Association between menopausal hormone therapy use and mortality risk: a Swedish population-based matched cohort study

• Published in: Acta oncologica 2022-05, Vol.61 (5), p.632-640
• Main Authors: Simin, Johanna, Khodir, Habiba, Fornes, Romina, Tamimi, Rulla M., Brusselaers, Nele
• Format: Article
• Language: English
• Subjects: cancer; cardiovascular; Cardiovascular Diseases; Cohort Studies; Estrogen Replacement Therapy - adverse effects; Estrogens - therapeutic use; Female; Hormone Replacement Therapy - adverse effects; Humans; Logistic Models; Medicin och hälsovetenskap; Menopausal hormone therapy; Menopause; mortality; Neoplasms - drug therapy; oestrogens; pharmacoepidemiology; progestins; Risk Factors; Sweden - epidemiology
• ISSN: 0284-186X; 1651-226X; 1651-226X
• DOI: 10.1080/0284186X.2022.2033316

The net effect of menopausal hormone therapy on the risk of death is understudied, and current evidence is conflicting. Our aim was to investigate the association between menopausal hormones and risk of all-cause, cardiovascular, and cancer-specific mortality, based on the Swedish Prescribed Drug Registry and National Patient Registry. This Swedish population-based matched cohort study included all women, 40 years or older, who had received at least one prescription of systemic menopausal hormone therapy between 2005-2014 (n = 290,186), group level matched 1:3 to non-users (n = 870,165). Multivariable conditional logistic regression models estimated the relative risk of all-cause and cause-specific mortality, adjusting for several clinical factors and comorbidities. Ever-use of menopausal hormones was associated with a slightly lower overall odds of all-cause (OR = 0.97, 95%CI 0.95-0.98) and cardiovascular (OR = 0.97, 95%CI 0.95-0.99) mortality, whilst 30% lower overall odds of cancer-related mortality (OR = 0.70, 95%CI 0.68-0.72) was shown. The odds of all-cause and cancer-related mortality were consistently reduced among women who began menopausal hormone therapy ≤60 years, whereas the association with cardiovascular mortality was inconsistent. In contrast, oestrogen-only therapy was associated with elevated odds of all-cause (OR = 1.14, 95%CI 1.11-1.16) and cardiovascular mortality (OR = 1.04, 95%CI 1.01-1.06) among women who began treatment at ≥70 years. Among current users, oestrogen-only therapy was associated with higher odds of all-cause (OR = 1.48, 95%CI 1.44-1.52) and cardiovascular mortality (OR = 1.24, 95%CI 1.20-1.28), whereas past use of oestrogen-only therapy suggested lower odds of mortality. Our generalisable data suggest that early menopausal hormone treatment initiation does not increase the odds of mortality. However, the role of oestrogens in particularly cardiovascular mortality remains to be investigated.