Contraceptive-related breast cancer may be preventable with more informed choices about the composition of contraceptives used, according to a study by a team from the Ecole Polytechnique Federale de Lausanne in Switzerland (1).
Hormonal contraceptives used by women – such as the pill or a vaginal ring – contain different hormones to prevent ovulation and avoid pregnancy. Typically, these products change the consistency of the cervical mucus, making it harder for sperm to move through the cervix or change the lining of the uterus to stop implantation.
These products are hugely popular, but they come with a health warning: hormonal contraceptives increase the risk of breast cancer, one of the most commonly diagnosed types of cancer and a common cause of death among women worldwide.
One of the main ingredients in these products are progestins, which mimic the female hormone progesterone. A team of researchers from the EPFL’s School of Life Sciences decided to closely examine the effects these progestins have on breast tissue. “Although we know how different contraceptive formulations affect the cardiovascular system, we know little about their effects on the breast,” said Professor Cathrin Brisken, lead researcher in this study. “So we developed new approaches to compare the most commonly used progestins in different hormonal contraceptives and were surprised to find that some of them stimulate cell proliferation in the breast – while others do not.”
To test the effects of prolonged exposure to different progestins, the team used mouse mammary tissue grafted with human breast cells into the animal’s milk ducts and monitored their development in vivo. This way, the grafted human cells were actually able to maintain their normal functions, including reactions to hormones.
It turned out that different progestins showed different androgenic properties. This is a technical term to explain how some substances can trigger the development of male features, including muscle mass and body hair, for example. This is not entirely surprising as, although progesterone is seen as a women’s hormone, it is used in the production of the male hormone testosterone in both men and women.
It turned out that androgenic progestins activated a protein called Rankl, which induced hyperproliferation and changes in cells, often associated with early, pre-malignant lesions of human breast cells. In contrast, anti-androgenic progestins did not have these effects.
“Hormonal contraception exposes women to different progestins with or without estrogen,” says Brisken. “The androgenic properties of progestins determine their biological activity in the breast epithelium and reveal an unexpected role for androgen receptor activity in the proliferation of breast epithelial cells.”
The take-home message for all women: progestins with anti-androgenic activity – such as cytoproterone acetate – present a much lower risk of breast cancer compared to androgenic versions, like levonorgestrel, which is commonly present in the morning after pill, for example. “It might be possible to prevent breast cancer associated with contraception by making more informed choices taking the molecular composition of a contraceptive into account,” concluded Brisken.
(1) Shamseddin M, Martino F, Constantin C, Scabia V, Lancelot A, Laszlo C, Ayyannan A, Battista L, Raffoul W, Gailloud-Matthieu M, Bucher P, Fiche M, Ambrosini G, Sflomos G, Brisken C (2021) Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation. EMBO Mol Med, e14314 https://doi.org/10.15252/emmm.202114314