Increased mortality and non-cancer morbidity risk may be associated with early menopause and varies with aetiology: An exploratory population-based study using data-linkage

Objective: Iatrogenic early menopause (EM), that is, menopause before the age of 45 years due to surgery or chemotherapy or radiotherapy, is associated with negative health impacts. However, it is unclear how these vary according to the cause of EM. We investigated mortality and non-cancer morbidity in women with iatrogenic EM of different aetiologies. Study design: Population-based retrospective cohort study with 36-year follow-up using data-linkage with the Western Australia hospital morbidity database, cancer, birth and death registries, the midwives notification system and the mental health information system. The sample comprised women aged 20–44 years at index date with iatrogenic EM associated with breast or gynaecological cancer (n = 607), or benign bilateral oophorectomy (n = 414), and age-matched female controls (n = 16,998). Index date (breast, ovarian or uterine cancer diagnosis or oophorectomy procedure) ranged from 1982 to 1997, with follow-up until 2018. Main outcome measures: Mortality and hospitalisation for circulatory disorders, endocrine, psychological, respiratory, musculoskeletal and gastrointestinal morbidities. Results: Significant differences in mortality were observed (% dead by follow-up: cancer, 53.0; oophorectomy, 10.9; and controls, 3.5; p < 0.001). Incidence rate ratios (IRRs) were increased for circulatory (1.23, 95 % CI 1.07–1.42) and endocrine disorders (1.31, 95%CI 1.08–1.56) and hip fracture (3.90, 95 % CI 1.83–7.40) in cancer survivors, compared with controls. IRRs for circulatory (0.62, 95 % CI 0.53–0.72) and endocrine disorders (0.62, 95 % CI 0.38–0.97) were reduced in the oophorectomy group, but were increased for psychological (8.53, 95 % CI 7.29–9.94) and gastrointestinal morbidities (1.43, 95%CI 1.21–1.67) compared with controls. Conclusion: Cancer-related or benign iatrogenic EM may be associated with increased mortality and morbidity, which vary with the cause of EM.