Aim To review the current evidence concerning the long-term harmful effects of premature or early menopause, and to discuss some of the clinical implications. Material and methods Narrative review of the literature. Results Women undergoing premature or early menopause, either following bilateral salpingo-oophorectomy or because of primary ovarian insufficiency, experience the early loss of estrogen and other ovarian hormones. The long-term consequences of premature or early menopause include adverse effects on cognition, mood, cardiovascular, bone, and sexual health, as well as an increased risk of early mortality. The use of hormone therapy has been shown to lessen some, although not all of these risks. Therefore, multiple medical societies recommend providing hormone therapy at least until the natural age of menopause. It is important to individualize hormone therapy for women with early estrogen deficiency, and higher dosages may be needed to approximate physiological concentrations found in premenopausal women. It is also important to address the psychological impact of early menopause and to review the options for fertility and the potential need for contraception, if the ovaries are intact. Conclusions Women who undergo premature or early menopause should receive individualized hormone therapy and counseling.

Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model. We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55–0.81. Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.

Genitourinary syndrome of menopause (GSM) describes the symptoms and physical changes that result from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition. There has not been a consensus reached about the number or type of symptoms needed to diagnose GSM, and the associated urinary symptoms are also linked with other common urologic conditions (e.g., overactive bladder) in older patients. This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events (AEs). The systematic review utilized in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ) and funded by the Patient Centered Outcomes Research Institute (PCORI). The EPC extracted and synthesized effectiveness and/or harms outcomes from 68 publications. An additional 66 publications evaluating 46 non-hormonal interventions, were described in an evidence map. Clinicians diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies. There is a large body of evidence examining the use of hormonal and non-hormonal treatment options to manage the symptoms of GSM; however, the local low-dose vaginal estrogen has the most robust evidence base. The strategies defined in this document were derived from evidence-based and consensus-based processes. Given that there is insufficient information to recommend one hormonal therapy over another, this guideline is not meant to support a stepwise progression through different hormonal approaches. The clinician should make treatment decisions in the context of shared decision-making considering patient goals and preferences, using the evidence of efficacy and AEs of each possible intervention as a guide.