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Overview

• What is Female Pelvic Medicine & Reconstructive Surgery (FPMRS) /urogynecology?? The Roles of the Patient, Primary Care • Review basics of Provider, and Urogynecologist in Managing Genitourinary Syndrome of Menopause • Define genitourinary syndrome of menopause (GSM) • Discuss the evaluation and treatment of Olivia Cardenas-Trowers, MD April 22, 2021 GSM

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FPMRS/Urogynecology Urogynecology Pelvic organ prolapse Recurrent • Boarded subspecialty of OBGYN and Urinary UTIs retention urology Fecal • Treats female pelvic floor disorders incontinence Overactive Pelvic bladder pain

Urinary incontinence Fistula

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Care Roles Menopause

Patient PCP • Definition: point in time following 1 year of menses cessation • Estradiol <30 pg/mL, FSH 30 mIU/mL • Average age is 51.5 years • Most women can expect to live 1/3rd of life in menopause

FPMRS

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GSM

• Estrogen receptors in , , Late menopause: bladder, urethra, pelvic floor ovarian failure • Definition: menopause + genital estrogen depletion symptoms of dryness, burning, and ( FSH, LH) irritation; sexual symptoms of absent lubrication, dyspareunia, and dysfunction; and urinary symptoms of urgency, dysuria, and recurrent urinary tract infections (rUTIs)

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Vaginal Epithelium Vulvovaginal Layers superficial • Atrophy with thin surface epithelium intermediate • Loss of collagen, adipose tissue, water parabasal retention basal • Decreased ratio of superficial to basal Estrogenized Atrophic cells* • Prone to petechia and bleeding • Vaginal pH > 4.5 • Decreased lactobacilli Three Types (Or Stages) of Vaginal Epithelial Cells • susceptibility to urogenital infections All scored to quantify estrogenization in the Vaginal Maturation Index The Vaginal Maturation Index quantifies the relative proportion of the vaginal parabasal (P), intermediate (I), and superficial (S) cells presented as % P / % I / % S.

LOUISVILLE.EDU Sources: Mills, Histology for Pathologists. 3rd Edition; LWW, 2006. Wheater, Functional Histology. 2nd Edition; Bibbo, 1997

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Vulvovaginal The Maturation Value is a clinical measure of vaginal estrogenization

Maturation Value = 1.0 x % superficial cells + 0.5 x % intermediate cells + 0.0 x % parabasal cells

Potential range: 0 – 100

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Vulvovaginal Urethral caruncle

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Dyspareunia & Sexual Urogenital Changes Dysfunction • Dysuria, urgency, urethral eversion or • 25% of postmenopausal women experience prolapse, and rUTIs dyspareunia • Thinning of urethral and bladder mucosa • Estrogen deficiency diminishes vaginal • Association between declining estrogen lubrication, flow, and vasocongestion levels and incontinence is controversial • Sexual problems, including lack of libido, • Pelvic organ prolapse increases with arousal disorder, and anorgasmia advancing age • Concomittant psychosocial and physiological changes and illnesses

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Evaluation Evaluation

• History • Questionnaires • Vaginal dryness, itching, irritation, • Most Bothersome Symptom (MBS) burning, soreness, discharge • Vulvovaginal Symptom Questionnaire • Dyspareunia, post-coital bleeding (VSQ)* • Urogenital atrophy-specific quality of life • Urinary frequency, urgency, instrument (UGAQoL) nocturia, incontinence, dysuria, • Urogenital Atrophy Questionnaire (UAQ) urinary tract infections • Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire

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VSQ MBS

• During the past week, have you been • Strong urge or need to urinate during the bothered by: day: • Your vulva itching? • Your vulva being irritated? • The appearance of your vulva? • The effects of your vulvar symptoms on your desire to be with people? • Vulvar and/or vaginal dryness: • The effects of your vulvar symptoms on your daily activities? • Are you currently sexually active with a partner?

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Evaluation Treatment

• Exam • Vaginal estrogen!!! • Labial thinning, retraction • Rahn D, et al. Vaginal estrogen for • Decreased genital hiatus genitourinary syndrome of menopause: a • Atrophy: pallor, petechiae, friability, systematic review. Obstet Gynecol, 2014. vaginal dryness, caruncle, thinning of • ACOG Practice Bulletin No. 141: vaginal epithelium, loss of rugae, Management of menopausal symptoms. decreased elasticity Obstet Gynecol, 2014 • Cytology -> vaginal maturation value • pH 5.5-6.0 • Scoring systems

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Treatment Treatment

• Rahn D, et al. Vaginal estrogen for • ACOG Practice Bulletin No. 141: genitourinary syndrome of menopause: a Management of menopausal symptoms. systematic review. Obstet Gynecol, 2014 Obstet Gynecol, 2014 • Improved dryness, dyspareunia, urinary • Estrogen therapy effectively alleviates atrophic urgency, frequency, SUI and UUI, rUTIs vaginal symptoms related to menopause. Local • Supported safety of vaginal estrogen therapy is advised for the treatment of women • Nonhormonal moisturizers are a beneficial with only vaginal symptoms (Level A) alternative for those with few or minor • Nonestrogen water-based or silicone-based atrophy-related symptoms and in patients at vaginal lubricants and moisturizers may risk for estrogen-related neoplasia alleviate vaginal symptoms related to menopause (Level B)

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Treatment Treatment • Farrell R. ACOG Committee Opinion No. • Vaginal estrogen 659: The Use of Vaginal Estrogen in • 17-B estradiol cream 0.01 mg/g Women With a History of Estrogen- (Estrace ®) 0.5g/d x2/wk Dependent Breast Cancer. Obstet Gynecol, • Conjugated estrogen cream 0.625 mg/g 2016 (Premarin ®) 0.5g/d x 2/wk • Data DO NOT show an increased risk of • Estradiol vaginal 10 mcg tablet (Vagifem cancer recurrence among women currently ®, Yuvafem ®) x 2/wk undergoing treatment for breast cancer or • 17-B estradiol 2 mg ring (Estring ®) those with a personal history of breast releases 7.5 mcg/d for 90 days* cancer who use vaginal estrogen to relieve • Compounding pharmacies*** GSM symptoms

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Treatment Treatment

• Nonhormonal approaches are the first- • Alternatives line choices for managing GSM • Water-based lubricants (e.g., KY jelly) symptoms experienced by women • Polymer-based lubricants (e.g., during or after treatment for breast Replens) cancer • Oil-based lubricants • Vaginal estrogen should be reserved for • Mineral oil those patients who are unresponsive to • Coconut oil nonhormonal remedies • Olive oil

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Dyspareunia “Vaginal rejuvenation”

• Ospemifene (SERM, Osphena®) • 60 mg PO tablet QD • Side effects (SE): hot flushes, UTIs • Prasterone (DHEA, Intrarosa ®) • 6.5 mg intravaginal application nightly • SE: increased discharge, ASCUS pap

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“Vaginal rejuvenation” Vaginal rejuvenation

• Laser therapy • Laser therapy • FDA warning on July 30, 2018 • Fractional microablative carbon- • Not for vaginal cosmesis dioxide laser therapy (e.g., MonaLisa • Fractional microablative carbon-dioxide Touch®) laser therapy (e.g., MonaLisa Touch®) • Improved vascularity, collagen • Erbium laser (e.g., Er:YAG) production, and epithelial thickness • Dynamic quadripolar radiofrequency (DQRF) lasers

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MonaLisa Touch

https://www.youtube.com/watch?v=7bOai FCBl6U

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Vaginal rejuvenation Vaginal rejuvenation

• Laser therapy • Laser therapy • Erbium laser (e.g., Er:YAG) • Dynamic quadripolar radiofrequency • Precise impulses are released to (DQRF) lasers raise the temperature of vaginal • Thickening and rearrangement of tissue, stimulating remodeling of collagen and elastin fibers • Improvement in vaginal laxity, sexual collagen satisfaction, dysuria, and incontinence • Improves vaginal dryness and • Lasers are an attractive nonhormonal dyspareunia up to 24 weeks after therapy option for GSM but more data treatment needed

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rUTIs rUTIs

• Brubaker L, et al. American • Exam +/- cystoscopy, imaging Urogynecologic Society Best-Practice • Suppressive therapy (3-6 months) Statement: Recurrent Urinary Tract • Antibiotics Infection in Adult Women. Female Pelvic • Nitrofurantoin monohydrate/ Medicine & Reconstructive Surgery, 2018 macrocrystals (Macrobid®) 50-100 • Definition: At least 2 (+) cultures in 6 mg PO QHS months or 3 (+) in 12 months • Trimethoprim/sulfamethoxazole (Bactrim®) 40/200 mg PO QD • Trimethoprim 100 mg PO QD

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OAB/UI OAB/UI

• International Continence Society (ICS) • 1st line: behavioral/lifestyle modifications • OAB: “Urinary urgency, usually • 2nd line: medications accompanied by increased daytime • Oxybutynin ER (Ditropan XL®) 5-20 mg frequency and/or nocturia, with urinary PO QD incontinence (OAB-wet) or without (OAB- • Mirabegron (Myrbetriq®) 25-50 mg PO dry), in the absence of urinary tract QD infection or other detectable disease” • 3rd line: intradetrusor injection of botox, • UI: “Complaint of involuntary loss of posterior tibial nerve stimulation (PTNS), urine” sacral neuromodulation (Interstim®) • History, physical (CST), +/- UDS

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2nd Line 3rd Line

***Mirabegron (Myrbetriq®) 25-50 mg PO QD***

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Summary Summary

• Menopause: point in time following 1 • Urogynecologists treat female pelvic year of menses cessation floor disorders • GSM: menopause + genital symptoms • All team members are important in of dryness, burning, and irritation; managing GSM sexual symptoms of absent lubrication, • The PCP can manage uncomplicated dyspareunia, and dysfunction; and GSM urinary symptoms of urgency, dysuria, • Consult with urogynecologist if patient’s and rUTIs history complicated and/or symptoms not improving

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Summary Summary

• History (questionnaires) + physical • OAB/UI • Treat w/ vaginal estrogen!**** • 1st line: behavioral/lifestyle • Nonestrogen treatment for women w/ modifications BRCA • 2nd line: medications • rUTIs: At least 2 (+) cultures in 6 • 3rd line: botox, PTNS, sacral months or 3 (+) in 12 months neuromodulation (Interstim®) • Estrogen +/- prophylactic antibiotics • Lasers are NOT FDA-approved for GSM

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Resources References

1. Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. eds. Williams Gynecology, 3e New York, NY: McGraw-Hill. 2. Rahn, D.D., et al., Vaginal estrogen for genitourinary syndrome of menopause: VoicesForPFDs.org a systematic review. Obstet Gynecol, 2014. 124(6): p. 1147-56. 3. ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol, 2014. 123(1): p. 202-16. 4. Farrell, R., ACOG Committee Opinion No. 659: The Use of Vaginal Estrogen in Women With a History of Estrogen-Dependent Breast Cancer. Obstet Gynecol, 2016. 127(3): p. e93-6. 5. Gandhi, J., et al., Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol, 2016. 215(6): p. 704-711. 6. Brubaker, L., et al., American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women. Female Pelvic Medicine & Reconstructive Surgery, 2018. 24(5): p. 321-335. 7. Portman, D.J., S.R. Goldstein, and R. Kagan, Treatment of moderate to severe AUGS.org dyspareunia with intravaginal prasterone therapy: a review. Climacteric, 2018: p. 1-8.

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