Autoimmune diseases more common in women who stop ovulating before 40

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Sep 30 2024

The findings underscore the need for future research on autoimmune factors in POI to improve prevention and treatment strategies.

In a recent study published in Human Reproduction, researchers evaluated the relationship between autoimmune diseases and premature ovarian insufficiency (POI).

Background

POI is a disorder in which ovaries cease releasing eggs before the age of 40, resulting in irregular periods and menopausal symptoms. According to studies, autoimmune disease accounts for 4-55% of all instances of POI. Females diagnosed with POI have a higher incidence of autoimmune antibodies, and thyroid antibody positivity raises the chance of developing POI.

Low anti-Müllerian hormone (AMH) levels among reproductive-aged women are associated with various autoimmune diseases, including thyroid autoimmunity, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.

About the study

In the current nationwide registry-based study, researchers investigated whether POI increases the risk of autoimmune disease.

The study included 3,972 females diagnosed with POI (cases) and a reference group of 15,708 age-matched females from the general population (controls). The researchers selected four controls for each POI woman. They identified POI women from Finland’s Social Insurance Institution (SII) registry who were granted medical reimbursement for hormonal replacement treatment (HRT) due to POI before 40 years of age in the 1988-2017 period. The date of granting reimbursement for HRT was the index date. Medical reimbursement for HRT due to POI followed the Human Reproduction and Embryology (ESHRE) criteria.

None of the participants had cancer or underwent bilateral oophorectomies or gender reassignment. The Hospital Discharge Registry (HDR) identified severe autoimmune disorders treated using the International Classification of Diseases (ICD)-8, 9, and 10 codes. The study included autoimmune conditions diagnosed and managed at specialized health centers between 1970 and 2017, excluding those primarily treated in primary care settings, like celiac disease and hypothyroidism.

Binary logistic regressions determined odds ratios (OR) for analysis. Standardized incidence ratios (SIR) denoted the ratio of the observed to expected cases of autoimmune diseases among females with POI in three-year periods of follow-up. The team followed the participants until the diagnosis of severe autoimmune disorder, December 31, 2017, or death, whichever occurred first.

Results and discussion

The median participant age at POI diagnosis was 36 years. Among females with POI, 223 (5.6%) developed one or more severe autoimmune diseases (OR, 2.6) compared to controls before the reimbursement date, and 503 (13%) received an autoimmune disorder diagnosis after the reimbursement date. The prevalence rates were higher for certain autoimmune diseases among cases before the reimbursement date than controls. These diseases included polyglandular autoimmune disorders, Addison’s disease, systemic lupus erythematosus, vasculitis, sarcoidosis, rheumatoid arthritis, hyperthyroidism, and inflammatory bowel disease, with OR values of 26, 23, 6.3, 10, 2.3, 2.3, 1.9, and 2.2, respectively.

The prevalence rates of ankylosing spondylitis and type 1 diabetes did not significantly differ between POI women and controls. The standardized incidence ratio for severe autoimmune disorder diagnoses after the diagnosis of POI was 2.80 during the initial three years following POI diagnosis. The SIR decreased progressively to 1.30 after 12.0 years of POI diagnosis.

Since severe autoimmune disorders and autoimmune-origin POI reflect universal sensitivity, it is realistic to expect severe autoimmune conditions to appear pre- or post-POI diagnosis. Studies report that cyclic synthesis of sex hormones by the ovaries plays a crucial part in regulating immune function, leading to the suggestion that early termination of ovarian activity may expose females to autoimmune disorders like rheumatoid arthritis.

The high frequency of incident severe autoimmune illnesses in the initial few years after POI diagnosis, as revealed in the current study, demonstrates that autoimmune systems are activated when POI develops in many individuals. However, the propensity to acquire autoimmune disorders among females with POI seems long-term, given the high frequency of autoimmune conditions before the diagnosis of premature ovarian inadequacy and the increasing incidence decades after POI diagnosis.

Conclusions

The study findings showed that women with early ovarian insufficiency, or periods that end before 40 years of age, are more likely to have serious autoimmune illnesses. Before POI diagnosis, the prevalence of severe autoimmune disorders was more than double that of controls, and the frequency of severe autoimmune diseases remained two- to three-fold higher for several years following.

Future studies should investigate the biological mechanisms underlying the association between POI and autoimmune diseases. Identifying molecular pathways linking POI to autoimmune illnesses may aid in the development of preventative therapies for autoimmune-origin POI and other autoimmune diseases. Further investigation is required to determine whether long-term hormone replacement treatment can prevent the development of additional diseases in POI women.