Autoimmune Diseases in Patients with Premature Ovarian Insufficiency—Our Current State of Knowledge

Abstract

Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4–30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave’s disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto’s type thyroid antibodies and has a prevalence of 10–40%. 21OH-Antibodies in Addison’s disease (AD) can develop in association to APS-2.

Endocrinopathies in Inborn Errors of Immunity

“…The onset of the two conditions occurs from early childhood and can be obvious at any age. Ovary is also would be a major target of autoimmune response, and approximately 40-70% of women with APECED will develop premature ovarian failure (63)(64)(65). On the other hand, T1DM and hypothyroidism affects less than 5-10% and 20-25% of the patients, respectively (65), and the age of onset is during adulthood than childhood.…”

Interplay Between mTOR and Hippo Signaling in the Ovary: Clinical Choice Guidance Between Different Gonadotropin Preparations for Better IVF

“…In addition, vitamin D deficiency decreases mTOR activation in rat models ( 59 ) and human uterine fibroid cells ( 60 ). These are conditions that can influence the IVF outcomes ( 61 – 64 ). Future studies addressing the effects of the various gonadotropin combinations on the PI3k/Akt/mTOR and Hippo pathways in physiological conditions (including ageing) and disease states, are expected to increase our understanding of follicle development and develop personalized treatment plans that will help clinician’s decision and improve the success rate of IVF.…”

The Role of Noncoding RNA in the Pathophysiology and Treatment of Premature Ovarian Insufficiency

“…Autoimmune diseases are considered to be responsible for 4-30% of POI cases [40]. The most common of these are Hashimoto thyroiditis, Graves' disease, Addison's disease, diabetes type 1, celiac disease, myasthenia gravis, systemic lupus erythematosus and autoimmune polyglandular syndromes (APS) [41]. The autoimmune mechanisms involved in developing POI include lymphocytic oophoritis and the presence of anti-oocyte antibodies (AOAs).…”

“…The inflammatory response affects ovarian steroid production and ovarian function [42,43]. AOAs can be detected in 24-73% of patients with POI and may appear years before POI diagnosis [41,44]. Moreover, there are some reports of POI developing after viral infections, including one case report of COVID-19-related POI and AOA formation after anti-HPV vaccination [45,46].…”