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Menopause

Berek & Novak's Gynecology — Chapter 18 (Shifren & Schiff)

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Definition & Epidemiology

• Menopause = permanent cessation of menstruation due to ovarian failure
• Average age: 52 years (range 40–58)
• Age at menopause is genetically determined and unaffected by age at menarche or use of oral contraceptives
• Women in the developed world spend >30 years (>1/3 of their life) beyond menopause
• Premature menopause = before age 40 (also called premature ovarian insufficiency)

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Health Concerns After Menopause

1. Vasomotor Symptoms (VMS)

• Affect up to 75% of perimenopausal women
• Most last 1–2 years, but may persist ≥10 years
• Hot flashes are the primary reason women seek menopausal care

• Central event (likely hypothalamic) → ↑ core body temperature → peripheral vasodilation + sweating
• Triggered by noradrenergic, serotonergic, and/or dopaminergic activation
• KNDy neurons (kisspeptin, neurokinin B, dynorphin) play a key role — peripheral NKB infusion induces a typical hot flash; blocking NKB reduces them
• VMS are due to estrogen withdrawal, not simply estrogen deficiency
  • Example: Turner syndrome patients (high FSH, low estrogen) have no hot flashes until estrogen is given and then withdrawn

Hormone therapy is the most effective treatment for VMS.

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2. Genitourinary Syndrome of Menopause (GSM)

• Affects at least 60% (some reports ≥50%) of menopausal women
• Encompasses anatomic changes + symptoms affecting labia, vagina, urethra, and bladder due to estrogen deficiency
• Symptoms: genital dryness, irritation, burning; dysuria, urgency, recurrent UTIs; dyspareunia
• Unlike VMS, GSM worsens with time in the absence of treatment

• First-line non-hormonal: Vaginal lubricants (water/silicone/oil-based) + vaginal moisturizers 2–3×/week
• Pelvic PT and vaginal dilators for severe dyspareunia
• Topical estrogen (preferred if no VMS): Low-dose vaginal estradiol cream, tablet (10 µg or 4 µg), or ring (7.5 µg/day)
  • Minimal systemic absorption; safe; no concurrent progestin needed
  • No increased endometrial, breast cancer, or CVD risk confirmed in WHI observational data (n > 45,000)
• Vaginal DHEA (0.5% daily, prasterone) — approved for moderate-to-severe dyspareunia; serum hormone levels remain in postmenopausal range
• Ospemifene (60 mg/day oral SERM) — approved for moderate-to-severe dyspareunia from VVA; improves sexual function, confirmed endometrial safety

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3. Sexual Dysfunction

• Sexual concerns are common after menopause; etiology is multifactorial
• Effective treatment options exist

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4. Osteoporosis

• Risk increases markedly at menopause
• Pharmacologic treatment indicated for: T-score < –2.5; prior hip/vertebral fracture; low BMD at high fracture risk (by FRAX tool)

Combined calcium + vitamin D with even very low-dose ET (CE 0.3 mg/day or transdermal E2 0.014 mg/day) produces significant BMD gains vs. placebo.

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5. Cardiovascular Disease

• Important health concern for menopausal women
• Timing hypothesis: Early HT initiation (closer to menopause, when less atherosclerosis is present) yields more favorable CV risk-benefit profile
• ELITE trial: HT initiated within 6 years of menopause → slower CIMT progression; no effect if started >10 years after menopause
• Lifestyle interventions + management of hyperlipidemia, hypertension, and diabetes are essential

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6. Breast Cancer

• Most common cancer in women; #2 cause of cancer death
• Lifetime risk: 12%
• Risk factors: age, family history, early menarche, late menopause, genetic mutations (BRCA), prior epithelial atypia
• EPT (estrogen + progestin): WHI showed increased breast cancer risk
• ET alone: WHI showed reduced risk during poststopping phase
• Screening: mammography starting at age 40 (no later than 50); every 1–2 years; continue at least to age 75

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7. Dementia / Cognitive Decline

• Highly prevalent in older women
• Depression can cause pseudodementia (characterized by reported, not hidden, memory loss)
• Risk reduction should be optimized; role of HT in dementia prevention remains uncertain

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Hormone Therapy (HT)

Regimens

• Women without a uterus: Estrogen alone (ET)
• Women with a uterus: Combined estrogen + progestin (EPT) — unopposed estrogen → endometrial hyperplasia and cancer
  • Sequential: Estrogen daily + progestin 12–14 days/month → predictable bleeding
  • Continuous-combined: Daily estrogen + lower-dose progestin → amenorrhea in most by 1 year

Routes

• Oral: Standard; first-pass hepatic effect → ↑ sex hormone-binding globulin (SHBG), ↑ triglycerides, ↑ clotting factors
• Transdermal (patch, gel, spray, intravaginal ring): Avoids first-pass effect; no change in SHBG → free testosterone preserved (benefit for libido); no increased VTE risk in observational studies; lower gallbladder disease risk

Bioidentical Hormones

• Refer to hormones structurally identical to ovarian hormones (estradiol, progesterone)
• FDA-approved oral and transdermal estradiol + oral micronized progesterone available
• Custom-compounded "bioidentical" preparations: potentially significant risk with no known added benefit — should be avoided; FDA-approved formulations preferred

Contraindications to HT

WHI Findings (Key Summary)

• Overall absolute risk of adverse events was considerably lower in women aged 50–59 than older women
• Both EPT and ET associated with: ↓ VMS, ↓ diabetes, ↓ hip fractures; ↑ VTE, ↑ gallbladder disease, ↑ stroke
• EPT → ↑ breast cancer risk; ET → ↓ breast cancer risk (poststopping phase)
• Neither EPT nor ET was associated with increased all-cause, cancer, or CV mortality at 18 years of follow-up
• WHI used only oral CE + MPA — results may not apply to transdermal estradiol or other progestins

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Menopausal Mood and Mental Health

• Menopause may have mood effects in some women — partly secondary to sleep disruption from hot flashes
• SSRIs may both treat depression and ameliorate hot flashes
• Patients with prior PMS or postpartum depression are at higher risk for perimenopausal depression
• All menopausal women with depression should be assessed for psychosocial precipitants and domestic abuse

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Source: Berek & Novak's Gynecology (Berek & Novak's Gynecology, Chapter 18), Jan L. Shifren & Isaac Schiff