Genitourinary Syndrome of Menopause

CLINICAL

Genitourinary syndrome of menopause

Elizabeth Farrell AM

Background enitourinary syndrome of oestrogen receptor alpha almost solely Genitourinary syndrome of menopause menopause (GSM) is a more active postmenopause. Testosterone (GSM) is the new term for vulvovaginal G accurate and inclusive term that receptors are concentrated mainly in atrophy (VVA). Oestrogen deficiency describes the multiple changes occurring the vulval tissues and less in the vagina, symptoms in the genitourinary tract in the external genitalia, pelvic floor whereas progesterone receptors are are bothersome in more than 50% of tissues, bladder and urethra, and the found only in the vagina and at the women, having an adverse impact sexual sequelae of loss of sexual function vulvovaginal epithelial junction. on quality of life, social activity and and libido, caused by hypoestrogenism The loss of oestrogen causes sexual relationships. GSM is a chronic during the menopause transition and anatomical and functional changes, and progressive syndrome that is postmenopause.1 These genitourinary leading to physical symptoms in all of underdiagnosed and undertreated. changes primarily occur in response to the genitourinary tissues (Box 1). The reduced oestrogen levels and ageing, and tissues lose collagen and elastin; have Objective do not settle with time. altered smooth muscle cell function; The aim of this article is to increase have a reduction in the number of blood Pathophysiology and vessels and increased connective tissue, knowledge and understanding of GSM, anatomical changes improving the ability of healthcare leading to thinning of the epithelium; professionals to discuss and obtain an Oestrogen receptors are present in the diminished blood flow; and reduced appropriate history sensitively, and treat vagina, vestibule of the vulva, urethra and elasticity. Thinning is also related to the accordingly. trigone of the bladder, and on autonomic change in the vaginal epithelial cells. and sensory neurons in the vagina and Premenopausally, the predominant cells Discussion vulva. The highest concentration of are intermediate and superficial, and there oestrogen receptors is in the vagina, with are few parabasal cells, whereas after GSM includes conditions of the vagina, vulva, pelvic floor tissues, urinary tract, and sexual dysfunction and loss of libido. Box 1. Anatomical and functional changes in the genitourinary tissues Many women are reluctant to report these symptoms to their healthcare professional • Loss of labial and vulval fullness for many reasons. • Contraction of labia majora and clitoral hood • Narrowing and stenosis of the introitus • Loss of hymenal remnants or reduced elasticity • Vaginal shortening and narrowing • Prolapse • Pelvic floor weakening • Vaginal epithelium dry and thin with petechiae • Loss of superficial cells and increase in parabasal cells • Loss of vaginal rugae • Inflamed vaginal tissues • Alkaline pH changes the vaginal microbiome with loss of Lactobacilli (vaginal pH >4.5) • Persistent or recurrent discharge with odour (not Candida in postmenopause) • Urethral meatal prominence and prolapse with thinning of the urethral epithelium • Touch perception altered either hypersensitive or decreased feeling • Loss of clitoral stimulation

menopause, the number of parabasal their symptoms with loss of oestrogen at Second, the healthcare professional cells increase, and sometimes there is an menopause.4 may be embarrassed or reluctant to ask increase in intermediate cells and loss of The most bothersome symptoms appropriate questions (especially about superficial cells.2 reported were vaginal dryness and sexual function), dismiss the symptoms dyspareunia; some women have as part of normal ageing, or feel pressured Symptoms multiple symptoms, whereas others are for time. Healthcare professionals may GSM symptoms are manifestations asymptomatic. In the Women’s Health also be unaware of available treatments or of the changes that occur during Initiative Study, 60% of participants had their recommended doses, and may treat menopause and lead to complaints physical evidence of vaginal atrophy, but inadequately and in the short term.7 of vaginal dryness, loss of lubrication, only 10% declared they had symptoms. dyspareunia, vaginal wall prolapse, vaginal Estimations suggest that only 7% of Assessment bleeding and discharge. Vulval burning, women are treated.5 Many women were A careful history and examination should dryness, irritation or itching, and entry unaware that there were treatments be performed to identify bothersome dyspareunia with fissuring are some of available.6 Symptoms after surgical symptoms, their impact on quality of life the vulval symptoms. Urinary symptoms menopause, treatment for breast cancer and sexual function. Acknowledging that include recurrent urinary tract infections, and premature menopause are often more GSM symptoms are common is a useful urgency and urge incontinence, stress severe and debilitating. strategy to start the discussion. Being incontinence, dysuria, and voiding issues. Societal views about women’s sexuality proactive by asking questions specifically There may be loss of libido, dyspareunia at older ages are essentially negative, and or as part of a systematic review in on entry, within the vagina or deep in the sexual problems are often considered a sensitive, respectful and culturally pelvis, and sexual dysfunction of arousal to be part of normal ageing leading to appropriate manner, and asking open- and orgasm. Bleeding or spotting may many women not seeking help for their ended questions, may assist in gaining occur during or after intercourse. Risk symptoms. the woman’s trust to inform you of her factors for GSM are listed in Box 2. There is a disparity between the concerns and symptoms. number of women who experience The woman’s past history may Frequency of symptoms bothersome symptoms and those who are reveal risk factors predisposing her to Many studies have surveyed the treated. First, women are unwilling, shy or GSM. Her medical, surgical, menstrual, frequency, type of symptoms, and their embarrassed to discuss their symptoms gynaecological and obstetric histories may impact on health and quality of life. In the with their healthcare professional, be relevant to development of particular Melbourne Women’s Midlife Study, the especially if: symptoms and subsequent management. prevalence of vaginal dryness increased • the healthcare professional is young and Ask about vulval hygiene and the use of with age – 4% in early perimenopause, male possible irritants such as soap, bath gels, rising to 25% at one year postmenopause • the patient has had a previous powders, lubricants, condoms, panty and 47% three years after the negative experience with a healthcare liners or pads that could cause symptoms. menopause. The symptoms range from professional Identify and document the onset of mild, moderate to debilitating.3 Other • the patient regards her symptoms as a symptoms, their description, duration, studies have found that 50% of women natural part of ageing that she should how bothersome or distressing the aged 50–60 years report symptoms, ‘put up with’. symptoms are, and their impact on quality increasing to 72% in women aged older Women often wait for their healthcare of life. The patient’s psychosocial and than 70 years, but only 4% associated professional to ask the questions. sexual history should include the presence of a long-term or new partner, partner relationship, frequency of sexual activity, Box 2. Risk factors for genitourinary syndrome of menopause history of sexually transmissible infections • Menopause (STIs) and the effect of her symptoms on • Bilateral oophorectomy her sexual intimacy. • Premature ovarian failure Ask the woman’s permission and explain • Smoking how you will conduct the examination. • Alcohol abuse Some conditions of the vulva and vagina • Decreased sexual frequency or abstinence may be identified or excluded by the • Lack of a vaginal birth examination. Using Box 1 as a checklist will • Other causes of low oestrogen (eg postpartum period, hypothalamic amenorrhoea) help healthcare professionals to determine • Cancer treatments, including pelvic irradiation, chemotherapy and endocrine therapy the extent and severity of the changes.

482 REPRINTED FROM AFP VOL.46, NO.7, JULY 2017 © The Royal Australian College of General Practitioners 2017 GENITOURINARY SYNDROME OF MENOPAUSE CLINICAL

Where there is introital narrowing, Personal lubricants and vaginal Box 3. Differential diagnosis visualisation of the vagina, cervix or vaginal moisturisers • Dermatological conditions of the vulva vault may require a very small or paediatric Lubricants and vaginal moisturisers are (eg lichen sclerosus or planus, eczema, speculum. Digital examination may elicit effective in relieving discomfort, friction and dermatitis, chronic vulvovaginitis) a narrowed introitus, especially of the pain with penetrative sex. Lubricants are • Vulvodynia, vaginismus posterior fourchette with reduced elasticity. used at the time of intercourse, whereas • Autoimmune disorders The pelvic floor muscles may be relaxed, vaginal moisturisers provide longer term • Malignancy tense and painful or in severe spasm relief. Lubricants can be water-based or • Chronic pelvic pain (vaginismus). The vaginal epithelium may silicone-based. Water-based lubricants are • Trauma, foreign bodies feel thin, lacking in lubrication with loss of non-staining and have fewer side effects • Diabetes rugae. Palpating the vaginal vault, cervix than silicone-based lubricants. However, • Lupus and fornices will help to exclude pelvic the efficacy of lubricants depends on pathology. the osmolality, pH and additives of each individual product. High osmolality, >1200 stimulation. The safety in breast cancer Management mOsm/kg, is associated with irritation, survivors is not established, especially The aim of management and treatment contact dermatitis and cytotoxicity. Oils, with aromatase inhibitors, because of GSM is to provide symptom relief. such as olive or sweet almond oil, are of the possible risk of recurrence.10 However, the consultation is also an alternatives. In women with breast cancer, vaginal appropriate time to discuss lifestyle, diet Moisturisers rehydrate dry tissues by oestriol preparations are prescribed on and exercise, smoking cessation and changing the fluid content in the vaginal an individual basis, in consultation with appropriate alcohol consumption. Also epithelium, absorbing and adhering to it, the woman and her breast physicians, use the time to perform routine cervical mimicking vaginal secretions, and lowering depending on symptoms and their impact screening and STI tests, if indicated. the pH. The effect lasts about three on quality of life. days. Moisturisers contain polymers for Systemic hormone therapy (ie MHT) Investigations adherence and other additives that effect will improve the vasomotor symptoms Investigations are not routinely performed, osmolality and pH.8 of menopause and may improve but are ordered depending on specific genitourinary symptoms; however, findings and possible differential Hormonal therapies in some women, a vaginal oestrogen diagnoses (Box 3). Investigation of any Oestrogen vaginal preparations reduce may also be needed. Individualising the postmenopausal bleeding to exclude symptoms and reverse the atrophic vaginal oestrogen therapy, discussing gynaecological malignancy is imperative. changes in pelvic tissues, and improve which preparation the woman would A vaginal or vulval swab may be blood flow and the thickness of the prefer and instructing her in how to use taken if there is a vaginal discharge epithelium in the vagina, bladder and it, will increase the woman’s adherence or a vulvitis to exclude infection. A urethra. There is minimal systemic to therapy. The recommended therapy is vulval biopsy may be necessary if the absorption, with an initial peak, then almost daily use (at night) for two weeks, then a vulval findings are suspicious or do not no further absorption.Vaginal oestriol maintenance dose of two to three times respond to the recommended treatment. preparations of cream and pessaries per week. After improvement is noted Urine investigations may be required if provide a human oestrogen. Oestriol is the in the woman’s symptoms, it may be symptoms are related to bladder and weakest oestrogen and has one-tenth of possible to reduce the frequency to the urethra. the potency of oestradiol. There is minimal lowest effective dose. absorption systemically and oestriol cannot Treatment be metabolised to oestradiol or oestrone. Sexual dysfunction Treatment will depend on the symptoms Low-dose vaginal oestradiol tablets are Management of a woman with sexual and signs, and the degree of severity. also very effective in relieving atrophic dysfunction, including loss of libido, Non-hormonal therapies include personal symptoms. The individual dose is 10 μg, dyspareunia due to vulvovaginal atrophy lubricants, vaginal moisturisers and vaginal and studies have found that the annual and pelvic floor tension, requires a laser (long-term safety and efficacy have absorption of oestradiol is only 1.14 mg.9 more complex and multidisciplinary not been established). Hormonal therapies There are no studies on the long-term approach. The severity of the symptoms include vaginal oestriol cream or pessaries, risks of vaginal oestrogen preparations, but will determine the therapies required. vaginal oestradiol tablets, or systemic absorption is negligible once the atrophic Lubricants and moisturisers may be hormone therapy (menopause hormone changes are reversed. Added progestogens recommended initially for dryness and therapy [MHT]). are not needed to prevent endometrial loss of lubrication with intercourse. Vaginal

oestrogens are prescribed when severe The healthcare professional is in a unique International Menopause Society atrophic changes are present. position to sensitively discuss symptoms, • www.imsociety.org If there is pelvic floor dysfunction, pelvic such as incontinence, sexual pain, Dermnet NZ pain or urinary symptoms, referral to a prolapse, vaginal irritation and dryness, pelvic floor physiotherapist for pelvic floor and to advise, educate and manage • www.dermnetnz.org training and relaxation will help to reduce accordingly, providing long-term follow-up. symptoms. Sometimes, vaginal trainers Author will help dilate the vaginal introitus. Key points Elizabeth Farrell AM, MBBS, Hon LLD, FRANZCOG, FRCOG, Gynaecologist and Medical Director, Jean Consider changing regular • GSM is very common and does not Hailes for Women’s Health, Vic. elizabeth.farrell@ medications that affect sexual function improve with time after menopause. jeanhailes.org.au (eg antidepressants), and referral • Symptoms can have a severe impact Competing interests and funding: None. Provenance and peer review: Commissioned, to a sexual therapist and/or couple on quality of life, sexual function and externally peer reviewed. counseling may be necessary. relationships. • Women are often embarrassed References Newer or other treatments or reluctant to inform healthcare 1. Portman DJ, Gass ML, Vulvovaginal Atrophy Terminology Consensus Conference Panel. Newer treatments are becoming available. professionals. Genitourinary syndrome of the menopause: Vaginal laser therapy is being trialled for • Direct questioning, initially with open- New terminology for vulvovaginal atrophy from the International Society for the Study vaginal dryness, but long-term data are ended questions, is needed. of Women’s Sexual Health and The North not available. • Examination of the vulva and vagina American Menopause Society. Climacteric A number of preparations that improve is necessary to provide appropriate 2014;17(5):557−63. 2. Gandhi J, Chen A, Dagur G, et al. Genitourinary atrophic symptoms, but are currently not treatments. syndrome of menopause: An overview of clinical available in Australia, are ospemifeme, • Non-hormonal and hormonal therapies manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet an oral selective oestrogen receptor are available. Gynecol 2016;215(6):704–11. modulator (SERM), and a vaginal gel • A multidisciplinary team improves 3. Dennerstein L, Dudley E, Hopper J, Guthrie J, of dehydroepiandrosterone (DHEA). outcomes. Burger H. A prospective population-based study of menopause symptoms. Obstet Gynecol Research is ongoing into new and • Use the consultation to discuss lifestyle 2000;96(3):351–58. improved vaginal oestrogen preparations. and health. 4. Nappi RE, Kokot-Kierepa M. Vaginal Health: Insights, views and attitudes (VIVA): Results from an international survey. Climacteric Follow-up Resources 2012;15(1):36–44. Follow-up visits should be regular 5. Archer DF, Labrie F, Bouchard C, et al. Treatment Australasian Menopause Society of pain at sexual activity (dyspareunia) to review the woman’s response to with intravaginal dehydroepiandrosterone treatment and her ongoing needs. The • www.menopause.org.au (prasterone). Menopause 2015;22(9):950–63. frequency will depend on whether the • www.menopause.org.au/images/ 6 Nappi, M. Kokot-Kierepa. Women’s voices in the menopause: Results from an international survey management strategies are successful. stories/infosheets/docs/AMS_Genito_ on vaginal atrophy. Maturitas 2010;67(3): 233–38. urinary_syndrome_of_menopause.pdf 7. Archer DF. Efficacy and tolerability of local Conclusion estrogen therapy for urogenital atrophy. • www.menopause.org.au/for-women/ Menopause 2010;17:194–203 GSM is a chronic complex syndrome of information-sheets/974-vaginal-health- 8. Edwards D, Panay N. Treating vulvovaginal multiple changes in the genitourinary after-breast-cancer-a-guide-for-patients atrophy/genitourinary syndrome of menopause: How important is vaginal lubricant and tissues in response to the loss of Jean Hailes for Women’s Health moisturizer composition? Climacteric oestrogen with menopause. The 2016;19(2):151–61. experience of atrophic symptoms varies • https://jeanhailes.org.au/contents/ 9. Simon J, Nachtigall L, Ulrich LG, Eugster- Hausmann M, Gut R. Endometrial safety of and ranges from mild to debilitating, documents/Resources/Booklets/The_ ultra-low-dose estradiol vaginal tablets. Obstet with effects on genitourinary function, vulva.pdf Gynecol 2010;116:876–83. 10. Moegele M, Buchholz S, Seitz S, Ortmann O. sexual function, relationships and quality • https://jeanhailes.org.au/health-a-z/ Vaginal estrogen therapy in postmenopausal of life. Treatments, ranging from simple vulva-vagina-ovaries-uterus/vulva- breast cancer patients treated with measures (eg lubricants, moisturisers) vaginal-irritation aromatase inhibitors. Arch Gynecol Obstet 2012;285(5):1397–402. to vaginal oestrogen preparations North American Menopause Society and hormone replacement therapy, are available to reduce symptoms. • www.menopause.org A multidisciplinary approach may be • www.menopause.org/docs/default- necessary where there are complex source/2013/vva-position-statement. problems, including sexual dysfunction. pdf?sfvrsn=0