Progesterone is administered along with estrogen for women undergoing peri-menopause. It may help contribute to the relief of menopausal and may enhance well-being, energy, and libido. Progesterone is given with estrogen to women who have not undergone hysterectomy to balance the effects of estrogen on the uterine endometrium and reduce the risk of unopposed endometrial stimulation. In a study of 50,000 postmenopausal women followed for an 5.8 year study period it was discovered that bioidentical progesterone decreased the risk of breast cancer (RR= 9; P <.001) while synthetic progestin use increased the risk of breast cancer (RR = 1.4).
Most epidemiological studies have shown an increase in breast cancer risk related to hormone replacement therapy (HRT) use. A recent large cohort study showed effects of similar magnitude for different types of progestogens and for different routes of administration of estrogens evaluated. Further investigation of these issues is of importance. We assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women who had never taken any HRT 1 year before entering the E3N-EPIC cohort study (mean age at inclusion: 52.8 years); 948 primary invasive breast cancers were diagnosed during follow-up (mean duration: 5.8 years). Data were analyzed using multivariate Cox proportional hazards models. In this cohort where the mean duration of HRT use was 2.8 years, an increased risk in HRT users compared to nonusers was found (relative risk (RR) 1.2 [95% confidence interval 1.1-1.4]). The RR was 1.1 [0.8-1.6] for estrogens used alone and 1.3 [1.1-1.5] when used in combination with oral progestogens. The risk was significantly greater (p <0.001) with HRT containing synthetic progestins than with HRT containing micronized progesterone, the RRs being 1.4 [1.2-1.7] and 0.9 [0.7-1.2], respectively. When combined with synthetic progestins, both oral and transdermal/percutaneous estrogens use were associated with a significantly increased risk; for transdermal/percutaneous estrogens, this was the case even when exposure was less than 2 years. Our results suggest that, when combined with synthetic progestins, even short-term use of estrogens may increase breast cancer risk. Micronized progesterone may be preferred to synthetic progestins in short-term HRT. This finding needs further investigation. (c) 2004 Wiley-Liss, Inc.