Combined and Progesterone-Only Contraceptives Have a Similar Risk of Breast Cancer

A new study has found that both combined and progesterone-only hormonal contraceptives are associated with a similar relative increase in breast cancer risk of around 20–30%. The research is published in PLOS Medicine.

The pros and cons of contraceptives

The combined oral contraceptive pill contains artificial versions of the hormones estrogen and progesterone, whereas the progesterone-only pill does not include estrogen. Other hormonal contraceptive preparations using progesterone only or combined progesterone and estrogen include injections, implants and intrauterine devices (IUDs).

The use of the oral combined pill has gathered interest due to its adverse effects, as it is associated with a small increase in the risk of developing breast cancer (though risk does decline after stopping use, returning to baseline after around 10 years).

Use of the progesterone-only pill has increased in popularity in recent years, particularly in England, where prescriptions have almost doubled in the last 10 years. Given this rise in popularity, it is important to understand the advantages and disadvantages compared to the combined pill, as data on how it may influence breast cancer risk is limited.

To this end, the researchers in the current study analyzed data from over 25,000 women from a UK primary care database to determine whether various hormonal contraceptives are linked to breast cancer risk.

Risk increases with age

The study included almost 10,000 women over 50 years of age who were diagnosed with breast cancer between 1996–2017, as well as over 18,000 closely matched controls without breast cancer for comparison.

The findings revealed that on average, 44% of the women with breast cancer had been prescribed hormonal contraceptives, compared to 39% of the control group – and approximately half of these prescriptions were progesterone-only.

Breast cancer risk was increased with hormonal contraceptive use, regardless of whether it was combined or progesterone-only. Additionally, breast cancer risk was also raised regardless of the method of delivery, be it an oral pill, injection, implant or IUD.

The researchers combined these results with outcomes from similar studies to estimate the 15-year absolute excess risk of breast cancer (i.e., the difference in risk between the cancer and control groups) associated with 5 years of oral combined or progesterone-only contraceptive use. This revealed differences in absolute excess risk depending on age – ranging from 8 breast cancer cases per 100,000 users at 16–20 years of age, up to 265 cases per 100,000 users at 35–39 years of age.

“These findings suggest that current or recent use of all types of progestogen-only contraceptives is associated with a slight increase in breast cancer risk, similar to that associated with use of combined oral contraceptives,” explained Kirstin Pirie, one of the study’s co-authors and statistical programmer at the University of Oxford.

What mechanisms are responsible?

Additionally, the authors highlight that lack of complete information on prescription history obtained from the database made long-term investigation difficult, and they could only assess short-term risk.

Nonetheless, the study provides an important insight into the impact of hormonal contraception on breast cancer risk, though additional research is needed to determine the mechanism(s) responsible.

“Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive will be smaller in women who use it at younger rather than at older ages,” the authors write. “These excess risks must, however, be viewed in the context of the well-established benefits of contraceptive use in women's reproductive years.”

Reference: Fitzpatrick D, Pirie K, Reeves G, Green J, Beral V. Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case–control study and meta-analysis. PLoS Med. 2023;20(3):e1004188. doi: 10.1371/journal.pmed.1004188

This article is a rework of a press release issued by PLOS. Material has been edited for length and content.