Volume 12, Issue 2 (April 2016)

This clinical e-newsletter from The North American Menopause Society (NAMS) presents questions and cases commonly seen in a menopause specialist’s practice. Recognized experts in the field provide their opinions and practical advice. Kathryn M. Macaulay, MD, NCMP, the Editor of Menopause e-Consult, encourages your suggestions for future topics. Note that the opinions expressed in the commentaries are those of the authors and are not necessarily endorsed by NAMS or by Dr. Macaulay.

Question perimenopausal women report these 2 We often see patients start to complain about symptoms. vasomotor symptoms even though they are still having menses, albeit irregularly. What In a woman in her late 40s or early 50s who is the ideal hormone regimen for these reports characteristic VMS and has had patients? If their menses remain irregular, normal thyroid-stimulating hormone levels in should we be concerned? What regimen the last year or so, additional medical/ would best regulate their cycles? Do we need endocrine evaluation is not recommended. to more aggressively evaluate the patient for other medical issues that may cause hot If bleeding is heavy or prolonged, flashes? endometrial evaluation is appropriate. However, if menses are simply less regular Commentary by (or the patient reports a skipped/ oligomenorrheic menstrual pattern), endo- Andrew M Kaunitz, MD, FACOG, metrial evaluation is not indicated. NCMP Professor and Associate Chairman Medical Director and Director If the VMS are bothersome and disrupting of Menopause and Gynecologic normal activities, including sleep, treatment Ultrasound Services is appropriate. UF Southside Women’s Health Department of Obstetrics and Gynecology Whether birth control is needed, combination University of Florida College (estrogen-progestin) hormone contraceptives of Medicine Jacksonville, Florida (CHCs, including combination oral contra- ceptives [COCs]), suppress VMS, cause rregular menses and vasomotor symptoms regular withdrawal bleeding, and reduce the I (VMS) represent the hallmark of the amount of bleeding, as well as perimenopause transition, a time in a dysmenorrhea. woman’s life some have described as “hormonal chaos.”1 In addition, these agents carry additional health benefits, including prevention of Vasomotor symptoms are most prevalent ovarian and endometrial cancer and (when during the later stages of perimenopause; the used in women during the late Study of Women’s Health Across the Nation perimenopause transition) increased bone indicated that as many as 70% of mass.

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On what appears to be a dose-related basis, As women age, the prevalence of use of CHCs increases risk of venous comorbidities, including obesity, hyper- thromboembolic events (VTEs). Although tension, and VTEs, which increase the their use has not been extensively studied in cardiovascular risks associated with CHC older reproductive-aged women, use of use, grows. In addition, CHC use is not CHCs does not appear to affect risk of breast appropriate for older reproductive-aged cancer. women who smoke or have migraine headaches. Almost all CHCs are formulated with the potent, synthetic estrogen ethinyl estradiol Combination hormone formulations indi- (EE)—5 μg of EE is approximately cated for use as HT have estrogen doses equivalent to 0.625 mg of conjugated lower than those used in CHCs and can be estrogens; therefore, a 20-μg COC delivers used off-label to treat VMS in about 4-fold more estrogen than standard- perimenopausal women who are not dose hormone therapy (HT). candidates for CHCs. A prior history of VTE would contraindicate both CHC and HT use. A COC containing 10 μg of EE and 1 mg norethindrone is available in the United Optimal symptom management in States (but not in Canada). In addition, an perimenopausal women likely requires oral contraceptive formulation with estradiol consistent ovulation suppression, because the valerate (most pills contain 2 mg) and the occurrence of sporadic ovulation in such women can aggravate irregular uterine progestin dienogest is available in the United 5 States and Canada. The estrogen dose of bleeding. these COC formulations is in the range of use in HT. Accordingly, it is important that HT formulations used to suppress perimenopause Other CHCs include a monthly vaginal ring symptoms are formulated with contraceptive (available in the United States and Canada) doses of progestins. Continuous oral HT and a weekly patch (generic in the United formulations with norethindrone acetate States; Evra in Canada), both worn for 3 of 0.5 mg (combined with 1.0 mg estradiol) or 4 weeks. norethindrone acetate 1.0 mg (combined with 5 μg EE) likely suppress ovulation and can In women who seek treatment for be used off-label to effectively treat VMS perimenopause symptoms and also need and suppress menstruation in perimenopausal contraception and who are appropriate women. Both formulations are available in candidates for combination contraceptives, Canada as well as in the United Sates. these agents can be continued until they are References in their mid-50s. At that time, the likelihood 1. Berga SL. Disordered folliculogenesis during the of menopause is high (meaning that future menopausal transition: explaining chaos. Menopause. ovulation is unlikely), and patients can 2009;16(1):11-12. discontinue combination contraceptives and 2. Gold EB, Colvin A, Avis N, et al. Longitudinal 3,4 analysis of the association between vasomotor transition to conventional HT, if desired. symptoms and race/ethnicity across the menopausal transition: Study of Women’s Health Across the Nation. Am J Public Health. 2006;96(7):1226-1235. Women using CHCs strictly for 3. Allen RH, Cwiak CA, Kaunitz AM. Contraception in noncontraceptive indications may consider women over 40 years of age. CMAJ. 2013;185(7): stopping these methods in their early 50s. 565-573. 3

4. Allen RH, Cwiak CA. Contraception for midlife educate and counsel women is necessary women. Menopause. 2016;23(1):111-113. 5. Santoro N, Teal S, Gavito C, Cano S, Chosich J, when caring for this population. Sheeder J. Use of a levonorgestrel-containing intrauterine system with supplemental estrogen Vaginal atrophy describes changes that occur improves symptoms in perimenopausal women: a pilot study. Menopause. 2015;22(12):1301-1307. to the vagina after estrogen levels decrease after or during the menopause transition, Disclosures: Dr. Kaunitz reports consultant/advisory either naturally or because of cancer board for Allergan, Bayer, Merck, Pfizer; grant/ therapies. Anatomic changes include thin- research support for Bayer, Merck, TherapeuticsMD; ning of the vaginal tissues, reduction in the and royalties/patents for UpToDate. size of the labia minora, and retraction of the

vaginal introitus.4 Physiologically, vaginal Case pH may increase, vaginal epithelium may A woman who is 3 years postmenopausal become altered, and vaginal blood flow may comes in to your office with a chief be reduced. complaint of severe vaginal dryness. There are no visible signs of infection or lichen According to the 2013 North American sclerosis. She is severely atrophic and Menopause Society vulvovaginal atrophy frustrated. She has tried Estrace vaginal position statement, first-line treatment should cream, Vagifem, and Estring. Do you have include the use of vaginal moisturizers and any suggestions to help her severe dryness? lubricants.5 Vaginal moisturizers should be used on a regular basis every 3 days to Commentary by provide a moisture barrier within the vagina and reduce the symptoms of vaginal atrophy. Lisa Astalos Chism, DNP. APRN, NCMP, FAANP Clinical Director, Women’s Vaginal moisturizers typically do not cure Wellness Clinic vaginal atrophy; however, vaginal mois- Sexual Health Counselor turizers containing hyaluronic acid have been and Educator Karmanos Cancer Institute found to improve vaginal lubrication and Adjunct Assistant Professor, symptoms of vaginal atrophy, including Department of Surgery 6 Wayne State University School reducing pain with vaginal penetration. of Medicine

Detroit, Michigan Vaginal lubricants are to be used at the time of vaginal penetration to reduce pain with tudies have shown that vaginal atrophy penetration. Clinicians counseling women S may significantly interfere with a about vaginal lubricants should include a woman’s quality of life, especially in regard discussion that reviews the difference to vaginal dryness and pain with vaginal between water-based and silicone-based penetration.1,2 products.

Remarkably, 20% to 45% of women Oil- and petroleum-based lubricants should experience either decreased lubrication or be avoided because they can damage pain with penetration sometime during condoms and cause vaginal irritation. Water- midlife3; therefore, clinicians who care for based lubricants are safe for use with women during midlife will likely be asked to condoms but may dry out quickly and cause address these concerns. An understanding of more discomfort. Silicone-based lubricants vaginal atrophy as well as modalities to are safe with all condoms, do not absorb into 4 the skin, and may provide longer-lasting and arousal and reverse the physiologic signs comfort because of reduction in friction. of vaginal atrophy, including normalizing vaginal pH. Patients should be counseled that In addition to vaginal moisturizers and intravaginal DHEA has been studied in lubricants, clinicians should discuss vaginal phase 3 clinical trials but is not yet FDA stretching with their patients. Vaginal approved. stretching has been noted to reduce symptoms of vaginal atrophy, including pain Caring for women with vaginal atrophy and with penetration.5 Clinicians may counsel associated symptoms requires clinicians to women about vaginal stretching and use of carefully counsel women regarding all vaginal dilators, including teaching women treatment options. Nonprescriptive modal- how to use vaginal dilators. ities, such as educating women about types of vaginal moisturizers and lubricants, the The literature also has shown that the use of importance of vaginal stretching, and the vaginal stimulation may reduce pain with benefits of vaginal stimulation, should also penetration.7 Vaginal stimulation was shown be reviewed. to increase blood flow to the vagina and improve arousal, which overall reduced the If vaginal estrogen fails to adequately treat symptoms of vaginal atrophy. the symptoms of vaginal atrophy, women may be advised regarding various other Vaginal estrogen in the form of a vaginal prescriptive treatments such as ospemifene tablet, cream, or ring is considered a second- and intravaginal DHEA. A careful review of line therapy for the treatment of vaginal adverse effects and indications should be dryness.5 However, if vaginal estrogen has included. failed, other prescriptive treatment options may be discussed with the patient. References 1. Nappi RE, Kokot-Kierepa M. Vaginal health: insights, views & attitudes (VIVA)—results from an Ospemifene, a selective estrogen receptor international survey. Climacteric. 2012;15(1):36-44. modulator, has been approved by the US 2. Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Food and Drug Administration (FDA) for the Vulvar and vaginal atrophy in postmenopausal treatment of pain with intercourse.8 women: findings from the REVIVE (REal Women’s Ospemifene was shown to improve the Views of Treatment Options for Menopausal Vaginal ChangEs) survey. J Sex Med. 2013;10(7):1790-1799. symptoms of vaginal atrophy, including 3. Lindau ST, Schumm LP, Laumann EO, Levinson W, improving vaginal epithelial tissue and O’Muircheartaigh CA, Waite LJ. A study of sexuality decreasing vaginal pain with penetration.9 and health among older adults in the United States. N Engl J Med. 2007;357(8):762-774. Patients should be counseled that the risks 4. Portman D, Gass ML; Vulvovaginal Atrophy associated with ospemifene include venous Terminology Consensus Conference Panel. thrombus and stroke.8 Ospemifene was not Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the studied in a breast cancer population. International Society for the Study of Women’s Sexual Health and the North American Menopause Intravaginal dehydroepiandrosterone Society. J Sex Med. 2014;11(12):2865-2872. 5. Management of symptomatic vulvovaginal atrophy: (DHEA) has been found to reduce vaginal 2013 position statement of The North American atrophy and significantly improve Menopause Society. Menopause. 2013;20(9):888-902. symptoms.10,11 Intravaginal DHEA used 6. Jokar A, Davari T, Asadi N, Ahmadi F, Foruhari, S. Comparison of the hyaluronic acid vaginal cream and nightly (.5% or 1%) as an intravaginal ovule conjugated estrogen used in treatment of vaginal was shown to improve vaginal lubrication atrophy of menopause women: a randomized 5

controlled clinical trial. Int J Community Based Nurs 10. Labrie F, Archer D, Bouchard C, et al. Intravaginal Midwifery. 2016;4(1):68-78. dehydroepiandrosterone (Prasterone), a physiological 7. Schroder M, Mell LK, Hurteau JA, et al. Clitoral and highly efficient treatment of vaginal atrophy. therapy device for treatment of sexual dysfunction in Menopause. 2009;16(5):907-922. irradiated cervical cancer patients. Int J Radiat Oncol 11. Labrie F, Archer D, Bouchard C. et al. Effect of Biol Phys. 2005;61(4):1078-1086. intravaginal dehydroepiandrosterone (Prasterone) on 8. Soe LH, Wurz GT, Kao CJ, Degregorio MW. libido and sexual dysfunction in postmenopausal Ospemifene for the treatment of dyspareunia women. Menopause. 2009;16(5):923-931. associated with vulvar and vaginal atrophy: potential benefits in bone and breast. Int J Womens Health. Disclosures: Dr. Chism reports consultant/advisory 2013;5:605-611. board for Hologic and JDS Therapeutics and speakers’ 9. Portman DJ, Bachman GA, Simon JA; Ospemifene Study Group. Ospemifene, a novel selective estrogen bureau for JDS Therapeutics. receptor modulator for treating dyspareunia associated with postmenopausal vulvar or vaginal atrophy. Menopause. 2013;20(6):623-630.

What is your preferred treatment for women experiencing severe vaginal dryness even after trying several remedies? Have you discovered any treatments that work especially well? Visit our Member Forum to discuss the April Menopause e-Consult.

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