Response to: Progesterone and Breast Cancer Pathogenesis

We make it clear in our review (Horwitz and Sartorius 2020) that it is important to distinguish between the natural hormone progesterone, and synthetic versions thereof we call progestins. We attempt to make the case that, in the breast, progesterone is not carcinogenic. We point out however, that to be fair, the two major clinical studies of menopausal hormone therapies (MHT) - the Women’s Health Initiative (WHI) which enrolled women in the 1990’s and the Million Women Study (WMS) which began in 1996 – conclude that addition of a synthetic progestin to estrogens, increases the risk of breast cancer. We argue that this may reflect important functional differences between natural and synthetic progestational signaling, and that these differences require careful study.

Dr Bluming argues that the two MHT studies are statistically flawed, thus explaining the increased breast cancer incidence with the synthetic progestins.

That may be the case, but both MHT studies continue to be analyzed even today. Green et al, (Green, et al. 2019) recently concluded that for the WMS, a key finding continues to be that: “Use of oestrogen-progestagen preparations causes much greater increases in the risk of breast cancer than oestrogen-only preparations…” Similarly, for the WHI, Chlebowski et al (Chlebowski, et al. 2020) reported last month that, compared to placebo, estrogen plus medroxyprogesterone acetate (but not estrogen alone) “was significantly associated with a higher breast cancer incidence, but no significant difference in breast cancer mortality.”

In sum, we stand by the points we raise in our review and are pleased that they may lead not just to further discussion, but more importantly, to further experimentation.