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The past decades have seen contradictory research results on the health benefits and risks of menopausal hormone therapy (HT). In particular, long-term associations with overall cancer incidence and the potential interplay with other lifestyle factors remain undetermined. In a population-based prospective cohort, 29,152 women aged 50-64 years at entry (1993-1997) were followed through 2013 for incidence of cancer (99% complete follow-up). Cox' proportional hazards models were used to estimate cancer incidence according to baseline HT alone and in combination with lifestyle factors including alcohol intake, BMI, physical activity, diet, and smoking. Among 5484 women diagnosed with cancer, baseline HT was associated with an overall higher risk of cancer (HR 1.28; 95%CI, 1.21-1.36)-in particular, a higher risk of breast (HR 1.77; 95%CI, 1.61-1.95), ovarian (HR 1.68; 95%CI, 1.26-2.26), and endometrial (HR 1.86; 95%CI, 1.45-2.37) cancer. Combination with other lifestyle risk factors largely displayed additive associations. The risk of colorectal cancer was significantly lower (HR 0.79; 95%CI, 0.66-0.95). However, in the interaction analysis, only "healthy" subgroups of women using HT had a lower risk of colorectal cancer. With an overall higher risk of cancer among women on HT, this study underlined the importance of considering all female cancer risks in menopausal treatment guidelines. The largely additive associations between HT and the investigated lifestyle factors support the notion that high levels of hormones in itself play an important etiological role in female reproductive cancers, whereas the possible protective impact in colorectal cancer might be limited to women with an otherwise healthy lifestyle.

The Influence of Menopausal Hormone Therapy and Potential Lifestyle Interactions in Female Cancer Development—a Population-Based Prospective Study