Genitourinary Syndrome of Menopause (GSM) IUGA Workshop Linda Cardozo Professor of Urogynaecology King’s College Hospital, London Genitourinary Syndrome of Menopause (GSM) Linda Cardozo Disclosures: Atlantic Therapeutics, Boston Scientific, DEKA, Fotona, Merck GSM • Genitourinary Syndrome of Menopause (GSM) - Previously known as vulvovaginal / urogenital atrophy • Collection of signs and symptoms associated with a decrease in oestrogen and other sex steroids involving changes to the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra and bladder • Symptoms include - Dryness - Burning - Irritation - Sexual symptoms of lack of lubrication, discomfort or pain, and impaired function - LUTS: urgency, dysuria and recurrent urinary tract infections Consensus on Vaginal Atrophy Terminology Portman & Gass 2014 Ageing Population • Life expectancy for women in Europe is 84yrs and natural age of menopause is 51yrs – 40% of life postmenopausal • In Jan 2019 there were 3800 million women worldwide of which 266 million were over 65 years United Nations Department of Economic and Social Affairs: Population Division • The proportion of >65 yrs will double from 7.8% to 14.7% between 2010 and 2040 • The number of older people will increase from 530 million in 2010 to 1.3 billion in 2040 US Census Bureau, 2010 Prevalence Postmenopausal women • 40% have symptoms of urogenital atrophy Bachmann 2000 • Vaginal dryness in 27 - 85% • Dyspareunia in 32 - 41% • Urinary tract infection (UTI) in 4 - 15% • 40% on systemic HRT have persistent vaginal dryness • Only a third seek help Johnston 2004 Nappi et al 2017 Views and Attitudes Towards Vaginal Health (VIVA) 3520 postmenopausal women, 55-65 yrs • 1578 (45%) experienced vaginal discomfort Of these: • 83% experienced vaginal dryness • 42% had pain during intercourse • 30% had involuntary urination • 27% experienced soreness • 26% suffered from itching • 14% described burning • 11% had pain when touching the vagina Nappi et al 2011 Prevalence • 747 women aged 40-55 • Vaginal atrophy was diagnosed in 36.8% • 19.2% of 40-45 year olds, 53.8% of 52-55 year olds • 64% reported vaginal dryness • 54.5% reported dyspareunia • Other common symptoms reported were itching, burning and dysuria • Most signs and symptoms showed an age related increase in frequency and intensity Cagnacci 2019 GSM: REVIVE Study European REal Women’s VIews of Treatment Options for Menopausal Vaginal ChangEs 3768 Women • 50% suffered vaginal dryness in last month with an overall prevalence of 75 - 80% • 75% of women say that GSM interferes with their enjoyment of sexual intercourse • Despite this only 25% of British women are receiving treatment • Most common treatment was topical OTC preparations • Primary reason for not starting treatment was that their symptoms were not bothersome enough • Thoughts around the disadvantages of treatment differed from side effects to how messy preparations were and how much they cost Nappi et al 2017 Pathophysiology • Vagina and lower urinary tract have common embryological origin • Hypoestrogenism has both vulvovaginal and urological effects • Urogenital tissue receptors are dependent on endogenous oestrogen levels to maintain normal physiology • Number of receptors decrease in postmenopausal women but never disappear • In presence of exogenous oestrogen receptors can be replenished Gandhi et al 2016 Urogenital Ageing • Late manifestation of the menopause (>10 years after last menstrual period) • Incidence increases with age • Under recognised, inappropriately treated • May take long term replacement therapy (>1 year) to reverse the changes Urogenital changes after menopause Physiological changes Anatomical changes • Fewer blood vessels • Labia minora thin & • Reduced vaginal blood regress flow • Introitus retracts • Reduced collagen content • Hymenal carunculae • Decreased elastin involute • Decreased flexibility • Urethral meatus appears • Decreased vaginal tissue prominent relative to strength introitus • Diminished lubrication • Increased vaginal pH • Change in vaginal flora • Loss of lactobacilli Portman 2014 Genitourinary Syndrome of Menopause Symptoms Signs • Genital dryness • Decreased moisture • Decreased lubrication with sexual • Decreased elasticity activity • Labia minora resorption • Discomfort or pain with sexual • Pallor/erythema activity • Loss of vaginal rugae • Post-coital bleeding • Tissue fragility/fissures/petechiae • Decreased arousal, orgasm, • Urethral eversion or prolapse desire • Loss of hymenal remnants • Irritation /burning /itching of vulva • Prominence of urethral meatus or vagina • Introital retraction • Dysuria • Recurrent urinary tract infections • Urinary frequency/urgency Portman 2014 GSM Risk factors • Menopause (decreased ovarian function) • Premature menopause / ovarian failure • Surgical menopause - bilateral oophorectomy • Postpartum loss of placental oestrogen • Elevated prolactin level during lactation • Absence vaginal childbirth • Decreased frequency and abstinence sexual intercourse • Radiation • Chemotherapy • Autoimmune disorder • Cigarette smoking • Alcohol abuse • Lack of exercise Medication • Selective Oestrogen Re-uptake Modulators (SERMS) • Tamoxifen.. • Aromotase Inhibitors • Letrazole.. • Danazol • Medroxyprogesterone • GnRH analogues • Zoladex • Prostap LUT: Effect of Ageing Postmenopausal bladder changes • Capacity decreases • Compliance decreases • Post void residual increases • Glycosaminoglycan layer thins • Ability to initiate or suppress detrusor contractility impaired LUT: Effect of Ageing Postmenopausal urethral changes • Epithelium thins • Blood flow and vascular pulsations decrease • Total collagen reduced • α adrenergic receptors decrease • Slowing of nerve conduction time • Urethral support impaired by degenerative changes in elastic connective tissue Effect of ageing Vaginal Cytology Pre-menopausal Post-menopausal LUT: Effect of Ageing Postmenopausal physiological changes • Cardiac function impaired (nocturia) • Neurological disorders (incontinence) • Diabetes (frequency) • Mobility impaired (incontinence) • Drugs which affect lower urinary tract function Urogenital Ageing Conclusions • GSM replaces the old terminology of vulvovaginal or urogenital atrophy • GSM is common in postmenopausal women but can occur in peri-menopausal and post-partum women, the prevalence increases with age • The most common presenting symptom is vaginal dryness followed by vaginal discomfort and then LUTS • Symptom aetiology is multifactorial but is associated with decreased oestrogen and change in vaginal microbiome • GSM has a hugely negative impact on womens health related quality of life UKCS 2019.