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BASICS

DESCRIPTION
- Natural menopause: 12 consecutive months of amenorrhea in a nonpregnant person with a uterus ≥40 years old; mean age 51 years; due to loss of ovarian activity.
- Perimenopause/menopausal transition (MT): onset of irregular menses to final menstrual cycle; begins ~4 years before menopause; mean age 47 years.
- Postmenopause: usually >1/3 of a woman's life.
- Primary ovarian insufficiency: irregular or ceased ovulatory cycles before age 40.
- Surgical menopause: removal of hormone-producing ovaries causing immediate menopause.

EPIDEMIOLOGY

  • Median age of menopause: 51 years (US).
  • 5% undergo menopause after 55 years; 5% between 40 and 45 years.
  • Occurs earlier in Hispanic patients, later in Japanese American vs Caucasians.
  • 1.3 million patients reach menopause annually in the US.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Ovarian follicle number decreases with age → decreased estrogen production, variable then increased FSH.
  • Insufficient estradiol → absence of LH surge → anovulation → lack of progesterone.
  • Estrone (from adipose tissue) dominates estrogen in menopause.

RISK FACTORS

  • Oophorectomy/hysterectomy
  • Sex chromosome abnormalities (Turner syndrome, fragile X)
  • Family history of early menopause
  • Smoking (advances menopause by 2 years)
  • Chemotherapy/pelvic radiation
  • Low BMI

GENERAL PREVENTION

  • Menopause is physiologic and cannot be prevented.
  • Reduce cardiovascular disease (CVD) risk: exercise, healthy diet/weight, avoid tobacco, treat hypertension, hyperlipidemia, diabetes.
  • Prevent osteoporotic fractures: weight-bearing exercise, fall prevention, avoid smoking/alcohol, calcium 1,200 mg/day, vitamin D.

DIAGNOSIS

  • Based on 12 consecutive months of amenorrhea in nonpregnant woman ≥40 years.
  • Lab tests (FSH >30 mIU/mL) if <45 years or early menopause suspected.
  • Pregnancy test, TSH, prolactin if pituitary disease suspected.
  • Evaluate abnormal uterine bleeding with TVUS and/or endometrial biopsy (EMB).
  • Breast and osteoporosis screening per guidelines.

HISTORY

  • Cessation of menses preceded by irregular, heavy then diminished bleeding.
  • Vasomotor symptoms (80%): sudden heat, sweating (face/neck/chest), anxiety, palpitations.
  • Symptoms start ~2 years before final period, peak 1 year after, diminish later.
  • Frequency varies (daily in 87%, >10/day in ~33%), duration 4-10 years.
  • Varies by ethnicity and obesity.
  • Genitourinary syndrome: vulvovaginal atrophy in 50%, dryness, itching, dyspareunia, alkaline vaginal pH, increased infections.
  • Anxiety/depression risk increased 2.5 times in MT.
  • Sleep disturbance, migraine changes, skin thinning, brittle nails.

PHYSICAL EXAM

  • Decreased breast size, texture change.
  • Atrophic vulva/vaginal mucosa.
  • Possible uterine prolapse with Valsalva.

DIFFERENTIAL DIAGNOSIS

  • Pregnancy, thyroid disease, pituitary adenoma, Sheehan syndrome, hypothalamic dysfunction, anorexia nervosa, Asherman syndrome, uterine outflow obstruction.

DIAGNOSTIC TESTS & INTERPRETATION

  • Lab tests: Not routinely needed except if <45 years or other causes suspected.
  • Elevated serum FSH >30 mIU/mL indicates ovarian failure.
  • Estrogens, androgens, OCPs may alter labs.
  • Breast cancer and osteoporosis screening per guidelines.

TREATMENT

GENERAL MEASURES
- Behavioral modifications: lower ambient temperature, layered clothing, avoid triggers (heat, stress, caffeine, alcohol, tobacco, spicy foods).
- Portable fans, ice packs, relaxation techniques help during vasomotor episodes.

MEDICATION
- First Line: Hormone therapy (HT) is most effective for vasomotor symptoms and bone loss prevention.
- Individualize risk-benefit, especially <60 years or within 10 years of menopause onset.
- HT reduces hot flush frequency by ~75%, improves sleep and urogenital atrophy.
- Use lowest effective dose for shortest duration.
- Estrogen available orally, transdermally, intravaginally, or injectable.
- If uterus intact, give estrogen with progestin (micronized progesterone or medroxyprogesterone acetate) to reduce endometrial cancer risk.
- Tissue-selective estrogen complex (bazedoxifene + conjugated estrogens) offers endometrial protection without progesterone.

  • Precautions:
  • WHI study: CEE + MPA increased risk of CHD, breast cancer (after 5 years), stroke, PE, dementia, gallbladder disease.
  • HRT not recommended for cardioprotection.

  • Contraindications: estrogen-dependent malignancies, unexplained uterine bleeding, thromboembolism history, CAD, liver disease, untreated hypertension, breast cancer, smoking.

  • For genitourinary syndrome:

  • Topical estrogen (cream, tablet, ring) reverses vaginal atrophy.
  • Ospemifene (SERM) for dyspareunia.

  • Nonestrogen lubricants may help some.

  • Second Line:

  • Nonhormonal agents for vasomotor symptoms:
    • Paroxetine (7.5 mg/day) approved; SSRIs/SNRIs (venlafaxine, fluoxetine, citalopram) reduce hot flushes.
    • Gabapentin (300-900 mg/day) effective.
    • Clonidine less effective.

COMPLEMENTARY & ALTERNATIVE MEDICINE

  • Phytoestrogens, herbs, supplements lack clear benefit; some interact with warfarin.
  • Hypnotherapy, mindfulness may help.
  • Acupuncture, yoga not clearly effective for hot flashes but may help some symptoms.
  • Avoid compounded bioidentical HT due to safety concerns.

ONGOING CARE

  • Reassess HT need every 3 to 5 years; taper/discontinue to minimize risks.
  • Calcium-rich diet and vitamin D (800-1000 IU/day) to prevent osteoporosis.

PATIENT EDUCATION

  • Smoking cessation, reduce alcohol.
  • Exercise >30 min, 3x weekly.
  • Healthy nutrition for CVD prevention and BMI maintenance.

PROGNOSIS

  • Untreated vasomotor symptoms resolve eventually, but vaginal atrophy worsens.

COMPLICATIONS

  • Accelerated bone loss (3-5% per year for 5-7 years).
  • Increased cardiovascular disease risk post-menopause.

REFERENCES

  1. ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol. 2014;123(1):202-216.
  2. North American Menopause Society. The 2022 hormone therapy position statement of the North American Menopause Society. Menopause. 2022;29(7):767-794.
  3. Cobin RH, Goodman NF; for AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause-2017 update. Endocr Pract. 2017;23(7):869-880.

ICD10 Codes

  • E28.310 Symptomatic premature menopause
  • N95.1 Menopausal and female climacteric states
  • Z78.0 Asymptomatic menopausal state

Clinical Pearls

  • Menopause diagnosis is primarily clinical (history).
  • HT is effective for moderate-severe vasomotor symptoms; use lowest dose, shortest duration.
  • Estrogen must be combined with progestin in women with uterus to reduce endometrial cancer risk.