Better choice of contraceptives can prevent breast cancer
Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. This study suggests that different progestins have different activities on breast tissues.

Researchers hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, they show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-?B ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not.

Investigators develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone-responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti-androgenic, chlormadinone, and cyproterone acetate, do not.

Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist- and levonorgestrel-induced RANKL expression and reduces levonorgestrel-driven cell proliferation.

Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.

EMBO Molecular Medicine
Source: https://doi.org/10.15252/emmm.202114314
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