The E3N cohort study, WISDOM trial, and Women's Health Initiative (WHI) collectively established that the risk of breast cancer with combined (oestrogen + progestogen) HRT is primarily attributable to:

• A The oestrogen component regardless of progestogen type
• B Duration of HRT use only, not the type of hormone
• C Synthetic progestogens (especially medroxyprogesterone acetate) more than natural progesterone ✓
• D The route of administration (oral > transdermal)

Explanation

The French E3N cohort study (observational, 80,000 women) found that combined HRT using synthetic progestogens (especially medroxyprogesterone acetate, as used in WHI) was associated with significantly higher breast cancer risk compared to oestrogen combined with natural micronised progesterone. The WHI used conjugated equine oestrogen + MPA. The WISDOM trial further supported differential risk. Transdermal oestrogen has lower VTE and potentially lower BC risk than oral. These data support preferring natural progesterone over synthetic progestogens in HRT regimens.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.