treat. 1994;31(1):73-82. 631. Prata AB, Drum JN, Melo LF, Araujo ER, Sartori R. Effect of different chorionic gonadotropins on final growth of the dominant follicle in Bos indicus cows. Theriogenology. 2018;111:52-5. 632. Preston RA, Marbury TC, Wajima T, Graham S. The effect of renal and hepatic impairment on the pharmacokinetics of ospemifene, a tissue-selective estrogen agonist/antagonist. Am J Ther. 2015;22(3):171-81. 633. Preston RA, Norris PM, Alonso AB, Ni P, Hanes V, Karara AH. Randomized, placebo- controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide. Menopause. 2007;14(3 Pt 1):408-14. 634. Prince RL, Smith M, Dick IM, et al. Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy. N Engl J Med. 1991;325(17):1189-95. 635. Propst AM, Hill JA, Ginsburg ES, Hurwitz S, Politch J, Yanushpolsky EH. A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles. Fertil Steril. 2001;76(6):1144-9. 636. Quaranta L, Ottolina J, Parma M, et al. An alternative approach for the treatment of vaginal atrophy. Minerva Ginecol. 2014;66(4):377-81. 637. Rad M, Kluft C, Menard J, et al. Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral

97 contraceptive containing levonorgestrel on hemostasis variables. Am J Obstet Gynecol. 2006;195(1):72-7. 638. Raghunandan C, Agrawal S, Dubey P, Choudhury M, Jain A. A comparative study of the effects of local estrogen with or without local testosterone on vulvovaginal and sexual dysfunction in postmenopausal women. J Sex Med. 2010;7(3):1284-90. 639. Ragni G, Piloni S, Rossi P, et al. Endometrial morphology and ultrasound vascular findings. A randomized trial after intramuscular and vaginal progesterone supplementation in IVF. Gynecol Obstet Invest. 1999;47(3):151-6. 640. Rahn DD, Good MM, Roshanravan SM, et al. Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab. 2014;99(10):3728-36. 641. Raudaskoski T, Tapanainen J, Tomas E, et al. Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: clinical, endometrial and metabolic response. BJOG. 2002;109(2):136-44. 642. Raymundo N, Yu-cheng B, Zi-yan H, et al. Treatment of atrophic vaginitis with topical conjugated equine estrogens in postmenopausal Asian women. Climacteric. 2004;7(3):312-8. 643. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993;329(11):753-6. 644. Rebar RW, Trabal J, Mortola J. Low-dose esterified estrogens (0.3 mg/day): long-term and short-term effects on menopausal symptoms and quality of life in postmenopausal women. Climacteric. 2000;3(3):176-82. 645. Reed SD, Mitchell CM, Joffe H, et al. Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial. Obstet Gynecol. 2014;124(2 Pt 1):233- 41. 646. Reed SD, Newton KM, LaCroix AZ, Grothaus LC, Grieco VS, Ehrlich K. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study. Menopause. 2008;15(1):51-8. 647. Reindollar R, Koltun W, Parsons A, et al. Effects of oral raloxifene on serum estradiol levels and other markers of estrogenicity. Fertil Steril. 2002;78(3):469-72. 648. Rice C, Killick S, Hickling D, Coelingh Bennink H. Ovarian activity and vaginal bleeding patterns with a desogestrel-only preparation at three different doses. Hum Reprod. 1996;11(4):737-40. 649. Riman T, Dickman PW, Nilsson S, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst. 2002;94(7):497-504. 650. Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7(3):156-61. 651. Ronnberg L, Koskimies A, Laatikainen T, Ranta T, Saastamoinen J. Efficacy of gonadotropin-releasing hormone agonist (buserelin) in the treatment of endometriosis. Acta Obstet Gynecol Scand. 1989;68(1):49-53. 652. Ross D, Cooper AJ, Pryse-Davies J, Bergeron C, Collins WP, Whitehead MI. Randomized, double-blind, dose-ranging study of the endometrial effects of a vaginal progesterone gel in estrogen-treated postmenopausal women. Am J Obstet Gynecol. 1997;177(4):937-41.

653. Ross D, Godfree V, Cooper A, Pryse-Davies J, Whitehead MI. Endometrial effects of three doses of trimegestone, a new orally active progestogen, on the postmenopausal endometrium. Maturitas. 1997;28(1):83-8. 654. Rotem C, Kaplan B. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecol Endocrinol. 2007;23(2):117-22. 655. Roumen FJ, Dieben TO. Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive. Fertil Steril. 2006;85(1):57-62. 656. Roux C, Pelissier C, Fechtenbaum J, Loiseau-Peres S, Benhamou CL. Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol and norethindrone acetate in preventing postmenopausal bone loss. Osteoporos Int. 2002;13(3):241-8. 657. Rovati LC, Schmid K, Giacovelli G, et al. Efficacy on climacteric symptoms of a new estradiol transdermal patch with active matrix in comparison with a reference reservoir patch. Two long-term randomized multicenter parallel-group studies. Arzneimittel-Forschung. 1999;49(11):933-43. 658. Roy S, Mishell DR, Jr., Gray G, et al. Comparison of metabolic and clinical effects of four oral contraceptive formulations and a contraceptive vaginal ring. Am J Obstet Gynecol. 1980;136(7):920-31. 659. Rozenberg S, Pornel B, Koninckx PR, Palacios S, Christiansen C. Endometrium protection and acceptability of nasally administered continuously combined hormone therapy: a multicentre, multinational, double-blind trial in post-menopausal women evaluating three regimens of 17beta-estradiol and norethisterone when compared with an orally administered 17beta-estradiol norethisterone regimen. Hum Reprod. 2009;24(7):1739-47. 660. Rozenberg S, Ylikorkala O, Arrenbrecht S. Comparison of continuous and sequential transdermal progestogen with sequential oral progestogen in postmenopausal women using continuous transdermal estrogen: vasomotor symptoms, bleeding patterns, and serum lipids. Int J Fertil Womens Med. 1997;42 Suppl 2:376-87. 661. Roztocil A, Pilka L, Jelinek J, Koudelka M, Miklica J. A comparison of three preinduction cervical priming methods: prostaglandin E2 gel, Dilapan S rods and Estradiol gel. Ceska Gynekol. 1998;63(1):3-9. 662. Rufford J, Hextall A, Cardozo L, Khullar V. A double-blind placebo-controlled trial on the effects of 25 mg estradiol implants on the urge syndrome in postmenopausal women. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14(2):78-83. 663. Rungruxsirivorn T, Panyakamlerd K, Trerattanachart S, Taechakraichana N. Randomized comparison of lower and standard dosages of transdermal estradiol on serum estradiol levels and vaginal maturation index. J Med Assoc Thai. 2006;89(9):1362-7. 664. Russo R, Corosu R. The clinical use of a preparation based on phyto-oestrogens in the treatment of menopausal disorders. Acta Biomed. 2003;74(3):137-43. 665. Rutanen EM, Heikkinen J, Halonen K, Komi J, Lammintausta R, Ylikorkala O. Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial. Menopause. 2003;10(5):433-9. 666. Rymer J, Fogelman I, Chapman MG. The incidence of vaginal bleeding with tibolone treatment. British journal of obstetrics and gynaecology. 1994;101(1):53-6. 667. Saano V, Glue P, Banfield CR, et al. Effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive. Clin Pharmacol Ther. 1995;58(5):523-31.

668. Sabatini R, Cagiano R. Comparison profiles of cycle control, side effects and sexual satisfaction of three hormonal contraceptives. Contraception. 2006;74(3):220-3. 669. Sagsoz N, Yucel A, Noyan V, Bozdogan O. The effects of hormone therapy, estrogen therapy and tibolone on apoptosis and cyclin D1 expression in postmenopausal vaginal epithelium. European journal of obstetrics, gynecology, and reproductive biology. 2005;121(1):61-6. 670. Said S, Sadek W, Rocca M, et al. Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception. World Health Organization, Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Long- acting Systemic Agents for Fertility Regulation. Hum Reprod. 1996;11 Suppl 2:1-13. 671. Saleh WA, Burkman RT, Zacur HA, Kimball AW, Kwiterovich P, Bell WK. A randomized trial of three oral contraceptives: comparison of bleeding patterns by contraceptive types and steroid levels. Am J Obstet Gynecol. 1993;168(6 Pt 1):1740-5; discussion 5-7. 672. Salminen HS, Saaf ME, Johansson SE, Ringertz H, Strender LE. The effect of transvaginal estradiol on bone in aged women: a randomised controlled trial. Maturitas. 2007;57(4):370-81. 673. Sammour MB, El-Hafiz MA. The remote changes in the endometrial histology and the cervicovaginal cytology with the long acting hormonal contraceptive. Fertil Steril. 1970;21(6):464-8. 674. Samsioe G, Dvorak V, Genazzani AR, et al. One-year endometrial safety evaluation of a continuous combined transdermal matrix patch delivering low-dose estradiol-norethisterone acetate in postmenopausal women. Maturitas. 2007;57(2):171-81. 675. Sang GW, Shao QX, Ge RS, et al. A multicentred phase III comparative clinical trial of Mesigyna, Cyclofem and Injectable No. 1 given by intramuscular injection to Chinese women. II. The comparison of bleeding patterns. Contraception. 1995;51(3):185-92. 676. Santen RJ, Pinkerton JV, Conaway M, et al. Treatment of urogenital atrophy with low- dose estradiol: preliminary results. Menopause. 2002;9(3):179-87. 677. Sarrel PM. Ovarian hormones and vaginal blood flow: using laser Doppler velocimetry to measure effects in a clinical trial of post-menopausal women. Int J Impot Res. 1998;10 Suppl 2:S91-3; discussion S8-101. 678. Sarrel PM, Wiita B. Vasodilator effects of estrogen are not diminished by androgen in postmenopausal women. Fertil Steril. 1997;68(6):1125-7. 679. Sator PG, Schmidt JB, Sator MO, Huber JC, Honigsmann H. The influence of hormone replacement therapy on skin ageing: a pilot study. Maturitas. 2001;39(1):43-55. 680. Saunders N, Anderson D, Gilbert L, Sharp F. Unsatisfactory colposcopy and the response to orally administered oestrogen: a randomized double blind placebo controlled trial. British journal of obstetrics and gynaecology. 1990;97(8):731-3. 681. Saure A. Randomized comparison of a new estradiol-releasing vaginal ring versus estriol vaginal pessaries. Am J Obstet Gynecol. 1995;173(2):670-1. 682. Saure A, Planellas J, Poulsen HK, Jaszczak P. A double-blind, randomized, comparative study evaluating clinical effects of two sequential estradiol-progestogen combinations containing either desogestrel or medroxyprogesterone acetate in climacteric women. Maturitas. 2000;34(2):133-42.

100

683. Sawaya GF, Grady D, Kerlikowske K, et al. The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS). Ann Intern Med. 2000;133(12):942-50. 684. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause. 2000;7(2):105-11. 685. Schmidt G, Andersson SB, Nordle O, Johansson CJ, Gunnarsson PO. Release of 17-beta- oestradiol from a vaginal ring in postmenopausal women: pharmacokinetic evaluation. Gynecol Obstet Invest. 1994;38(4):253-60. 686. Schug BS, Donath F, Blume HH. Bioavailability and pharmacodynamics of two 10-mg estradiol valerate depot formulations following IM single dose administration in healthy postmenopausal volunteers. Int J Clin Pharmacol Ther. 2012;50(2):100-17. 687. Schwartz JL, Creinin MD, Pymar HC, Reid L. Predicting risk of ovulation in new start oral contraceptive users. Obstet Gynecol. 2002;99(2):177-82. 688. Schwarz BE, Pierce C, Walden CE, Knopp RH. Reference period analysis of vaginal bleeding with triphasic oral contraceptive agents containing norethindrone or levonorgestrel: a comparison study. Int J Fertil. 1992;37(3):176-82. 689. Seckin B, Ozaksit G, Oruc AS, Yilmaz N. Does the addition of recombinant luteinizing hormone to progesterone for luteal supplementation improve IVF outcomes in high-responder patients? A preliminary randomized controlled study. J Reprod Med. 2014;59(5-6):321-6. 690. Seely EW, Walsh BW, Gerhard MD, Williams GH. Estradiol with or without progesterone and ambulatory blood pressure in postmenopausal women. Hypertension. 1999;33(5):1190-4. 691. Segal S, Casper RF. Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin for triggering follicular maturation in in vitro fertilization. Fertil Steril. 1992;57(6):1254-8. 692. Shaaban MM. Contraception with progestogens and progesterone during lactation. J Steroid Biochem Mol Biol. 1991;40(4-6):705-10. 693. Shapiro H, Cowell C, Casper RF. The use of vaginal ultrasound for monitoring endometrial preparation in a donor oocyte program. Fertil Steril. 1993;59(5):1055-8. 694. Sho T, Hachisuga T, Koi C, et al. 17beta-Estradiol induces proliferation of endometrial NK cells (CD56+) in postmenopausal women. Climacteric. 2017;20(6):571-6. 695. Shulman LP, Yankov V, Uhl K. Safety and efficacy of a continuous once-a-week 17beta- estradiol/levonorgestrel transdermal system and its effects on vasomotor symptoms and endometrial safety in postmenopausal women: the results of two multicenter, double-blind, randomized, controlled trials. Menopause. 2002;9(3):195-207. 696. Siddle NC, Fraser D, Whitehead MI, et al. Endometrial, physical and psychological effects of postmenopausal oestrogen therapy with added dydrogesterone. British journal of obstetrics and gynaecology. 1990;97(12):1101-7. 697. Silverman S, Jr., Shouse C. Estrogen effects on human oral epithelium. Cytologic, histologic and clinical comparisons. J Oral Ther Pharmacol. 1966;3(2):87-93. 698. Simmons CE, Kuchuk I, Freedman OC, et al. Are Estring(R) and Vagifem(R) equally effective and safe for the treatment of urogenital atrophy in breast cancer patients on aromatase inhibitor therapy? Clin Oncol (R Coll Radiol). 2012;24(8):e128-9. 699. Simon A, Hurwitz A, Zentner BS, Bdolah Y, Laufer N. Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study. Hum Reprod. 1998;13(1O):2712-7.

101

700. Simon C, Oberye J, Bellver J, et al. Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles. Hum Reprod. 2005;20(12):3318-27. 701. Simon J, Nachtigall L, Gut R, Lang E, Archer DF, Utian W. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol. 2008;112(5):1053-60. 702. Simon J, Nachtigall L, Ulrich LG, Eugster-Hausmann M, Gut R. Endometrial safety of ultra-low-dose estradiol vaginal tablets. Obstet Gynecol. 2010;116(4):876-83. 703. Simon J, Portman D, Mabey RG, Jr., Ospemifene Study G. Long-term safety of ospemifene (52-week extension) in the treatment of vulvar and vaginal atrophy in hysterectomized postmenopausal women. Maturitas. 2014;77(3):274-81. 704. Simon JA, Altomare C, Cort S, Jiang W, Pinkerton JV. Overall Safety of Ospemifene in Postmenopausal Women from Placebo-Controlled Phase 2 and 3 Trials. J Womens Health (Larchmt). 2018;27(1):14-23. 705. Simon JA, Archer DF, Kagan R, et al. Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a double-blind, placebo-controlled trial. Menopause. 2017;24(9):1003-10. 706. Simon JA, Bouchard C, Waldbaum A, Utian W, Zborowski J, Snabes MC. Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2007;109(3):588-96. 707. Simon JA, Lin VH, Radovich C, Bachmann GA, Ospemifene Study G. One-year long- term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause. 2013;20(4):418-27. 708. Simon JA, Liu JH, Speroff L, Shumel BS, Symons JP. Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy. Am J Obstet Gynecol. 2003;188(1):92-9. 709. Simon JA, Reape KZ, Wininger S, Hait H. Randomized, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of synthetic conjugated estrogens B for the treatment of vulvovaginal atrophy in healthy postmenopausal women. Fertil Steril. 2008;90(4):1132-8. 710. Simunic V, Banovic I, Ciglar S, Jeren L, Pavicic Baldani D, Sprem M. Local estrogen treatment in patients with urogenital symptoms. Int J Gynaecol Obstet. 2003;82(2):187-97. 711. Sinofsky FE, Pasquale SA. The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives. Am J Obstet Gynecol. 1998;178(2):300-4. 712. Siseles NO, Halperin H, Benencia HJ, et al. A comparative study of two hormone replacement therapy regimens on safety and efficacy variables. Maturitas. 1995;21(3):201-10. 713. Sismondi P, Kimmig R, Kubista E, et al. Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial. Maturitas. 2011;70(4):365- 72. 714. Sit AS, Modugno F, Hill LM, Martin J, Weissfeld JL. Transvaginal ultrasound measurement of endometrial thickness as a biomarker for estrogen exposure. Cancer Epidemiol Biomarkers Prev. 2004;13(9):1459-65. 715. Sitruk-Ware R, Plu-Bureau G, Menard J, et al. Effects of oral and transvaginal ethinyl estradiol on hemostatic factors and hepatic proteins in a randomized, crossover study. J Clin Endocrinol Metab. 2007;92(6):2074-9.

102

716. Sitruk-Ware RL, Menard J, Rad M, et al. Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen. Contraception. 2007;75(6):430-7. 717. Sivin I, Mishell DR, Jr., Victor A, et al. A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II-Subjective and objective measures of effects. An international comparative trial. Contraception. 1981;24(4):359-76. 718. Smith DB, Boileau MA, Buan LD. A self-directed home biofeedback system for women with symptoms of stress, urge, and mixed incontinence. J Wound Ostomy Continence Nurs. 2000;27(4):240-6. 719. Smith GI, Reeds DN, Okunade AL, Patterson BW, Mittendorfer B. Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women. J Clin Endocrinol Metab. 2014;99(7):E1306-10. 720. Smitz J, Bourgain C, Van Waesberghe L, Camus M, Devroey P, Van Steirteghem AC. A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation. Hum Reprod. 1993;8(1):40-5. 721. Smitz J, Devroey P, Faguer B, Bourgain C, Camus M, Van Steirteghem AC. A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement. Hum Reprod. 1992;7(2):168-75. 722. Sonnendecker EW, Polakow ES. Effects of conjugated equine oestrogens with and without the addition of cyclical medrogestone on hot flushes, liver function, blood pressure and endocrinological indices. S Afr Med J. 1990;77(6):281-5. 723. Sonntag B, Loebbecke KC, Nofer JR, Kiesel L, Greb RR. Serum estradiol and progesterone in the mid-luteal phase predict clinical pregnancy outcome in IVF/ICSI cycles. Gynecol Endocrinol. 2013;29(7):700-3. 724. Souka AR, Kamel M, Einen MA, Saleh F, Sallam H. Vaginal administration of a combined oral contraceptive containing norethisterone acetate. Contraception. 1985;31(6):571- 81. 725. Speroff L. Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. Obstet Gynecol. 2003;102(4):823-34. 726. Speroff L, Haney AF, Gilbert RD, Ellman H, Estradiol Acetate Investigator G. Efficacy of a new, oral estradiol acetate formulation for relief of menopause symptoms. Menopause. 2006;13(3):442-50. 727. Spicer DV, Pike MC, Pike A, Rude R, Shoupe D, Richardson J. Pilot trial of a gonadotropin hormone agonist with replacement hormones as a prototype contraceptive to prevent breast cancer. Contraception. 1993;47(5):427-44. 728. Spiryda LB, Laufer MR, Soiffer RJ, Antin JA. Graft-versus-host disease of the vulva and/or vagina: diagnosis and treatment. Biol Blood Marrow Transplant. 2003;9(12):760-5. 729. Spritzer PM, Vitola D, Vilodre LC, et al. One year follow-up of hormone replacement therapy with percutaneous estradiol and low-dose vaginal natural progesterone in women with mild to moderate hypertension. Exp Clin Endocrinol Diabetes. 2003;111(5):267-73. 730. Stachenfeld NS, Keefe DL, Palter SF. Estrogen and progesterone effects on transcapillary fluid dynamics. Am J Physiol Regul Integr Comp Physiol. 2001;281(4):R1319-29. 731. Stark M, Adoni A, Milwidsky A, Gilon G, Palti Z. Can estrogens be useful for treatment of vaginal relaxation in elderly women? Am J Obstet Gynecol. 1978;131(5):585-6.

103

732. Steer CV, Tan SL, Dillon D, Mason BA, Campbell S. Vaginal color Doppler assessment of uterine artery impedance correlates with immunohistochemical markers of endometrial receptivity required for the implantation of an embryo. Fertil Steril. 1995;63(1):101-8. 733. Stephenson MD, Fluker MR. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril. 2000;74(6):1108-13. 734. Stomati M, Bersi C, Rubino S, et al. Neuroendocrine effects of different estradiol- progestin regimens in postmenopausal women. Maturitas. 1997;28(2):127-35. 735. Stone SC, Mickal A, Rye PH. Postmenopausal symptomatology, maturation index, and plasma estrogen levels. Obstet Gynecol. 1975;45(6):625-7. 736. Stratton P, Hartog B, Hajizadeh N, et al. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod. 2000;15(5):1092-9. 737. Streuli I, Fraisse T, Pillet C, Ibecheole V, Bischof P, de Ziegler D. Serum antimullerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertil Steril. 2008;90(2):395-400. 738. Sulak PJ, Caubel P, Lane R. Efficacy and safety of a constant-estrogen, pulsed-progestin regimen in hormone replacement therapy. Int J Fertil Womens Med. 1999;44(6):286-96. 739. Sulak PJ, Smith V, Coffee A, Witt I, Kuehl AL, Kuehl TJ. Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial. Obstet Gynecol. 2008;112(3):563-71. 740. Sun Z, Zhu L, Xu T, Shi X, Lang J. Effects of preoperative vaginal estrogen therapy for the incidence of mesh complication after pelvic organ prolapse surgery in postmenopausal women: is it helpful or a myth? A 1-year randomized controlled trial. Menopause. 2016;23(7):740-8. 741. Surrey ES, Judd HL. Reduction of vasomotor symptoms and bone mineral density loss with combined norethindrone and long-acting gonadotropin-releasing hormone agonist therapy of symptomatic endometriosis: a prospective randomized trial. J Clin Endocrinol Metab. 1992;75(2):558-63. 742. Surrey ES, Voigt B, Fournet N, Judd HL. Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low- dose norethindrone "add-back" therapy. Fertil Steril. 1995;63(4):747-55. 743. Suvanto-Luukkonen E, Kauppila A. The levonorgestrel intrauterine system in menopausal hormone replacement therapy: five-year experience. Fertil Steril. 1999;72(1):161-3. 744. Suwanvesh N, Manonai J, Sophonsritsuk A, Cherdshewasart W. Comparison of Pueraria mirifica gel and conjugated equine estrogen cream effects on vaginal health in postmenopausal women. Menopause. 2017;24(2):210-5. 745. Swanson SG, Drosman S, Helmond FA, Stathopoulos VM. Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo-controlled study. Menopause. 2006;13(6):917- 25. 746. Symons J, Kempfert N, Speroff L. Vaginal bleeding in postmenopausal women taking low-dose norethindrone acetate and ethinyl estradiol combinations. The FemHRT Study Investigators. Obstet Gynecol. 2000;96(3):366-72.

104

747. Taechakraichana N, Intraragsakul A, Panyakhamlerd K, Numchaisrika P, Limpaphayom K. Estradiol and follicle-stimulating hormone levels in oophorectomized women using vaginal estrogen. J Med Assoc Thai. 1997;80(10):626-30. 748. Tahara M, Shimizu T, Shimoura H. Preliminary report of treatment with oral contraceptive pills for intermenstrual vaginal bleeding secondary to a cesarean section scar. Fertil Steril. 2006;86(2):477-9. 749. Takahashi K, Okada M, Ozaki T, et al. Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Hum Reprod. 2000;15(5):1028-36. 750. Tan D, Haines CJ, Limpaphayom KK, Holinka CF, Ausmanas MK. Relief of vasomotor symptoms and vaginal atrophy with three doses of conjugated estrogens and medroxyprogesterone acetate in postmenopausal Asian women from 11 countries: The Pan-Asia menopause (PAM) study. Maturitas. 2005;52(1):35-51. 751. Tang OS, Gao PP, Cheng L, Lee SW, Ho PC. A randomized double-blind placebo- controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Hum Reprod. 1999;14(3):722-5. 752. Tanko LB, Warming L, Bagger YZ, Byrjalsen I, Jensen S, Christiansen C. Serum placental protein 14: a novel marker of selective oestrogen receptor modulator action on the postmenopausal endometrium. Biomarkers. 2002;7(3):257-66. 753. Tarkkila T, Hulkko S, Alapiessa U, Kauraniemi T. Clinical investigation of the biological effects of a new combination low-dose oral contraceptive ('Ovostat E'). Curr Med Res Opin. 1977;5(3):247-51. 754. Taskin O, Yalcinoglu AI, Kucuk S, Uryan I, Buhur A, Burak F. Effectiveness of tibolone on hypoestrogenic symptoms induced by goserelin treatment in patients with endometriosis. Fertil Steril. 1997;67(1):40-5. 755. Tay PY, Lenton EA. Inhibition of progesterone secretion by oestradiol administered in the luteal phase of assisted conception cycles. Med J Malaysia. 2003;58(2):187-95. 756. Tedeschi C, Benvenuti C, Research Group EG. Comparison of vaginal gel isoflavones versus no topical treatment in vaginal dystrophy: results of a preliminary prospective study. Gynecol Endocrinol. 2012;28(8):652-4. 757. Teichmann A, Apter D, Emerich J, et al. Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial. Contraception. 2009;80(6):504-11. 758. Teter J. The use of selected cytologic indices for evaluation of estrogenicity of synthetic compounds. Acta Cytol. 1972;16(4):366-75. 759. Thatcher SS, Boyle HP, Glasier AF, Hillier SG, Baird DT. A comparison of dosages of norethisterone for synchronization of cycles in a fixed regimen of follicular augmentation and in vitro fertilization. Fertil Steril. 1988;49(5):848-53. 760. Thijssen JH, Wiegerninck MA, Donker GH, Poortman J. Uptake and metabolism of oestriol in human target tissues. J Steroid Biochem. 1984;20(4B):955-8. 761. Thong KJ, Brooks AN, Baird DT. Dose and time dependent rise of plasma cortisol following administration of mifepristone in early pregnancy. British journal of obstetrics and gynaecology. 1993;100(9):880-2. 762. Timmer CJ, Mulders TM. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet. 2000;39(3):233-42. 763. Timmer CJ, Verheul HA, Doorstam DP. Pharmacokinetics of tibolone in early and late postmenopausal women. Br J Clin Pharmacol. 2002;54(2):101-6.

105

764. Tinelli A, Malvasi A, D'Anna L, Tinelli R, Perrone A, Tinelli FG. Presurgical promestriene therapy in postmenopausal women with stress urinary incontinence. Gynecol Endocrinol. 2007;23(8):445-50. 765. Toner JP. Vaginal delivery of progesterone in donor oocyte therapy. Hum Reprod. 2000;15 Suppl 1:166-71. 766. Tontivuthikul P, Sanmee U, Wongtra-Ngan S, Pongnarisorn C. Effect of Local Estrogen Cream on Vaginal Health after Pessary Use for Prolapsed Pelvic Organ: A Randomized Controlled Trial. J Med Assoc Thai. 2016;99(7):757-63. 767. Torella M, Del Deo F, Grimaldi A, et al. Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women. European journal of obstetrics, gynecology, and reproductive biology. 2016;207:125-8. 768. Torky HA, Taha A, Marie H, et al. Role of topical oxytocin in improving vaginal atrophy in postmenopausal women: a randomized, controlled trial. Climacteric. 2018;21(2):174-8. 769. Tourgeman DE, Boostanfar R, Chang L, Lu J, Stanczyk FZ, Paulson RJ. Is there evidence for preferential delivery of ovarian estradiol to the endometrium? Fertil Steril. 2001;75(6):1156-8. 770. Tourgeman DE, Gentzchein E, Stanczyk FZ, Paulson RJ. Serum and tissue hormone levels of vaginally and orally administered estradiol. Am J Obstet Gynecol. 1999;180(6 Pt 1):1480-3. 771. Tourgeman DE, Slater CC, Stanczyk FZ, Paulson RJ. Endocrine and clinical effects of micronized estradiol administered vaginally or orally. Fertil Steril. 2001;75(1):200-2. 772. Traina TA, Poggesi I, Robson M, et al. Pharmacokinetics and tolerability of exemestane in combination with raloxifene in postmenopausal women with a history of breast cancer. Breast Cancer Res Treat. 2008;111(2):377-88. 773. Tregon ML, Blumel JE, Tarin JJ, Cano A. The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen. Menopause. 2003;10(2):154-9. 774. Tromans PM, Beazley J, Shenouda PI. Comparative study of oestradiol and prostaglandin E2 vaginal gel for ripening the unfavourable cervix before induction of labour. Br Med J (Clin Res Ed). 1981;282(6265):679-81. 775. Trotter A, Maier L, Kohn T, Bohm W, Pohlandt F. Growth of the uterus and mammary glands and vaginal cytologic features in extremely premature infants with postnatal replacement of estradiol and progesterone. Am J Obstet Gynecol. 2002;186(2):184-8. 776. Tsai KS, Yen ML, Pan HA, et al. Raloxifene versus continuous combined estrogen/progestin therapy: densitometric and biochemical effects in healthy postmenopausal Taiwanese women. Osteoporos Int. 2001;12(12):1020-5. 777. Tsang KL, Ho SL, Lo SK. Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations. Neurology. 2000;54(12):2292-8. 778. Tseng LH, Wang AC, Chang YL, Soong YK, Lloyd LK, Ko YJ. Randomized comparison of tolterodine with vaginal estrogen cream versus tolterodine alone for the treatment of postmenopausal women with overactive bladder syndrome. Neurourol Urodyn. 2009;28(1):47-51. 779. Tuppurainen M, Klimscheffskij R, Venhola M, Dieben TO. The combined contraceptive vaginal ring (NuvaRing) and lipid metabolism: a comparative study. Contraception. 2004;69(5):389-94.

106

780. Uesugi T, Toda T, Okuhira T, Chen JT. Evidence of estrogenic effect by the three-month- intervention of isoflavone on vaginal maturation and bone metabolism in early postmenopausal women. Endocr J. 2003;50(5):613-9. 781. Ulrich LS, Naessen T, Elia D, Goldstein JA, Eugster-Hausmann M, investigators VAGt. Endometrial safety of ultra-low-dose Vagifem 10 microg in postmenopausal women with vaginal atrophy. Climacteric. 2010;13(3):228-37. 782. Unfer V, Casini ML, Costabile L, Gerli S, Baldini D, Di Renzo GC. 17 alpha- hydroxyprogesterone caproate versus intravaginal progesterone in IVF-embryo transfer cycles: a prospective randomized study. Reprod Biomed Online. 2004;9(1):17-21. 783. Unkila M, Kari S, Yatkin E, Lammintausta R. Vaginal effects of ospemifene in the ovariectomized rat preclinical model of menopause. J Steroid Biochem Mol Biol. 2013;138:107- 15. 784. Utian WH. Comparative trial of P1496, a new non-steroidal oestrogen analogue. Br Med J. 1973;1(5853):579-81. 785. Utian WH. Clinical experience with transdermal estradiol in the treatment of the climacteric. Minerva Endocrinol. 1989;14(1):45-8. 786. Utian WH, Gass ML, Pickar JH. Body mass index does not influence response to treatment, nor does body weight change with lower doses of conjugated estrogens and medroxyprogesterone acetate in early postmenopausal women. Menopause. 2004;11(3):306-14. 787. Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril. 2001;75(6):1065-79. 788. Utian WH, Speroff L, Ellman H, Dart C. Comparative controlled trial of a novel oral estrogen therapy, estradiol acetate, for relief of menopause symptoms. Menopause. 2005;12(6):708-15. 789. Uygur D, Yesildaglar N, Erkaya S. Effect on sexual life--a comparison between tibolone and continuous combined conjugated equine estrogens and medroxyprogesterone acetate. Gynecol Endocrinol. 2005;20(4):209-12. 790. Vaccaro CM, Mutema GK, Fellner AN, et al. Histologic and cytologic effects of vaginal estrogen in women with pelvic organ prolapse: a randomized controlled trial. Female Pelvic Med Reconstr Surg. 2013;19(1):34-9. 791. Valiati B, Capp E, Edelweiss MI, de Freitas FM, Wender MC. Effect of raloxifene and low-dose percutaneous 17beta-estradiol on menopause symptoms and endometrium--a randomized controlled trial. Maturitas. 2009;62(1):81-4. 792. van de Vijver A, Drakopoulos P, Polyzos NP, et al. Vitrified-warmed blastocyst transfer on the 5th or 7th day of progesterone supplementation in an artificial cycle: a randomised controlled trial. Gynecol Endocrinol. 2017;33(10):783-6. 793. van de Vijver A, Polyzos NP, Van Landuyt L, et al. What is the optimal duration of progesterone administration before transferring a vitrified-warmed cleavage stage embryo? A randomized controlled trial. Hum Reprod. 2016;31(5):1097-104. 794. van de Weijer PH, Barentsen R, de Vries M, Kenemans P. Relationship of estradiol levels to breakthrough bleeding during continuous combined hormone replacement therapy. Obstet Gynecol. 1999;93(4):551-7. 795. van de Weijer PH, Barentsen R, Kenemans P. Women's expectations and acceptance of cyclic induced HRT bleeds. Maturitas. 1998;30(3):257-63.

107

796. van de Weijer PH, Scholten PC, van der Mooren MJ, Barentsen R, Kenemans P. Bleeding patterns and endometrial histology during administration of low-dose estradiol sequentially combined with dydrogesterone. Climacteric. 1999;2(2):101-9. 797. van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception. 2005;72(3):168-74. 798. van der Laak JA, de Bie LM, de Leeuw H, de Wilde PC, Hanselaar AG. The effect of Replens on vaginal cytology in the treatment of postmenopausal atrophy: cytomorphology versus computerised cytometry. J Clin Pathol. 2002;55(6):446-51. 799. van der Linden MC, Gerretsen G, Brandhorst MS, Ooms EC, Kremer CM, Doesburg WH. The effect of estriol on the cytology of urethra and vagina in postmenopausal women with genito-urinary symptoms. European journal of obstetrics, gynecology, and reproductive biology. 1993;51(1):29-33. 800. van Haaften M, Donker GH, Haspels AA, Thijssen JH. Oestrogen concentrations in plasma, endometrium, myometrium and vagina of postmenopausal women, and effects of vaginal oestriol (E3) and oestradiol (E2) applications. J Steroid Biochem. 1989;33(4A):647-53. 801. van Haaften M, Donker GH, Sie-Go DM, Haspels AA, Thijssen JH. Biochemical and histological effects of vaginal estriol and estradiol applications on the endometrium, myometrium and vagina of postmenopausal women. Gynecol Endocrinol. 1997;11(3):175-85. 802. Van Leusden HA, Albertyn G, Verlaine C, Van Ruymbeke J. A comparative multicenter study of two transdermal estradiol replacement therapies in the treatment of postmenopausal symptoms. International journal of fertility and menopausal studies. 1993;38(4):210-8. 803. Var T, Tonguc EA, Doganay M, Gulerman C, Gungor T, Mollamahmutoglu L. A comparison of the effects of three different luteal phase support protocols on in vitro fertilization outcomes: a randomized clinical trial. Fertil Steril. 2011;95(3):985-9. 804. Vardy MD, Lindsay R, Scotti RJ, et al. Short-term urogenital effects of raloxifene, tamoxifen, and estrogen. Am J Obstet Gynecol. 2003;189(1):81-8. 805. Vartiainen J, Wahlstrom T, Nilsson CG. Effects and acceptability of a new 17 beta- oestradiol-releasing vaginal ring in the treatment of postmenopausal complaints. Maturitas. 1993;17(2):129-37. 806. Veerus P, Fischer K, Hovi SL, Karro H, Rahu M, Hemminki E. Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial. BMC Womens Health. 2008;8:5. 807. Vercellini P, Pietropaolo G, De Giorgi O, Pasin R, Chiodini A, Crosignani PG. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril. 2005;84(5):1375-87. 808. Veres S, Miller L, Burington B. A comparison between the vaginal ring and oral contraceptives. Obstet Gynecol. 2004;104(3):555-63. 809. Verheul HA, Blok LJ, Burger CW, Hanifi-Moghaddam P, Kloosterboer HJ. Levels of tibolone and estradiol and their nonsulfated and sulfated metabolites in serum, myometrium, and vagina of postmenopausal women following treatment for 21 days with tibolone, estradiol, or estradiol plus medroxyprogestrone acetate. Reprod Sci. 2007;14(2):160-8. 810. Verhoeven CH, Dieben TO. The combined contraceptive vaginal ring, NuvaRing, and tampon co-usage. Contraception. 2004;69(3):197-9. 811. Verhoeven CH, van den Heuvel MW, Mulders TM, Dieben TO. The contraceptive vaginal ring, NuvaRing, and antimycotic co-medication. Contraception. 2004;69(2):129-32.

108

812. Veronesi U, Maisonneuve P, Rotmensz N, et al. Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy. J Natl Cancer Inst. 2007;99(9):727-37. 813. Vestergaard P, Hermann AP, Stilgren L, et al. Effects of 5 years of hormonal replacement therapy on menopausal symptoms and blood pressure-a randomised controlled study. Maturitas. 2003;46(2):123-32. 814. Victor A, Lithell H, Selinus I, Vessby B. Pharmacodynamics of a contraceptive vaginal ring releasing norethindrone and estradiol: ovarian function, bleeding control and lipoprotein patterns. Ups J Med Sci. 1984;89(2):179-88. 815. Victor I, Fink RA. Comparing patient telephone callback rates for different hormonal birth control delivery systems. Am J Ther. 2006;13(6):507-12. 816. Vilodre LC, Osorio Wender MC, Sisson de Castro JA, et al. Endometrial response to a cyclic regimen of percutaneous 17beta-estradiol and low-dose vaginal micronized progesterone in women with mild-to-moderate hypertension. Gynecol Endocrinol. 2003;17(4):323-8. 817. Voipio SK, Komi J, Kangas L, Halonen K, DeGregorio MW, Erkkola RU. Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas. 2002;43(3):207-14. 818. von Holst T, Salbach B. Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints. Maturitas. 2000;34(2):143-53. 819. Wang Y, He Y, Zhao X, et al. Crinone Gel for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Prospective Randomized Clinical Trial in the Chinese Population. PLoS One. 2015;10(7):e0133027. 820. Warming L, Christoffersen C, Riis BJ, Stakkestad JA, Delmas PD, Christiansen C. Adverse effects of a SERM (Levormeloxifene). Safety parameters and bone mineral density 12 months after treatment withdrawal. Maturitas. 2003;44(3):189-99. 821. Warming L, Ravn P, Christiansen C. Levonorgestrel and 17beta-estradiol given transdermally for the prevention of postmenopausal osteoporosis. Maturitas. 2005;50(2):78-85. 822. Warren MP, Biller BM, Shangold MM. A new clinical option for hormone replacement therapy in women with secondary amenorrhea: effects of cyclic administration of progesterone from the sustained-release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding. Am J Obstet Gynecol. 1999;180(1 Pt 1):42-8. 823. Watts NB, Notelovitz M, Timmons MC, Addison WA, Wiita B, Downey LJ. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995;85(4):529-37. 824. Webb AM, Russell J, Elstein M. Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception. BMJ. 1992;305(6859):927-31. 825. Weeks AD, Duffy SR, Walker JJ. Uterine ultrasonographic changes with gonadotropin- releasing hormone agonists. Am J Obstet Gynecol. 1999;180(1 Pt 1):8-13. 826. Weidner AC, Wu JM, Kawasaki A, Myers ER. Computer modeling informs study design: vaginal estrogen to prevent mesh erosion after different routes of prolapse surgery. Int Urogynecol J. 2013;24(3):441-5. 827. Weinstein L. Efficacy of a continuous estrogen-progestin regimen in the menopausal patient. Obstet Gynecol. 1987;69(6):929-32. 828. Weisberg E, Ayton R, Darling G, et al. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric. 2005;8(1):83-92.

109

829. Weisberg E, Brache V, Alvarez F, et al. Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen. Contraception. 2005;72(1):46- 52. 830. Weisberg E, Fraser IS, Lacarra M, Mishell DR, Jr., Jackanicz T. Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring. Contraception. 1997;56(4):233-9. 831. Weisberg E, Fraser IS, Mishell DR, Jr., Lacarra M, Bardin CW. The acceptability of a combined oestrogen/progestogen contraceptive vaginal ring. Contraception. 1995;51(1):39-44. 832. Weisberg E, Fraser IS, Mishell DR, Jr., Lacarra M, Darney P, Jackanicz TM. A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol. Contraception. 1999;59(5):305-10. 833. Welton AJ, Vickers MR, Kim J, et al. Health related quality of life after combined hormone replacement therapy: randomised controlled trial. BMJ. 2008;337:a1190. 834. Werther GA, Warne GL, Ennis G, et al. Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial. J Paediatr Child Health. 1990;26(1):4-8. 835. Westergaard LG, Erb K, Laursen S, Rasmussen PE, Rex S. The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women. Hum Reprod. 1996;11(6):1209-13. 836. Westhoff C, Osborne LM, Schafer JE, Morroni C. Bleeding patterns after immediate initiation of an oral compared with a vaginal hormonal contraceptive. Obstet Gynecol. 2005;106(1):89-96. 837. Widholm O, Vartiainen E. The absorption of conjugated oestrogen and sodium oestrone sulphate from the vagina. Ann Chir Gynaecol Fenn. 1974;63(3):186-90. 838. Wihlback AC, Nyberg S, Andersson A, Bixo M, Backstrom T, Sundstrom-Poromaa I. Allopregnanolone serum concentrations and neurosteroid sensitivity during withdrawal from postmenopausal hormone therapy. Gynecol Endocrinol. 2007;23(10):590-6. 839. Wihlback AC, Nyberg S, Backstrom T, Bixo M, Sundstrom-Poromaa I. Estradiol and the addition of progesterone increase the sensitivity to a neurosteroid in postmenopausal women. Psychoneuroendocrinology. 2005;30(1):38-50. 840. Wiklund IK, Mattsson LA, Lindgren R, Limoni C. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative Medicine Group. Int J Clin Pharmacol Res. 1999;19(3):89-99. 841. Wilcox G, Wahlqvist ML, Burger HG, Medley G. Oestrogenic effects of plant foods in postmenopausal women. BMJ. 1990;301(6757):905-6. 842. Wildemeersch D, Schacht E. Endometrial suppression with a new 'frameless' levonorgestrel releasing intrauterine system in perimenopausal and postmenopausal women: a pilot study. Maturitas. 2000;36(1):63-8. 843. Williams DB, Voigt BJ, Fu YS, Schoenfeld MJ, Judd HL. Assessment of less than monthly progestin therapy in postmenopausal women given estrogen replacement. Obstet Gynecol. 1994;84(5):787-93.

110

844. Williams SC, Oehninger S, Gibbons WE, Van Cleave WC, Muasher SJ. Delaying the initiation of progesterone supplementation results in decreased pregnancy rates after in vitro fertilization: a randomized, prospective study. Fertil Steril. 2001;76(6):1140-3. 845. Williams SR, Frenchek B, Speroff T, Speroff L. A study of combined continuous ethinyl estradiol and norethindrone acetate for postmenopausal hormone replacement. Am J Obstet Gynecol. 1990;162(2):438-46. 846. Wilson JD, Lee RA, Balen AH, Rutherford AJ. Bacterial vaginal flora in relation to changing oestrogen levels. Int J STD AIDS. 2007;18(5):308-11. 847. Wilson PD, Faragher B, Butler B, Bu'Lock D, Robinson EL, Brown AD. Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. British journal of obstetrics and gynaecology. 1987;94(6):568-74. 848. Wishart JM. An open study of Triphasil and Diane 50 in the treatment of acne. Australas J Dermatol. 1991;32(1):51-4. 849. Witherby S, Johnson J, Demers L, et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. Oncologist. 2011;16(4):424-31. 850. Wolfe BM, Koval JJ, Nisker JA. Impact on postmenopausal symptoms of adding continuous C-21 versus C-19 progestin to estrogen. Maturitas. 1999;33(2):153-61. 851. Wolfe BM, Plunkett ER. Early effects of continuous low-dosage all-norgestrel administered alone or with estrogen. Maturitas. 1994;18(3):207-19. 852. Wolff EF, He Y, Black DM, et al. Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS). Fertil Steril. 2013;99(5):1385-91. 853. Wolff JP, Cachelou R, Gueritee N. Absence of systemic hormonal effects in an oestradiol diether topically active on the vaginal mucosa. Maturitas. 1982;4(4):239-46. 854. Wright KP, Guibert J, Weitzen S, Davy C, Fauque P, Olivennes F. Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer. Reprod Biomed Online. 2006;13(3):321-5. 855. Wu MH, Pan HA, Wang ST, Hsu CC, Chang FM, Huang KE. Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy. Climacteric. 2001;4(4):314-9. 856. Wuttke W, Gorkow C, Seidlova-Wuttke D. Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Menopause. 2006;13(2):185-96. 857. Wuttke W, Seidlova-Wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas. 2003;44 Suppl 1:S67-77. 858. Xiao B, Zeng T, Wu S, Sun H, Xiao N. Effect of levonorgestrel-releasing intrauterine device on hormonal profile and menstrual pattern after long-term use. Contraception. 1995;51(6):359-65. 859. Xiao BL, Zhang XL, Feng DD. Pharmacokinetic and pharmacodynamic studies of vaginal rings releasing low-dose levonorgestrel. Contraception. 1985;32(5):455-71. 860. Xing S, Wu Y, Liu J, Xu R, Zhang Z, Wang Y. A comparison of two different dosages of conjugated equine estrogen in continuous combined hormone replacement therapy with progestin. Chinese medical journal. 2003;116(4):584-7.

111

861. Xu JX, Yan JH, Fan DZ, Zhang DW. Billings natural family planning in Shanghai, China. Adv Contracept. 1994;10(3):195-204. 862. Yagel S, Ben-Chetrit A, Anteby E, Zacut D, Hochner-Celnikier D, Ron M. The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Steril. 1992;57(1):33-6. 863. Yang JM, Huang WC. Factors associated with voiding function in women with lower urinary tract symptoms: a mathematic model explanation. Neurourol Urodyn. 2003;22(6):574- 81. 864. Yang TS, Tsan SH, Chen CR, Chang SP, Yuan CC. Evaluation of conjugated estrogen plus medroxyprogesterone acetate versus tibolone in early postmenopausal Chinese women. Zhonghua Yi Xue Za Zhi (Taipei). 1999;62(5):308-15. 865. Yanushpolsky E, Hurwitz S, Greenberg L, Racowsky C, Hornstein M. Patterns of luteal phase bleeding in in vitro fertilization cycles supplemented with Crinone vaginal gel and with intramuscular progesterone--impact of luteal estrogen: prospective, randomized study and post hoc analysis. Fertil Steril. 2011;95(2):617-20. 866. Yasmeen S, Romano PS, Pettinger M, et al. Incidence of cervical cytological abnormalities with aging in the women's health initiative: a randomized controlled trial. Obstet Gynecol. 2006;108(2):410-9. 867. Yasui T, Uemura H, Tezuka M, et al. Biological effects of hormone replacement therapy in relation to serum estradiol levels. Horm Res. 2001;56(1-2):38-44. 868. Yasui T, Uemura H, Umino Y, et al. Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women. Maturitas. 2005;50(1):19-29. 869. Yildirim G, Tugrul S, Uslu H, Pekin O, Eren S. Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding. Arch Gynecol Obstet. 2006;273(5):268-73. 870. Young RL, Snabes MC, Frank ML, Reilly M. A randomized, double-blind, placebo- controlled comparison of the impact of low-dose and triphasic oral contraceptives on follicular development. Am J Obstet Gynecol. 1992;167(3):678-82. 871. Young SB, Howard AE, Baker SP. Mersilene mesh sling: short- and long-term clinical and urodynamic outcomes. Am J Obstet Gynecol. 2001;185(1):32-40. 872. Yu J, Ma Y, Wu Z, et al. Endometrial preparation protocol of the frozen-thawed embryo transfer in patients with polycystic ovary syndrome. Arch Gynecol Obstet. 2015;291(1):201-11. 873. Yumru AE, Bozkurt M, Inci Coskun E, Baykan G. The use of local 17beta-oestradiol treatment for improving vaginal symptoms associated with post-menopausal oestrogen deficiency. J Int Med Res. 2009;37(1):198-204. 874. Yung SSF, Lee VCY, Chiu PCN, et al. The effect of 7 days of letrozole pretreatment combined with misoprostol on the expression of progesterone receptor and apoptotic factors of placental and decidual tissues from first-trimester abortion: a randomized controlled trial. Contraception. 2016;93(4):323-30. 875. Zahradnik HP, Goldberg J, Andreas JO. Efficacy and safety of the new antiandrogenic oral contraceptive Belara. Contraception. 1998;57(2):103-9. 876. Zalanyi S. Danazol mimics antigestagen action in first trimester termination of pregnancy. European journal of obstetrics, gynecology, and reproductive biology. 2001;99(1):93-6.

112

877. Zegers-Hochschild F, Balmaceda JP, Fabres C, et al. Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing progesterone for IVF and oocyte donation. Hum Reprod. 2000;15(10):2093-7. 878. Zervoudis S, Iatrakis G, Peitsidis P, et al. Tibolone vaginal versus per os administration in the management of post-menopausal symptoms. Rev Med Chir Soc Med Nat Iasi. 2009;113(2):471-7. 879. Zeyneloglu HB, Oktem M, Haberal NA, Esinler I, Kuscu E. The effect of raloxifene in association with vitamin D on vaginal maturation index and urogenital symptoms in postmenopausal osteoporotic women. Fertil Steril. 2007;88(2):530-2. 880. Zheng TP, Sun AJ, Xue W, et al. Efficacy and safety of Cimicifuga foetida extract on menopausal syndrome in Chinese women. Chinese medical journal. 2013;126(11):2034-8. 881. Zhou J, Qu F, Nan R, Tang D. The effect of chinese medicinal herbs in relieving menopausal symptoms in ovariectomized chinese women. Explore (NY). 2007;3(5):478-84. 882. Ziaei S, Rajaei L, Faghihzadeh S, Lamyian M. Comparative study and evaluation of side effects of low-dose contraceptive pills administered by the oral and vaginal route. Contraception. 2002;65(5):329-31. 883. Zinaman MJ, Cartledge T, Tomai T, Tippett P, Merriam GR. Pulsatile GnRH stimulates normal cyclic ovarian function in amenorrheic lactating postpartum women. J Clin Endocrinol Metab. 1995;80(7):2088-93. 884. Zucchini G, Armstrong AC, Wardley AM, et al. A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition. Eur J Cancer. 2015;51(18):2725-31. 885. Zullo MA, Plotti F, Calcagno M, et al. Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial. Menopause. 2005;12(4):421-7. 886. Carlstrom K, Karlgren E, Furuhjelm M, Ryd-Kjellen E. Effects of intravaginal oestrogen treatment upon the vaginal absorption of conjugated equine oestrogens. Maturitas. 1982;4(4):277-83. 887. Deutsch S, Ossowski R, Benjamin I. Comparison between degree of systemic absorption of vaginally and orally administered estrogens at different dose levels in postmenopausal women. Am J Obstet Gynecol. 1981;139(8):967-8. 888. Englund DE, Johansson ED. Plasma levels of oestrone, oestradiol and gonadotrophins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin). British journal of obstetrics and gynaecology. 1978;85(12):957-64. 889. Furuhjelm M, Karlgren E, Carlstrom K. Intravaginal administration of conjugated estrogens in premenopausal and postmenopausal women. Int J Gynaecol Obstet. 1980;17(4):335- 9. 890. Gabrielsson J, Wallenbeck I, Larsson G, Birgerson L, Heimer G. New kinetic data on estradiol in light of the vaginal ring concept. Maturitas. 1995;22 Suppl:S35-9. 891. Handa VL, Bachus KE, Johnston WW, Robboy SJ, Hammond CB. Vaginal administration of low-dose conjugated estrogens: systemic absorption and effects on the endometrium. Obstet Gynecol. 1994;84(2):215-8. 892. Luisi M, Franchi F, Kicovic PM. A group-comparative study of effects of Ovestin cream versus Premarin cream in post-menopausal women with vaginal atrophy. Maturitas. 1980;2(4):311-9.

113

893. Mandel FP, Geola FL, Meldrum DR, et al. Biological effects of various doses of vaginally administered conjugated equine estrogens in postmenopausal women. J Clin Endocrinol Metab. 1983;57(1):133-9. 894. Martin PL, Yen SS, Burnier AM, Hermann H. Systemic absorption and sustained effects of vaginal estrogen creams. JAMA. 1979;242(24):2699-700. 895. Nilsson K, Heimer G. Low-dose 17 beta-oestradiol during maintenance therapy--a pharmacokinetic and pharmacodynamic study. Maturitas. 1995;21(1):33-8. 896. Rigg LA, Hermann H, Yen SS. Absorption of estrogens from vaginal creams. N Engl J Med. 1978;298(4):195-7. 897. Smith P, Heimer G, Lindskog M, Ulmsten U. Oestradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy. Maturitas. 1993;16(2):145-54.

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