Autoimmune Disorders in Women Under 40 Linked to Early Menopause

Researchers recently examined the connection between autoimmune disorders and premature ovarian insufficiency (POI), with findings published in Human Reproduction.

Context

With POI, the ovaries stop producing eggs before the age of forty, which causes irregular menstrual cycles and menopausal symptoms. Studies show that 4-55% of all cases of POI are caused by autoimmune diseases. Thyroid antibody positivity increases the risk of developing POI, and autoimmune antibodies are more common in females with POI diagnoses.

Women who are reproductive age and have low levels of anti-Müllerian hormone (AMH) have been linked to a number of autoimmune conditions, such as ankylosing spondylitis, thyroid autoimmunity, type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus.

About the study
Whether POI raises the risk of autoimmune disease was examined in the current national registry-based study.

3,972 girls with POI diagnoses (cases) and 15,708 age-matched control females from the general population made up the reference group in this study. For every woman with POI, four controls were chosen by the researchers. They identified POI women from the Social Insurance Institution (SII) registry in Finland who, between 1988 and 2017, were awarded medical reimbursement for hormone replacement therapy (HRT) because they had POI prior to turning 40. The index date was the day that HRT reimbursement was granted. The Human Reproduction and Embryology (ESHRE) standards were followed for medical reimbursement for HRT resulting from POI.

None of the individuals underwent gender reassignment, double oophorectomies, or cancer. The International Classification of Diseases (ICD)-8, 9, and 10 codes were used to identify severe autoimmune illnesses treated by the Hospital Discharge Registry (HDR). The study covered autoimmune diseases diagnosed and treated at specialty clinics between 1970 and 2017, excluding out disorders like celiac disease and hypothyroidism that are mainly handled in primary care settings.

Odds ratios (OR) for analysis were obtained using binary logistic regressions. In females with POI, standardized incidence ratios (SIR) represented the ratio of observed to predicted cases of autoimmune disorders across three-year follow-up periods. The individuals were monitored by the team until December 31, 2017, or until a serious autoimmune condition diagnosis was made, whichever came first.

Findings and conversation
When POI was diagnosed, the median participant age was 36. Before the payment date, 223 (5.6%) of the females with POI experienced one or more serious autoimmune disorders (OR, 2.6) in comparison to the controls, while 503 (13%) were diagnosed with an autoimmune disorder after the reimbursement date. When comparing patients prior to the payment date to controls, there were greater prevalence rates for specific autoimmune illnesses. With OR values of 26, 23, 6.3, 10, 2.3, 2.3, 1.9, and 2.2, respectively, these illnesses comprised polyglandular autoimmune disorders, Addison’s disease, systemic lupus erythematosus, vasculitis, sarcoidosis, rheumatoid arthritis, hyperthyroidism, and inflammatory bowel disease.

There was no discernible difference in the prevalence rates of type 1 diabetes and ankylosing spondylitis between women with POI and controls. After POI diagnosis, the standardized incidence ratio for diagnoses of serious autoimmune disorders was 2.80 in the first three years after the diagnosis. Once POI was diagnosed, the SIR gradually dropped to 1.30 after 12.0 years.

Given the universal sensitivity of severe autoimmune disorders and autoimmune-origin POI, it is reasonable to anticipate the emergence of severe autoimmune conditions either before to or following a diagnosis of POI. Research indicates that the ovaries’ cyclical production of sex hormones regulates immunological function, which raises the possibility that early cessation of ovarian activity could put women at risk for autoimmune diseases like rheumatoid arthritis.

The current study shows that autoimmune systems are triggered when POI develops in many people, as evidenced by the high incidence of incident severe autoimmune disorders in the first several years following diagnosis. But considering the high frequency of autoimmune problems prior to the diagnosis of premature ovarian insufficiency and the rising incidence decades after the diagnosis of POI, the tendency for autoimmune disorders to develop in females with POI appears to be long-term.

In conclusion
According to the study, women who have early ovarian insufficiency, or whose periods stop before the age of 40, are at a higher risk of developing severe autoimmune diseases. Severe autoimmune disorders were more than twice as common in POI patients than in controls before to diagnosis, and the frequency of these conditions stayed two- to three-fold higher for a number of years after.

Future research ought to look into the molecular processes that underlie the link between autoimmune disorders and POI. The development of preventative therapeutics for autoimmune-origin POI and other autoimmune diseases may be aided by the identification of molecular mechanisms connecting the condition to autoimmune illnesses. If long-term hormone replacement therapy can stop POI women from developing new disorders, that has to be investigated further.

For more information: Excess of severe autoimmune diseases in women with premature ovarian insufficiency: a population-based study, Human Reproduction, https://doi.org/10.1093/humrep/deae213