Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population-based matched-cohort study

Although menopausal hormone therapy (MHT) seemingly increases the risk of ovarian cancer, evidence is insufficient whether the riskvaries between various MHT formulations, regimens and administration modes. With the aim of filling these knowledge gaps, we investigated the effect of different MHT treatment options on the risk of ovarian cancer. This prospective Swedish population basedmatched-cohort study included all women ≥40 years having used systemic MHT between 2005-2012 (288,950 ever-users), group-level matched (1:3) to 866,546 non-users. MHT use was ascertained from the Swedish Prescribed Drug Registry and data was linked to several national health data registries. Multivariable conditional logistic regression provided odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for parity, and comorbidities. Current EP-MHT use was associated with a modestly increased risk of ovariancancer (OR=1.38, 95%CI 1.18-1.62), whilst no consistent risk was found among past users (OR=1.00, 95%CI 0.84-1.18). Current continuous testosterone derived (OR=1.50, 95%CI 1.15-1.96) regimens increased the risk whereas progesterone derived (OR=1.48, 95%CI 1.00-2.21) regimens increased the risk marginally. Non-significant positive associations were observed for sequential regimens (OR=1.87, 95%CI 0.70-5.08; OR=1.54, 95%CI 0.96-2.47, respectively). An inverse relationship was observed for all E-MHT use (OR=0.25, 95% CI 0.22-0.29), but this association might partly be explained by underreporting of oophorectomies or tubal ligations. Current cutaneous EP-MHT (OR=1.28, 95%CI 0.81-2.02) suggested a possibly lower risk than oral MHT (OR=1.48, 95%CI 1.25-1.75). In conclusion EP-MHT, notably continuous regimens, were associated with a modestly increased risk of ovarian cancer. The role of E-MHT requires further clarification.