Autoimmune Disease is Increased in Women with Primary Ovarian Insufficiency.

Context: Autoimmune disease is common in women with primary ovarian insufficiency (POI) and the genetic etiology of autoimmune disease suggests that it could be hereditary in families of women with POI.

Objective: We hypothesized that a subset of women with POI and their family members would have increased risk for autoimmune disorders.

Design: Population-based study using electronic health records from 1995-2022.

Setting: Two major Utah healthcare systems serving 85% of the state.

Subjects: Women with POI (n=610) were identified using ICD codes and chart reviewed for accuracy. First-, second-, and third-degree relatives were identified using genealogy data in the Utah Population Database.

Intervention: Autoimmune diagnoses were identified using ICD codes.

Main Outcome Measures: The relative risk of autoimmune disease in women with POI and relatives was estimated by comparison to population rates.

Results: At least one autoimmune disease was identified in 25% of women with POI. The relative risk of autoimmune hypothyroidism (OR [95%CI] 6.88 [5.71, 8.22]; p<0.001), adrenal insufficiency (4.72 [1.73, 10.28]; p=0.0020), type 1 diabetes (4.13 [2.14, 7.22]; p=5.25X10-5), rheumatoid arthritis (5.66 [3.10, 9.50]; p=3.70X10-7), vitiligo (15.33 [6.16, 31.58]; p=5.25X10-7), celiac disease (7.58 [3.47, 14.39]; p=4.47X10-6), psoriasis (3.90 [2.01, 6.81]; p=9.04X10-5) and systemic lupus erythematosus (4.43 [1.63, 9.64]; p=0.0027) were increased in women with POI compared to population rates. There was no increased risk of autoimmune disease in family members.

Conclusions: Data confirm increased autoimmune disease in women with POI. The increased risk is largely related to autoimmune polyglandular syndrome types 1 through 4 and autoimmune hypothyroidism. The absence of risk in family members may result from differences in environmental influences or hormone milieu.