How Progestins in HRT Impact Risk of Breast Cancer


The risk of breast cancer associated with the use of synthetic progesterone known as progestins has been a topic of much controversy and concern for many years. Now a new study reports on the impact of progestins on breast cancer in animals models.

Impact of Progestins

In 2002, the large, well-known Women’s Health Initiative (WHI) Estrogen plus Progestin Study was stopped because the investigators found an increased risk of breast cancer and cardiovascular disease in women who were taking the active pills (that included progestins) compared with women taking placebo.

A subsequent study (2008) found that estrogen plus progestin HRT increased the risk that women will have abnormal mammograms and breast biopsies. Then in 2009, a new study of WHI participants found that women who stopped taking the estrogen plus progestin had a significant decline in breast cancer risk.

Progestin Study
Now researchers at the University of Missouri have compared four types of progestins used in HRT and discovered found four distinctly different outcomes on the progression of breast cancer. The four synthetic progestins used included medroxporgresterone acetate (MPA), norgesterel (N-EL), norethindrone (N-ONE), and megestrol acetate (MGA).


Salman Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center, noted that the majority of women on HRT take MPA, which is found in Prempro.

In the study, the researchers used rat models to determine the impact of the progestins on breast cancer development. Hyder and his team found that while previous research showed that “MPA functions as a tumor promoter,” that “N-EL and N-ONE, when administrated using the same protocol as used for MPA, strongly inhibited tumor development.”

More specifically, N-EL demonstrated only a 10 percent tumor incidence after a 70-day latency period, while N-ONE showed no tumors after more than a 90-day latency period. Tumor latency is the period from when the animal is first exposed to tumor cells to the first sign of cancer.

Therefore, Hyder explained that N-EL and N-ONE may have some protective effect in women who do not have a personal or family history of breast cancer. They may also play a preventive role in post-menopausal women who have an increased risk of breast cancer because they used MPA HRT.

Hyder warns, however, that “clinical use of progestins requires caution. These powerful steroids should only be prescribed when a person has no latent, or dormant, cancer and does not have a family history of cancer.” The results of this study provide important information for women regarding the use of progestins in HRT and their impact on the risk of breast cancer.

University of Missouri news release
Women’s Health Initiative