Menopause and Related Problems (MBBS Notes)

1. Definitions

• Menopause is permanent cessation of menstruation from loss of ovarian follicular activity. It is diagnosed retrospectively after 12 months of amenorrhea. - Textbook of Family Medicine 9e
• Perimenopause (menopausal transition) is the years of variable cycles before the final menstrual period, plus the first year after it.
• Postmenopause is the period after the final menstrual period.
• Climacteric is the whole phase of transition from reproductive to non-reproductive life.
• Premature ovarian insufficiency (POI) is menopause before age 40. It may be associated with autoimmune disease. - Textbook of Family Medicine 9e
• Early menopause is menopause at 40 to 45 years.
• Average age is about 52 years in the US, and most women reach menopause between 40 and 58. Smoking and family history lower the age. India reports a lower mean, around 46 to 48 years.
• Causes of non-natural menopause: bilateral oophorectomy, chemotherapy, pelvic radiotherapy, Turner syndrome, and autoimmune oophoritis.

2. Physiology

1. The follicle pool falls. Follicles are exhausted from about 1 million at birth to almost none at menopause.
2. Inhibin B falls first. This is the earliest hormonal change. - Textbook of Family Medicine 9e
3. Loss of negative feedback raises FSH, and later LH.
4. Estradiol (E2) from the ovary falls. Ovarian follicles stop responding to gonadotropins.
5. After menopause the main circulating estrogen is estrone. It comes from peripheral aromatization of androstenedione in adipose tissue.
6. The ovarian stroma continues to make some androgen, so testosterone falls only modestly.
7. Cycles become irregular and anovulatory. Estrogen can fluctuate widely from cycle to cycle in perimenopause.

3. Clinical Features

• Menstrual change: oligomenorrhea, then amenorrhea. Heavy or irregular bleeding in perimenopause is mostly from anovulation.
• Vasomotor symptoms: hot flashes and night sweats are the most common symptom. They affect up to 75% of perimenopausal women and can last 10 years or more. About 10% continue into their 70s. - Berek & Novak's Gynecology; Textbook of Family Medicine 9e
• Symptoms are worse after POI or premenopausal oophorectomy, and in obesity or depression.
• Mechanism: a narrowed thermoneutral zone in the hypothalamus, with peripheral vasodilatation and sweating.
• Psychological and sleep symptoms: insomnia (often secondary to night sweats), irritability, mood swings, poor concentration. The link with true depression is debated, but women with prior PMS or postpartum depression are more vulnerable. - Berek & Novak's Gynecology

• Genitourinary syndrome of menopause (GSM) replaces the older term "vulvovaginal atrophy". It affects at least 60% of menopausal women. - Berek & Novak's Gynecology
• Features: vaginal dryness, dyspareunia, burning, urinary urgency, recurrent UTI, and raised vaginal pH (more than 4.5) with loss of lactobacilli.
• Uterovaginal prolapse and stress incontinence can follow loss of tissue support.
• Sexual dysfunction: reduced libido and arousal.
• Skin and hair: thinning, dryness, loss of collagen.

• Osteoporosis.
• Cardiovascular disease.
• Cognitive decline.

4. Related Problems

A. Osteoporosis

• Estrogen deficiency increases osteoclast activity (more RANKL, less OPG), so bone resorption exceeds formation.
• Bone loss is fastest in the first 5 to 7 years after menopause (trabecular bone first).
• Fractures: vertebral (wedge, crush), distal radius (Colles), neck of femur.
• Risk factors: early menopause, low BMI, smoking, alcohol, steroids, family history, low calcium or vitamin D, sedentary life.
• Diagnosis (DEXA, T-score):
  • Normal: -1 or higher.
  • Osteopenia: -1 to -2.5.
  • Osteoporosis: -2.5 or lower.
  • Severe osteoporosis: -2.5 or lower plus a fragility fracture.
• Management:
  • Calcium 1000 to 1200 mg/day, vitamin D 800 IU/day, weight-bearing exercise, stop smoking and alcohol.
  • Bisphosphonates (alendronate, risedronate, zoledronate) are first line.
  • Others: denosumab, raloxifene (SERM), teriparatide (anabolic), calcitonin, strontium. Hormone therapy is used mainly when menopausal symptoms are also present.

B. Cardiovascular disease

• Before menopause, estrogen raises HDL and lowers LDL, and promotes vasodilatation.
• After menopause, CVD risk rises: LDL and triglycerides increase, and central obesity, hypertension and insulin resistance become more common.
• Hormone therapy does not prevent CVD. The Women's Health Initiative (WHI) showed no cardioprotection and an increased breast cancer risk. - Textbook of Family Medicine 9e

C. Genitourinary syndrome, incontinence and prolapse

• Treat with local vaginal estrogen, lubricants and moisturizers. Ospemifene and vaginal DHEA are other options.

D. Abnormal uterine bleeding

• Any postmenopausal bleeding (PMB) is endometrial carcinoma until proven otherwise.
• Evaluate with transvaginal ultrasound (endometrial thickness of 4 mm or less makes cancer unlikely), endometrial biopsy and hysteroscopy.
• Other causes: atrophic vaginitis or endometritis (the most common), endometrial polyp, hyperplasia, HT use, cervical cancer.

E. Cancers

• Endometrial cancer risk rises with unopposed estrogen and obesity.
• Breast cancer risk rises with long-term combined estrogen plus progestin therapy. - GOLDMAN-CECIL Medicine

F. Neuropsychiatric

• Mood symptoms, sleep disturbance, and a possible dementia link. HT started late does not protect against dementia.

5. Investigations

• FSH: greater than 40 IU/L on two occasions supports the diagnosis. - Textbook of Family Medicine 9e. Hormone tests are used mainly in women under 40 or 45, or after hysterectomy.
• Estradiol is low. Also check TSH and prolactin, and do a pregnancy test where relevant.
• Baseline checks before HT: BP, BMI, breast examination and mammography, Pap smear, lipid profile, and DEXA.
• For PMB or abnormal bleeding: ultrasound and endometrial sampling.

6. Management

A. Lifestyle (all women)

• Layered cotton clothing, avoid spicy food, alcohol and hot environments, exercise, weight control, stop smoking. - Textbook of Family Medicine 9e
• Calcium and vitamin D, weight-bearing exercise, pelvic floor exercises.

B. Menopausal hormone therapy (MHT/HRT)

• Moderate to severe vasomotor symptoms (the most effective treatment). - Berek & Novak's Gynecology
• GSM (local estrogen preferred when this is the only symptom).
• Prevention of osteoporosis in women at risk, where other drugs are unsuitable.
• POI or early menopause. Give HT until about age 50 to 51, the usual age of natural menopause.

• Uterus present: estrogen plus a progestogen (to prevent endometrial hyperplasia and cancer).
  • Cyclical (sequential): for perimenopausal women.
  • Continuous combined: for postmenopausal women, usually 1 year or more after the last period.
• Post-hysterectomy: estrogen alone.
• Routes: oral, transdermal (patch or gel), vaginal. Transdermal has lower thromboembolism risk. - Textbook of Family Medicine 9e
• Others: tibolone, estrogen plus bazedoxifene.
• Principle: lowest effective dose for the shortest time needed.

• Known or suspected breast or endometrial cancer.
• Undiagnosed abnormal vaginal bleeding.
• Coronary heart disease, stroke, thromboembolic disease.
• Active liver or gallbladder disease.

C. Non-hormonal drugs for hot flashes

• SSRIs and SNRIs (paroxetine, fluoxetine, venlafaxine). Low-dose paroxetine is an approved option.
• Gabapentin 900 mg/day. - Textbook of Family Medicine 9e
• Clonidine.
• Newer neurokinin-3 receptor antagonists (fezolinetant, elinzanetant) have been approved in some countries. Check current local guidance.
• Soy isoflavones, black cohosh and acupuncture have limited efficacy beyond placebo.

D. GSM

• First line: vaginal lubricants and moisturizers.
• Low-dose vaginal estrogen (cream, tablet, ring) is effective and safe. - Berek & Novak's Gynecology
• Other options: ospemifene, intravaginal DHEA, systemic HT.

7. Recent Evidence Update

8. High-Yield One-Liners

• Earliest hormone change in menopause: fall in inhibin B.
• Main postmenopausal estrogen: estrone, from peripheral conversion.
• Hot flashes: the most common symptom.
• Any postmenopausal bleeding needs endometrial evaluation.
• HT in a woman with a uterus must include a progestogen.
• HT does not prevent cardiovascular disease (WHI).
• Transdermal estrogen carries a lower VTE risk than oral.
• Local vaginal estrogen is first line for isolated GSM.
• First-line osteoporosis drug: bisphosphonate. DEXA T-score of -2.5 or lower defines osteoporosis.
• Premature ovarian insufficiency: menopause before age 40.

9. Likely Exam Questions

• Long essay: Define menopause. Describe its physiology, clinical features and management, including the role of HRT.
• Short notes: HRT (indications, contraindications, risks); postmenopausal bleeding; GSM; osteoporosis in the postmenopausal woman; non-hormonal treatment of hot flashes; WHI trial.