When to Start Hormone Replacement Therapy
For women with natural menopause, HRT should be initiated at the onset of bothersome menopausal symptoms, ideally before age 60 or within 10 years of menopause onset, as this timing window provides the most favorable benefit-risk profile. 1, 2
Age-Based Timing Recommendations
Natural Menopause (Median Age 51)
- Start HRT when vasomotor symptoms (hot flashes, night sweats) or genitourinary symptoms begin, typically around the median menopause age of 51 years (range 41-59 years). 1
- The critical "10-year window" means women under 60 OR within 10 years of menopause have the most favorable risk-benefit balance. 1, 3, 4
- Do not delay treatment waiting for a specific age—symptom onset is the trigger, not reaching a particular birthday. 1, 5
Premature Ovarian Insufficiency (POI)
- For women with chemotherapy- or radiation-induced POI, initiate HRT immediately at diagnosis to prevent long-term cardiovascular, bone, and cognitive consequences. 6, 1
- In pre/peripubertal girls with iatrogenic POI, pubertal induction should begin between 11-12 years of age (with FSH ≥10 U/L at age 10+ as a reasonable indicator). 6
- This early timing facilitates positive psychosocial adaptation, optimizes uterine development for future fertility, and supports bone mass accrual. 6
Surgical Menopause
- Women with surgical menopause before age 45-50 should start HRT immediately post-surgery unless contraindications exist. 1, 7
- Continue HRT at least until the average age of natural menopause (51 years), then reassess. 6, 1
Critical Timing Pitfalls to Avoid
The "Too Late" Problem
- Never initiate HRT for the first time in women over 60 or more than 10 years past menopause for chronic disease prevention—this increases cardiovascular risks (8 additional strokes per 10,000 women-years) and mortality. 1, 3
- Women already on HRT who reach age 65 should be reassessed, with attempts at discontinuation or dose reduction to the absolute minimum. 1
The "Wrong Indication" Problem
- Never start HRT solely for osteoporosis or cardiovascular disease prevention in asymptomatic women—the USPSTF gives this a Grade D recommendation (harmful). 1, 3
- HRT is indicated for symptom management, not primary prevention of chronic conditions. 1, 3
Contraindications That Override Timing
Absolute contraindications regardless of age or timing include: 1, 3
- History of breast cancer or hormone-sensitive cancers
- Coronary heart disease or prior myocardial infarction
- Previous venous thromboembolism or stroke
- Active liver disease
- Antiphospholipid syndrome or positive antiphospholipid antibodies
Special Population Considerations
Cancer Survivors
- Women with non-hormone-sensitive cancers who develop vasomotor symptoms may consider HRT until age 51, then reassess. 6, 1
- Women with hormone-sensitive breast cancer should avoid systemic HRT entirely. 6, 3
Family History of Breast Cancer
- Family history alone (without personal breast cancer or confirmed BRCA mutation) is not an absolute contraindication to HRT. 1
- Consider genetic testing for BRCA1/2 if strong family history exists; short-term HRT following risk-reducing surgery is safe in healthy BRCA carriers without personal breast cancer. 1
Optimal Regimen at Initiation
When starting HRT in the appropriate timing window: 1, 2
- First-line: Transdermal estradiol patch 0.05 mg/day (changed twice weekly) to avoid hepatic first-pass metabolism and reduce thrombotic risk
- Add micronized progesterone 200 mg orally at bedtime for women with intact uterus (required to prevent endometrial cancer)
- Women without a uterus can use estrogen-alone therapy safely
Duration Philosophy
- Use the lowest effective dose for the shortest duration that controls symptoms. 1, 3
- Breast cancer risk increases significantly beyond 5 years of combined estrogen-progestin therapy (8 additional cases per 10,000 women-years). 1, 3
- Regular reassessment is mandatory—HRT should not continue indefinitely without periodic evaluation of ongoing need. 1, 7