Dr. Weeks’ Comment: Nature has the cure. Follow nature.
“…Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin...”
Syst Rev. 2016 Jul 26;5(1):121. doi: 10.1186/s13643-016-0294-5.
Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.
Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events.
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model.
We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesteronewas associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81.
Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.
Climacteric. 2018 Aug;21(4):326-332. doi: 10.1080/13697137.2018.1476483. Epub 2018 Jun 1.
Progesterone, progestins and the breast in menopause treatment.
Breast cancer is the main risk associated with menopause hormone therapy (MHT). It is a hormone-dependent cancer. In postmenopausal women, about 80% of cases are estradiol receptor-positive. In cohort studies only estradiol receptor-positive breast cancers are promoted by MHT. Different levels of risk with estrogen-only treatment and combined treatment with estrogen + progestin are shown in randomized trials and observational studies. Several non-randomized studies show a lower risk with progesterone and retroprogesterone than with synthetic progestins. Progesterone and progestin are non-selective ligands for the progesterone receptor and bind also with other steroid receptors, with agonistic or antagonistic effects according to the structure of the molecule. Their half-life and metabolism are also different, progesterone being rapidly degraded with a short half-life. These aspects will be discussed in this review.