Hormone Replacement Therapy Guidelines
Primary Recommendation
HRT should be used exclusively for managing bothersome menopausal symptoms (vasomotor symptoms, genitourinary syndrome) using the lowest effective dose for the shortest duration—NOT for chronic disease prevention—and is most appropriate for women under 60 years or within 10 years of menopause onset. 1
When to Initiate HRT
Appropriate Candidates
- Women experiencing moderate to severe vasomotor symptoms (hot flashes, night sweats) or genitourinary symptoms should consider HRT at symptom onset, typically around age 51 but can begin during perimenopause 1
- The risk-benefit profile is most favorable for women ≤60 years old or within 10 years of menopause onset 1
- Women with premature ovarian insufficiency (surgical menopause before age 45, chemotherapy-induced menopause) should initiate HRT immediately at diagnosis to prevent long-term cardiovascular and bone health consequences 1
Absolute Contraindications
- History of breast cancer or hormone-sensitive malignancies 2
- Active or history of venous thromboembolism or stroke 2
- Coronary heart disease or myocardial infarction 2
- Active liver disease 2
- Antiphospholipid syndrome or positive antiphospholipid antibodies 2
- Unexplained abnormal vaginal bleeding 2
What NOT to Use HRT For
HRT is explicitly contraindicated for primary or secondary prevention of cardiovascular disease, as it does not reduce and may actually increase coronary heart disease risk 3, 4
HRT should not be routinely used for osteoporosis prevention alone (USPSTF Grade D recommendation)—alternative therapies like bisphosphonates, denosumab, or SERMs should be considered first 2
Formulation Selection Algorithm
Step 1: Route Selection
Transdermal estradiol patches should be first-line over oral formulations because they:
- Avoid hepatic first-pass metabolism 1
- Have more favorable cardiovascular and thrombotic risk profiles 1
- Demonstrate better bone mass accrual 1
Starting dose: 50 μg estradiol patch applied twice weekly 1
Step 2: Progestin Requirements
For women with an intact uterus, progestin MUST be added to prevent endometrial cancer (reduces risk by ~90%) 1, 5
Progestin hierarchy (in order of preference):
- Micronized progesterone 200 mg daily (first-line—lacks antiapoptotic effects on breast tissue) 1
- Combined estradiol/progestin patches (50 μg estradiol + 10 μg levonorgestrel daily) 1
- Medroxyprogesterone acetate 10 mg daily for 12-14 days 1
- Dydrogesterone 10 mg daily for 12-14 days 1
For women without a uterus (post-hysterectomy), estrogen-alone therapy is appropriate and reduces vasomotor symptoms by ~75% 1
Step 3: Local vs Systemic Therapy
For isolated genitourinary symptoms without vasomotor symptoms:
- Low-dose vaginal estrogen preparations are preferred (improve symptoms by 60-80% with minimal systemic absorption) 1
- Vaginal moisturizers and lubricants reduce symptoms by up to 50% and are safe non-hormonal alternatives 1, 2
Risk Profile: What to Counsel Patients
Established Risks (per 10,000 women-years on combined estrogen-progestin)
- 7 additional coronary heart disease events 1
- 8 additional strokes 1
- 8 additional pulmonary emboli 1
- 8 additional invasive breast cancers 1
- Increased gallbladder disease risk (RR 1.48-2.5 depending on duration) 3
Established Benefits (per 10,000 women-years)
- 6 fewer colorectal cancers 1
- 5 fewer hip fractures 1
- 30-50% reduction in osteoporotic fractures overall 1
Critical Distinction on Breast Cancer Risk
The progestin component drives breast cancer risk, NOT estrogen alone:
- Combined estrogen-progestin: HR 1.26 (8 additional cases per 10,000 women-years) 1
- Unopposed estrogen in hysterectomized women: NO increased risk (RR 0.80) 1
- Risk increases with duration beyond 5 years 1
Duration and Monitoring
Treatment Duration
Use the lowest effective dose for the shortest time necessary to control symptoms 1, 4, 5
Reassess necessity every 3-6 months 5
For women with surgical menopause before age 45, continue HRT until at least age 51 (average natural menopause age), then reassess 1
When to Stop or Avoid Initiation
Do NOT initiate HRT in women >60 years or >10 years past menopause for chronic disease prevention—harmful effects exceed benefits 1, 2
For women already on HRT at age 65, reassess necessity and attempt discontinuation; if continuation is essential, reduce to lowest effective dose 1
Women who develop breast cancer while on HRT must immediately discontinue regardless of hormone receptor status 1
Special Populations
Women with Family History of Breast Cancer (No Personal History)
Family history alone WITHOUT confirmed BRCA mutation or personal breast cancer diagnosis is NOT an absolute contraindication to HRT 1
Consider BRCA1/2 genetic testing given family history; short-term HRT following risk-reducing salpingo-oophorectomy is safe in healthy BRCA carriers without personal breast cancer 1
Continue HRT until at least age 51, then reassess 1
Women with Non-Hormone-Sensitive Cancers
HRT may be considered after oncology consultation for vasomotor symptoms, but re-evaluate at age 51 1, 2
High-Risk Patients Requiring Non-Hormonal Management
For women with absolute contraindications:
- Vaginal moisturizers/lubricants (50% symptom reduction) 2
- Low-dose vaginal estrogen after careful risk assessment (60-80% improvement, minimal systemic absorption) 2
- SSRIs or gabapentin for vasomotor symptoms 2
Critical Pitfalls to Avoid
Do NOT initiate HRT solely for cardiovascular disease prevention or osteoporosis prevention without considering alternative therapies first 3, 4, 2
Do NOT assume all estrogen formulations carry equal breast cancer risk—the progestin type and presence matters significantly 1
Do NOT use estrogen without progestin in women with an intact uterus, even for low-dose vaginal preparations 2
Do NOT delay HRT initiation in women with surgical menopause before age 45 who lack contraindications—the window for cardiovascular protection is time-sensitive 1
Do NOT continue HRT beyond symptom management needs—breast cancer and cardiovascular risks increase with duration 1, 4
Do NOT use oral estrogen in women ≥60 years or >10 years past menopause due to excess stroke risk; transdermal routes are safer if HRT is necessary 1, 2