Reproductive · Menopause
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Menopause is defined as 12 consecutive months of amenorrhea resulting from the permanent cessation of ovarian function.
Menopause is a clinical diagnosis; when laboratory testing is needed (typically only in women under 45), an elevated serum follicle-stimulating hormone (FSH) level is the test used, although FSH fluctuates widely during the transition.
The primary mechanism of menopause is follicular depletion, leading to decreased estradiol and loss of negative feedback on the pituitary.
Vasomotor symptoms (hot flashes) are the most common clinical complaint and are caused by hypothalamic thermoregulatory dysfunction.
Genitourinary syndrome of menopause (GSM) presents with vaginal dryness, dyspareunia, and recurrent UTIs due to estrogen-deficient urogenital atrophy.
Systemic menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms in women under 60 or within 10 years of onset, provided there are no contraindications.
Women with an intact uterus should receive endometrial protection with a progestogen (or, alternatively, bazedoxifene paired with conjugated estrogens) in combination with estrogen during MHT to prevent endometrial hyperplasia and carcinoma.
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Etiology / Epidemiology
Defined as 12 months of amenorrhea due to ovarian failure. Average age is 51 years.
Clinical Manifestations
Vasomotor symptoms (hot flashes) and genitourinary syndrome of menopause. Vaginal dryness and dyspareunia are classic.
Diagnosis
Clinical diagnosis. An elevated FSH (commonly cited >30 IU/L; >25 IU/L for POI per ESHRE 2024) supports ovarian failure if testing is required, though levels fluctuate during the menopause transition.
Treatment
Estrogen therapy (with progestin if uterus present) is first-line. History of breast cancer is a contraindication (FDA labeling for systemic estrogen).
Prognosis
Increased risk of osteoporosis and cardiovascular disease. Monitor for endometrial hyperplasia.
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Epidemiology & Etiology
Menopause is the permanent cessation of menses resulting from the loss of ovarian follicular activity. Premature ovarian insufficiency is loss of ovarian activity before age 40 with elevated FSH; unlike menopause, ovarian function can be intermittent and spontaneous pregnancy remains possible. Smoking is a known risk factor for earlier onset.
Pertinent Anatomy
The ovaries undergo follicular depletion, leading to a decline in estrogen and inhibin production. The vagina and urethra are estrogen-sensitive tissues that undergo atrophy, leading to dyspareunia and urinary urgency.
Pathophysiology
Decreased estrogen levels lead to a loss of negative feedback on the hypothalamus and pituitary. This results in a significant rise in FSH and LH levels. The loss of estrogen causes vasomotor instability and accelerated bone resorption.
Clinical Manifestations
Patients present with hot flashes, sleep disturbances, and mood changes. Genitourinary syndrome of menopause includes vaginal dryness, dyspareunia, and recurrent UTIs. Postmenopausal bleeding should be promptly investigated to rule out endometrial cancer.
Diagnosis
Diagnosis is clinical in women >45 with typical symptoms and 12 months of amenorrhea. An elevated FSH can support the diagnosis if uncertain (e.g., age <45), though levels fluctuate widely during the transition. Postmenopausal bleeding may be evaluated first with transvaginal ultrasound (endometrial thickness ≤4 mm has a very high negative predictive value) or with endometrial biopsy; biopsy provides the definitive tissue diagnosis.
Treatment
Systemic estrogen is the most effective treatment for vasomotor symptoms. Women with a uterus should receive progestin to prevent endometrial cancer. Contraindications (FDA labeling) include undiagnosed vaginal bleeding, history of VTE, and hormone-sensitive cancers.
Prognosis
Long-term risks include osteoporosis and increased cardiovascular mortality. Patients should be screened with DEXA scans starting at age 65 or earlier based on risk factors.
Differential Diagnosis
Pregnancy: should be ruled out in perimenopausal women
Hyperthyroidism: presents with palpitations and heat intolerance
Endometrial cancer: presents with postmenopausal bleeding
Pheochromocytoma: presents with episodic hypertension and flushing
Carcinoid syndrome: presents with flushing and diarrhea