Women with premature ovarian insufficiency face higher risk of autoimmune diseases

By Dr. Liji Thomas, MDReviewed by Danielle Ellis, B.Sc.Dec 2 2024

Study highlights significant associations with autoimmune hypothyroidism, vitiligo, and other conditions, while family members show no increased risk

Autoimmune disease frequently occurs in women with primary ovarian insufficiency (POI). It is postulated that women with POI might be at hereditary risk for autoimmune disease, which has genetic underpinnings.

A recent study in The Journal of Clinical Endocrinology & Metabolism examined the association of autoimmune risk among women with POI and their close relatives.

About the study

The current study was population-based, using electronic health records (EHR) from 1995 to 2022. These records were maintained by two healthcare systems serving 85% of Utah residents. The study included 610 women, all with POI, and their first-, second-, and third-degree relatives.

The occurrence of autoimmune disease in this cohort was traced, and the relative risk estimate was calculated by comparing the recorded risk with the population risk for autoimmune disease.

Increased autoimmune risk among women with POI

The study showed that at least 25% of women with POI had one or more autoimmune diseases. In 80% of these cases, the diagnosis was hypothyroidism. A similar percentage had a single autoimmune disorder.

Of the 22% with more than one autoimmune disorder, there were ten or fewer women who had adrenal insufficiency, all of whom had APS type 1 or 2.

The relative risk varied with the specific condition. The risk of autoimmune hypothyroidism was seven times that of the general population, and the risk of psoriasis was fourfold. The relative risks for SLE, adrenal insufficiency, and T1DM were all increased between 4.1 and 4.7 times.

Women with T1DM may have a lower ovarian reserve, perhaps due to poorer blood supply or glycosylation due to hyperglycemia rather than autoimmunity per se.

The odds for RA were 5.6-fold, while celiac disease and vitiligo risks were raised to 15- and 7.6-fold, respectively.

No increased risk in family members

Interestingly, the risk for autoimmune disease was not raised in the family member cohort.

Earlier research has established that certain autoimmune disorders, including T1DM, Crohn’s disease, and psoriasis, occur among close relatives. Others, like SLE, do not show this association, perhaps because they are less common. Hence, studies are likely to be underpowered.

Again, autoimmune disease has high heritability, as shown by higher rates of the same autoimmune disorder among identical twins compared to fraternal. However, environmental exposures and variations in sex steroid levels may also play a role in the development of autoimmune disease, while some cases may have been missed. Overlapping genes may further complicate the scenario.

Conclusions

The analysis confirms prior studies showing that multiple autoimmune diseases are more likely among women with POI. The conditions contributing most to this increased risk include autoimmune polyglandular syndrome types 1, 2, 3, and 4 and autoimmune hypothyroidism. However, autoimmune hypothyroidism is not a cause of POI, according to current knowledge.

The authors emphasize that the absence of increased risk for autoimmune disease among family members does not mean that there is no genetic predisposition for autoimmune disease in POI. They suggest that “other factors in addition to shared POI and autoimmune genetic risk play a role in the increased autoimmune disease burden in POI.”