Menopause is the natural biological process marking the permanent cessation of menstrual cycles and the end of a woman's reproductive years, typically occurring between the ages of 45 and 55, with an average age of onset around 51 [1][2]. It is confirmed after a woman has gone 12 consecutive months without a menstrual period, reflecting a decline in ovarian function and reduced production of key hormones such as estrogen and progesterone [3]. The transition leading up to menopause, known as perimenopause, is characterized by hormonal fluctuations that can cause a wide range of physical and emotional symptoms, including hot flashes, night sweats, sleep disturbances, vaginal dryness, and mood changes [4]. These symptoms arise from dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, particularly involving follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which rise as ovarian feedback diminishes [5]. Management options include menopausal hormone therapy (MHT) for symptom relief and prevention of osteoporosis, as well as non-hormonal treatments such as SSRIs, gabapentin, and newer agents like neurokinin-3 (NK3) receptor antagonists (e.g., fezolinetant) [6]. Lifestyle modifications, including diet, physical activity, and cognitive-behavioral therapy (CBT), also play a crucial role in symptom management and long-term health [7]. The experience of menopause is influenced by sociocultural factors, with variations in symptom perception and help-seeking behaviors across different racial, ethnic, and socioeconomic groups, as well as between high-income and low- and middle-income countries [8].
Definition and Diagnosis of Menopause
Menopause is defined as the point at which a woman has experienced 12 consecutive months without a menstrual period, marking the permanent cessation of ovarian function and the end of her reproductive years [4]. This natural biological process occurs when the ovaries cease releasing eggs and significantly reduce the production of key hormones such as estrogen and progesterone [1]. It is not a disease but a milestone in a woman’s life, typically occurring between the ages of 45 and 55, with the average age of onset around 51 years, particularly in the United States and many other countries [2][12]. While this represents the typical range, menopause can occur earlier due to factors such as genetics, surgical removal of the ovaries (bilateral oophorectomy), chemotherapy, or certain health conditions [4].
Stages of the Menopausal Transition
The journey to menopause involves three distinct stages: perimenopause, menopause, and postmenopause. Perimenopause is the transitional phase leading up to menopause, typically beginning in a woman’s 40s but sometimes as early as the 30s or as late as the 50s [14]. During this time, the ovaries gradually produce less estrogen and progesterone, leading to irregular menstrual cycles and symptoms such as hot flashes, mood swings, sleep disturbances, and vaginal dryness [15]. Perimenopause can last for several years—on average around four, but sometimes up to ten—before menopause occurs [16]. Menopause is the specific point confirmed after 12 consecutive months without a period, signifying the end of fertility [3]. Postmenopause begins immediately after menopause and lasts for the rest of a woman’s life [18]. During this phase, hormone levels stabilize at low levels, and while many symptoms may decrease, the long-term effects of low estrogen increase the risk of conditions such as osteoporosis and heart disease [19].
Key Diagnostic Criteria and Clinical Indicators
The diagnosis of physiological menopause in women aged 45 years and older is primarily clinical, based on age, symptoms, and menstrual history, and does not routinely require laboratory confirmation [7]. The primary clinical indicator is the absence of menstrual periods for 12 consecutive months in the absence of other biological or physiological causes such as pregnancy or hormonal contraception [21]. Supportive symptoms that align with this diagnosis include vasomotor symptoms (hot flashes, night sweats), menstrual irregularity progressing to amenorrhea, sleep disturbances, mood changes, and vaginal dryness [1]. Current guidelines from the National Institute for Health and Care Excellence (NICE), the European Society of Endocrinology, and other professional bodies emphasize that routine hormone testing is not recommended for diagnosing menopause in this age group due to the significant fluctuations in hormone levels during perimenopause, which render single measurements unreliable [7].
Hormonal Markers and Laboratory Testing
While laboratory testing is not routinely needed, certain hormonal markers can provide supportive evidence in specific clinical scenarios. Follicle-stimulating hormone (FSH) is the most widely used endocrine marker. As ovarian follicular reserve declines, reduced negative feedback from inhibin B and estradiol leads to elevated FSH levels. A single FSH level greater than 30 mIU/mL is generally considered indicative of ovarian insufficiency and may support a diagnosis of perimenopause or early postmenopause [24]. However, due to cycle-to-cycle variability during perimenopause, a normal or low FSH level does not exclude the diagnosis, especially in women with classic symptoms [25]. Estradiol levels, the primary biologically active estrogen, typically fall below 30 pg/mL in postmenopause, but their high variability during perimenopause limits their diagnostic utility [26]. Anti-Müllerian hormone (AMH), a sensitive biomarker of ovarian reserve, declines progressively and can become undetectable several years before the final menstrual period, making it useful for predicting the timing of menopause but not for confirming its occurrence [27]. Hormonal assays are most appropriate for women under 45 with suspected premature ovarian insufficiency, those with unclear menstrual status (e.g., after hysterectomy), or for fertility counseling [28].
Differentiating Normal, Premature, and Pathological Menopause
It is crucial to differentiate normal physiological menopause from premature or pathological forms. Premature menopause, also known as primary ovarian insufficiency (POI), is defined as menopause occurring before age 40 and affects approximately 1% of women [29]. It is diagnosed by the absence of menstruation for at least four months, elevated FSH levels (>25–30 IU/L) on two occasions at least 4–6 weeks apart, and associated symptoms [30]. A comprehensive evaluation is required, including pregnancy exclusion, karyotype analysis, and genetic testing for conditions like fragile X premutation [31]. Early menopause, occurring between ages 40 and 45, also warrants evaluation to rule out contributing factors such as autoimmune disease or chemotherapy exposure [7]. Pathological (induced) menopause results from medical interventions such as bilateral oophorectomy, chemotherapy, or pelvic radiation, which cause an abrupt and immediate loss of ovarian function, often leading to more severe symptoms than natural menopause [2]. This distinction is vital for appropriate counseling and long-term health management, particularly regarding bone and cardiovascular health.
Biological and Hormonal Changes
Menopause is fundamentally driven by the natural aging of the female reproductive system, particularly the progressive decline and eventual cessation of ovarian function. This process, known as ovarian aging, results in a profound shift in the endocrine system, disrupting the delicate balance of hormones that regulate the menstrual cycle, fertility, and various physiological processes throughout the body. The biological changes culminate in the permanent cessation of menstruation and mark the transition from a reproductive to a non-reproductive state.
Ovarian Aging and Follicular Depletion
The biological foundation of menopause lies in the depletion of the ovarian reserve—the finite pool of oocytes (egg cells) and their surrounding follicles present at birth. Throughout a woman's life, this reserve is gradually depleted through the processes of ovulation and atresia (natural degeneration). By the time of menopause, the ovarian follicles are nearly exhausted, leading to a loss of cyclic follicular development and ovulation [34]. This depletion begins long before the final menstrual period and is the primary trigger for the cascade of hormonal changes associated with the menopausal transition. The loss of follicular activity means the ovaries can no longer produce the hormones necessary to sustain the menstrual cycle.
Key Hormonal Shifts and the Hypothalamic–Pituitary–Gonadal (HPG) Axis
The hormonal changes of menopause are governed by the disruption of the hypothalamic–pituitary–gonadal (HPG) axis. This complex feedback system, which normally regulates reproductive function, becomes dysregulated as ovarian function declines.
Decline in Ovarian Hormones
The most significant hormonal changes are the dramatic reduction in the production of two key ovarian hormones: estrogen (specifically estradiol) and progesterone. Estradiol, the primary biologically active estrogen, is secreted by developing ovarian follicles. As follicles are depleted, estradiol levels fall, leading to a sustained hypoestrogenic state in postmenopause, with levels typically dropping below 20 pg/mL [35]. Progesterone, produced by the corpus luteum after ovulation, also plummets as ovulation ceases. The decline in these hormones is responsible for the wide array of physical and emotional symptoms experienced during menopause, including hot flashes, vaginal dryness, and mood changes.
Rise in Pituitary Hormones
As estrogen and inhibin (a hormone that suppresses follicle-stimulating hormone) levels fall, the negative feedback on the pituitary gland is lost. In response, the pituitary dramatically increases its secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in an attempt to stimulate the non-responsive ovaries. This results in a characteristic and sustained elevation of these gonadotropins. FSH levels, in particular, rise sharply and are a key diagnostic marker, often exceeding 30 IU/L and reaching up to 134.8 IU/L in postmenopause, compared to 4.7–21.5 IU/L in reproductive years [36]. LH levels also increase, peaking two to three years after menopause before gradually declining [37]. This persistent elevation of FSH and LH is a hallmark of postmenopause.
Hormonal Markers and the Menopausal Transition
The menopausal transition, or perimenopause, is characterized by increasing hormonal variability rather than a simple linear decline. This phase can last several years and is marked by erratic fluctuations in hormone levels.
Fluctuating Estradiol and Inhibin
During perimenopause, estradiol levels can be highly variable, sometimes reaching supraphysiological levels due to erratic follicular development and anovulatory cycles, followed by prolonged periods of hypoestrogenism [35]. Similarly, inhibin B, which provides a key brake on FSH secretion, declines early and consistently, contributing to the rise in FSH even before estradiol levels drop significantly [39].
Anti-Müllerian Hormone (AMH) as a Marker of Ovarian Reserve
Anti-Müllerian hormone (AMH), produced by preantral and small antral follicles, is a sensitive biomarker of ovarian reserve. AMH levels decline progressively during the menopausal transition and typically become undetectable about five years before the final menstrual period, reflecting the diminishing number of developing follicles [27]. While AMH is a valuable tool for assessing ovarian reserve and predicting the timing of menopause, it does not confirm menopausal status, as it can still be detectable in perimenopausal women with symptoms.
Neuroendocrine Mechanisms of Vasomotor Symptoms
The decline in estrogen has profound effects on the central nervous system, particularly in the hypothalamus, which governs thermoregulation. The loss of estrogen's stabilizing influence on the hypothalamic thermostat narrows the body's thermoneutral zone—the range of temperatures within which no heat-loss or heat-conservation mechanisms are triggered. This makes the system hypersensitive to minor changes in core temperature, leading to inappropriate activation of heat-dissipation responses like sweating and vasodilation, experienced as a hot flash or night sweat [41].
A key neuroendocrine mechanism involves the kisspeptin-neurokinin B-dynorphin (KNDy) neurons in the hypothalamic arcuate nucleus. As estrogen levels fall, these neurons become hyperactive, increasing the release of neurokinin B (NKB). NKB acts on neurokinin 3 receptors (NK3R) in the preoptic area of the hypothalamus, directly triggering the heat-loss response. This pathway explains the effectiveness of newer non-hormonal treatments like fezolinetant, an NK3 receptor antagonist, which blocks this signaling cascade to reduce vasomotor symptoms [42].
Common Signs and Symptoms
Menopause is a natural biological process marking the end of menstrual cycles and fertility in women, typically occurring between the ages of 45 and 55. It is diagnosed after 12 consecutive months without a menstrual period. The transition leading up to menopause, known as perimenopause, often brings a wide range of physical and emotional symptoms due to hormonal fluctuations, particularly declining estrogen levels [4].
Most Common Physical Symptoms
Hot Flashes and Night Sweats
Hot flashes are among the most prevalent symptoms, affecting up to 75% of women. They involve sudden feelings of intense heat, often in the face, neck, and chest, accompanied by flushing, sweating, and sometimes chills afterward. These episodes can last from 30 seconds to several minutes and may continue for months or years [1]. Night sweats—hot flashes that occur during sleep—can disrupt rest and contribute to fatigue [45].
Sleep Disturbances
Many women experience sleep problems during menopause, including difficulty falling or staying asleep, and non-restorative sleep. These issues are often linked to night sweats but can also result from hormonal changes affecting sleep regulation, mood, or conditions like restless leg syndrome [46].
Vaginal and Urinary Changes
Declining estrogen leads to vaginal dryness, thinning of vaginal tissues, and reduced lubrication, which can cause discomfort or pain during sexual activity (dyspareunia) [47]. Urinary symptoms may include increased frequency, urgency, urinary tract infections (UTIs), and incontinence due to weakened pelvic floor muscles [48].
Menstrual Irregularities
During perimenopause, menstrual cycles often become irregular—longer, shorter, heavier, or lighter—before eventually stopping altogether. This is one of the earliest signs of the transition [49].
Emotional and Cognitive Symptoms
Mood Changes
Mood swings, irritability, anxiety, and low mood are commonly reported. These emotional shifts may be influenced by hormonal changes affecting brain chemicals like serotonin, as well as disrupted sleep and stress [50].
Cognitive Difficulties
Some women describe "brain fog," which includes forgetfulness, difficulty concentrating, and reduced mental clarity. While these changes are usually mild, they can affect daily functioning and are often temporary [49].
Other Common Symptoms
- Reduced libido: Decreased interest in sex is frequently reported, potentially due to hormonal changes, vaginal discomfort, or psychological factors [52].
- Joint and muscle pain: Women may experience aches, stiffness, or general discomfort in muscles and joints [49].
- Weight gain and body changes: Metabolism slows during menopause, often leading to weight gain, particularly around the abdomen. Changes in fat distribution and skin elasticity are also common [47].
- Skin and hair changes: Skin may become drier and less elastic, while hair may thin on the scalp and increase on the face due to hormonal shifts [55].
Variability of Symptoms
The type, severity, and duration of menopausal symptoms vary widely among individuals. Some women experience only mild symptoms, while others face significant challenges that impact quality of life. Factors such as genetics, lifestyle, overall health, and psychological well-being can influence symptom experience [47].
Symptoms typically begin during perimenopause and may persist for several years after menopause, with hot flashes and sleep disturbances sometimes lasting a decade or more [48]. Fortunately, various management strategies—including lifestyle modifications, menopausal hormone therapy (MHT), and nonhormonal treatments—are available to help alleviate symptoms and support well-being.
Stages of the Menopausal Transition
The menopausal transition is a multi-phase process that marks the end of a woman’s reproductive life, characterized by progressive changes in menstrual cycling and hormonal fluctuations. It is divided into three distinct stages: perimenopause, menopause, and postmenopause. Each stage is defined by specific physiological and clinical criteria, reflecting the gradual decline in ovarian function and reproductive hormone production [14].
Perimenopause
Perimenopause, also known as the menopausal transition, is the initial phase during which ovarian function begins to decline, leading to irregular menstrual cycles and the onset of menopausal symptoms. It typically begins in a woman’s 40s but can start as early as the 30s or extend into the early 50s [15]. This stage is marked by fluctuating levels of estrogen and progesterone, which disrupt the regularity of ovulation and menstruation [16].
During perimenopause, women may experience a range of physical and emotional symptoms, including hot flashes, mood swings, sleep disturbances, vaginal dryness, and irregular periods—ranging from shorter to longer cycles, or from light to heavy bleeding [4]. These symptoms arise from the dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, particularly due to declining levels of inhibin B and rising follicle-stimulating hormone (FSH) [39].
Perimenopause can last for several years, with an average duration of about four years, though it may extend up to ten years before the final menstrual period [16]. Hormonal testing during this phase is generally not recommended for diagnosis due to significant cycle-to-cycle variability; instead, clinical evaluation based on symptoms and menstrual history is sufficient for women over 45 [7].
Menopause
Menopause is not a process but a specific milestone defined as the point when a woman has gone 12 consecutive months without a menstrual period, confirming the permanent cessation of ovarian function [4]. It marks the end of fertility and typically occurs between the ages of 45 and 55, with an average age of onset around 51 [3].
At this stage, the ovaries have ceased releasing eggs and significantly reduced the production of key hormones, particularly estrogen and progesterone. This hormonal shift leads to the stabilization of symptoms for some women, although many continue to experience vasomotor symptoms such as hot flashes and night sweats for several years after menopause [48].
Menopause can also occur earlier due to medical interventions such as bilateral oophorectomy (surgical removal of the ovaries), chemotherapy, or pelvic radiation, which cause abrupt ovarian failure and are referred to as induced or pathological menopause [2]. Women undergoing surgical menopause often experience more severe symptoms due to the sudden drop in hormone levels, compared to the gradual decline seen in natural menopause.
Postmenopause
Postmenopause begins immediately after the 12-month mark of amenorrhea and continues for the remainder of a woman’s life [18]. During this phase, hormone levels stabilize at consistently low levels, particularly estrogen, which remains below 30 pg/mL, primarily derived from peripheral conversion of androgens in adipose tissue rather than ovarian synthesis [35].
While many acute symptoms such as hot flashes may diminish over time, the long-term hypoestrogenic state increases the risk of several chronic health conditions. These include osteoporosis due to accelerated bone loss, cardiovascular disease linked to adverse changes in lipid profiles and endothelial function, and genitourinary syndrome of menopause (GSM), which encompasses vaginal atrophy, dryness, and urinary symptoms such as urgency and recurrent infections [19].
Management during postmenopause often involves ongoing strategies to mitigate these risks, including lifestyle modifications such as dietary adjustments, regular physical activity, and, when appropriate, the use of menopausal hormone therapy (MHT) or non-hormonal treatments [72]. Women who initiated MHT during perimenopause or early postmenopause may continue treatment if benefits outweigh risks, with regular reassessment recommended every 6–12 months [73].
In summary, the menopausal transition is a dynamic process involving distinct stages—perimenopause, menopause, and postmenopause—each characterized by unique hormonal, physiological, and clinical features. Understanding these stages is essential for accurate diagnosis, effective symptom management, and long-term health promotion.
Management and Treatment Options
The management of menopausal symptoms is highly individualized, incorporating a range of hormonal and non-hormonal therapies, lifestyle modifications, and behavioral interventions tailored to symptom severity, patient preferences, and underlying health risks. Treatment decisions are guided by robust evidence from major clinical guidelines issued by organizations such as the North American Menopause Society (NAMS), the European Society of Endocrinology (ESE), and the National Institute for Health and Care Excellence (NICE) [74][7]. The overarching goal is to alleviate symptoms such as vasomotor symptoms, improve quality of life, and address long-term health risks like osteoporosis and cardiovascular disease.
Hormone Therapy: First-Line for Moderate to Severe Symptoms
Menopausal hormone therapy (MHT), also known as hormone replacement therapy (HRT), is the most effective treatment for moderate to severe vasomotor symptoms, including hot flashes and night sweats [76]. The 2022 NAMS position statement affirms that the benefits of MHT outweigh the risks for most healthy women under 60 years of age or within 10 years of menopause onset [76]. For women with an intact uterus, combined estrogen-progestogen therapy is required to prevent endometrial hyperplasia and cancer, while those who have undergone hysterectomy may receive estrogen-only therapy, which carries a more favorable risk profile [78]. Transdermal estrogen is preferred over oral formulations in women with increased cardiovascular risk due to its lower association with venous thromboembolism (VTE) [7]. The 2024 International Menopause Society White Paper emphasizes the use of low-dose and ultra-low-dose regimens to minimize systemic exposure while maintaining efficacy [80].
Non-Hormonal Pharmacological Therapies
For women who cannot or prefer not to use MHT, several evidence-based non-hormonal pharmacological options are available. The 2023 NAMS Nonhormone Therapy Position Statement identifies the following as having strong scientific evidence (Level I) for reducing vasomotor symptoms [73]:
- Selective serotonin reuptake inhibitors (SSRIs): Paroxetine (7.5 mg daily) is FDA-approved for vasomotor symptoms and reduces hot flash frequency and severity by 37–64% [73].
- Serotonin-norepinephrine reuptake inhibitors (SNRIs): Venlafaxine (37.5–75 mg/day) and desvenlafaxine (50–100 mg/day) are effective, particularly in women with comorbid depression or anxiety [73].
- Gabapentin and pregabalin: These anticonvulsants reduce vasomotor symptoms by 30–40%, with gabapentin particularly effective for night sweats [73].
- Fezolinetant: A neurokinin 3 (NK3) receptor antagonist approved in 2023, it targets the thermoregulatory center in the hypothalamus and significantly reduces vasomotor symptoms without hormonal effects [73].
- Oxybutynin: A low-dose transdermal formulation has shown modest benefit in reducing hot flashes, especially in women with concurrent overactive bladder [73].
Emerging Therapies: Neurokinin-3 Receptor Antagonists
Neurokinin-3 (NK3) receptor antagonists represent a paradigm shift in the treatment of vasomotor symptoms by directly targeting the neurokinin B (NKB) signaling pathway in the hypothalamic arcuate nucleus. During menopause, declining estrogen levels disinhibit KNDy neurons (kisspeptin-neurokinin B-dynorphin), leading to increased NKB release and overstimulation of NK3 receptors, which triggers inappropriate heat-dissipation responses [87]. Fezolinetant (Veozah) and elinzanetant block this pathway, providing hormone-free relief with high efficacy. In phase 3 trials, fezolinetant 45 mg daily reduced hot flash frequency by approximately 7–8 episodes per day by week 4, with a 73% responder rate (≥50% reduction in hot flash score) at 24 weeks [88]. These agents offer a significant advantage over traditional non-hormonal options, particularly for women with a history of breast cancer or thromboembolic disease, who cannot safely use MHT [89]. However, fezolinetant carries a boxed warning for rare serious liver injury, necessitating baseline and periodic monitoring of liver enzymes [90].
Local Treatments for Genitourinary Symptoms
The genitourinary syndrome of menopause (GSM), characterized by vaginal atrophy, dryness, itching, and discomfort during intercourse (dyspareunia), is effectively managed with local therapies. Low-dose vaginal estrogen, administered as creams, tablets, or rings, acts directly on urogenital tissues with minimal systemic absorption, making it safer for many women, including some with contraindications to systemic MHT [6]. In 2025, the FDA removed the black box warning from low-dose vaginal estrogen products, reflecting updated evidence on their safety profile [92]. For women who prefer non-hormonal options, vaginal moisturizers and lubricants are recommended as first-line treatments [93]. Systemic non-hormonal options include the oral selective estrogen receptor modulator (SERM) ospemifene, FDA-approved for moderate-to-severe dyspareunia, and intravaginal dehydroepiandrosterone (DHEA), which is locally converted into estrogen and androgens to improve tissue health [94][95].
Lifestyle and Behavioral Interventions
Lifestyle modifications play a foundational role in managing menopausal symptoms and promoting long-term health. Recommended strategies include:
- Diet and exercise: A balanced diet rich in calcium and vitamin D, combined with regular weight-bearing and aerobic activities like walking or dancing, supports bone health and may reduce symptom severity [96]. The has been shown to improve lipid profiles, lower blood pressure, and reduce inflammation [97].
- Managing hot flashes: Wearing light clothing, keeping rooms cool with fans or air conditioning, and avoiding triggers such as spicy foods, caffeine, alcohol, and stress can help reduce the frequency and intensity of hot flashes [98].
- Mental well-being: Practices such as yoga, meditation, tai chi, and cognitive-behavioral therapy (CBT) can help manage mood swings, anxiety, and sleep disturbances [96]. CBT is particularly effective, with evidence showing it reduces depressive symptoms, anxiety, and even the frequency and severity of hot flashes [100].
- Weight management: Even modest weight loss (5–10% of body weight) can significantly improve insulin sensitivity, lipid profiles, and blood pressure, and reduce the frequency of hot flashes [101].
Tailoring Treatment by Menopausal Stage
Treatment approaches must be individualized based on the stage of the menopausal transition, as defined by the Stages of Reproductive Aging Workshop (STRAW) criteria [102].
- Perimenopause: Characterized by erratic ovarian function and fluctuating hormone levels, management often includes low-dose combined hormonal contraceptives (CHCs) for women under 50 without contraindications to regulate cycles and alleviate symptoms [103]. The levonorgestrel-releasing intrauterine system (LNG-IUS) is highly effective for heavy menstrual bleeding and can be combined with systemic estrogen if needed [104].
- Early postmenopause: This period, within 10 years of the final menstrual period and typically before age 60, represents the optimal window for initiating MHT, known as the "timing hypothesis" [78].
- Late postmenopause: Initiating MHT after age 65 or more than 10 years from menopause onset is associated with increased risks and is generally not recommended [106]. Non-hormonal therapies are preferred for new-onset symptoms in this group.
Clinical Decision-Support Tools
Recent advances include the development of clinical decision-support tools to guide personalized treatment. The Menopause Decision-Support Algorithm and MenoPro app, developed by NAMS, integrate symptom severity, risk factors, and contraindications to recommend appropriate therapies [107]. Similarly, the MQ6 Menopause Management Tools provide interactive pathways for hormone and non-hormone therapy selection [108]. These tools support shared decision-making and reflect the shift toward precision pharmacology in menopause care [109].
Long-Term Health Risks and Prevention
The menopausal transition marks a pivotal period in a woman’s life associated with significant physiological changes that elevate long-term health risks, particularly in the domains of cardiovascular health, metabolic function, and bone integrity. The decline in estrogen levels removes protective effects on the cardiovascular system, alters body composition, and accelerates bone resorption, increasing susceptibility to chronic conditions such as cardiovascular disease (CVD), type 2 diabetes, and osteoporosis. However, this phase also presents a critical "window of opportunity" for early intervention, where evidence-based strategies can mitigate risks and promote healthy aging [110].
Cardiovascular and Metabolic Risks
Cardiovascular disease is the leading cause of death among postmenopausal women, with risk accelerating during the menopausal transition independent of chronological aging. The loss of estrogen contributes to a pro-atherogenic lipid profile, characterized by increased total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, along with decreased high-density lipoprotein (HDL) cholesterol [111]. Additionally, estrogen deficiency promotes visceral fat accumulation, insulin resistance, and endothelial dysfunction, all of which contribute to the development of metabolic syndrome and type 2 diabetes [112]. The ZOE PREDICT study demonstrated that postmenopausal women exhibit altered postprandial metabolic responses, including higher and more prolonged blood glucose and lipid excursions after meals, further amplifying cardiometabolic risk [113].
Elevated blood pressure, arterial stiffness, and a pro-inflammatory state also develop during this period, compounding cardiovascular vulnerability [114]. Notably, women are disproportionately affected by heart failure with preserved ejection fraction (HFpEF) after menopause, a condition linked to long-standing metabolic syndrome and diastolic dysfunction [115]. Early identification of these risks through routine screening—such as measuring blood pressure, fasting lipid panels, glucose, HbA1c, and waist circumference—is essential for timely intervention [116].
Bone Health and Osteoporosis Prevention
The decline in estrogen during menopause leads to accelerated bone loss, increasing the risk of osteoporosis and fractures. Bone mineral density (BMD) testing via dual-energy x-ray absorptiometry (DXA) is recommended by the U.S. Preventive Services Task Force (USPSTF) for all women aged 65 and older, and for younger postmenopausal women with fracture risk equivalent to that of a 65-year-old woman [117]. For women with premature ovarian insufficiency or early menopause (before age 45), screening should begin at diagnosis due to their significantly elevated risk [118].
Non-pharmacological prevention strategies are foundational and include weight-bearing and resistance exercises such as walking, jogging, and strength training, which improve bone density and reduce fall risk [119]. Adequate dietary intake of calcium (approximately 1,200 mg/day) and vitamin D (800 IU/day) is essential for bone metabolism and calcium absorption [120]. Smoking cessation, limiting alcohol intake, and maintaining a healthy body weight are also critical [121].
Pharmacological treatment is indicated for women with a T-score of ≤−2.5 (diagnostic of osteoporosis), a history of fragility fracture, or elevated fracture risk as determined by the Fracture Risk Assessment Tool (FRAX®) [122]. First-line agents include bisphosphonates such as alendronate and zoledronic acid, which reduce vertebral and non-vertebral fractures [123]. Menopausal hormone therapy (MHT) is also effective for preventing bone loss and is particularly beneficial for younger postmenopausal women with significant symptoms, though its use must be balanced against potential risks [124].
Evidence-Based Strategies for Long-Term Risk Reduction
Effective long-term risk reduction requires a multifaceted approach centered on lifestyle modification, individualized medical therapy, and regular monitoring. The Mediterranean diet, rich in fruits, vegetables, whole grains, and healthy fats, has strong evidence for improving lipid profiles, lowering blood pressure, and reducing inflammation [97]. Combined aerobic and resistance training improves insulin sensitivity, reduces visceral fat, and enhances glucose homeostasis [126].
For women with moderate to severe vasomotor symptoms, menopausal hormone therapy (MHT) initiated near menopause onset (before age 60 or within 10 years of menopause) is associated with a neutral or potentially beneficial cardiovascular profile, a concept known as the "timing hypothesis" [127]. Transdermal estrogen is preferred over oral formulations in women with cardiovascular risk factors due to a lower risk of venous thromboembolism [128]. For women who cannot use MHT, non-hormonal pharmacologic interventions such as SSRIs, gabapentin, and newer agents like neurokinin-3 (NK3) receptor antagonists (e.g., fezolinetant) are effective alternatives [73].
In high-risk women, pharmacologic interventions such as statins for lipid management and GLP-1 receptor agonists for weight loss and glycemic control may be indicated [130]. Clinical decision-support tools like the MenoPro app and organ-specific algorithms help tailor interventions based on individual risk profiles, supporting shared decision-making and precision pharmacology in menopause care [107].
Psychological and Emotional Well-Being
The menopausal transition is a significant developmental phase that brings profound biological, psychological, and social changes, often converging to influence women's mental health. Hormonal fluctuations, particularly the decline and variability of estrogen and progesterone, interact with midlife psychosocial stressors to shape the emotional experience of menopause. This interplay can lead to a range of psychological challenges, including mood swings, anxiety, and depressive symptoms, which are reported across multiple studies and are linked to the neurobiological shifts characteristic of this life stage [132]. Research indicates that approximately 28% of postmenopausal women experience depression, with elevated rates of anxiety and depressive symptoms observed during the perimenopausal phase [133]. Sleep disturbances, often triggered by vasomotor symptoms such as hot flashes and night sweats, further exacerbate mood instability and emotional regulation [134].
Hormonal Influences on Mood and Cognition
The primary hormonal changes during menopause play a central role in emotional and cognitive health. Estrogen has neuroactive properties that influence key brain regions involved in mood regulation, including the prefrontal cortex, hippocampus, and amygdala [135]. It modulates neurotransmitters such as serotonin, dopamine, and norepinephrine, which are critical for emotional stability [136]. As estrogen levels decline, particularly during perimenopause, disruptions in these systems can increase vulnerability to mood disorders [50]. Women with a history of depression, premenstrual dysphoric disorder (PMDD), or postpartum depression are at higher risk for first-onset or recurrent mood disorders during the menopausal transition [138]. The Study of Women’s Health Across the Nation (SWAN) found that the risk of depressive symptoms increases during perimenopause, independent of life stressors, underscoring the biological vulnerability conferred by hormonal changes [139]. Cognitive changes—commonly described as "brain fog"—are also prevalent, including difficulties with concentration, memory lapses, and reduced processing speed, particularly affecting verbal memory [140]. While these cognitive symptoms are typically transient and improve after menopause, they can significantly impact daily functioning and self-confidence [141].
Interaction with Midlife Life Stressors
Hormonal shifts often coincide with major psychosocial transitions that amplify mental health challenges, creating what some researchers describe as a "midlife collision," where biological, psychological, and social stressors intersect [142]. As children leave home, many women experience "empty nest syndrome"—a term describing feelings of grief, loss of purpose, and loneliness [143]. While not a clinical diagnosis, this transition can trigger identity shifts and depressive symptoms, particularly when it coincides with menopausal symptoms, reducing psychological resilience [144]. Midlife women are frequently part of the "sandwich generation," balancing responsibilities for children and aging parents [145]. The emotional toll of witnessing parental decline, managing healthcare decisions, and providing practical support contributes to chronic stress, burnout, and anxiety [146]. This role strain is associated with increased cortisol levels and reduced mental well-being [147]. Midlife often involves career reevaluation, job changes, or challenges related to ageism and workplace dynamics. Women may face pressures to remain competitive in evolving industries while managing health changes and caregiving duties [142]. These stressors can erode self-esteem and contribute to anxiety or depressive symptoms, particularly when compounded by menopausal fatigue or cognitive changes.
Evidence-Based Psychological Interventions
Effective psychological support for menopausal women integrates biological understanding with psychosocial context. Cognitive-behavioral therapy (CBT) is a first-line psychological intervention for managing menopausal emotional symptoms. It helps women identify and reframe negative thought patterns related to aging, body image, and role changes. Clinical trials, including the MENOS1 and MENOS2 studies, demonstrate that CBT reduces depressive symptoms, anxiety, and sleep disturbances, and can even decrease the frequency and severity of hot flashes [100]. NICE guidelines recommend access to CBT as part of comprehensive menopause care [150]. Mindfulness-based interventions, including Mindfulness-Based Stress Reduction (MBSR), have shown significant benefits in reducing anxiety, depression, and perceived stress during menopause [151]. By cultivating present-moment awareness and non-judgmental acceptance, mindfulness helps women manage physical symptoms and emotional reactivity [152]. A 2023 meta-analysis confirmed that mindfulness practices improve psychological well-being and quality of life in menopausal women [153]. Supportive interventions should also address systemic factors, including psychoeducation about menopause, peer support groups to reduce isolation, workplace accommodations, and culturally responsive care [154].
Sociocultural Influences on Emotional Experience
Sociocultural factors profoundly shape women’s emotional experiences and coping strategies during menopause. In many Western societies, aging in women is often stigmatized, with cultural narratives emphasizing youth, fertility, and physical appearance as central to female value [155]. This can lead to internalized ageism and body dissatisfaction, exacerbating emotional distress such as anxiety, depression, and lowered self-esteem [156]. Conversely, in some non-Western or Indigenous cultures, menopause is viewed more positively—as a transition into elder status, wisdom, and increased social authority. For example, in certain matrilineal societies such as the Mosuo in China, menopause is associated with greater autonomy and social power, contributing to lower rates of depression and fewer reported symptoms compared to patriarchal societies [157]. Racial and ethnic identity also plays a critical role; research consistently shows that Black, Hispanic, and other racially and ethnically minoritized (REM) women in the United States experience more severe menopausal symptoms, including hot flashes, sleep disturbances, and depressive symptoms, compared to their White counterparts [158]. These disparities are rooted in systemic racism, chronic stress, and inequitable access to healthcare [159]. Socioeconomic status (SES) intersects with race and gender to further shape emotional outcomes, with women of lower SES facing greater psychosocial stressors linked to earlier menopause onset and increased symptom severity [160].
Sociocultural and Global Perspectives
The experience of menopause is profoundly shaped by sociocultural factors, including societal attitudes toward aging, gender roles, racial and ethnic identity, and socioeconomic status. These elements influence how menopause is perceived—whether as a natural life stage, a medical condition, or a source of stigma—and affect symptom reporting, help-seeking behaviors, and access to care. Cultural narratives around femininity, fertility, and the value of older women play a critical role in determining whether menopause is experienced as a crisis or a transition into a phase of wisdom and empowerment [8].
Cultural Interpretations of Menopause
Menopause is not merely a biological event but a socially constructed phenomenon, interpreted differently across cultures. In many Western societies, menopause has been medicalized as a hormonal deficiency requiring intervention, reinforcing the idea that aging in women is a pathological process [162]. This framing often equates female value with youth and fertility, contributing to negative self-perceptions and psychological distress during the menopausal transition [163]. In contrast, some non-Western and Indigenous cultures view menopause as a rite of passage into elder status, associated with increased social authority, spiritual maturity, and liberation from reproductive responsibilities.
For example, among the Mosuo people of China, a matrilineal society, menopausal women often become household heads and key decision-makers, managing property and mediating family disputes [164]. Similarly, Māori women in New Zealand are reclaiming ruahinetanga—the Māori concept of menopause—as a culturally significant transition involving spiritual renewal and increased responsibility [165]. These cultural frameworks position menopausal women as knowledge-holders and community leaders, fostering a sense of identity and purpose that contrasts sharply with the medicalized model.
Racial and Ethnic Disparities in Symptom Experience and Care
Racial and ethnic background significantly influences both the severity of menopausal symptoms and access to treatment. Studies show that Black, Hispanic, and other racially and ethnically minoritized (REM) women in the United States experience more severe vasomotor and psychological symptoms than their White counterparts [158]. Black women reach menopause approximately 8.5 months earlier on average and face a higher burden of hot flashes, sleep disturbances, and depressive symptoms [167].
These disparities are rooted in systemic racism, chronic stress, and inequitable access to healthcare. Despite higher symptom severity, REM women are less likely to receive menopausal hormone therapy (MHT) or mental health support, reflecting broader inequities in women’s health care [168]. Cultural beliefs also shape symptom interpretation; for instance, among women of African descent, menopause may be understood through spiritual or community-based frameworks that emphasize endurance and resilience [169]. In South Asian Canadian women, cultural expectations around modesty and family honor may discourage open discussion of menopausal symptoms, affecting emotional well-being and self-image [170].
Socioeconomic Status and Access to Care
Socioeconomic status (SES) intersects with race and gender to shape menopausal experiences. Women with lower SES often face greater psychosocial stressors—such as financial insecurity, unsafe neighborhoods, and limited healthcare access—which are linked to earlier menopause onset and increased symptom severity [160]. Chronic stress activates physiological pathways that may worsen vasomotor and mood symptoms, creating a feedback loop between social adversity and emotional distress [172].
In high-income countries (HICs), women are more likely to seek medical care for menopausal symptoms, supported by greater awareness and availability of treatments like MHT. However, even within HICs, access to care is unequal. In the UK, for example, access to menopause care is described as a “postcode lottery,” where treatment availability varies by region, and socioeconomic marginalization is linked to delayed diagnosis and unmet care needs [173]. Women with higher income, education, and stable partnerships are more likely to receive MHT, while those from deprived backgrounds face systemic barriers [174].
Global Disparities in Menopause Care
In low- and middle-income countries (LMICs), women face substantial obstacles to help-seeking due to cultural stigma, silence, and taboos around menopause and sexual health [175]. In Iran, postmenopausal women report barriers related to social taboos and lack of knowledge, particularly regarding sexual symptoms, which are rarely discussed with healthcare providers [176]. In India, rural women face limited healthcare access, low awareness, and higher rates of premature menopause, compounding the challenges of seeking care [175].
Pharmacist surveys in Sri Lanka, Nepal, and Nigeria reveal inconsistent availability of HRT, with access rates ranging from 42% in Nigeria to 92.7% in Nepal, highlighting supply chain and regulatory challenges [178]. Cost is another major barrier: even when available, HRT may be unaffordable for many women, particularly in rural or impoverished areas [179]. Healthcare providers in LMICs often lack training in menopause management, contributing to low recognition and treatment of symptoms [180].
Traditional and Indigenous Remedies
In many LMICs and non-Western communities, traditional and complementary medicine (T&CM) plays a critical role in menopause management due to limited access to formal healthcare. Women frequently rely on herbal remedies and indigenous knowledge passed through generations. In South Africa, Sceletium tortuosum (kanna) and Buddleja salviifolia (lelothoane) are used to manage mood swings and hot flashes [181]. In Burkina Faso, traditional healers use plant-based treatments for menopause-related disorders, reflecting a deep integration of local knowledge into health practices [182].
In East Asia, Traditional Chinese Medicine (TCM), Japanese Kampō, and Korean medicine utilize herbal formulations, acupuncture, and qi regulation to restore balance during the menopausal transition [183]. These systems conceptualize menopause through frameworks such as kidney deficiency or yin-yang imbalance, emphasizing holistic regulation rather than isolated symptom treatment [184]. Women in non-Western communities often engage in “medical pluralism,” strategically navigating multiple healing systems based on symptom severity, accessibility, and cultural resonance [185].
Gender Norms and Power Dynamics
Gender norms and power dynamics within families and communities determine whether menopause is seen as a source of stigma or as a transition toward social empowerment. In patriarchal societies, menopause is often associated with the loss of reproductive capacity and diminished social value. In China, menopausal women may be labeled as “abnormal” or “hysterical,” leading to social exclusion and emotional abuse [186]. In Western workplaces, menopause is often framed as a source of “dirty” femininity, with symptoms like hot flashes seen as unprofessional, reinforcing shame and silence [187].
Conversely, in cultures where older women hold respected roles, menopause can be a rite of passage into authority. Among First Nations, Aboriginal, and African diasporic communities, menopause is often understood through Indigenous knowledge systems that emphasize balance, intergenerational connection, and holistic well-being [169]. These frameworks position menopausal women as healers and elders, whose lived experience confers legitimacy and leadership.
Shifting Discourses and Global Advocacy
A growing global movement is challenging the stigma of menopause and promoting narratives of empowerment. Organizations such as Menoglobal and the Menopause Global Alliance are advocating for menopause to be recognized as a natural life stage rather than a medical problem, promoting education, workplace support, and policy change [189]. In HICs, increased media attention and public campaigns have contributed to greater awareness and empowerment [190]. The World Health Organization (WHO) advocates for equitable, evidence-based, and culturally sensitive menopause care, emphasizing the need for national policies that address social determinants of health [2].
Clinical Guidelines and Patient Care
Clinical guidelines for menopause emphasize a patient-centered, evidence-based approach to diagnosis, symptom management, and long-term health promotion. These recommendations are developed by leading professional organizations such as the North American Menopause Society (NAMS), the European Society of Endocrinology (ESE), the National Institute for Health and Care Excellence (NICE), and the International Menopause Society (IMS), and are designed to support healthcare providers in delivering individualized care [74][7]. The foundation of effective menopause care lies in accurate diagnosis, shared decision-making, and the integration of hormonal and non-hormonal strategies tailored to a woman’s symptoms, medical history, and personal preferences.
Diagnosis and Clinical Evaluation
The diagnosis of menopause is primarily clinical and does not require laboratory confirmation in most cases. In women aged 45 years and older, menopause is confirmed after 12 consecutive months of amenorrhea in the absence of other biological causes [7]. This definition is supported by the World Health Organization (WHO) and major clinical guidelines [2]. Common symptoms that support the diagnosis include vasomotor symptoms such as hot flashes and night sweats, sleep disturbances, mood changes, and vaginal dryness.
Hormonal testing is not routinely recommended for diagnosing menopause in women over 45 with classic symptoms, due to the significant fluctuations in hormone levels during the perimenopausal transition [7]. However, in women aged 40–45 with irregular bleeding or uncertain diagnosis, measurement of follicle-stimulating hormone (FSH) may be helpful. A consistently elevated FSH level (>30 IU/L) on two occasions at least 4–6 weeks apart supports the diagnosis [36]. For women under 40 with amenorrhea and menopausal symptoms, evaluation for primary ovarian insufficiency (POI) is essential, involving FSH testing, karyotype analysis, and genetic screening for conditions such as fragile X premutation [31].
Hormonal and Non-Hormonal Treatment Strategies
Menopausal hormone therapy (MHT) remains the most effective treatment for moderate to severe vasomotor symptoms and is recommended as first-line therapy for symptomatic women under 60 years or within 10 years of menopause onset, when benefits outweigh risks [76]. For women with an intact uterus, combined estrogen-progestogen therapy is required to prevent endometrial hyperplasia, while those who have undergone hysterectomy may receive estrogen-only therapy [78]. Transdermal estrogen is preferred over oral formulations in women with increased cardiovascular risk due to its lower thrombotic risk [7].
For women who prefer or require non-hormonal options, several evidence-based alternatives are available. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine (7.5 mg daily) and serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine are effective for reducing hot flashes, particularly in women with comorbid depression or anxiety [73]. Anticonvulsants such as gabapentin and pregabalin also reduce vasomotor symptoms by 30–40%, with gabapentin particularly effective for night sweats [73]. Emerging therapies like neurokinin-3 (NK3) receptor antagonists (e.g., fezolinetant) offer a novel, non-hormonal mechanism by targeting the KNDy neuron pathway in the hypothalamus, providing significant relief without systemic hormonal effects [73].
Management of Genitourinary Symptoms
Genitourinary syndrome of menopause (GSM), encompassing vaginal atrophy, dyspareunia, and urinary symptoms, is effectively managed with low-dose vaginal estrogen in the form of creams, tablets, or rings [6]. These local treatments act directly on urogenital tissues with minimal systemic absorption, making them safer for many women [206]. For those who cannot or prefer not to use estrogen, non-hormonal options include vaginal moisturizers and lubricants, which improve epithelial integrity and reduce discomfort during intercourse [93]. Oral selective estrogen receptor modulators such as ospemifene are FDA-approved for treating moderate-to-severe dyspareunia, though they carry a black-box warning for endometrial hyperplasia [94].
Long-Term Health and Risk Reduction
The menopausal transition is associated with increased risks of osteoporosis and cardiovascular disease, necessitating proactive screening and prevention strategies. Bone mineral density (BMD) testing using dual-energy x-ray absorptiometry (DXA) is recommended for all women aged 65 and older, and earlier for those with elevated fracture risk or premature ovarian insufficiency [117]. Pharmacologic treatment with bisphosphonates is indicated for women with osteoporosis or high fracture risk, while menopausal hormone therapy may be considered for bone protection in younger postmenopausal women [122].
Cardiovascular risk assessment should include evaluation of blood pressure, lipid profile, glucose levels, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk using tools like the Pooled Cohort Equations [116]. Lifestyle interventions such as a heart-healthy diet, regular aerobic and resistance exercise, and weight management are foundational for reducing cardiometabolic risk [212]. Menopausal hormone therapy may have neutral or beneficial cardiovascular effects when initiated early in the menopausal transition, but is generally avoided in women with established cardiovascular disease [110].
Psychological and Behavioral Support
Psychological symptoms such as anxiety, irritability, and low mood are common during menopause and are influenced by both hormonal changes and life stressors such as the "empty nest" or caregiving responsibilities [133]. Cognitive-behavioral therapy (CBT) is a first-line non-pharmacological intervention, supported by strong evidence for reducing depressive symptoms, sleep disturbances, and vasomotor symptoms [150]. Mindfulness-based stress reduction (MBSR) and other mindfulness practices have also been shown to improve emotional regulation and quality of life [153]. These approaches are particularly effective when adapted to address midlife transitions and cultural narratives around aging and femininity [217].
Special Considerations and Contraindications
Clinicians must carefully evaluate contraindications and drug interactions when prescribing menopausal treatments. MHT is contraindicated in women with a history of hormone-sensitive cancers, active thromboembolic disease, unexplained vaginal bleeding, or severe liver dysfunction [218]. Drug interactions include CYP450 enzyme inducers (e.g., rifampicin) that reduce estrogen efficacy, and CYP2D6 inhibitors (e.g., paroxetine) that may interfere with tamoxifen metabolism in breast cancer patients [219]. For non-hormonal agents, fezolinetant requires monitoring of liver enzymes due to a boxed warning for rare but serious liver injury [90].
Cultural and Global Perspectives in Care
Sociocultural factors significantly influence how menopause is experienced and managed. In high-income countries, menopause is often medicalized, while in many low- and middle-income countries, it may be viewed as a natural life stage or even a transition to elder status [8]. These cultural beliefs affect symptom reporting, help-seeking behaviors, and trust in healthcare systems. Traditional and indigenous remedies, such as herbal medicines and community-based healing practices, often coexist with biomedical approaches, particularly in non-Western communities [169]. Culturally responsive care that integrates patient agency and respects diverse health beliefs is essential for equitable menopause management [154].