Infertility affects 1 in 6 reproductive-aged couples, and declining ovarian function is a common cause of infertility among women in their late 30s to early 40s.
Vasomotor symptoms (VMS) related to the menopausal transition affect the majority of women and contribute to significant quality of life burden. Incidence, length, severity and report of symptoms vary by race, ethnicity, and coexisting health conditions. The pathophysiology of VMS is not fully understood and is likely multifactorial, involving changes in the hypothalamicpituitary-ovarian axis during the menopausal transition. Treatment approaches include lifestyle modifications, hormonal and non-hormonal therapies, including integrative and complementary medicine approaches. Systemic hormone therapy with estrogen is the most effective treatment. Emerging evidence suggests that treatment with SSRIs, SNRIs, and gabapentin is effective for many women who want to avoid hormone therapy. A shared decision approach to treatment decisions involves consideration of risks with treatment options and discussion of patient priorities.
No abstract is included with this article.
The Clinical Problem
Because there is no universal definition of normal sexual function, what constitutes sexual difficulty is determined by a person’s subjective definition of unsatisfactory sexual well-being. The condition is usually described as unsatisfactory interest, arousal, orgasm, or other aspects of sexuality (e.g., sexual self-image), and the symptoms often coexist. The term “sexual dysfunction” is used when at least one of the symptoms is of substantial concern to the affected person. Sexual dysfunction negatively affects mental health, vitality, and social functioning and has an overall effect on quality of life that is of similar magnitude to that associated with chronic back pain or diabetes.
Objectives. To conduct a systematic review of evidence regarding genitourinary syndrome of menopause (GSM) screening, treatment, and surveillance.
Data sources. Ovid/Medline®, Embase®, and EBSCOhost/CINAHL® from database inception through December 11, 2023.
Review methods. We employed methods consistent with the Agency for Healthcare Research and Quality Evidence-based Practice Center Program Methods Guidance to identify studies and synthesize findings for Key Questions related to screening for GSM, effectiveness and harms of U.S.-available interventions for GSM, appropriate followup intervals for patients using GSM treatments, and endometrial surveillance for patients using hormonal GSM treatments. For vaginal estrogen and vaginal or systemic non-estrogen hormonal interventions, energy-based interventions, and vaginal moisturizers, we first assessed study quality and then, for moderate or high-quality studies, reviewed outcomes related to GSM symptoms, treatment satisfaction, and adverse effects. For low-quality studies, we described limited study characteristics only. For studies of other non-hormonal interventions, we created an evidence map describing study characteristics without assessing study quality.
Results. After assessing 107 publications for risk of bias (RoB), we extracted and synthesized effectiveness and/or harms outcomes from 68 publications describing trials or prospective, controlled observational studies that were rated low, some concerns, or moderate RoB (24 estrogen publications, 35 non-estrogen, 11 energy-based, and 4 moisturizers). Of 39 high, serious, or critical RoB publications, we extracted long-term harms from only 15 uncontrolled studies of energy-based interventions (all serious or critical RoB due to confounding). An additional 66 publications evaluating 46 non-hormonal interventions, including natural products, mind/body practices, and educational interventions, were described in an evidence map. Across all 172 publications, studies differed in GSM definitions, diagnosis, enrollment criteria, and outcomes assessed. Few studies enrolled women with a history of breast or gynecologic cancers. Overall, we found that vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), vaginal moisturizers, and oral ospemifene may all improve at least some GSM symptoms, while evidence does not demonstrate the efficacy of energy-based therapies, vaginal or systemic testosterone, vaginal oxytocin, or oral raloxifene or bazedoxifene for any GSM symptoms. Harms reporting was limited, in part, by studies not being sufficiently powered to evaluate infrequent but serious harms, though most studies did not report frequent serious harms. Common non-serious adverse effects varied by treatment and dose. No studies evaluated GSM screening or directly addressed appropriate followup intervals or the effectiveness and harms of endometrial surveillance among women with a uterus receiving hormonal therapy for GSM. The longest followup period for active endometrial surveillance in an included trial was 12 weeks (vaginal estrogen) or 1 year (non-estrogen hormonal interventions).
Conclusions. This systematic review provides comprehensive, up-to-date information to guide patients, clinicians, and policymakers regarding GSM. Despite the breadth of included studies, findings were limited by several factors, including heterogeneity in intervention-comparator-outcome combinations. Future studies would be strengthened by a standard definition and uniform diagnostic criteria for GSM, a common set of validated outcome measures and reporting standards, and attention to clinically relevant populations and intervention comparisons. Lack of long-term data assessing efficacy, tolerability, and safety of GSM treatments leaves postmenopausal women and clinicians without evidence to guide treatment longer than 1 year.
This JAMA Internal Medicine Patient Page describes urinary tract infections, their causes, and how to treat them and prevent future episodes.
Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years.
Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up.
Conclusions and relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.
Menopause is defined as 1 year of amenorrhea caused by
declining ovarian reserve or as the onset of vasomotor
symptoms in people with iatrogenic amenorrhea. It is preceded
by perimenopause or the menopause transition, which can last
for as long as 10 years. Although many treatments exist for
menopausal symptoms, fears around the risks of menopausal
hormone therapy and lack of knowledge regarding treatment
options often impede patients from receiving treatment. In this
review, we summarize the evidence for treating menopausal
symptoms and discuss their risks and benefits to help guide
clinicians to evaluate and treat patients during the menopausal
transition (Box 1).
• Menopausal symptoms can occur for as long as 10 years before
the last menstrual period and are associated with substantial
morbidity and negative impacts on quality of life.
• Menopausal hormone therapy is indicated as first-line
treatment of vasomotor symptoms, and is a safe treatment
option for patients with no contraindications.
• Though less effective, nonhormonal treatments also exist to
treat vasomotor symptoms and sleep disturbances.
• It is critical that clinicians inquire about symptoms during the
menopause transition and discuss treatment options with
their patients.
Importance: Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]).
Observations: Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene.
Conclusions and relevance: During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.
An otherwise healthy 71-year-old woman presented to our clinic with a history of pruritus and burning of the vulva. On examination, we observed an atrophic, white, shiny plaque involving the vulva, perineum and perianal areas. The clitoral hood and labia minora were completely scarred and the introitus was narrow (Figure 1). We diagnosed vulvar lichen sclerosus, a chronic inflammatory disease affecting the anogenital area that can present in any age group, though it is most common before puberty and after menopause. We noted no areas of concern for malignant disease, so we did not take a biopsy. We treated the patient with high-potency steroids (clobetasol ointment twice daily for 6 wk, then weekly). She responded well to treatment, and once her disease settled, we switched her to mid-potency steroids (betamethasone valerate 0.1% ointment daily).
