The association between primary ovarian insufficiency and increased multimorbidity in a large prospective cohort (Canadian Longitudinal Study on Aging).

Objective: To describe the prevalence of multimorbidity among individuals with primary ovarian insufficiency (POI) and early menopause compared with those with the average age of menopause.

Design: Prospective cohort.

Subjects: This prospective cohort encompassed female postmenopausal individuals from the Canadian Longitudinal Study on Aging. The Canadian Longitudinal Study on Aging collected cross-sectional data from 50,000 community-dwelling Canadians aged 45-85 years between 2010 and 2015.

Exposure: The primary exposure was POI (defined by onset of menopause at the age of <40 years). Comparators included average age of menopause (age, 46-55 years), early menopause (40-45 years), and late-onset menopause (56-65 years) and those who underwent hysterectomy.

Main Outcome Measure(s): The primary outcome was multimorbidity, which was defined as two or more chronic conditions. The secondary outcomes were severe multimorbidity (defined as 3 or more chronic conditions) and frequencies of specific chronic conditions among a comprehensive list of 15 individual conditions. We assessed the association between multimorbidity and age at menopause using logistic regression and odds ratios (ORs), with confidence intervals (CIs) set at 95%. The ORs were adjusted for known predictors of multimorbidity, including age, menopausal hormone therapy, education, ethnicity, self-reported loneliness, living alone, body mass index, smoking habits, nutritional risk, social participation, and physical activity.

Result(s): A total of 12,339 postmenopausal participants were included, of whom 374 (3.0%) experienced POI and 1,396 (11.3%) experienced early menopause. The prevalence rates of multimorbidity were 64.8% and 51.1% among those with POI and early menopause, respectively. In contrast, only 43.9% of individuals with average age of menopause (age, 46-55 years) had multimorbidity. The OR for multimorbidity in the POI population was 2.5 (95% CI, 2.0-3.1) compared with that in individuals who had the average age of menopause. This relationship was maintained after adjustment for confounders (adjusted OR [aOR], 2.0; 95% CI, 1.5-2.5). The prevalence of severe multimorbidity was also double in the POI group compared with that in the average age group (39.2% vs. 21.1%). There were significantly increased risks of ischemic heart disease (aOR, 2.8; 95% CI, 1.7-4.7), gastric ulcers (aOR, 1.6; 95% CI, 1.1-2.3), and osteoporosis (aOR, 1.6; 95% CI, 1.2-2.1) in the POI group.

Conclusion(s): Individuals with POI and early menopause experience increased multimorbidity compared with those undergoing menopause at an average age. This trend persists even after adjusting for significant multimorbidity risk factors.