Innovations in the Treatment of Dyspareunia

David J. Portman, MD
Director Emeritus, Columbus Center for Women’s Health Research
Adjunct Instructor of Obstetrics and Gynecology
Ohio State University
Columbus, OH

INTRODUCTION

The aging of the US population has led to a substantial increase in the number of postmenopausal women. Currently, there are an estimated 64 million women in the United States who are postmenopausal, and that number is estimated to reach 1.1 billion women world-wide by 2025.¹ Diminishing hormonal levels associated with the menopausal transition began years earlier, and can result in vasomotor symptoms (VMS), vulvovaginal atrophy (VVA), urinary symptoms, and dyspareunia. At least two-thirds of menopausal women experience VMS, which are often considered the “cardinal symptoms of menopause.”² VMS, which include hot flashes and night sweats, can have a significant effect on quality of life, and lead many women to seek treatment for their symptoms.³ VMS typically are self-limiting, last for 4 years, on average, before spontaneously resolving, and are readily associated with menopause by both women and their health care provider (HCP).^3,4 However, in a number of women, VMS can last 10 years or longer. In contrast, the symptoms of VVA, which result from thinning and inflammation of the vaginal walls, are chronic and progressive. VVA can cause vaginal dry-ness, itching, and soreness, and often leads to pain with sex and sexual dysfunction. Although at least 32 million women experience symptoms of VVA and/or dyspareunia, because these symptoms often do not manifest in and around the time of the last menses, a majority of these women are unaware that their symptoms are the result of underlying vulvovaginal and hormonal changes stemming from menopause.^1,5 The overwhelm-ing majority of US women—approximately 93%—fail to seek treatment for VVA or dyspareunia.¹

Dyspareunia Associated with Vulvovaginal Atrophy: Innovations in Counseling, Diagnosis, and Management

This activity is designed to meet the educational needs of the obstetrician and gynecologist, family physician, internal medicine physician, physician assistant, nurse practitioner, and certified nurse midwife.

Start CME/CE Activity

Supported by an educational grant from:

AMAG Pharmaceuticals Inc.

Activity Information

Expired

Date of Original Release: May 7, 2018
Date Credits Expire: May 7, 2019

EXPIRED

FACULTY

Murray A. Freedman, MS, MD, FACOG, IF
Clinical Professor of Obstetrics
and Gynecology
Medical College of Georgia
Augusta, GA

Sheryl A. Kingsberg, PhD
Professor of Reproductive Biology
and Psychiatry
Case Western Reserve University
School of Medicine
Cleveland, OH

David J. Portman, MD
Director Emeritus, Columbus Center
for Women’s Health Research
Adjunct Instructor of Obstetrics
and Gynecology
Ohio State University
Columbus, OH

Disclosure of Conflicts of Interest:
In accordance with the ACCME Standards for Commercial Support, The Omnia-Prova Education Collaborative (TOPEC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. TOPEC resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.

Faculty
Murray A. Freedman, MS, MD, FACOG, IF Consulting Fees: AMAG Pharmaceuticals; Commercial Interest Speakers Bureau: Valeant Pharmaceuticals; Contracted Research: Procter and Gamble

Sheryl A. Kingsberg, PhD Consulting Fees: AMAG Pharmaceuticals, Emotional Brain, Palatin, Valeant Pharmaceuticals; Commercial Interest Speakers Bureau: AMAG Pharmaceuticals, Palatin, Valeant Pharmaceuticals; Contracted
Research: Palatin

David J. Portman, MD Consulting Fees: AMAG Pharmaceuticals, Palatin, Valeant Pharmaceuticals; Commercial Interest Speakers Bureau: AMAG Pharmaceuticals, Palatin, Valeant Pharmaceuticals; Contracted Research: Endoceutics

Reviewers/Planners/Authors:
Sean T. Barrett has nothing to disclose.
Carole Drexel, PhD, CHCP has nothing to disclose.
Amanda Hilferty has nothing to disclose.
Ashley Rosenthal has nothing to disclose.
Robert Schneider, MSW has nothing to disclose.

LEARNING OBJECTIVES

After participating in this educational activity, participants should be better able to:

Define vulvovaginal atrophy (VVA), and genitourinary syndrome (GSM) and their impact on post-menopausal dyspareunia
Identify the factors, both clinician-based and patient-based, that may inhibit diagnosis of dyspareunia
Describe clinician counseling approaches to facilitate a discussion with patients about their symptoms
Discuss the benefits and risks of innovative therapeutic interventions indicated for the management of menopause-related dyspareunia

ACCREDITATION AND CREDIT DESIGNATION STATEMENTS:

The Omnia-Prova Education Collaborative, Inc. is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The Omnia-Prova Education Collaborative, Inc. designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The posttest and evaluation of this activity may be taken online by visiting www.omniaeducation.com/dyspareunia. CME credit may also be claimed by faxing the posttest/evaluation to 215.358.0556. A copy of the posttest/evaluation may also be mailed to Omnia Education 500 Office Center Drive, Suite 300 Fort Washington, PA 19034.

PROVIDER

Omnia Education has a core focus on women’s health and the ways in which diseases and conditions impact the female patient. That unique focus has transformed the CME learning environment for healthcare professionals nationwide. We impact thousands of clinicians annually, many of whom return each year for clinical updates and connectivity with regional peers.

COMMERCIAL SUPPORT

This activity is supported by an independent educational grant from AMAG Pharmaceuticals Inc.

Disclaimer
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of TOPEC and Omnia Education. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of Omnia Education you are subject to the terms and conditions of use, including copyright and licensing restriction, of that site.

Reproduction Prohibited
Reproduction of this material is not permitted without written permission from the copyright owner.

References

Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women’s VIews of Treatment Options for Menopausal Vaginal ChangEs) Survey. J Sex Med. 2013;10(7):1790-1799.
Thurston RC, Joffe H. Vasomotor symptoms and menopause: find-ings from the Study of Women’s Health Across the Nation. Obstet Gynecol Clin North Am. 2011;38(3):489-501.
Umland EM, Falconieri L. Treatment options for vasomotor symp-toms in menopause: focus on desvenlafaxine. Int J Women’s Health. 2012;4:305-319.
Avis NE et al JAMA Intern Med. 2015 Apr;175(4):531-9.
Krychman M, Graham S, Bernick B, et al. The Women’s EMPOWER Survey: Women’s knowledge and awareness of treatment options for vulvar and vaginal atrophy remains inadequate. J Sex Med. 2017;14(3):425-433.
REVEAL. REvealing Vaginal Effects At mid-Life: Surveys of post-menopausal women and health care professionals who treat postmenopausal women. Madison, NJ: Wyeth; 2009.
Simon JA, Kokot-Kierepa M, Goldstein J, Nappi RE. Vaginal health in the United States: results from the Vaginal Health: Insights, Views & Attitudes survey. Menopause. 2013;20(10):1043-1048.
Simon JA, Nappi RE, Kingsberg SA, et al. Clarifying Vaginal Atrophy’s Impact on Sex and Relationships (CLOSER) survey: emotional and physical impact of vaginal discomfort on North American postmenopausal women and their partners. Menopause. 2014;21(2):137-142.
Thomas HN, Hess R, Thurston RC. Correlates of sexual activity and satisfaction in midlife and older women. Ann Fam Med. 2015;13(4):336-342.
Vaginal and vulvar comfort: lubricants, moisturizers, and low-dose vaginal estrogen. Pepper Pike, OH: The North American Menopause Society; 2013. Available at http://www.menopause.org/for-women/sexual-health-menopause-online/effective-treatments-for-sexual-problems/vaginal-and-vulvar-comfort-lubricants-moisturizers-and-low-dose-vaginal-estrogen. Accessed February 14, 2018.
Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006;18(4):CD001500.
Goldstein I. Recognizing and treating urogenital atrophy in postmeno-pausal women. J Womens Health (Larchmt). 2010;19(3):425-432.
Minkin MJ, Maamari R, Reiter S. Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy. Int J Womens Health. 2013;5:133-139.
Palma F, Xholli A, Cagnacci A; the writing group of the AGATA study. Management of vaginal atrophy: a real mess. Results from the AGATA study. Gynecol Endocrinol. 2017;33(9)702-707.
Gandhi J, Chen A, Dagur G, et al. Genitourinary syndrome of menopause:xJason GandhiSearch for articles by this author an over-view of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016;215(6):704-711.
Edwards D, Panay N. Treating vulvovaginal atrophy/genitourinary syndrome of menopause: how important is vaginal lubricant and moisturizer composition? Climacteric. 2016;19(2):151-161.
Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril. 1994;61(1):178-180.
Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause. 2010;17(1):194-203.
Management of symptomatic vulvovaginal atrophy: 2013 posi-tion statement of The North American Menopause Society. Menopause. 2013;20(9):888-902.
Notelovitz M, Mattox JH. Suppression of vasomotor and vulvovaginal symptoms with continuous oral 17beta-estradiol. Menopause. 2000;7(5):310-317.
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):1132-1138.
Estrogen vaginal. Bethesda, MD: National Institutes of Health, National Library of Medicine; 2016 July. Available at http://www.nlm.nih.gov/medlineplus/druginfo/meds/a606005.html. Accessed February 14, 2018.
Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999-2010. Obstet Gynecol. 2012;120(3):595-603.
MacBride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc. 2010;85(1):87-94.
Bachmann G, Lobo RA, Gut R, et al. Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Obstet Gynecol. 2008;111(1):67-76.
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):83-93.
Buckler H, al Azzawi F. The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women. Brit J Obstet Gynecol. 2003;110(8):753-759.
Pinkerton JV, Thomas S. Use of SERMs for treatment in postmeno-pausal women. J Steroid Biochem Mol Biol. 2014;142:142-154.
Voipio SK, Komi J, Kangas L, et al. Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas. 2002;43(3):207-214.
Bachmann GA, Komi JO. Ospemifene effectively treats vulvovagi-nal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010;17(3):480-486.
Portman DJ, Bachmann G, Simon J; The Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623-630.
Portman D, Palacios S, Nappi RE, Mueck AO. Ospemifene, a non-oestrogen selective oestrogen receptor modulator for the treat-ment of vaginal dryness associated with postmenopausal vulvar and vaginal atrophy: a randomised, placebo-controlled, phase III trial. Maturitas. 2014;78(2):91-98.
Constantine GD, Archer DF, Pollycove R, et al. Ospemifene’s effect on vasomotor symptoms: a post hoc analysis of phase 2 and 3 clinical data. Menopause. 2016;23(9):957-964.
Simon J, Portman D, Mabey RG, Jr. Long-term safety of ospemi-fene (52-week extension) in the treatment of vulvar and vaginal atrophy in hysterectomized postmenopausal women. Maturitas. 2014;77(3):274-281.
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.
Osphena (ospemifene ) [package insert]. Florham Park, NJ: Shion-ogi Inc; 2015.
Simon JA, Lin VH, Radovich C, Bachmann GA. 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):418-427.
Goldstein SR, Bachmann GA, Koninckx PR, et al. Ospemifene 12-month safety and efficacy in postmenopausal women with vulvar and vaginal atrophy. Climacteric. 2014;17(2):173-182.
Labrie F, Archer DF, Koltun W, et al; VVA Prasterone Research Group Collaborators. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016;23(3):243-56.
Portman DJ, Labrie F, Archer DF; other participating members of VVA Prasterone Group. Lack of effect of intravaginal dehydroepi-androsterone (DHEA, prasterone) on the endometrium in post-menopausal women. Menopause. 2015;22(12):1289-1295.
Baxendale PM, Reed MJ, James VH. Inability of human endome-trium or myometrium to aromatize androstenedione. J Steroid Biochem. 1981;14(3):305-306.
Ke Y, Gonthier R, Simard JN, et al. Serum steroids remain within the same normal postmenopausal values during 12-month intra-vaginal 0.50% DHEA. Horm Mol Biol Clin Invest. 2015;24(3):117-129.
Intrarosa (prasterone) [package insert]. Waltham, MA: Endoceutics Inc.; April 2017.
Archer DF, Labrie F, Bouchard C, et al; VVA Prasterone Group Collaborators. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause. 2015;22(9):950-963.
Bouchard C, Labrie F, Archer DF, et al. Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atro-phy. Climacteric. 2015;18(4):590-607.

Disclosures