The net effect of menopausal hormone therapy on the risk of cancer: A Swedish population based cohort study

Statement of the Problem: Menopausal hormone therapy (MHT) appears to influence carcinogenesis. Whereas studies of individual cancer sites are crucial for causal inference, the net effect of MHT on the total cancer risk remains unknown, and can provide valuable insights for clinical management and guidance of women with menopause related symptoms. Methodology and Theoretical Orientation: This nationwide Swedish population-based cohort study was based on the Swedish Prescribed Drug Registry. All 290,186 women aged  ≥40 years having received dispensed prescriptions of systemic MHT during 2005-2012 were included. The risk of cancer was presented as standardized incidence ratios (SIRs) and 95% confidence intervals (95%CI), comparing MHT ever-users to the entire Swedish female background population. Findings:  The risk of any incident cancer following MHT ever-use was slightly increased (SIR=1.09, 95%CI 1.07-1.11). The risk was lower among oestrogen only (E-MHT) users (SIR=1.04, 95%CI 1.01-1.06) than oestrogen combined progestin (EP-MHT) users (SIR=1.14, 95%CI 1.12-1.17). Of the oestrogen formulations, tibolone increased the risk (SIR=1.14, 95%CI 1.08-1.21). Of the EP-MHT regimens, continous progesterone (SIR=1.12, 95%CI 1.07-1.17) and testosterone derived (SIR=1.24, 95%CI 1.20-1.28) regimens increased the cancer risk, whereas no apparent association was found for sequential regimens. The risk of main female repreductive organ cancers was increased, notably among women ≥70 (SIR=2.25, 95%CI 2.08-2.42). In contrast, an inverse association was observed for combined gastrointestinal tract cancers (SIR=0.90, 95%CI 0.86-0.94). Conclusion and significance: MHT, notably EP-MHT use, was associated with a limited increase in overall cancer risk. However, different formulations and regimens might affect the cancer risk.