HRT Risks in Women Over 65: Current Evidence
Yes, the risks of stroke, VTE, and dementia remain substantially elevated with HRT use in women over 65, and this population should generally avoid systemic hormone therapy. 1, 2
Stroke Risk
The evidence consistently demonstrates increased stroke risk with HRT in older women:
- Meta-analyses show a 12-32% increased stroke incidence with HRT use (RR 1.12-1.32), primarily driven by thromboembolic strokes 1
- The WHI trial confirmed a 36-41% increased stroke risk in women taking estrogen alone (HR 1.36) and combined estrogen-progestin (RH 1.41) 1
- For women initiating HRT more than 10 years after menopause (typically over age 60), stroke risk remains significantly elevated (RR 1.21) with high-quality evidence 3, 2
- The absolute risk translates to 6 additional strokes per 1,000 women treated (NNTH = 165) 3
Venous Thromboembolism Risk
VTE risk is particularly concerning in older women on HRT:
- HRT more than doubles VTE risk across all formulations (RR 2.14, with WHI confirming RH 2.11) 1, 4
- The risk is highest in the first year of use (RR 3.49), making initiation in older women especially hazardous 1
- Women starting HRT >10 years post-menopause face nearly doubled VTE risk (RR 1.96) compared to placebo 3
- The absolute risk increase is 8 additional VTE events per 1,000 women (NNTH = 118) and 4 additional pulmonary emboli per 1,000 (NNTH = 242) 3
- Combined estrogen-progestin carries higher VTE risk than estrogen alone, with the progestin component contributing additional prothrombotic effects 4, 5
Dementia Risk
The cognitive safety profile is particularly unfavorable in women ≥65:
- The WHI Memory Study (women aged 65-79) demonstrated a doubled risk of probable dementia with combined estrogen-progestin (HR 2.05) after 4 years 1
- Estrogen alone showed a trend toward increased dementia risk (HR 1.49), though not statistically significant 1
- Both formulations significantly increased the composite outcome of dementia or mild cognitive impairment (HR 1.44 for combined therapy, HR 1.38 for estrogen alone) 1
- The 2022 NAMS guidelines explicitly state that for women initiating HRT after age 60 or >10 years post-menopause, the benefit-risk ratio is unfavorable due to greater absolute risks including dementia 2
Critical Age and Timing Considerations
The "timing hypothesis" is crucial for understanding these risks:
- Women starting HRT <10 years after menopause (typically under age 60) show lower mortality and CHD risk, but still face elevated VTE risk (RR 1.74) 3
- Women starting HRT ≥10 years post-menopause or age ≥60 face increased risks without cardiovascular benefit, making the risk-benefit ratio clearly unfavorable 1, 2
- The USPSTF and NAMS both conclude that initiating HRT in women over 60 increases absolute risks of stroke, VTE, and dementia 1, 2
Clinical Implications for Your Practice
When encountering older women currently on HRT:
- For women >65 on systemic HRT, strongly consider discontinuation unless there are compelling, documented indications with shared decision-making 2
- If genitourinary symptoms are the primary concern, switch to low-dose vaginal estrogen, which avoids systemic absorption and does not increase VTE or stroke risk 6, 2
- Transdermal estrogen has lower but not absent VTE risk (OR 0.9 vs 4.2 for oral), but should still be avoided in women with prior VTE history 6
- Any woman with history of stroke, VTE, or cardiovascular disease should have systemic HRT discontinued immediately 7, 6
Common Pitfalls to Avoid
- Do not assume that "natural" or bioidentical hormones are safer—the risks apply to all systemic estrogen formulations 2
- Do not continue HRT indefinitely without periodic reevaluation—the risks accumulate with duration of use 2
- Do not prescribe systemic HRT for osteoporosis prevention alone in women >65—other effective therapies exist without the cardiovascular and cognitive risks 1, 2
- Do not confuse vaginal estrogen safety with systemic HRT risks—low-dose vaginal estrogen is safe even in women with prior VTE 6