DOCSLIB.ORG

Medical Grand Rounds USE of ESTROGENS AFTER THE

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Medical Grand Rounds USE of ESTROGENS AFTER THE Medical Grand Rounds USE OF ESTROGENS AFTER THE MENOPAUSE 10 July 1980 Jean D. Wilson Outline I. GENERAL REVIEWS II. ENDOCRINOLOGY OF MENOPAUSE A. Origin of estrogen before or after the menopause B. Effect of weight on estrogen formation in peripheral tissues Ill. ESTROGENS AVAILABLE FOR REPLACEMENT THERAPY IV. EFFECTS OF ESTROGENS IN THE AGING WOMAN A. Vasomotor Instability B. Urogenital Epethelium and Skin C. Atherosclerosis, Myocardial Infarction and Stroke D. Hypertension E. Thromboembolic Disease F. Gallbladder Disease G. Benign and Malignant Breast Tumors H. Endometrial Carcinoma I. Osteoporosis V. CONCLUSIONS -I- I. GENERAL REVIEWS I. Lauritzen, C.H. The female climacteric syndrome: significance, problems, treatment. Acta Obstet. Gynecol. Scand. ~:47-61, 1976. 2. Campbell, S., Ed. The fv1anagement of the Menopause and Post­ Menopausal Years. University Park Press, Baltimore, 1976. 3. VanKeep, P.A., R.B. Greenblatt, and M. Albeaux-Ferret. Consensus on menopausal research. University Park Press, Baltimore, 1976. 4. Gambrell, R.D., Jr. Postmenopausal bleeding. Clin. Obstet. Gynecol. ~:129-143, 1977. 5. Studd, J., S. Chakravarti, and D. Oram. The climacteric. Clin. Obstet. Gynecol. :t:3-29, 1977. 6. Shoemaker, E.S., J.P. Forney, and P.C. MacDonald. Estrogen treatment of postmenopausal women, benefits and risks. J. Amer. Med. Assoc. 138:1524, 1977. 7. Utian, W.H. Current status of menopause and postmenopausal estrogen therapy. Obstet. Gynecol. Surv. 32:193-204, 1977. 8. Greenblatt, R.B. Geriatric Endocrinology, Vol. 5, Raven Press, New York, 1978. 9. Lauritzen, C., and P.A. VanKeep. Frontiers of Hormone Research. S. Karger, Basel, Vol. 5, 1978. 10. Silverberg, S.G., and F.J. Major. Estrogens and Cancer. John Wiley and Sons, New York, 1978. II. Quigley, M.M., and C.B. Hammond. Estrogen-replacement therapy - help or hazard? N. Engl. J. Med. 301:646-648, 1979. 12. Landau, R.L. What you should know about estrogens. JAMA 241:47-51, 1979. 13. Ryan, K.J. Estrogen after the menopause: risk vs. benefits. Consultant _!:218-221, April, 1980. Following the introduction of estrogens into clinical medicine in the late 1930's their use in menopausal women become more and more widespread as the result of several interlocking phenomena. Within medicine, powerful advocates argued that needless suffering of millions of women could be prevented by adequate estrogen replacement therapy (14, 15). -2- FrG.l. Woman showing some of the stigmata of "Xature's defeminization! ' The general Hifine==5 of muscles and lig::Lments , the "dowager's hump" and the "negativistic" expres­ sion are part of a picture usually attributed to age alone. Some of these "·omen exhibit signs and symptoms similar to those in the early stages of Parkinson's di seuse. They exjst ro.ther than live. (14) 14. Wilson, R.A., and T.A. Wilson. The fate of the nontreated postmeno­ pausal woman: a plea for the maintenance of adequate estrogen from puberty to the grave. J. Am. Geriatr. Soc. !!:347-362, 1963. 15. Jern, H.Z. Hormone therapy of the menopause and aging. Charles C. Thomas, Springfield, IL, 1973. (Dedicated to millions of women suffering needlessly.) This viewpoint was promoted aggressively by the pharmaceutical industry. -3- ~ ..... - . , ~ :;- I' Fig. 2 Jn ansu·uing adt'ertiumeniJ p/tnJe mtmion JOURNAl. OF CLINICAL ENDOCRINOLOGY AND METABOLISM The use of estrogen was made scientifically respectable by Fuller Albright who advanced the thesis that osteoporosis is the result of the menopausal state, that premature menopause is associated with worsening of osteoporosis, and that osteroporosis can be prevented by estrogen administration. 16. Albright, F., P.H. Smith, and A.M. Richardson. Postmenopausal osteoporosis. J. Amer. Med. Assoc . .!.!..§_:2465-2474, 1941. -4- After the long term results of such treatment from Albright's clinic were published by Henneman and Wallach (17) it became generally accepted that osteoporosis was a preventable disease. 0 1.0 HEIGHT LOSS 2.0 IN INCH£$ 3.0 4.0 s.o 50 2$ 20 1$ 10 II $ 10 15 20 25 PRE Pa ESTROGEN THERAPY YEARS Figure 3. Loss of height in osteoporotic women treated wi th estrogen and untreated. [From Henneman and Wallach(l7),Arch Intern Med 100:71 5. copyright 1957 Ameri­ can Medical Association.] 17. Henneman, P.H., and S. Wallach. The use of androgens and estrogens and their metabolic effects. Arch. Int. Med. 100:715-723, 1957. Simultaneously, the public at large was propagandized by advertisements, magazine articles, and books (such as Feminine Forever by Robert A. Wilson, M.D., published in 1966) to the belief that a perpetual Spring could be induced in the aging womm by the routine use of estrogens. By the mid 1960's it .was acceptable, indeed standard practice in many areas, including the Endocrine Clinic of Parkland Memorial Hospital, to prescribe estrogens routinely for women undergoing natural or surgically induced menopause. By 1973 51% of menopausal women in Seattle, Washington, used estrogen for a median period of 10 years (18). By 1975 the use of estrogens in this country approached the status of a several hundred million dollar industry, involving some 30 million prescriptions per year. 5- Fig.~. The numbers of estrogen pnoscriptiono rose dramatically during the period when use of the synthetic hormones peaked, and then fell off sharply after studies showing an increase In the risk of endometrial concer _, publicized. I.Jlgging somewhot behind Wll 1 concomitant rise ond fill in the Incidence of endometrial concor. 1. Source: N1tlonel Pretcription Audit. 2. Source: Nation•! Cancer lnatttute. 18. Stadel, B.V., and N. Weiss. Characteristics of menopausal women: a survey of King and Prince Counties in Washington, 1973-74. Am. J. Epidemiol. 102:209, 1975. Then, beginning in the mid 1970's a series of papers was published to suggest that an increase had occurred in the prevalence of endometrial cancer in menopausal women in this country (of epidemic proportions) and that this increase was the direct result of estrogen therapy. These claims have provoked a literal avalanche of papers in the past few years, relating both to the question of the purported relation of estrogen odministration to cancer and to the overall question of benefit to risk ratios of estrogen therapy. Coincidental to this new interest in the subject, the role of estrogen therapy in preventing osteoporosis is also undergoing reevaluation. What I propose to do today is to review the endocrine changes that take place at' menopause, the current concepts of the pathophysiology of the menopausal syndrome, the comparative pharmacology of the estrogens now available for replacement therapy, and the effects and side effects of estrogens in the aging woman. II. ENDOCRINOLOGY OF THE MENOPAUSE One of the major developments in steroid hormone physiology during the past 20 years was the demonstration by Drs. MacDonald and Siiteri and their colleagues at this institution that circulating estrogens can be derived both from direct secretion by the ovary and from formation in peripheral tissues from c androgens (19, 20). 19 Androstenedione Testosterone (Adrenal Androgen) l Estrtne ~ 1713-Estradiol ( -6- Prior to the menopause about 60% of estrogen formation is in the form of estradiol secreted into the plasma by the ovaries whereas 40% is estrone formed predominately by peripheral aromati.wtion of androgens. 200 ,.. NORMAL FEMALE-OVULATORY MENSES 0 0 'c 160 .9 0 .g 120 e a.. 80 40 4 6 8 w ~ ~ • ~ w u ~ ~ u Day of Cycle FIC. 5. Sources of estrogen production during a normal ovula­ tory ~menst rual cycle. Total height of bars represents sum of estrone a nd estradiol production; the hatclud portion , that amount derived fro.;, plasma andros tenedione. (Ref . 20) As the result of the menopause, the ovarian component of direct estrogen production is virtually obliterated, but the peripheral aromatase system remains intact so that estrone production remains substantialy unchanged. As a result, there is a switch from estradiol to estrone as the predominant estrogen in the aging woman. 1 BO 10 •• [, ~ ...... · A Ipq 124 ... 70 • PREIOO" ·A I •o .~ 50 ~ 4 0 ~ 30 I ·' 20 10 1- OflR. R. E S R.BI. LF. 0~P. H. ~L .SI. FIC. 6. Estrogen production from circulating androstenedione in normal postmenopausal women. PREI, total estrone production rate; PREI 4 • . A, production rate of estrone from plasma andro· stenedione; and PREl J.l A• -"• amount of estrone derived from androstenedione that enters the plasma as free estrone. As indi~ cated in text, formation and release of estrone sulfate likely ac ~ counts for difference between PRE I•• -• and PRE I' •'·• . (Ref. 20) -7- r The factors that regulate the rate of estrogen formation in peripheral tissues are largely undefined, but ane major determinant is body weight, a relation that is true both for the rate of estrogen formation (20) and for the plasma levels of estrogens in postmenopausal women (4). 12 510 iii e; 8 >z 8 6 .... z ~ 4 0:: w 0.. 2 0 o 40 80 120 160 200 240 280 320 360 BODY WEIGHT (lbs.l FIG. 7. Correlati on of extent of com·crsion of androstenedione tn estronC., ( p ) 1~li 1 , with body weig hl in postwenopausal women. Cc~r ­ rela lion coefficient = 0.7+.(Rei . 20) .. 20 ~ ....ll: , 0 ~ E 10 . •• so 40 ~ ...z 0 E 20 10 _, 0 2S ~ 75 100 EXCESS FAT ( lbsl FIG. 8. Correlation of estradiol and estrone levels with excess fat in postmenopausal patients with endometrial cancer (•) and without endometrial cancer (0 ). Dashed regression line is for all patients, while solid line is for cancer patients only. (Ref . 21) -8- Exactly why peripheral oromotose activity is enhanced in obesity is unclear, presumably due to an increase in the number of odipocytes and pre-odipocytes (23). In some postmenopausal women mean estrogen production may be as high or higher than prior to the menopause - the predominant estrogen being changed and the secretory rate constant rather than intermittent (20).
Load more

Recommended publications
  • Estrone with Pipera- with an Anabolic Steroid and a Progestogen for Osteoporosis
    Estradiol/Ethinylestradiol 2101 Estrapronicate (rINN) menopausal atrophic vaginitis and kraurosis vulvae. A dose of Estrapronicato; Estrapronicatum. Oestradiol 17-nicotinate 3- 500 micrograms may be given as a 0.01% or 0.1% cream or as a pessary; initial treatment may be given once daily, then reduced propionate. O to twice each week. NH CH3 Эстрапроникат Estriol has also been given orally for infertility (p.2080) caused HN C27H31NO4 = 433.5. by poor cervical penetration, in a dose of 0.25 to 1 mg daily on H CAS — 4140-20-9. days 6 to 15 of the menstrual cycle. O Estriol succinate has also been given orally in the treatment of HO HH menopausal disorders. The sodium succinate salt has been used S N parenterally in the treatment of haemorrhage and thrombocyto- O penia. O Preparations Pharmacopoeias. In Br. and US. BP 2008: Estriol Cream. BP 2008 (Estropipate). A white or almost white crystalline pow- Proprietary Preparations (details are given in Part 3) O O der. Very slightly soluble in water, in alcohol, in chloroform, and Arg.: Colpoestriol; Orgestriol; Austral.: Ovestin; Austria: Ortho-Gynest; in ether. H3C Ovestin; Styptanon; Belg.: Aacifemine; Ortho-Gynest; Braz.: Estriopax; Hormocervix; Hormoniol; Ovestrion; Styptanon; Chile: Ovestin; Sina- USP 31 (Estropipate). A white to yellowish-white fine crystal- pause; Vacidox; Cz.: Ortho-Gynest; Ovestin; Denm.: Ovestin; Fin.: Oves- line powder, odourless or may have a slight odour. Very slightly H tin; Pausanol; Fr.: Gydrelle; Physiogine; Trophicreme; Ger.: Cordes Estriol; soluble in water, in alcohol, in chloroform, and in ether; soluble Gynasan†; OeKolp; Oestro-Gynaedron M; Ortho-Gynest; Ovestin; Syna- 1 in 500 of warm alcohol; soluble in warm water.
    [Show full text]
  • To See References
    Longevity & Bioidentical Hormones Friedrich N, Haring R, Nauck M, et al. Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations. J Clin Endocrinol Metab. 2009 May;94(5):1732-9. Malkin CJ, Pugh PJ, Morris PD, et al. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart. 2004 Aug;90(8):871-6. Besson A, Salemi S, Gallati S, et al. Reduced longevity in untreated patients with isolated growth hormone deficiency. J Clin Endocrinol Metab. 2003 Aug;88(8):3664- 7. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004 Jan;89(1):114-120. Moffat SD, Zonderman AB, Metter EJ, et al. Free testosterone and risk for Alzheimer disease in older men. Neurology. 2004 Jan 27;62(2):188-193. Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007 Dec 4;116(23):2694-701. Malkin CJ, Pugh PJ, Jones RD, et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004 Jul;89(7):3313-3318. Selvin E, Feinleib M, Zhang L, et al. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,723,320 B2 Bunschoten Et Al
    US007723320B2 (12) United States Patent (10) Patent No.: US 7,723,320 B2 Bunschoten et al. (45) Date of Patent: May 25, 2010 (54) USE OF ESTROGEN COMPOUNDS TO DE 23,36434. A 4, 1975 INCREASE LIBDO IN WOMEN WO WO96 O3929 A 2, 1996 (75) Inventors: Evert Johannes Bunschoten, Heesch OTHER PUBLICATIONS (NL); Herman Jan Tijmen Coelingh Bennink, Driebergen (NL); Christian Holinka CF et al: “Comparison of Effects of Estetrol and Taxoxifen Franz Holinka, New York, NY (US) with Those of Estriol and Estradiol on the Immature Rat Uterus'; Biology of Reproduction; 1980; pp. 913-926; vol. 22, No. 4. (73) Assignee: Pantarhei Bioscience B.V., Al Zeist Holinka CF et al; "In-Vivo Effects of Estetrol on the Immature Rat (NL) Uterus'; Biology of Reproduction; 1979: pp. 242-246; vol. 20, No. 2. Albertazzi Paola et al.; "The Effect of Tibolone Versus Continuous Combined Norethisterone Acetate and Oestradiol on Memory, (*) Notice: Subject to any disclaimer, the term of this Libido and Mood of Postmenopausal Women: A pilot study': Data patent is extended or adjusted under 35 base Biosis "Online!; Oct. 31, 2000: pp. 223-229; vol. 36, No. 3; U.S.C. 154(b) by 1072 days. Biosciences Information Service.: Philadelphia, PA, US. Visser et al., “In vitro effects of estetrol on receptor binding, drug (21) Appl. No.: 10/478,264 targets and human liver cell metabolism.” Climacteric (2008) 11(1) Appx. II: 1-5. (22) PCT Filed: May 17, 2002 Visser et al., “First human exposure to exogenous single-dose oral estetrol in early postmenopausal women.” Climacteric (2008) 11(1): (86).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,284,263 B1 Place (45) Date of Patent: Sep
    USOO6284263B1 (12) United States Patent (10) Patent No.: US 6,284,263 B1 Place (45) Date of Patent: Sep. 4, 2001 (54) BUCCAL DRUG ADMINISTRATION IN THE 4,755,386 7/1988 Hsiao et al. TREATMENT OF FEMALE SEXUAL 4,764,378 8/1988 Keith et al.. DYSFUNCTION 4,877,774 10/1989 Pitha et al.. 5,135,752 8/1992 Snipes. 5,190,967 3/1993 Riley. (76) Inventor: Virgil A. Place, P.O. Box 44555-10 5,346,701 9/1994 Heiber et al. Ala Kahua, Kawaihae, HI (US) 96743 5,516,523 5/1996 Heiber et al. 5,543,154 8/1996 Rork et al. ........................ 424/133.1 (*) Notice: Subject to any disclaimer, the term of this 5,639,743 6/1997 Kaswan et al. patent is extended or adjusted under 35 6,180,682 1/2001 Place. U.S.C. 154(b) by 0 days. * cited by examiner (21) Appl. No.: 09/626,772 Primary Examiner Thurman K. Page ASSistant Examiner-Rachel M. Bennett (22) Filed: Jul. 27, 2000 (74) Attorney, Agent, or Firm-Dianne E. Reed; Reed & Related U.S. Application Data ASSciates (62) Division of application No. 09/237,713, filed on Jan. 26, (57) ABSTRACT 1999, now Pat. No. 6,117,446. A buccal dosage unit is provided for administering a com (51) Int. Cl. ............................. A61F 13/02; A61 K9/20; bination of Steroidal active agents to a female individual. A61K 47/30 The novel buccal drug delivery Systems may be used in (52) U.S. Cl. .......................... 424/435; 424/434; 424/464; female hormone replacement therapy, in female 514/772.3 contraception, to treat female Sexual dysfunction, and to treat or prevent a variety of conditions and disorders which (58) Field of Search ....................................
    [Show full text]
  • WO 2008/089405 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 24 July 2008 (24.07.2008) WO 2008/089405 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/56 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, (21) International Application Number: CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, PCT/US2008/051431 EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, (22) International Filing Date: 18 January 2008 (18.01.2008) LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, (25) Filing Language: English PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (26) Publication Language: English ZA, ZM, ZW (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 60/881,528 19 January 2007 (19.01.2007) US kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): NEU- GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ROSCI, INC. [US/US]; 1458 Clear Brook Drive, Dayton, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), OH 45440 (US).
    [Show full text]
  • Network-Based Characterization of Drug-Protein Interaction Signatures
    Tabei et al. BMC Systems Biology 2019, 13(Suppl 2):39 https://doi.org/10.1186/s12918-019-0691-1 RESEARCH Open Access Network-based characterization of drug-protein interaction signatures with a space-efficient approach Yasuo Tabei1*, Masaaki Kotera2, Ryusuke Sawada3 and Yoshihiro Yamanishi3,4 From The 17th Asia Pacific Bioinformatics Conference (APBC 2019) Wuhan, China. 14–16 January 2019 Abstract Background: Characterization of drug-protein interaction networks with biological features has recently become challenging in recent pharmaceutical science toward a better understanding of polypharmacology. Results: We present a novel method for systematic analyses of the underlying features characteristic of drug-protein interaction networks, which we call “drug-protein interaction signatures” from the integration of large-scale heterogeneous data of drugs and proteins. We develop a new efficient algorithm for extracting informative drug- protein interaction signatures from the integration of large-scale heterogeneous data of drugs and proteins, which is made possible by space-efficient representations for fingerprints of drug-protein pairs and sparsity-induced classifiers. Conclusions: Our method infers a set of drug-protein interaction signatures consisting of the associations between drug chemical substructures, adverse drug reactions, protein domains, biological pathways, and pathway modules. We argue the these signatures are biologically meaningful and useful for predicting unknown drug-protein interactions and are expected to contribute to rational drug design. Keywords: Drug-protein interaction prediction, Drug discovery, Large-scale prediction Background similar drugs are expected to interact with similar pro- Target proteins of drug molecules are classified into a pri- teins, with which the similarity of drugs and proteins are mary target and off-targets.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Estriol: Safety and Efficacy
    Estriol: Safety and Efficacy by Kathleen A. Head, N.D. Abstract While conventional hormone replacement therapy provides certain benefits, it is not without significant risks. Estriol has been found to provide some of the protection without the risks associated with stronger estrogens. Depending upon the situation, estriol may exert either agonistic or antagonistic effects on estrogen. Estriol appears to be effective at controlling symptoms of menopause, including hot flashes, insomnia, vaginal dryness, and frequent urinary tract infections. Results of research on its bone- density-maintaining effects have been contradictory, with the most promising results coming from Japanese studies. Estriol’s effect on cardiac risk factors has also been somewhat equivocal; however, unlike conventional estrogen prescriptions, it does not seem to contribute to hypertension. Although estriol appears to be much safer than estrone or estradiol, its continuous use in high doses may have a stimulatory effect on both breast and endometrial tissue. (Alt Med Rev 1998;3(2):101-113) Introduction A significant problem facing peri- and postmenopausal women, as well as their healthcare practitioners, is determining what approach to take regarding hormone replacement. There are many options, ranging from no intervention at all to conventional hormone replacement therapy (HRT). Approaches which lie somewhere in between involve the use of herbal and nutritional approaches or the use of “friendlier” more gentle hormone replacement regimes than those typically prescribed. One of the hormones which has been virtually ignored by conventional medicine but which shows some promise of effectiveness without as many side-effects is es- triol. Its use is increasing in popularity, prescribed either alone or in the form of triple estrogen (80% estriol, 10% estrone, 10% estradiol).
    [Show full text]
  • Hormone Replacement Therapy Part I: Prescribing HRT-Recent Trends
    Hormone Replacement Therapy Part I: Prescribing HRT -Recent Trends Page 1 of 13 Hormone Replacement Therapy Part I: Prescribing HRT-Recent Trends Select a Speciality Dr Neerja Goel,Department of Obstetrics & Gynaecology, Guru Teg Gynaecology Bahadur Hospital, Delhi Ask Indegene With the steady increase in life expectancy of women in India (62.5 years), a majority of them survive an age well past the menopause. Presently about 60 million of the Discussions population of India are women aged 55 years and over. The menopause constitutes a Notice Board watershed in a woman‘s life with average age of reaching it 47.5 years. The Journal Scan postmenopausal period is associated with a significant increase in the incidence of age Conferences related health hazards like diabetes and hypertension along with estrogen deprivation Online Library effects. In the short term these falling estrogen levels commonly result in a spectrum of Medico-Legal Cases unpleasant symptoms such as hot flushes, night sweats, sleep disturbances, vaginal dryness and depression. In the long term absolute estrogen deficiency leads to generalized atrophy of the skin, decrease in lean body mass, an accelerated rate of bone loss from the skeleton producing osteoporosis and a rapid increase in the incidence of coronary heart disease . Table 1 . Acute and Chronic sequelae of menopause Duration System Symptoms/Disease Hot flushes, night sweats, insomnia, mood changes, Acute Neuroendocrine anxiety, irritability, loss of memory and concentration Genital tract atrophy, Lower urogenital Menstruation stops dyspareunia, loss of libido, tract urethral syndrome Coronary heart disease, Arterial Chronic thrombosis Skeletal Osteoporosis Each of these adverse sequelae could potentially be reversed by Hormone Replacement Therapy (HRT) and the process of aging could be arrested to some extent.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Pharmacology of Estrogens and Progestogens: Influence of Different Routes of Administration
    CLIMACTERIC 2005;8(Suppl 1):3–63 Pharmacology of estrogens and progestogens: influence of different routes of administration H. Kuhl Department of Obstetrics and Gynecology, J. W. Goethe University of Frankfurt, Germany Key words: ESTROGENS, PROGESTOGENS, PHARMACOKINETICS, PHARMACODYNAMICS, HORMONE REPLACEMENT THERAPY ABSTRACT This review comprises the pharmacokinetics and pharmacodynamics of natural and synthetic estrogens and progestogens used in contraception and therapy, with special consideration of hormone replacement therapy. The paper describes the mechanisms of action, the relation between structure and hormonal activity, differences in hormonal pattern and potency, peculiarities in the properties of certain steroids, tissue-specific effects, and the metabolism of the available estrogens and progestogens. The influence of the route of administration on pharmacokinetics, hormonal activity and metabolism is presented, and the effects of oral and transdermal treatment with estrogens on tissues, clinical and serum parameters are compared. The effects of oral, transdermal (patch and gel), intranasal, sublingual, buccal, vaginal, subcutaneous and intramuscular adminis- tration of estrogens, as well as of oral, vaginal, transdermal, intranasal, buccal, intramuscular and intrauterine application of progestogens are discussed. The various types of progestogens, their receptor interaction, hormonal pattern and the hormonal activity of certain metabolites are described in detail. The structural formulae, serum concentrations, binding affinities to steroid receptors and serum binding globulins, and the relative potencies of the available estrogens and progestins are presented. Differences in the tissue-specific effects of the various compounds and regimens and their potential implications with the risks and benefits of hormone replacement therapy are discussed. INTRODUCTION The aim of any hormonal treatment of postmen- tance of pharmacological knowledge for an opausal women is not to restore the physiological optimal use of hormone therapy.
    [Show full text]
  • Estriol; the ‘Good’ Estrogen Advances and Updates in Its Clinical Uses
    Estriol; the ‘Good’ Estrogen Advances and Updates in its Clinical Uses Erin Lommen, NDa ©2013, Erin Lommen, ND Jay H Mead, MDb Journal Compilation ©2013, AARM DOI 10.14200/jrm.2013.2.0103 ABSTRACT Estriol, coined the “weaker” of the three endogenous estrogens, has significant therapeutic effects, some of which are little known to clinicians. Estriol provides numerous clinical benefits, commanding the attention of researchers dating as far back as 1966 and continues to garner substantial consideration as a valuable and viable therapeutic agent. Some of the most common and effective treatments that employ estriol include: hot flashes, insomnia, skin enhancement, vaginal atrophy and reduced frequency of urinary tract infections. Most recently, estriol has shown the potential to treat individuals with Th1-mediated autoimmune illnesses, including multiple sclerosis and rheumatoid arthritis. This review article will update the clinical effects and benefits of estriol and further clarify the documented advances which support the substantial therapeutic benefits of estriol for autoimmune conditions. The availability of compounded estriol preparations will also be addressed. Keywords: Cytokines; Dendritic cells; Estriol; Menopause; Multiple sclerosis; Rheumatoid arthritis; Th1 autoimmunity a Corresponding author: Labrix Clinical Services, 16255 SE 130th Avenue, Clackamas OR 97015, USA, Tel.: 503-656-9596; Fax: 503-656-9756; Cell: 503-516-4741, E-mail: [email protected] b Labrix Clinical Services, 16255 SE 130th Avenue, Clackamas OR 97015, USA Journal of Restorative Medicine 2013; 2: page 45 Estriol; the ‘Good’ Estrogen INTRODUCTION Due to the well-known and documented risks naturally occurring estrogens in women: estrone (E1), associated with estradiol (E2), estriol (E3) has long E2, and E3.8 The developing follicles in the ovaries piqued the interest of researchers and clinicians.1 For are responsible for producing the majority of the estro- decades, E3 has proven its efficacy in the success- gens.
    [Show full text]