Menopausal Hormone Therapy Formulation and Breast Cancer Risk

Objective: To evaluate whether the increased risk of breast cancer is dependent on the formulation of menopausal hormone therapy (HT) used.

Methods: We performed a population-based case-control study of women aged 50 years or older using data from the U.K. Clinical Practice Research Datalink. Women with incident cases of breast cancer were age-matched (1:10) with a control group of women with comparable follow-up time with no history of breast cancer. Exposures were classified as ever or never for the following menopausal HT formulations: bioidentical estrogens, animal-derived estrogens, micronized progesterone, and synthetic progestin. Logistic regression analyses were performed to estimate the adjusted effect of menopausal HT formulation on breast cancer risk.

Results: Between 1995 and 2014, 43,183 cases of breast cancer were identified and matched to 431,830 women in a control group. In adjusted analyses, compared with women who never used menopausal HT, its use was associated with an increased risk of breast cancer (odds ratio [OR] 1.12, 95% CI 1.09-1.15). Compared with never users, estrogens were not associated with breast cancer (bioidentical estrogens: OR 1.04, 95% CI 1.00-1.09; animal-derived estrogens: OR 1.01, 95% CI 0.96-1.06; both: OR 0.96, 95% CI 0.89-1.03). Progestogens appeared to be differentially associated with breast cancer (micronized progesterone: OR 0.99, 95% CI 0.55-1.79; synthetic progestin: OR 1.28, 95% CI 1.22-1.35; both OR 1.31, 0.30-5.73).

Conclusion: Although menopausal HT use appears to be associated with an overall increased risk of breast cancer, this risk appears predominantly mediated through formulations containing synthetic progestins. When prescribing menopausal HT, micronized progesterone may be the safer progestogen to be used.