Is Vaginal Estrogen Safe If I had Cancer or a Heart Attack? 27th Annual Primary Health Care of Women Conference Samantha Kempner, MD Assistant Professor Department of Obstetrics and Gynecology Michigan Medicine Please consider the environment before printing this PowerPoint Learning Objectives Describe prevalence and impact of vaginal atrophy for menopausal women Review evidence-based approach to management of vaginal menopausal symptoms Discuss safety of vaginal estrogen for patients with cardiovascular disease or breast cancer Clinical Presentation 52yo G3P2012 calls office with 3rd complaint of dysuria in past 2 months. First time urine culture was obtained and showed E.Coli, second time no improvement on empiric antibiotics, third time culture negative. DDx: ?? Atrophy Sex Med. 2013 Dec: 1 (2): 44-53 D D X Please consider the environment before printing this PowerPoint Clin Med Insights Reprod Health. 2014 Jun 8;8:23-30. Sex Med. 2013 Dec: 1 (2): 44-53 Vulvovaginal Atrophy GSM (genitourinary syndrome of menopause) Impacts up to 85% of menopausal women Up to 70% of women do not discuss condition with a healthcare provider Symptoms include: • Vaginal or vulvar dryness • Dyspareunia • Discharge • Worsening Incontinence • Itching • UTIs Rx: Non-Hormonal Hormonal Other Medications Vaginal lubricants (use Local low-dose vaginal Prasterone (Vaginal DHEA) during intercourse) estrogen is the most • FDA approved vaginal Replens, Vagisil effective treatment for suppository Moisturizer, KY moderate to severe GSM: • MOA likely local Liquibeads aromatization 2 wk daily induction Vaginal moisturizers followed by 2x/wk Ospemifene (SERM) (routine use 2-3x/wk) • Taken orally water based (Astroglide, KY) • Cream (Conjugated 0.5- • Possible increased risk silicone based 2g/daily or Estradiol in hot flashes or oil based 2g.daily) thromboembolism • Tablets (Estradiol 25mcg daily) • Ring (Estring 0.05mg/d) Rx: Non-Hormonal Hormonal Other Medications Vaginal lubricants (use Local low-dose vaginal Prasterone (Vaginal DHEA) during intercourse) estrogen is the most • FDA approved vaginal Replens, Vagisil effective treatment for suppository Moisturizer, KY moderate to severe GSM: • MOA likely local Liquibeads aromatization No difference in 2 wk daily induction Vaginalefficacy moisturizers between followed by 2x/wk Ospemifene (SERM) various(routine preparationsuse 2-3x/wk) • Taken orally water based (Astroglide, KY) • Cream (Conjugated 0.5- • Possible increased risk silicone based 2g/daily or Estradiol in hot flashes or (Cochraneoil based Review) 2g.daily) thromboembolism • Tablets (Estradiol 25mcg daily) • Ring (Estring 0.05mg/d) Benefits of (Systemic) MHT: - Decreased vasomotor Risks of (Systemic) MHT: symptoms - Decreased risk of - Increased risk of CHD Colorectal CA - Increased risk of stroke - Decreased risk of Hip - Increased risk of breast Fractures cancer - Increased risk of endometrial cancer (if unopposed estrogen) Safety of Local (Vaginal) Estrogen Serum estradiol levels on low-dose preparations are only slightly higher than the average level for postmenopausal women (7-8pg/mL to 11-23pg/mL) “Lowest-Dose” = 4mcg tablet or 7.5mcg/day ring showed no increase Maximal doses of various creams may produce premenopausal plasma levels of estradiol Severe atrophy may impact ( ) systemic absorption So… “Is Vaginal Estrogen safe if I had breast cancer or a heart attack?” Women with a history of BREAST CANCER Vaginal/Menopausal complaints are common Nonhormonal methods should be considered first-line therapy for vaginal atrophy for women with a history of hormone-sensitive breast cancer (Level C) Short-term use of hormonal methods may be considered after other options have failed, following consultation with their oncologist Women with a history of BREAST CANCER • Single study of low-dose vaginal estrogen did not show increased risk of cancer recurrence • More likely to be safe in patients on Tamoxifen (vs. patients on Aromatase Inhibitors) • Remember to ask about “lowest dose” preparations • Prasterone unlikely to effective for patients using Aromatase Inhibitors • Ospemifene potentially has protective effect in preclinical studies Women with a history of HEART ATTACK Rates of systemic absorption VERY low* * If used correctly (lowest with ring and pill) Large prospective cohort study (WHI-OS) found NO increased risk of cardiovascular disease and cancer in post- menopausal women using vaginal estrogens Take Home Points Genitourinary syndrome of menopause (vaginal atrophy) is common and can be treated with lubricants, moisturizers, or vaginal estrogen therapy Systemic absorption of vaginal creams, pills, and rings is very low (lowest for Estring and Vagifem) Consult with patient’s oncologist before starting vaginal estrogen in patient with history of ER/PR+ breast cancer, more likely to be safe if on tamoxifen and less likely to be safe if on aromatase inhibitor Safe in patients with history of CHD Resources ACOG Practice Bulletin 141, Management of Menopausal Symptoms (January 2014, reaffirmed 2018) ACOG Practice Bulletin 126, Management of Gynecologic Issues in Women With Breast Cancer (March 2012, reaffirmed 2016) Treatment of genitourinary syndrome of menopause (www.uptodate.com) Menopausal hormone therapy: Benefits and risks (www.uptodate.com) Castelo-Branco C et al. Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas 2005; 52(suppl 1): S46-52). Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016 Aug 31 (8). Breast Cancer, Endometrial Cancer, and Cardiovascular Events in Participants who used Vaginal Estrogen in the Women’s Health Initiative Observational Study. Menopause. 2018 Jan: 25(1):11-20. Please consider the environment before printing this PowerPoint Questions? Samantha Kempner, MD [email protected] Please consider the environment before printing this PowerPoint.