What happens during menopause?

What Happens During Menopause

Menopause is the permanent cessation of menstruation caused by loss of ovarian follicular activity, occurring when remaining follicle count reaches ≤1,000, typically between ages 45-56 years (median age 51), and is definitively diagnosed after 12 consecutive months without menses. 1, 2

Physiological Changes

Hormonal Transitions

The menopausal transition involves profound hormonal shifts that begin years before the final menstrual period:

• Follicle-Stimulating Hormone (FSH) rises several years before clinical signs appear, driven by declining inhibin B levels as ovarian follicle numbers fall 3
• Estradiol levels fluctuate greatly during perimenopause—they may remain unchanged or even rise initially (due to elevated FSH stimulation), then fall profoundly over 3-4 years around the final menses 3
• Progesterone production becomes erratic as ovulation becomes irregular 4
• Testosterone declines by approximately 50% during reproductive years (ages 20-40) but changes little during the actual transition and may even rise after menopause 3
• Hormone levels vary markedly during the transition, making FSH and estradiol unreliable guides to menopausal status 3

Ovarian and Reproductive Changes

• Ovarian follicular activity ceases as the profound depletion of ovarian follicles progresses, with menopause occurring when follicle count reaches approximately 1,000 or fewer 1
• Estrogen production decreases permanently, representing a profound, permanent decrease in ovarian estrogen synthesis 1
• Ovarian senescence occurs alongside age-related biochemical and immunologic transitions 5

Clinical Manifestations

Vasomotor Symptoms

• Hot flashes and night sweats affect 50-75% of women during the menopausal transition 2, 6
• Duration is typically 7+ years, though some women experience them for a decade or more, while a small proportion never become free of them 2, 6
• Approximately one-third of women find these symptoms moderately to severely problematic 6

Genitourinary Changes

• Genitourinary syndrome of menopause (GSM) affects more than 50% of women and includes vaginal dryness, dyspareunia, and urinary complaints 2
• Vaginal symptoms affect approximately one-third of women in later transition stages 6
• Unlike hot flashes, vaginal symptoms will not resolve without treatment and are often chronic 2, 6

Psychological and Sleep Disturbances

• Poor sleep becomes more common, related both to the menopausal transition and aging 6
• Depressed mood and anxiety increase, with an abrupt rise in prevalence as women approach later transition stages with longer amenorrhea periods 6
• Symptoms often interact—depressed women tend to experience worse hot flashes and worse sleep 6

Musculoskeletal Changes

• Bone mineral density loss begins in late perimenopause, with bone density decreasing by 2% annually during the first 5 years after menopause, then approximately 1% annually thereafter 5
• Up to 70% of women older than 80 have osteoporosis based on commonly used criteria 5
• Arthralgias and myalgias can occur as menopausal symptoms 5

Metabolic Changes

• Lower circulating estrogen contributes to accelerated bone loss and increased low-density lipoprotein levels around menopause 5
• Several important metabolic and cardiovascular disease risks emerge during the menopausal transition 7

Long-Term Health Implications

Women in developed countries can expect to live approximately 30 years postmenopause, representing up to one-third of their lifespan 1, 4. The lifetime probability of developing chronic diseases after menopause includes:

• 46% for coronary heart disease 5
• 20% for stroke 5
• 15% for hip fracture 5
• 10% for breast cancer 5
• 2.6% for endometrial cancer 5
• 1.4- to 3.0-fold higher risk for Alzheimer disease compared to men 5

Critical Diagnostic Considerations

Amenorrhea after chemotherapy is NOT a reliable indicator of true menopausal status because ovarian function may resume even after >12 months of amenorrhea 1. For women with therapy-induced amenorrhea, require amenorrhea for at least 2 years and serial FSH and/or estradiol measurements are mandatory 1.

The NCCN provides specific criteria: menopause is confirmed by prior bilateral oophorectomy, age ≥60 years, or age <60 years with amenorrhea ≥12 months in the absence of chemotherapy/tamoxifen/ovarian suppression AND FSH and estradiol in postmenopausal range 1.