Excess of severe autoimmune diseases in women with premature ovarian insufficiency: a population-based study

• Published in: Human reproduction (Oxford) 2024-11, Vol.39 (11), p.2601-2607
• Main Authors: Savukoski, S M, Silvén, H, Pesonen, P, Pukkala, E, Gissler, M, Suvanto, E, Ollila, M-M, Niinimäki, M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autoimmune Diseases - complications; Autoimmune Diseases - epidemiology; Case-Control Studies; Cohort Studies; Female; Finland - epidemiology; Humans; Middle Aged; Original; Prevalence; Primary Ovarian Insufficiency - epidemiology; Registries; Young Adult
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/deae213

Is there an association between premature ovarian insufficiency (POI) and severe autoimmune diseases before and after POI diagnosis? Women with POI had at least one hospital-treated autoimmune disorder preceding POI diagnosis 2.6 times more often compared with matched female controls, and a 2- to 3-fold risk for these diseases for several years after POI diagnosis. It has been suggested that autoimmunity is an important factor in the pathogenesis of POI. Estimations of the prevalence of POI cases with autoimmune origin have ranged from 4% to 50%. This population-based registry study included 3972 women diagnosed with spontaneous POI between 1988 and 2017 and 15 708 female population controls and used both case-control and cohort analysis. Autoimmune disease diagnoses were evaluated from childhood until the end of the year 2017. Women with POI were identified from the reimbursement registry of the Finnish Social Insurance Institution by their right to hormone replacement therapy (HRT). Four female population controls matched by age and municipality of residence were searched for each POI case to form a reference cohort. Women with a history of cancer or bilateral oophorectomy were excluded. Severe autoimmune disorder diagnoses for the years 1970-2017 were identified from the Hospital Discharge Registry. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using binary logistic regression for cases of having any, or one or more, specific autoimmune diseases preceding the index date (the date when reimbursement for HRT was granted for the POI) among women with POI as compared to controls. Standardized incidence ratios (SIR) with 95% CIs for getting diagnosed with an autoimmune disease after the index date in 3-year follow-up periods among women with POI (who did not have these diseases prior to the index date) were also calculated. The expected numbers of autoimmune disease cases were based on the incidence of first-onset severe autoimmune disease among the controls. The prevalence of having at least one severe autoimmune disease in women with POI was 5.6% (n = 233), with an OR of 2.6 (95% CI 2.2, 3.1) when compared to population controls. Women with POI had an increased prevalence of several specific autoimmune diseases prior to the index date compared to controls: polyglandular autoimmune diseases (OR 25.8, 95% CI 9.0, 74.1), Addison's disease (OR 22.9, 95% CI 7.9, 66.1), vasculitis (OR 10.2, 95% 4.3, 24.5), systemic lupus erythematosus (OR