Inserm (Institut National de la Santé et de la Recherche Médicale), CESP (Centre de recherche en Epidémiologie et Santé des Populations), Unit 1018, Villejuif, France ; University Paris-Sud, UMRS 1018, Villejuif, France.
PLoS One. 2013 Nov 1;8(11):e78016. doi: 10.1371/journal.pone.0078016. eCollection 2013.
There is extensive epidemiological evidence that menopausal hormone therapy (MHT) increases breast cancer risk, particularly combinations of estrogen and progestagen (EP). We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen), and time interval between onset of menopause and start of MHT were examined.
We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls). Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated.
We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49) for progesterone-derived and 3.35 (1.07-10.4) for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment.
This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.
大量流行病学证据表明，激素替代疗法（MHT）会增加乳腺癌风险，尤其是雌激素和孕激素（EP）联合使用时。我们研究了法国女性使用的特定配方和类型的治疗方法的影响。我们检查了孕激素成分、方案（孕激素连续或序贯治疗）以及绝经后开始 MHT 的时间间隔。
我们在法国进行了一项基于人群的病例对照研究，纳入了 1555 名绝经后妇女（739 例病例和 816 例对照）。通过面对面访谈获得了 MHT 使用的详细信息。计算了调整乳腺癌风险因素后的比值比和 95%置信区间。
我们发现，当前 EP 治疗使用者的孕激素类型不同，乳腺癌风险也不同。使用天然微粒化孕酮的 EP 治疗使用者不存在风险增加。在使用含有合成孕激素的 EP 治疗使用者中，孕酮衍生孕激素的比值比为 1.57（0.99-2.49），而睾酮衍生孕激素的比值比为 3.35（1.07-10.4）。连续治疗方案的女性比序贯治疗方案的女性风险更高，但由于几乎所有含有睾酮衍生孕激素的 EP 组合都采用连续治疗，反之亦然，因此无法独立研究方案和孕激素类型。替勃龙也与乳腺癌风险增加相关。绝经后早期开始 MHT 的女性比延迟治疗的女性风险更高。
这项研究证实了孕激素和方案对法国特定使用的乳腺癌风险的不同影响。法国经常开的含有天然孕酮的 EP 疗法配方与乳腺癌风险增加无关，但可能对子宫内膜癌的保护作用较差。
