Continuing Education Activity

Menopause represents the natural and permanent cessation of menstruation resulting from declining ovarian function and estrogen deficiency. The term signifying the end of the reproductive years is defined as  12 months of amenorrhea. Natural menopause most commonly occurs between ages 45 and 56, with a median age of 51 in the United States. This course details the physiology of menopause, which involves the progressive depletion of ovarian follicles, reducing granulosa cell activity and lowering estradiol, inhibin, and antimullerian hormone levels, thereby increasing follicle-stimulating hormone and luteinizing hormone concentrations. Hormonal shifts disrupt the hypothalamic-pituitary-ovarian axis, resulting in irregular cycles that eventually cease. Clinical manifestations of menopause are also discussed, which frequently include vasomotor disturbances, eg, hot flashes and night sweats, genitourinary syndrome, sleep disruption, mood changes, decreased sexual function, and bone loss, as well as its long-term health risks, including osteoporosis and cardiovascular disease, making menopause an important period for preventive care and individualized management strategies.

This activity reviews the diagnostic considerations, the spectrum of systemic and local hormonal therapies, nonhormonal pharmacologic options, lifestyle strategies, and approaches to preventing long-term complications in patients who are menopausal. Participants will also gain an understanding of patient-centered counseling strategies that support safe, individualized treatment and optimized long-term health outcomes for women during the menopausal transition and postmenopausal years. This activity for healthcare professionals is designed to enhance the learner's competence in identifying patients with menopausal features, understanding menopausal physiology, selecting appropriate therapies, performing the recommended evaluation, and implementing an appropriate interprofessional approach when managing this condition to improve outcomes and quality of life in affected patients.

Objectives:

• Identify the physiologic changes associated with the menopausal transition.
• Assess common clinical manifestations of menopause.
• Differentiate normal menopausal changes from other causes of abnormal uterine bleeding.
• Implement interprofessional team strategies to improve care coordination and outcomes in patients with menopause.

Introduction

Menopause refers to the natural and permanent cessation of menstruation caused by estrogen deficiency unrelated to a pathologic process. The term menopause derives from the Greek words pausis, meaning pause, and men, meaning month. Amenorrhea persisting for 12 months marks the end of a woman’s reproductive and childbearing period.[1] Natural menopause commonly occurs between ages 45 and 56, with a median age of 51 years in the United States.[2]

Vasomotor symptoms affect most women during the menopausal transition, although menopause influences multiple organ systems, including urogenital, psychogenic, and cardiovascular systems. This review discusses hormonal and nonhormonal treatment approaches as well as complications associated with menopause. Increasing life expectancy results in women spending approximately 40% of their lives in the postmenopausal stage, which corresponds to more than 30 years for many individuals.[2]

Etiology

Advancing age leads to progressive depletion of ovarian follicles through atresia and ovulation.[1] Granulosa cell numbers within the ovary decline, reducing production of estradiol and inhibin B.[3] Levels of antimullerian hormone (AMH), another hormone secreted by ovarian granulosa cells, also decrease. Reduced inhibitory feedback from estrogen and inhibin A and B results in increased production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).[4] Declining estrogen levels disrupt the hypothalamic-pituitary-ovarian axis and impair normal endometrial development. These hormonal and physiologic changes contribute to irregular menstrual cycles that ultimately progress to complete cessation of menses.

During the perimenopausal period, the earliest menstrual change commonly involves shortening of the follicular phase, which leads to more frequent menses. Subsequent progression usually produces longer menstrual cycles. Many cycles become anovulatory, resulting in perimenopausal abnormal uterine bleeding. Menstruation eventually ceases completely.[1] Testosterone levels change minimally during early menopause, creating a relative increase in the testosterone-to-estrogen ratio that may produce symptoms associated with androgen excess.[5]

Menopause may also result from surgical procedures, eg, bilateral oophorectomy. Additional causes include treatments for certain medical conditions, including endometriosis, cancer chemotherapy—particularly with alkylating agents—radiation therapy, chronic illnesses, eg, HIV-AIDS, and therapies involving antiestrogenic agents.[6] This discussion focuses on natural menopause.

Epidemiology

In the United States, approximately 1.3 million women enter menopause each year. Natural menopause most commonly develops between the ages of 45 and 56.[7] Early natural menopause occurs in about 5% of women and typically develops between the ages of 40 and 45. Primary ovarian insufficiency affects approximately 1% of women and leads to complete cessation of menses before age 40 as a result of permanent ovarian failure.[8]

Premature and early menopause occur more frequently among Black and Hispanic women than among White women. The incidence of premature menopause among Black and Hispanic women reaches 1.4%, compared with 1% among White women. Early menopause develops in 3.7% to 4.1% of Black and Hispanic women, compared with 2.9% among White women. Adjustment for confounding factors reduces the influence of race on the timing of menopause for an individual patient, although population-level differences remain apparent.[8][9]

Black women also report more severe vasomotor symptoms than other racial groups. Approximately 80% of Black women experience vasomotor symptoms with a median duration of 10.1 years. Among White women, 65% report vasomotor symptoms with a median duration of 6.5 years.[9]

Pathophysiology

Menopause represents a normal physiologic process of aging in women characterized by a rapid decline in the number of primary ovarian follicles, leaving an insufficient quantity to respond to follicle-stimulating hormone (FSH). Absence of an adequate follicular response prevents the luteinizing hormone (LH) surge and ovulation, leading to reduced estrogen production and eventual cessation of menstruation. Following menopause, LH and FSH remain uninhibited and persist at elevated levels for years. Small amounts of estrogen may continue to form through peripheral conversion of testosterone released by the adrenal glands, potentially resulting in minimal symptoms beyond the cessation of menstruation in some individuals.[10]

More than 80% of women experience symptoms during the menopausal transition, although individual experiences vary widely. Multiple factors influence physiologic changes associated with menopause, including diet, smoking status, ethnicity, medical conditions, exercise habits, socioeconomic background, body mass index, and overall gynecologic health.[5]

Histopathology

Although menopause affects various tissues at a microscopic level, the focus discussed here will be mainly on the gynecologic manifestations of the condition.

Ovaries

The maximum and finite number of follicles in the ovary occurs in neonatal life. Approximately 1 million follicles are present at birth. At puberty, 250,000 to 400,000 follicles remain. In menopause, follicles age, and structures within the ovaries change. Ovarian aging involves not only a decrease in the number of follicles but also a decline in oocyte quality. Changes are noted in the telomere, mitochondria, and other components of the ovary. The mechanisms involved in ovarian aging are not yet fully understood at the cellular level.[11]

Urogenital

Urogenital changes occur during menopause as declining estrogen levels affect vulvar and vaginal tissues. Inflammation of mucosal surfaces develops, producing erythema and increased tissue friability. Vaginal pH rises, and parabasal cell populations increase. Structural alterations also occur, including narrowing of the introitus, thinning of the labia, and reductions in both vaginal depth and width.[12]

History and Physical

Clinical history and physical examination related to menopause should emphasize symptoms associated with estrogen deficiency and the physiologic changes that accompany the menopausal transition.

Vasomotor Symptoms

Vasomotor symptoms represent the most common manifestations during the menopausal transition. Approximately 75% to 80% of women experience these symptoms with varying severity. Common manifestations include hot flashes, night sweats, palpitations, and migraines. Hot flashes occur unpredictably during both daytime and nighttime and typically last about 3 to 4 minutes. Each episode begins with a sensation of flushing that spreads across the upper body, reflecting central nervous system alterations in thermoregulation. Such episodes may disrupt daily activities and impair sleep quality. Vasomotor symptoms persist for an average duration of 1 to 6 years and continue for as long as 15 years in 10% to 15% of postmenopausal women.[5] Alcohol consumption, smoking, obesity, physical inactivity, and emotional stress may worsen symptom severity.

Migraine patterns may change during the menopausal transition. Migraines represent neurovascular headaches frequently triggered by fluctuations in estrogen levels. Early menopausal hormonal variability may worsen migraine severity or frequency. Many women experience migraine improvement after menopause, although some report worsening symptoms. Migraine with aura carries an increased risk of stroke, particularly among individuals who smoke or use oral contraceptives.[13] Other headache types, including cluster headaches and tension headaches, may also increase with hormonal fluctuations.

Genitourinary Symptoms

Genitourinary syndrome of menopause affects approximately 50% to 75% of women. Thinning of the vaginal mucosa and reduced vaginal elasticity develop as estrogen levels decline. These physiologic changes may produce vaginal dryness, burning, pruritus, and irritation. Urinary symptoms, eg, frequency and urgency, frequently occur because estrogen receptors exist within the bladder and urethra. Urethral atrophy may lead to frequency, urgency, and dysuria.[5]

Reduced estrogen levels may also increase the risk of recurrent urinary tract infections. Elevated vaginal pH promotes bacterial colonization of the vagina by bladder pathogens.[12] Urinary incontinence does not result directly from menopausal estrogen decline. Instead, risk correlates with factors such as overweight status, diabetes, and advancing age. Sexual function may decline nearly 2 years before the final menstrual period. This decline appears less pronounced among Black women compared with White and Japanese women.[12]

Psychogenic Symptoms

Psychogenic symptoms occur in up to 70% of women during perimenopause and menopause.[14] Common manifestations include anger or irritability, anxiety or tension, depression, impaired concentration, and reduced self-esteem or confidence. Sleep apnea, insomnia, and restless legs syndrome may contribute to sleep disturbances beyond those associated with night sweats. Estrogen receptors are present in multiple brain regions involved in mood and cognitive regulation. Declining estrogen levels, therefore, influence emotional regulation.

Estrogen also modulates serotonin and noradrenaline transmission, which supports mood stability.[14] Some mood changes may reflect evolving personal or social circumstances rather than hormonal influences alone.[5] Perimenopausal women demonstrate a higher risk of depressive symptoms and greater symptom severity compared with premenopausal women. Vasomotor symptoms and additional factors that remain incompletely defined may contribute to this increased risk of depression during perimenopause and menopause.[15]

Physical Examination

Physical examination findings may reflect systemic effects of estrogen decline. Blood pressure may increase as a result of arterial vasoconstriction. Many women report weight gain during the menopausal transition, with data from the North American Menopause Society indicating an average increase of 5 pounds (2 kg). Height reduction may occur due to osteoporosis-related bone loss. Breast tissue commonly undergoes increased fatty deposition and involution after menopause. Vaginal examination may reveal dryness and signs of urogenital atrophy. Arthralgias and sarcopenia, defined as a gradual loss of muscle mass, function, and strength, may also develop.

Sleep

Menopausal women frequently report greater sleep disturbances than premenopausal women, regardless of hormone replacement therapy (HRT) use or the presence of vasomotor symptoms. Common complaints include difficulty initiating sleep, early morning awakening, and repeated nighttime awakenings. Black and White women report nighttime awakenings more frequently than other racial or ethnic groups, whereas Hispanic women report fewer sleep difficulties.[16]

Cognitive Performance

Some aspects of cognitive performance may decline temporarily during perimenopause, particularly learning processes. Cognitive function generally improves during postmenopausal years. Age-related cognitive decline shows a stronger association with advancing age than with time since menopause onset.[16] [16] 

Sexual Function

Estrogen plays a critical role in female sexual function.[17] The menopausal transition may lead to reduced sexual desire and diminished sexual function. Dyspareunia may also increase during this period.[16]

Bone

Healthy normal bone is constantly remodeled via a 5-step process, which involves osteoclast resorption and osteoblast production. During menopause, estrogen deficiency increases osteoclastic activity, leading to an imbalance between osteoclastic and osteoblastic activity. This results in increased bone reabsorption and overall bone loss. Bone mineral density loss likely begins several years before menopause starts.[16]

Cardiovascular Disease

Cardiovascular risk increases around menopause due to multiple physiologic changes, including altered autonomic regulation, metabolic shifts, vascular changes, and reduced estradiol levels. Enhanced sympathetic activity and hormonal alterations contribute to vascular changes and common menopausal symptoms, eg, hot flashes and sleep disturbances. Estrogen therapy may alleviate certain manifestations but does not fully reverse menopause-related autonomic dysfunction.[18]

Both menopause and menopausal hormone therapy influence cardiovascular risk factors and clinical events. Older oral hormone formulations are associated with higher risks of coronary disease and stroke, whereas contemporary low-dose transdermal and micronized formulations demonstrate lower risk profiles. Personalized assessment that includes age, duration since menopause, baseline cardiovascular risk, and menopausal hormone therapy formulation supports safe treatment decisions. Menopause represents an important opportunity for cardiovascular prevention, and individualized strategies promote safety while ongoing research continues to clarify long-term outcomes.[19]

Evaluation

Diagnosis of menopause generally relies on clinical evaluation based on a patient’s age and symptoms, and laboratory testing usually remains unnecessary.[1] Symptoms often develop before measurable hormonal changes appear. Certain clinical situations may require hormone measurement to support diagnosis. Examples include women with amenorrhea following hysterectomy or endometrial ablation and individuals with anovulatory cycles. In such cases, assessment of FSH and estradiol levels may assist diagnostic evaluation. Serum antimullerian hormone AMH measurement as a predictor of menopausal age remains controversial. Additional research remains necessary, particularly studies comparing AMH levels among different ethnic groups. AMH levels may reflect functional ovarian reserve; however, variability in the rate of decline among women limits predictive accuracy. Reliable prediction of menopausal age using AMH likely requires the incorporation of additional variables.[20]

Serum FSH levels greater than 30 mIU/mL provide an objective indicator of menopause. Pelvic surgery may cause transient elevations in FSH, which requires delaying measurement until at least 3 months after surgery when evaluating menopausal status.[6] Estradiol concentrations below 20 pg/mL suggest menopause.[9] However, FSH levels among women aged 40 to 50 years vary widely and typically stabilize only 3 to 6 years after menopause.[21] Routine measurement of inhibin B and AMH does not assist in the diagnosis of menopause.

Substantial hormonal variability during the menopausal transition limits the routine diagnostic value of FSH and estradiol testing.[7] Estradiol concentrations during perimenopause average approximately 20% to 30% higher than levels observed in premenopausal women. Additional laboratory studies may assist evaluation of amenorrhea unrelated to menopause, including testing for human chorionic gonadotropin, thyroid-stimulating hormone, and prolactin. Certain medications, including estrogens, androgens, and hormonal contraceptives, may alter FSH results. Hormonal laboratory testing should occur at least 2 weeks after discontinuation of hormonal medications.[1]

Treatment / Management

Guidance from the 2022 North American Menopause Society Position Statement emphasizes minimizing disruptive menopausal symptoms while preventing long-term complications. The timing hypothesis for HRT supports initiation within 10 years of the final menstrual period and before age 60 to reduce the incidence of stroke, systemic embolism, and transient ischemic attack. Initiation beyond 10 years after the final menstrual period or after age 60 carries a less favorable risk-to-benefit profile. No universal recommendation defines an age for discontinuing HRT because vasomotor symptoms may persist for many years. Treatment decisions, therefore, require individualized assessment, with therapy maintained at the lowest effective dose that adequately controls symptoms.

Systemic Hormonal Treatment 

Systemic hormonal therapy serves as the primary treatment for moderate to severe vasomotor symptoms.[7] Multiple formulations exist, including tablets, sprays, gels, vaginal rings, and patches, which are administered via continuous or cyclic regimens. Available options include estrogen alone, estrogen-progestin combinations, estrogen-bazedoxifene formulations, and progestin alone. Unopposed estrogen should not be prescribed for individuals with an intact uterus because progesterone protects against endometrial hyperplasia and malignancy. Estrogen monotherapy in women with a uterus increases the incidence of endometrial hyperplasia to approximately 30% within 1 year. Bazedoxifene, a selective estrogen receptor modulator, offers an alternative to progesterone for reducing endometrial hyperplasia and cancer risk.[7]

In November 2025, the Food and Drug Administration (FDA) recommended the removal of the boxed warning for estrogen replacement therapy and initiated collaboration with manufacturers to update hormone therapy labeling. Updated labeling aims to provide balanced information regarding benefits and risks, enabling informed decision-making between patients and clinicians. Revised labeling removes references to cardiovascular disease, breast cancer, and probable dementia while maintaining the boxed warning for endometrial cancer associated with systemic estrogen-only products. Federal guidance continues to recommend initiating systemic hormone therapy within 10 years of menopause onset or before age 60, with treatment timing and duration determined jointly by the clinician and patient.

Systemic hormonal therapy markedly reduces the severity and frequency of hot flashes while improving urogenital atrophy and sleep disturbances. Preventive benefits for osteoporosis and fracture reduction also occur. Despite these advantages, therapy should continue for the shortest duration and at the lowest effective dose because estrogen therapy alone increases the relative risk of deep venous thromboembolism and stroke. Combination HRT may increase breast cancer risk, although the absolute risk increase remains minimal among women in early menopause.[7]

Evidence regarding systemic HRT and coronary heart disease risk remains inconclusive. Estrogen combined with progesterone increases the risk of breast cancer, stroke, pulmonary embolism, and deep vein thrombosis but does not increase coronary heart disease risk. Contraindications to estrogen therapy include prior breast cancer, endometrial cancer, deep vein thrombosis, pulmonary embolism, liver disease, and unexplained vaginal bleeding. Levonorgestrel-containing intrauterine devices are sometimes used off-label for endometrial protection but lack FDA approval for this indication.[7]

Cardiovascular effects of systemic HRT depend strongly on treatment timing. Initiation within 10 years of the final menstrual period is associated with reduced cardiovascular disease and all-cause mortality. Hormone therapy, however, should not serve as a primary strategy for preventing heart disease.[22]

Transdermal estrogen is associated with fewer adverse effects on coagulation and inflammatory markers than oral estrogen and may reduce the risk of venous thromboembolism. Migraine with aura, therefore, does not contraindicate transdermal estrogen therapy.[13] Evidence also supports transdermal estrogen for the management of mood symptoms during the perimenopausal period.[14] Compounded bioidentical hormone preparations lack FDA approval because quality control, safety, and efficacy evaluations remain insufficient. Absence of controlled studies further limits their use, and avoidance of these products remains recommended.[7]

A United States Preventive Services Task Force statement published in November 2022 advises against systemic HRT for the primary prevention of chronic conditions in postmenopausal individuals.[7] Evidence supporting this recommendation derives largely from the Women's Health Initiative trials, which are the only studies with sufficient numbers of participants to evaluate the prevention of multiple chronic conditions.[2] Current indications for systemic HRT, therefore, focus exclusively on the treatment of menopausal symptoms.

Testosterone Treatment

Testosterone therapy may improve sexual desire, arousal, orgasm, and distress among postmenopausal women with hypoactive sexual desire disorder. Although guidelines support treatment because of quality-of-life effects, testosterone levels should not guide diagnosis and should serve only to prevent excessive dosing. Evidence does not demonstrate meaningful benefits for overall well-being, mood, cognitive performance, or musculoskeletal health, and current data do not support testosterone therapy for these aspects of menopause management.[23]

Local Estrogen Treatment

Local estrogen therapy addresses genitourinary syndrome of menopause, which frequently develops among women who do not receive systemic hormone therapy. Some individuals using systemic therapy also require additional local estrogen treatment for persistent urogenital symptoms. Systemic HRT alone does not reduce the risk of recurrent urinary tract infections, whereas local estrogen therapy lowers risk by acidifying vaginal pH and promoting a lactobacillus-dominant flora.[12]

Vaginal rings, creams, and tablets improve blood flow and reverse vaginal atrophy. Many women who are unable to receive systemic hormone therapy remain eligible for local estrogen therapy without progesterone supplementation. Full improvement in vulvovaginal health typically develops after 2 to 3 months of therapy.[12] Intravaginal dehydroepiandrosterone provides another treatment option for local menopausal symptoms and improves dyspareunia, vaginal dryness, vaginal pH, and vaginal maturation index.

Selective Estrogen Receptor Modulators 

Selective estrogen receptor modulators (SERMs), eg, raloxifene, tamoxifen, bazedoxifene, and ospemifene, demonstrate tissue-specific actions.[24] A SERM may act as an estrogen agonist in one type of tissue while functioning as an antagonist in another. Ospemifene carries approval for the treatment of genitourinary syndrome of menopause.[24] These compounds serve as versatile therapeutic agents for multiple medical conditions and may provide benefits for selected menopausal patients.

Additionally, oral ospemifene carries FDA approval for the treatment of dyspareunia related to menopause. Once-daily dosing produces improvements in vulvovaginal symptoms similar to local estrogen therapy. Breast cancer remains a contraindication, and therapy may increase venous thromboembolism risk.[12] 

Nonhormonal Treatment

Nonhormonal treatment options include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentin for vasomotor symptom management. Agents, eg, paroxetine, escitalopram, and venlafaxine, reduce hot flashes. Paroxetine remains the only FDA-approved medication for this indication and produces symptom improvement within 1 week of treatment initiation. Concurrent use of paroxetine or fluoxetine with tamoxifen should be avoided because of CYP2D6 inhibition.[25][26]

Gabapentin lacks FDA approval for vasomotor symptom treatment but demonstrates effectiveness in reducing hot flashes among menopausal women. Doses ranging from 900 mg/d to 2400 mg/d reduce hot flashes to a degree comparable with estrogen and may decrease episodes by up to 2 per day. Clonidine may offer modest benefit for mild symptoms but demonstrates lower effectiveness than SSRIs, SNRIs, and gabapentin, and therefore receives a limited recommendation.[25]

Recent research implicates neurokinin B activity at neurokinin 3 receptors (NK3R) within the hypothalamic infundibular nucleus in the pathogenesis of hot flashes. Neurokinin receptor antagonists demonstrate promising safety and effectiveness as nonhormonal therapies. Early studies suggest greater effectiveness than SNRIs.[26] Fezolinetant received FDA approval as a neurokinin 3 receptor antagonist for moderate-to-severe vasomotor symptoms and requires a single daily dose of 45 mg without titration. Headache represents the most common adverse effect. Oxybutynin administered at 2.5 mg or 5 mg twice daily or up to 15 mg extended-release daily may improve vasomotor symptoms in a dose-dependent manner.[25] Elinzanetant, a neurokinin-1,3 receptor antagonist, also modulates thermoregulatory pathways and offers another option for patients unable to receive hormonal therapy.[23][27]

Osteoporosis-Specific Treatment

Systemic HRT is FDA-approved for osteoporosis prevention but not for treatment. Women with osteoporosis who lack bothersome vasomotor symptoms should not receive HRT solely for bone disease management.[7] Bisphosphonates, denosumab, calcium supplementation, and vitamin D represent primary treatment strategies for menopausal osteoporosis. Bisphosphonates inhibit osteoclast-mediated bone resorption and demonstrate established safety and efficacy. High doses and prolonged use may lead to adynamic bone, which supports periodic treatment interruption because bone density preservation persists for several years.

Denosumab is a monoclonal antibody that targets the receptor activator of nuclear factor kappa-B ligand (RANKL). Inhibition of osteoclast activity decreases bone resorption and increases bone density, reducing fracture risk in menopausal women with osteoporosis. Administration is via subcutaneous injection every 6 months.[28]

Nonpharmacologic Remedies

Evidence supporting dietary modification for vasomotor symptom relief remains limited.[25] Complementary and alternative approaches include phytoestrogens, vitamin E, and omega-3 fatty acids. Vitamin E, milk thistle, and omega-3 fatty acids are safe but do not perform better than a placebo in clinical studies. Other interventions, eg, relaxation therapy, cannabinoids, wild yam, dong quai, evening primrose oil, ginseng, chaste berry, phytoestrogens, exercise, black cohosh, chiropractic therapy, and acupuncture, show no consistent benefit for vasomotor symptoms.[7]

Lifestyle measures, including breathable clothing, fans or cold packs under pillows, cooler room temperatures, and forehead cooling devices, remain feasible but lack demonstrated benefit in clinical trials. Exercise, yoga, and avoidance of triggers such as hot beverages and certain foods also lack consistent evidence. Weight reduction, hypnosis, and cognitive behavioral therapy may provide improvement for some women experiencing vasomotor symptoms.[25]

Minimally ablative fractional carbon dioxide laser therapy of the vagina causes skin resurfacing but remains a controversial and costly approach with unknown long-term effects on the vagina. More studies must be performed before the wide use of laser therapy is recommended.[12]

Differential Diagnosis

Typical menopausal symptoms occurring at age 45 or older support a clinical diagnosis of menopause without the need for laboratory testing. Evaluation in younger women requires exclusion of alternative causes of secondary amenorrhea. Pregnancy represents the most common cause of secondary amenorrhea and requires initial exclusion during diagnostic assessment.[29]

Anatomic abnormalities may contribute to amenorrhea in women younger than 45 years. Asherman syndrome, characterized by scarring of the uterine cavity, frequently develops after dilation and curettage. Chronic endometritis associated with infections, particularly tuberculosis, may also produce intrauterine scarring and disrupt normal menstruation.[30]

Dysfunction of the hypothalamic-pituitary-gonadal axis also contributes to amenorrhea. Potential etiologies include obesity, anorexia, bulimia, chronic illnesses, eg, kidney disease and inflammatory bowel disease, certain medications, excessive exercise, poor nutrition, psychological stress, and malignancy.[29] Additional considerations include celiac disease, adrenal disorders, chemotherapy or radiation exposure, Sheehan syndrome involving necrosis of the anterior pituitary, and pituitary adenoma. Ovarian dysfunction related to ovarian tumors, polycystic ovarian syndrome, and premature ovarian insufficiency also forms part of the differential diagnosis for absent menses in women younger than 45 years.[29]

Staging

During the Stages of Reproductive Aging Workshop (STRAW) in 2011, 41 scientists convened to establish the STRAW +10 staging system, which proposed modifications to the original STRAW staging framework.[6] This system subsequently became the gold standard for staging menopause and has advanced the understanding of women’s health.[31] The STRAW +10 criteria apply to most women and rely primarily on menstrual cycle characteristics, with laboratory findings serving as supportive criteria. The system divides the female reproductive lifespan into 3 broad categories: reproductive, menopausal transition, and postmenopause. Menopause corresponds to point 0 within this framework. The STRAW criteria describe 10 stages, with 5 stages preceding the final menstrual cycle and 2 stages following.[31]

Reproductive Stage (Stages -5, -4, -3b and -3a)

The reproductive stage includes stages -5, -4, and -3b and -3a, and begins with menarche. Regular menstrual cycles characterize this phase, although early cycles following menarche may demonstrate variability. Slight changes in menstrual flow, including lighter or heavier bleeding, and variations in cycle duration may occur before progression to later stages.

Supportive laboratory evaluation during the late reproductive stage may show low to variable FSH levels when blood samples are collected between days 2 and 5 of the menstrual cycle. Stage -3 of the late reproductive period includes the substages -3b and -3a, which differ in menstrual cycle characteristics and associated FSH levels.[31]

Menopausal Transition Stage (Stages -2 and -1)

The menopausal transition stage includes stages -2 and -1 and represents the period during which perimenopause commonly occurs. This phase is divided into early menopausal transition (-2) and late menopausal transition (-1). Early in this transition, menstrual cycle length becomes variable, with cycle intervals differing by 7 or more days between cycles. Progressive changes during this stage may lead to episodes of amenorrhea lasting 60 or more days.

Development of such prolonged amenorrhea signals entry into the late menopausal transition stage (-1), which typically occurs 1 to 3 years before the final menstrual period. Supportive laboratory findings may demonstrate variable elevation of FSH during the early transition phase and FSH levels greater than 25 IU/L during the late transition phase. Declining estrogen production contributes to the FSH elevation above 25 IU/L.[31] Vasomotor symptoms frequently begin during stage -1.[31]

Postmenopause Stage (Stages +1a, +1b, +1c, and stage +2)

Postmenopause begins after cessation of menstruation. Perimenopause continues until the absence of menstruation persists for 1 year. Early postmenopause corresponds to stage +1 and includes substages +1a, +1b, and +1c. Stage +1a encompasses the 12 months following the final menstrual period. Stage +1b represents the year preceding stage +1c. Stage +1c marks stabilization of elevated FSH levels and low estradiol concentrations, after which early postmenopause continues for an additional year.

Supportive laboratory evaluation during this interval typically demonstrates FSH levels greater than 40 IU/L, and vasomotor symptoms frequently occur. As postmenopause progresses, laboratory findings show stabilization of FSH levels along with a very low antral follicle count. After 3 to 6 years, progression to late postmenopause, designated as stage +2, occurs. Symptoms of urogenital atrophy often become more prominent during this stage. Stage +2 continues through the remainder of life.[31]

Prognosis

Menopause is defined as the point occurring 12 months after a woman’s final menstrual period. The menopausal transition and postmenopausal stages, however, can span several years. Vasomotor symptoms, including hot flashes and night sweats, commonly persist for more than 7 years and may continue beyond 10 years after the final menstrual period in some women.[7] Without treatment, these symptoms typically resolve after approximately 7.4 years, although 10% to 20% of women experience intolerable hot flashes.[26] The Study of Women’s Health Across the Nation (SWAN), one of the largest and longest longitudinal studies, began in 1996 and followed over 3,000 women across multiple sites in the United States. This study collected interviews and questionnaires from diverse racial and ethnic groups to improve understanding of the menopausal transition and midlife aging.

For women experiencing moderate to severe vasomotor symptoms, HRT may provide significant relief. Additional pharmacologic options can be tailored to address specific bothersome symptoms. With appropriate treatment, the overall prognosis for managing menopausal symptoms is favorable, allowing most women to maintain quality of life throughout the transition.

Complications

Long-term complications of menopause are largely linked to decreased estrogen levels, with cardiovascular disease and osteoporosis representing the most significant health concerns.

Cardiovascular Disease

The decline in estrogen during menopause increases a woman’s risk for cardiovascular disease. This heightened risk results from multiple physiologic changes, including adverse shifts in lipid profiles, impaired arterial endothelial function, and activation of the renin-angiotensin system.[22] Women who have reached menopause experience coronary heart disease rates 2 to 3 times higher than those of the same age who remain premenopausal. To reduce potential risk factors, menopausal and postmenopausal women are advised to follow a heart-healthy diet, engage in regular physical activity, and maintain a healthy lifestyle.

Osteoporosis

Osteoporosis affects more than 250,000 menopausal and postmenopausal women. Bone loss, or decreased bone density, results primarily from estrogen deficiency. Starting at age 40, women lose bone at a rate of 0.3% to 0.5% per year. During menopause, the rate accelerates to 3% to 5% per year for 5 to 7 years. The Women’s Health Initiative and other studies demonstrated that hormone therapy effectively reduces osteoporotic fractures by protecting against bone loss. Long-term hormone therapy carries certain risks, prompting the use of additional preventive strategies. Recommended measures include smoking cessation, regular physical activity, adequate calcium intake, and nonhormonal treatments, eg, bisphosphonates and denosumab, which inhibit bone resorption. Anabolic agents like teriparatide and romosozumab provide a second class of therapy to stimulate bone formation in postmenopausal women.[32]

Deterrence and Patient Education

Key educational information that should be shared with patients includes:

• Patients should be encouraged to stop smoking, especially if considering starting HRT.
• Women should aim to do 150 minutes of cardiovascular exercise per week and 2 to 3 days of weight-bearing exercise.
• Women should eat a healthy diet to maintain a healthy weight.
• Women should feel comfortable speaking to a healthcare practitioner if they are having painful intercourse. 
• Contraception is recommended until menopause or age 50 to 55, as the specific age at which reproductive capacity ends is unknown. HRT is not a reliable method of contraception.[21]
• If bothersome menopausal symptoms are present, discussion with a clinician is encouraged because many treatment options are available. 
• Compounded bioidentical hormone therapy is not recommended for use due to a lack of data regarding efficacy and safety, as well as unsubstantiated marketing claims.[33] 

Pearls and Other Issues

Menopause is a natural, irreversible transition marked by estrogen deficiency leading to vasomotor, genitourinary, and metabolic changes. Key pearls to clinicians should bear in mind include individualized symptom management, attention to cardiovascular and bone health, and counseling on hormone and nonhormonal therapies. Pitfalls include overlooking genitourinary syndrome of menopause and underestimating symptom burden; prevention focuses on lifestyle optimization and early evaluation to support long-term health and quality of life. Contraception is recommended for 1 year after menopause for women older than 50 and for 2 years after menopause for women younger than 50.[23]

Enhancing Healthcare Team Outcomes

Although menopause is a physiological condition and not a disease, it can have significant associated morbidity. The symptoms of menopause, particularly vasomotor symptoms, are at times poorly tolerated and lead to poor quality of life. Most menopausal women are seen in clinical practice by advanced care practitioners, gynecologists, primary care physicians, or internists. Effective care for menopausal patients requires collaboration among physicians, general practitioners, advanced practitioners, nurses, pharmacists, and other healthcare professionals.

Healthcare professionals, including nurses and pharmacists, should educate patients on the stages and expectations of menopause and the perimenopausal years. Women who struggle to tolerate symptoms of menopause should be offered individualized treatment based on their symptoms, desires, and risk factors. Hormonal agents should only be used to treat vasomotor symptoms for the shortest period of time needed and at the lowest dose for symptom relief. HRT is not recommended to prevent chronic diseases; therefore, additional skills, strategies, and care coordination of health professionals are necessary to utilize other methods of chronic disease prevention for women.

Nurses can play various roles, including emphasizing patient education and preventative measures. Dietitians can help educate patients on maintaining a healthy diet and weight. Women should be encouraged to exercise regularly, discontinue smoking, and be offered systemic or local estrogen therapy if symptoms indicate a need. Since perimenopause can also result in mood changes, a mental health care practitioner may be recommended to enhance patient outcomes. Clinicians should be aware of the various body systems affected by menopause and be alert to strategies to minimize postmenopausal complications. The pharmacist may help in communication by teaching and urging women not to take untested, unregulated compounded hormones and products and to seek guidance from reliable clinicians. Clear interprofessional communication and coordinated care help optimize treatment selection, address patient concerns, reduce complications, and improve patient-centered outcomes throughout the menopausal transition and postmenopausal years.

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References

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Disclosure: Karen Carlson declares no relevant financial relationships with ineligible companies.

Disclosure: Elsa Vadakekut declares no relevant financial relationships with ineligible companies.