The Women's Health Initiative (WHI) trial fundamentally altered HRT prescribing after publication. Which specific finding from the WHI combined HRT (oestrogen + progestogen) arm is now considered overestimated due to design limitations?
- A The increase in breast cancer risk, which was driven largely by the older age of enrolled women and prior HRT use rather than initiation in newly menopausal women ✓
- B The increase in venous thromboembolism risk with oral HRT
- C The reduction in colorectal cancer with combined HRT
- D The increase in coronary heart disease was not a WHI finding
Explanation
The WHI (2002) enrolled women aged 50–79 years (mean age 63), many of whom were >10 years post-menopause — well outside the current 'window of opportunity' hypothesis for cardiovascular benefit. The modest increase in breast cancer risk (HR 1.26 in combined arm) is now attributed partly to the pre-existing breast cancer risk in older, mostly obese, prior HRT-using women and the use of medroxyprogesterone acetate (not body-identical progestogen). Re-analyses and the KEEPS/ELITE trials confirm that HRT initiated within 10 years of menopause in women aged 50–60 does not increase cardiovascular risk. VTE risk with oral HRT is real and mechanistically established; transdermal HRT avoids this risk.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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Written and medically reviewed by the StethoPrep medical team.