EMAS position statement: Vitamin D and menopausal health.

INTRODUCTION: There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM: This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.

Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society.

This care pathway from the European Menopause and Andropause Society (EMAS) provides an updated pathway for monitoring and guidance of women at midlife, focusing on those approaching the end of the reproductive life-cycle, going through the menopausal transition and beyond. The care pathway is written by professionals involved in women's health and provides a stepwise individualized approach, stratified according to needs, symptoms and reproductive stage. Furthermore, the pathway provides details on screening for chronic diseases related to menopause and ageing. Treatment options for climacteric symptoms range from menopausal hormone therapy to non-hormonal alternatives and lifestyle modifications. Therapy should be tailored to personal needs and wishes. The pathway aims to offer a holistic, balanced approach for monitoring middle-aged women, aiming to control health problems effectively and ensure healthy ageing.

Topical estrogens and non-hormonal preparations for postmenopausal vulvovaginal atrophy: An EMAS clinical guide.

INTRODUCTION: Vulvovaginal atrophy (VVA) is a chronic condition caused by estrogen deficiency. It affects around 50% of postmenopausal women, reducing their general and sexual quality of life as well as the quality of their personal relationships. AIM: The aim of this clinical guide is to set out an individualized approach to the management of VVA with topical estrogens and non-hormonal preparations. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: An individualized approach is required for the management of VVA. Topical low-dose estrogens are effective and also alleviate urinary incontinence and prevent recurrent urinary tract infections. Women should not be denied long-term use of topical estrogens as long as they feel that this treatment is of benefit to them, because the safety data are reassuring. Non-hormonal preparations (lubricants and moisturizers) should be the first-line treatment for VVA in women taking adjuvant endocrine therapies for cancers considered to be hormone-dependent. They can be used over the long term.

Management of urinary incontinence in postmenopausal women: An EMAS clinical guide.

INTRODUCTION: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care. AIM: The aim of this clinical guide is to provide an evidence-based approach to the management of urinary incontinence in postmenopausal women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Healthcare professionals should consider urinary incontinence a clinical priority and develop appropriate diagnostic skills. They should be able to identify and manage any relevant modifiable factors that could alleviate the condition. A wide range of treatment options is available. First-line management includes lifestyle and behavioral modification, pelvic floor exercises and bladder training. Estrogens and other pharmacological interventions are helpful in the treatment of urgency incontinence that does not respond to conservative measures. Third-line therapies (e.g. sacral neuromodulation, intravesical onabotulinum toxin-A injections and posterior tibial nerve stimulation) are useful in selected patients with refractory urge incontinence. Surgery should be considered in postmenopausal women with stress incontinence. Midurethral slings, including retropubic and transobturator approaches, are safe and effective and should be offered.

The Mediterranean diet and menopausal health: An EMAS position statement.

INTRODUCTION: Globally, 985 million women are aged 50 and over, leading to increasing concerns about chronic conditions such as cardiovascular disease, osteoporosis, dementia, and cognitive decline, which can adversely affect quality of life and independent living. AIM: To evaluate the evidence from observational studies and randomized trials on the effects of the Mediterranean diet on short- and long-term menopausal health: estrogen deficiency symptoms, cardiovascular disease, osteoporosis, cognitive and mental health, breast cancer, and all-cause mortality. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: The Mediterranean diet is a non-restrictive dietary pattern common in the olive-growing areas of the Mediterranean basin. It may improve vasomotor symptoms, cardiovascular risk factors such as blood pressure, cholesterol and blood glucose levels, as well as mood and symptoms of depression. Long-term adherence may: improve cardiovascular risk and events, and death; improve bone mineral density; prevent cognitive decline; and reduce the risk of breast cancer and all-cause mortality.

Menopause symptom management in women with dyslipidemias: An EMAS clinical guide.

INTRODUCTION: Dyslipidemias are common and increase the risk of cardiovascular disease. The menopause transition is associated with an atherogenic lipid profile, with an increase in the concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein B (apoB) and potentially lipoprotein (a) [Lp(a)], and a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C). AIM: The aim of this clinical guide is to provide an evidence-based approach to management of menopausal symptoms and dyslipidemia in postmenopausal women. The guide evaluates the effects on the lipid profile both of menopausal hormone therapy and of non-estrogen-based treatments for menopausal symptoms. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Initial management depends on whether the dyslipidemia is primary or secondary. An assessment of the 10-year risk of fatal cardiovascular disease, based on the Systematic Coronary Risk Estimation (SCORE) system, should be used to set the optimal LDL-C target. Dietary changes and pharmacological management of dyslipidemias should be tailored to the type of dyslipidemia, with statins constituting the mainstay of treatment. With regard to menopausal hormone therapy, systemic estrogens induce a dose-dependent reduction in TC, LDL-C and Lp(a), as well as an increase in HDL-C concentrations; these effects are more prominent with oral administration. Transdermal rather than oral estrogens should be used in women with hypertriglyceridemia. Micronized progesterone or dydrogesterone are the preferred progestogens due to their neutral effect on the lipid profile. Tibolone may decrease TC, LDL-C, TG and Lp(a), but also HDL-C concentrations. Low-dose vaginal estrogen and ospemifene exert a favorable effect on the lipid profile, but data are scant regarding dehydroepiandrosterone (DHEA). Non-estrogen-based therapies, such as fluoxetine and citalopram, exert a more favorable effect on the lipid profile than do sertraline, paroxetine and venlafaxine. Non-oral testosterone, used for the treatment of hypoactive sexual desire disorder/dysfunction, has little or no effect on the lipid profile.

Vaginal Colpectomy in Transgender Men: A Retrospective Cohort Study on Surgical Procedure and Outcomes.

BACKGROUND: Colpectomy, removal of the vaginal epithelium, may be performed in transgender men because of a disturbed male self-image, to reduce vaginal discharge, or to reduce the risk of fistula formation at the urethral-neourethral junction in future phalloplasty or metaidoioplasty. AIM: To demonstrate that vaginal colpectomy in transgender men, either alone or in combination with, for example, laparoscopic hysterectomy, metaidoioplasty, scrotoplasty, or urethroplasty, is a feasible procedure. METHODS: This single-center retrospective cohort study included 143 transgender men who underwent vaginal colpectomy between January 2006 and April 2018. Surgical details and clinical outcomes were collected from all patients. OUTCOMES: The primary outcome was the number of perioperative and postoperative complications, including intraoperative blood loss. Secondary outcomes were operating time, change in hemoglobin level, and duration of hospital stay. RESULTS: In 109 patients (76%), the procedure consisted of colpectomy only, whereas in 34 patients (23%), colpectomy was combined with other procedures. In the whole group (combined procedures included), the median blood loss was 300 mL (interquartile range [IQR] = 250 mL), the mean operating time was 132 ± 62 minutes, and the mean duration of hospital admission was 3.6 ± 1.9 days. In the colpectomy-only group, the median blood loss was 300 mL (IQR = 250 mL), mean operating time was 112 ± 40 minutes, and mean duration of hospital admission was 3.2 ± 1.5 days. For the total group, 15 patients (10%) experienced a major perioperative complication (ie, bowel injury, ureter injury, urethra injury, bladder injury, hemorrhage requiring transfusion and/or intervention and conversion to laparoscopy), and 1 patient (0.7%) had a minor perioperative complication (hemorrhage). Major postoperative complications (hemorrhage, hematoma, fistula, wound infection and prolonged pain complaints) were reported in 17 patients (12%), and minor postoperative complications (urinary tract infection, urinary retention, hemorrhage, and hematoma) occurred in 50 patients (35%). CLINICAL IMPLICATIONS: This study provides a detailed description of our technique and comprehensive reporting on perioperative and postoperative complications and reintervention rate. STRENGTHS & LIMITATIONS: Study strengths include the large number of patients included and the detailed reporting on the complications of vaginal colpectomy. The main limitation is the retrospective design, which can cause data to go missing during extraction and is prone to bias. CONCLUSION: Vaginal colpectomy is a procedure with a high complication rate, but its advantages seem to outweigh its disadvantages. In all but 1 case, no long-term sequelae were reported. However, the high complication rate and reintervention rate should be discussed with patients who are considering undergoing this procedure. Nikkels C, van Trotsenburg M, Huirne J, et al. Vaginal Colpectomy in Transgender Men: A Retrospective Cohort Study on Surgical Procedure and Outcomes. J Sex Med 2019;16:924-933.

Effects of long-term exogenous testosterone administration on ovarian morphology, determined by transvaginal (3D) ultrasound in female-to-male transsexuals.

STUDY QUESTION: Does long-term exogenous testosterone administration result in polycystic ovarian morphology (PCOM), determined by (3D) transvaginal ultrasound (TVU) in female-to-male transsexuals (FtMs). SUMMARY ANSWER: Long-term exogenous testosterone administration in FtMs does not result in PCOM determined by (3D) TVU. WHAT IS KNOWN ALREADY: The role of androgens in the pathophysiology of polycystic ovary syndrome (PCOS) is still unclear. From animal studies, intra-ovarian androgens have been suggested to disturb folliculogenesis, through a pro-atretic effect on growing follicles. It remains debatable whether exogenous androgens induce PCOM in humans. In the past histomorphologic studies indicated that androgen administration in FtMs could cause PCO-like changes. However, ultrasound morphology is an established criterion for PCOS, TVU data of ovaries after prolonged androgen exposure are lacking. STUDY DESIGN, SIZE, DURATION: Prospective, observational, case-control study, in an academic setting, performed in 2014-2015, including 56 FtMs and 80 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population consisted of adult FtMs treated with long-term testosterone, as part of their cross-sex hormone treatment, and scheduled for sex-reassignment surgery (bilateral salpingo-oophorectomy). Prior to the operation, under anaesthetics TVU measurements (3D transvaginal probe 3-9 MHz; HD11, Philips Ultrasound, Inc.) of the ovaries were performed. The control group consisted of females from a general population who underwent the same TVU and analysis. Antral follicle count (AFC) (3D) and ovarian volume (3D) were calculated using specialized software. PCOM was defined as AFC of 12 or more follicles (2-10 mm) in at least one ovary. MAIN RESULTS AND THE ROLE OF CHANCE: Prevalence rates of PCOM were not significantly different in the FtMs compared to controls, determined by (3D) TVU: 32.1% (17/53) versus 30.7% (23/75), P = 0.87. LIMITATIONS, REASONS FOR CAUTION: Testosterone levels in FtMs are supraphysiological, and may not be comparable to the testosterone levels in women with PCOS. However, we applied a unique and ethically acceptable opportunity of exploring the effects of androgens on human ovaries. WIDER IMPLICATIONS OF THE FINDINGS: This first explorative study shows that long-term exogenous testosterone administration in adult women does not seem to induce PCOM determined by TVU. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: The trial was registered at the Dutch Trial Register (www.trialregister.nl), registration number NTR4784.

Robot-assisted laparoscopic colpectomy in female-to-male transgender patients; technique and outcomes of a prospective cohort study.

BACKGROUND: Gender-affirming surgeries in female-to-male (FtM) transgender patients include mostly hysterectomy, bilateral salpingo-oophorectomy and mastectomy. Sometimes further surgery is performed, such as phalloplasty. Colpectomy may be performed to overcome gender dysphoria and disturbing vaginal discharge; furthermore, it may be important in reducing the risk of fistulas due to the phalloplasty procedure with urethral elongation. Colpectomy prior to the reconstruction of the neourethra seems to reduce fistula rates on the very first anastomosis. Therefore, at our center, colpectomy has become a standard procedure prior to phalloplasty and metoidioplasty with urethral elongation. Colpectomy is known as a procedure with potentially serious complications, e.g., extensive bloodloss, vesicovaginal fistula or rectovaginal fistula. Colpectomy performed via the vaginal route can be a challenging procedure due to lack of exposure of the surgical field, as many patients are virginal. Therefore, we investigated whether robot-assisted laparoscopic hysterectomy with bilateral salpingo-oophorectomy (TLH-BSO) followed by robot-assisted laparoscopic colpectomy (RaLC) is an alternative for the vaginal approach. METHODS: Robot TLH/BSO and RaLC as a single-step procedure was performed in 36 FtM patients in a prospective cohort study. RESULTS: Median length of the procedure was 230 min (197-278), which reduced in the second half of the patients, median blood loss was 75 mL (30-200), and median discharge was 3 days (2-3) postoperatively. One patient with a major complication (postoperative bleeding with readmission and transfusion) was reported. CONCLUSION: To our knowledge, this is the first report of RaLC. Our results show that RaLC combined with robot TLH-BSO is feasible as a single-step surgical procedure in FtM transgender surgery. Future studies are needed to compare this technique to the two-step surgical approach and on its outcome and complication rates of subsequent phalloplasty.

Antimüllerian hormone levels decrease in female-to-male transsexuals using testosterone as cross-sex therapy.

OBJECTIVE: To investigate the effect of hormonal androgenic treatment on antimüllerian hormone (AMH) serum levels in female-to-male (FtM) transsexuals. Polycystic ovary syndrome (PCOS) is associated with elevated AMH levels. Some hypothesize that the high AMH level is a consequence of androgen-induced excessive development of small antral follicles. However, this role of androgens is not yet clear. DESIGN: Observational, prospective, cohort study. SETTING: Tertiary academic medical center. PATIENT(S): Twenty-two FtM transsexuals, healthy native females receiving cross-sex hormone therapy/androgenic treatment. INTERVENTION(S): Androgenic treatment with testosterone (T) and an aromatase inhibitor while endogenous hormone secretion was suppressed with the use of a GnRH agonist. MAIN OUTCOME MEASURE(S): Hormone concentrations were measured before and after androgenic treatment (administration of T and aromatase inhibitor). Measured hormones: AMH, inhibin B, T, androstenedione, DHEAS, E2, SHBG, LH, and FSH. RESULT(S): AMH concentrations were significantly lower after androgenic treatment (4.4 ± 4.4 µg/L vs. 1.4 ± 2.1 µg/L). Androgenic treatment resulted in a strong suppression of AMH secretion over a relative short period of 16 weeks. CONCLUSION(S): Our data underscore the likely important role of androgens in the dynamics of folliculogenesis. It challenges the idea that androgens induce high AMH levels, which is gaining more interest nowadays as an important particular PCOS feature. This strong decline furthermore indicates that AMH must be interpreted in the context of other reproductive endocrine conditions. CLINICAL TRIAL REGISTRATION NUMBER: NTR2493.