A common misconception when it comes to hormone replacement therapy, (HRT) is that progestins are the same as progesterone. Progestins used interchangeably with progesterone even in medical articles. But synthetic progestins are very different from bioidentical progesterone. The reality is that progestins act more like estrogen in the body, amplifying the harmful effects of estrogen and increasing the risk of cancer, while progesterone helps to lower these risks.
Structural differences between progesterone and progestins.
So what is the difference between bioidentical progesterone and synthetic progestins? Micronized progesterone is a bioidentical hormone with a molecular structure identical to the endogenous progesterone produced by the ovary. Synthetic progestins, in contrast, have a completely different chemical structure from progesterone. They are made from various steroid “base” molecules, such as estrogen and testosterone.
The Radically Different Effects of Progesterone and Progestins
One family of progestins, norethisterone, norethisterone acetate and norethindrone, in particular, are metabolized and actually become estrogens in the body. Medroxyprogesterone, the progestin most commonly used in HRT, acts like prednisone in the breast tissue and causes breast cells to proliferate. It potentiates the proliferative action of estrogens, decreases insulin sensitivity, increases the levels and activity of insulin-like growth factor-I, (IGF1) which plays a major role in the cancer process) and decreases levels of sex hormone binding globulin, (SHBG) which helps to protect against cancer. Beyond cancer, progestins can cause cardiovascular damage and increase risks of heart attacks, while progesterone has no adverse effects on the heart. Progesterone is “pro-gestation” and pro-fertility, hence the name, while progestins are used in contraceptive pills because of their anti-fertility effects.
Controlled and observational studies suggest that the addition of synthetic progestins to estrogen in hormone replacement therapy, particularly in a continuous-combined regimen increases risk of breast cancer even when compared to the risk of using estrogen alone. One study, the Women’s Health Initiative trial of combined estrogen plus progestin had to be stopped early when overall health risks, including the risk of invasive breast cancer, became too great. Even the relatively short-term use of estrogen plus progestins significantly increases the risk of breast cancer. Using unopposed estrogen and estrogen plus progestin for long periods of time has also been associated with increased ovarian cancer risk.
In contrast, observational studies suggest that in menopausal women, the use of estrogen with progesterone may be associated with a lower breast cancer risk when compared to the use of estrogen and a synthetic progestin. We can extrapolate, based on the fact that women with progesterone deficiency have 5.4 times the risk of premenopausal breast cancer when compared to women with normal hormone levels, that progesterone is in fact protective against breast cancer.
In the Million Women Study, when progesterone was included in the hormone replacement therapy formulation, the odds ratio of developing breast cancer fell significantly, indicating the protective effect of progesterone. In reality, therefore, progestins are almost the polar opposites of true bioidentical progesterone. Proper HRT should always include progesterone to counter any cancer risk caused by taking estrogen and/or a synthetic progestin.
