The SWAN (Study of Women's Health Across the Nation) and MWS (Million Women Study) provided evidence on hormone replacement therapy (HRT) risks. Which specific HRT formulation has been shown to have the LOWEST risk of breast cancer compared to other formulations?
- A Combined continuous estrogen-progestogen therapy (oral conjugated equine estrogen + medroxyprogesterone acetate)
- B Sequential estrogen-progestogen (oral estrogen + cyclical norethisterone)
- C Estrogen-only HRT in women with prior hysterectomy ✓
- D Transdermal estrogen with vaginal progesterone (micronized progesterone)
Explanation
Multiple large studies (WHI, MWS) demonstrate that estrogen-only HRT (used only in women who have had a hysterectomy, as unopposed estrogen increases endometrial cancer risk) has the lowest breast cancer risk among HRT formulations, and some analyses suggest no increased risk or even a slight decrease. Combined E+P HRT increases breast cancer risk, with the degree depending on the progestogen: synthetic progestogens (MPA, norethisterone) confer higher risk than micronized progesterone/dydrogesterone. However, overall breast cancer risk is lowest for estrogen alone vs. any combined formulation. Transdermal estrogen with micronized progesterone has the lowest risk among combined regimens.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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Written and medically reviewed by the StethoPrep medical team.