Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis

Abstract

BackgroundUse 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.MethodsWe 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.ResultsWe 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. Progesterone was 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.ConclusionsObservational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0294-5) contains supplementary material, which is available to authorized users.

Effects of drospirenone and norethisterone acetate combined with estradiol on mammographic density and proliferation of breast epithelial cells—A prospective randomized trial

“…There is ongoing search for new compounds able to control excessive endometrial stimulation from the estrogen component but without stimulatory effects on the breast. Lower doses of conventional progestogens, intra-uterine and other non-oral administrations [8,11], as well as the native progesterone hormone itself [26], have been suggested as candidates for safe combinations with estrogen. The combination of estrogen with a selective estrogen receptor modulator (SERM) is an alternative which seems to avoid stimulation of the breast [27].…”

The endometrial and breast safety of menopausal hormone therapy containing micronised progesterone: A short review

“…Nevertheless, EPIC is easily the largest cohort study of MHT containing mP4 yet performed and in combination with the Asi et al . meta‐analysis would suggest that MHT regimens containing mP4 are associated with a significantly lower risk of breast cancer than those containing progestins.…”

“…Only three useful studies were found examining breast cancer risk; nevertheless, they do supply some compelling data. The E3N‐EPIC Study is a French prospective cohort study investigating cancer risk factors in nearly 100 000 women born between 1925 and 1950 …”

“…Asi et al . recently performed a systematic review and meta‐analysis on the breast cancer risk associated with progestins and mP4 . They found two more smaller studies to use in their analysis as well as the EPIC study.…”

The effectiveness and safety of mht depending on the type, route of administration of estrogens, and the type of progestogen. Analysis of data from clinical trials and international recommendations

“…В мета-анализе N. Asi и соавторов [20] было показано, что прогестерон связан с меньшим риском РМЖ по сравнению с синтетическими прогестинами в сочетании с эстрогеном (RR = 0,67, 95% ДИ 0,55-0,81, I 2 = 42%, p < 0,0001) 1 , однако ка-чество доказательств было низким из-за наблюдательной природы исследования. Для исключения женщин в пост-менопаузе, получавших синтетические прогестины, отлич-ные от МПА, проводился анализ чувствительности.…”