Sunday, January 3, 2016
Synthetic progestins (birth control and HRT) associated with increased breast cancer risk, but not natural progesterone
"The Women's Health Initiative (WHI) formally tested these questions in a double-blind, randomized, phase III clinical trial. The results show that HRT with oral continuous combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) significantly increases invasive breast cancer risk, and thus, HRT should be avoided if possible (Chlebowski et al., 2003, Chlebowski et al., 2009 and Chlebowski et al., 2010). In addition, data from a separate arm of that clinical trial indicate that post-menopausal women with prior hysterectomy, treated with estrogen-only HRT, have a reduced risk of breast cancer, suggesting that estrogens alone may be protective in this cohort (Anderson et al., 2012 and LaCroix et al., 2011). The average women's age in the WHI trial was 63 years, suggesting that these findings may not apply to women using HRT shortly after menopause (within 5 years). Post-hoc analysis in these early-menopausal women indicate that estrogens alone do not increase or decrease risk, whereas estrogen plus progestins increase breast cancer risk (Santen, 2013). Furthermore, an observational study by the Million Women Study Collaborators indicates that post-menopausal women on progestin-containing HRT are at higher risk of developing breast cancer than women on estrogens-only HRT or other HRT regimens, such as tibolone (Million Women Study Collaborators, 2003). Additional evidence in non-human primates shows that treatment with estrogen plus MPA upregulates proliferative genes, compared to estrogens alone (Wood et al., 2013). Thus, these data suggest that elevated progestin levels in post-menopausal women markedly contribute to aggressive tumor development. Conversely, however, a prospective study compared women taking HRT regimens of estrogen plus MPA versus estrogen plus progesterone and found that women in the estrogen plus progesterone cohort did not have increased breast cancer risk (Fournier et al., 2005 and Fournier et al., 2008). This study did confirm the WHI clinical trial that estrogen plus MPA regimens increase invasive breast cancer risk compared to placebo."
Pharmacol Ther. 2014 Apr;142(1):114-25. doi: 10.1016/j.pharmthera.2013.11.010. Epub 2013 Nov 26.
Tracking progesterone receptor-mediated actions in breast cancer.
Knutson TP1, Lange CA2.