Vulvovaginal atrophy: an undertreated disorder
James A. Simon, MD, CCD, NCMP, IF, FACOG
Clinical Professor
George Washington University School of Medicine
President and Medical Director
IntimMedicine Specialists®
Washington, District of Columbia
Estrogen and androgen deficiency from menopause causes vulvovaginal and urogenital changes and a plethora of symptoms, most prominently dyspareunia. The nomenclature recently has been expanded to genitourinary syndrome of menopause (GSM).
Reproductive hormone deficiency leads to vulvar and vaginal thinning, loss of rugal folds, diminished elasticity, diminished vaginal glycogen, and decreased acidity (increased pH) of the vaginal secretions, thereby reducing the vagina’s natural defenses.1
Few women with GSM report their symptoms to their health care professionals,2 and conversely most health care professionals do not sufficiently query patients or inform them of their therapeutic options. Furthermore, class label-ling of most available treatments has emphasized unsubstantiated risks3 (ie, increased endometrial cancer, stroke, myocardial infarction [MI], deep vein thrombosis [DVT], pulmonary embolism [PE], probable dementia, and invasive breast cancer), thus resulting in only 7% of symptomatic women using any pharmacologic agent.4
CLINICAL DEVELOPMENT AND FDA APPROVAL
Until recently, all available vulvovaginal atrophy (VVA)/GSM treatments were systemic or local steroid hormones (estradiol, conjugated estrogens, dehydroepiandrosterone [DHEA]). Fear of estrogens from the “class labeling” and the nuisance of vaginal administration undermines utilization for some women.
Ospemifene, a third-generation selective estrogen receptor modulator (SERM) originally developed for osteoporosis, has estrogenic effects on bone, lipids, and vaginal tissue while remaining antiestrogenic or neutral in the breast and endometrium, respectively.5 Multiple phase 3, placebo-controlled, clinical trials6,7 resulted in US Food and Drug Administration (FDA) approval for moderate to severe dyspareunia from vulvovaginal atrophy of menopause. The American College of Obstetricians and Gynecologists (ACOG) endorsed ospemifene (Level A evidence) as first-line therapy for dyspareunia noting absent endometrial stimulation.8 The most common adverse reactions in these ospemifene trials versus placebo were hot flashes and sweating (9.1% vs 3.2%), and muscle spasms (3.2% vs 0.9%), mostly leg cramps.6,7 Only 1% of participants discontinued due to hot flashes, and there were no differences in rates of bleeding or breast tenderness.
Ospemifene, an oral SERM for dyspareunia of menopause: Is it being underutilized?
This activity was planned for obstetricians and gynecologists and women’s health care providers.
Activity Information
Date of Original Release: February 1, 2019
Date Credits Expire: January 31, 2022
This activity is supported by an educational grant from Duchesnay.
CME credit is awarded upon successful completion of the posttest and evaluation.
To access posttest and evaluation, visit www.worldclasscme.com/nonestrogenoraltherapy
World Class CME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
World Class CME designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Faculty
Program Director
Steven R. Goldstein, MD, CCD, NCMP, FACOG
Professor of Obstetrics and Gynecology
New York University School of Medicine
Director of Gynecological Ultrasound
Co-Director of Bone Densitometry and Body Composition
Department of Obstetrics and Gynecology
New York University Medical Center
New York, New York
Author
James A. Simon, MD, CCD, NCMP, IF, FACOG
Clinical Professor
George Washington University School of Medicine
President and Medical Director
IntimMedicine Specialists®
Washington, District of Columbia
Learning Objectives
At the conclusion of this activity, the participant will be able to:
- Understand the pathophysiology of dyspareunia due to vulvovaginal atrophy (VVA) of menopause.
- Appreciate the underrecognition and undertreatment of dyspareunia due to VVA.
- Discuss efficacy results of randomized placebo controlled trials of ospemifene.
- Understand the adverse events associated with ospemifene.
- Appreciate the safety data of ospemifine as well as other oral selective estrogen receptor modulators and estrogens.
Conflict of interest disclosure
Steven R. Goldstein, MD
Consultant: Cook Ob/Gyn, Cooper Surgical, IBSA, PfizerGYN Advisory Board: AbbVie, Allergan, AMAG, Shionogi, TherapeuticsMD
Speakers Bureau: AMAG, Duchesnay, TherapeuticsMDEquipment Loan: GE Ultrasound
James A. Simon, MD
Advisory Board/Consultant: AbbVie, Inc. (North Chicago, IL), Allergan, Plc (Parsippany, NJ), AMAG Pharmaceuticals, Inc. (Waltham, MA), Amgen (Thousand Oaks, CA), Ascend Therapeutics (Herndon, VA), Bayer HealthCare Pharmaceuticals Inc. (Whippany, NJ), CEEK Enterprises, LLC. (Cambridge, MA), Covance Inc., (Princeton, NJ), Millendo Therapeutics, Inc. (Ann Arbor, MI), Mitsubishi Tanabe Pharma Development America, Inc. (Jersey City, NJ), ObsEva SA (Geneva, Switzerland), Radius Health, Inc. (Waltham, MA), Sanofi S.A. (Paris, France), Sebela Pharmaceuticals, Inc. (Roswell, GA), Shionogi Inc. (Florham Park, NJ), Symbiotec Pharmalab (Indore, India), TherapeuticsMD (Boca Raton, FL), Valeant Pharmaceuticals (Laval, Canada) Speaker: AMAG Pharmaceuticals, Inc., Duchesnay USA (Rosemont, PA), Novo Nordisk (Bagsvrerd, Denmark), Shionogi Inc., Valeant Pharmaceuticals (Laval, Canada)Grants/Research: AbbVie, Inc., Allergan, Plc, Agile Therapeutics (Princeton, NJ), Bayer Healthcare LLC. (Tarrytown, NY), Dornier MedTech (Munich, Germany), Endoceutics, Inc. (Quebec, Canada), GTx, Inc. (Memphis, TN), Ipsen (Paris, France), Myovant Sciences (Basel, Switzerland), New England Research Institute, Inc. (Watertown, MA), ObsEva SA (Geneva, Switzerland), Palatin Technologies (Cranbury, NJ), Symbio Research, Inc. (Port Jefferson, NY), TherapeuticsMD, Tissue Genesis (Honolulu, HI) Stock Shareholder: Pharmaceuticals (Columbus, OH)
No disclosures to declare
Heidi M. Wilson, Course Director
References
- Wilson JD, Lee RA, Balen AH, Rutherford AJ. Bacterial vaginal flora in relation to changing oestrogen levels. Int J STD AIDS. 2007;18(5):308-311.
- Parish SJ, Nappi RE, Krychman ML, et al. Impact of vulvovaginal health on postmenopausal women: a review of surveys on symptoms of vulvo-vaginal atrophy. Int J Womens Health. 2013;5:437-447.
- Crandall CJ, Hovey KM, Andrews CA, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative Observational Study. Menopause. 2018;25(1):11-20.
- Kingsberg SA, Krychman M, Graham S, et al. The Women’s EMPOWER Survey: Identifying Women’s Perceptions on Vulvar and Vaginal Atrophy and Its Treatment. J Sex Med. 2017;14(3):413-424.
- Berga SL. Profile of ospemifene in the breast. Reprod Sci. 2013;20(10):1130-1136.
- Bachmann GA, Komi JO; Ospemifene Study Group. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010;17(3):480-486.
- Portman DJ, Bachmann GA, Simon JA; 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.
- ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol. 2014;123(1):202-216.