Menopause is the permanent stoppage of menstrual periods because the ovaries lose follicular activity. Perimenopause refers to the transition period before menopause and the first year after it. HRT is mainly used to treat troublesome menopausal symptoms such as hot flashes, night sweats, and vaginal dryness.
Physiology:
The hypothalamus releases GnRH → pituitary releases FSH & LH → ovaries produce estrogen (estradiol), progesterone, and small amounts of androgens (testosterone, androstenedione). Estrogen and progesterone provide negative feedback.
In menopause, ovarian follicles stop functioning. Estrogen levels drop >90%, progesterone production stops, and FSH rises sharply (FSH >40 IU/L). These hormonal changes cause vasomotor symptoms and long-term bone loss.
Clinical Presentation of Menopause
- Hot flashes, night sweats (vasomotor symptoms)
- Vaginal dryness, painful intercourse, urogenital atrophy
- Sleep problems, fatigue
- Reduced concentration and memory issues
- Mood swings, depression (uncertain association)
- Joint pains, muscle pains
- Long-term: accelerated bone loss & osteoporosis
Diagnosis
- Confirmed after 12 months without menstrual periods
- FSH >40 IU/L indicates ovarian failure
- Rule out thyroid disorders and pregnancy
- Day-2 or Day-3 FSH >10–12 IU/L suggests perimenopause
Treatment Overview
Non-Drug Measures
- Lifestyle modification: weight control, exercise, smoking cessation
- Vaginal moisturizers or lubricants for mild dryness
- Phytoestrogens (soy, flaxseed) help lipids and bone but do not reduce hot flashes effectively
Hormonal Regimens
Women with a uterus require estrogen + progestogen to prevent endometrial cancer. Women without a uterus may take estrogen alone.
1) Estrogens
Estrogens relieve hot flashes and prevent bone loss. No single preparation is superior. Available as oral, transdermal (patch/gel), intranasal, and vaginal forms.
Key Points
- Transdermal & intranasal forms avoid first-pass metabolism
- Vaginal estrogen is best for local symptoms (dryness, atrophy)
- Low doses & ultralow doses are effective for many women
Adverse Effects
- Nausea, headache, breast tenderness
- Heavy bleeding
- Serious risks: coronary disease, stroke, venous thromboembolism, breast cancer, gallbladder disease
- Transdermal forms have lower risk of DVT and gallbladder disease
2) Progestogens
Needed for women with an intact uterus to prevent endometrial hyperplasia. Common forms include medroxyprogesterone acetate, micronized progesterone, and norethisterone acetate.
Regimens
- Continuous-cyclic (sequential): monthly withdrawal bleeding
- Continuous-combined: no bleeding after initial spotting
- Continuous long-cycle: 6 periods per year
- Intermittent-combined: 3 days estrogen alone + 3 days combined
Adverse Effects
- Depression, irritability, mood swings
- Headache, sleep disturbance
- Fluid retention
3) Androgens
Testosterone use in women is controversial and not routinely recommended. Benefits seen in surgically menopausal women, but long-term safety is unclear.
Contraindications
- Pregnancy & breastfeeding
- Androgen-dependent tumors
Adverse Effects
- Virilization (deep voice, increased hair growth)
- Fluid retention
- Unfavorable lipid changes
4) SERMs (Selective Estrogen-Receptor Modulators)
SERMs act like estrogen on bones but block estrogen in breast tissue.
Raloxifene prevents bone loss and vertebral fractures, improves lipids, but may worsen hot flashes and increase clot risk.
5) Tibolone
A synthetic steroid with estrogenic, progestogenic, and androgenic activity. Helps mood, libido, hot flashes, and vaginal atrophy; protects bone and lowers lipids.
Risks
- Breast cancer risk may increase
- Stroke risk increases in older women
- Weight gain, bloating
Benefits of HRT
- Best treatment for hot flashes and night sweats
- Effective for vaginal dryness (systemic or local estrogen)
- Improves mood in symptomatic women
- Prevents osteoporosis in high-risk women
- Lowers risk of colon cancer (from WHI trial)
Risks of HRT
- Higher risk of coronary heart disease (especially in first year)
- Increased stroke risk (estrogen alone or combined)
- Higher risk of venous thromboembolism
- Breast cancer risk increases with combined therapy after 3 years
- Ovarian cancer risk may increase
- Gallbladder disease risk increases
- Dementia risk doubles in women ≥65 years using combined therapy
Detailed Notes:
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