Antiovarian antibodies do not correlate with the presence or severity of oophritis and do not predict when ovarian failure will occur, so the measuring of these antibodies is not recommended
Steroid producing cells (hillar cells, granulosa cells, theca internal and corpus luteum). Autoantibodies to steroid producing cells are widely present in POF associated with Addison’s disease (75). In autoimmune oophoritis, lymphatic infiltration is confined to secondary and antral follicles that have theca cells. This finding shows that steroid producing cells express the antigens that stimulate the immune response (74).
3?-hydroxysteroid dehydrogenase (3?-HSD). This enzyme is involved in the steroid metabolic pathway. 3?-HSD autoantibodies were found in 2-21% patients with isolated POF (76, 77). However, Florni et al. showed that 3?-HSD is not a major autoantigen in autoimmune POF and suggested that this marker does not appear to be useful in routine clinical practice (75). The differences in the 3?-HSD antibody assay may in part explain the differences observed in these studies. The antibodies against steroidogenic enzymes such as 21- hydroxylase, 17- hydroxylase and side chain cleavage were seen in patients with histologically confirmed autoimmune oophoritis (72).
Gonadotropin receptor blocking antibodies. Tang et al. (78) have found a relation between POF and FSHR (FSH-receptor) antibodies in their patients, but in later published studies, the gonadotropin receptor blocking antibodies have not been detected in POF women (79). Thus gonadotropin receptor blocking antibodies are a rare causes of POF.
Bakalov et al
The published incidence of antiovarian antibodies in patients with POF ranges widely (7-67%) due to the heterogeneity of investigation methods, multiple ovarian antibody targets (including antibodies against steroidogenic enzymes, gonadotropins and their receptors, the corpus luteum, zona pellucida and oocytes), the transient appearance of antiovarian antibodies, different stages of disease, as well as variations in antibody test format and antigen presentation (15). Therefore interpretation of the role of antiovarian antibodies in POF is problematic. In addition, it is uncertain whether antiovarian antibodies are pathogenic or secondary to antigen release after cellular damage.
Approximately 3% of women with POF have an associated endocrine dysfunction known as autoimmune polyglandular syndrome (APS), types I and II. The type I syndrome is a rare autosomal recessive disorder in young children, characterized by multiple organ-specific autoimmunity secondary to a variety of autoantibodies directed against key intracellular enzymes. POF in the form of prienorrhea develops in 60% of these patients. APS type II is an autosomal dominant disorder, and is associated with gonadal failure in 4% of patients (82). Addison’s disease is a component of both ASP types. Approximately 10% of women with Addison’s have POF (73) and 2-10% of POF cases show evidence of autoimmunity against the adrenal (71 useful content, 83). Sharing of autoantigens between ovary and adrenal glands, particularly the P450 side-chain cleavage enzyme, may explain the association of ovarian failure with Addison’s disease. In subclinical patients (presence of adrenal antibodies in absence of hypocortisolism), Addison’s disease may develop by the age of 8-14 (83).
Circulating 21-hydroxylase antibodies are the best immune markers of autoimmune adrenal insufficiency (75). Testing for anti-adrenal and anti-21-hydroxylase antibodies by indirect immunofluorescence not only identifies POF-diagnosed women who have steroidogenic cell autoimmunity and occult adrenal insufficiency at the time of initial presentation, but also identifies patients who should be monitored for the subsequent development of adrenal insufficiency, a potentially fatal disorder (15, 75, 83). showed that morning serum cortisol levels have low sensitivity and specificity, and ACTH stimulation tests have a high false positive rate when used as screening tests in these patients (83). Thus, the ACTH stimulation test should be used as a diagnostic test for patients with symptoms of adrenal insufficiency or with positive adrenal autoantibodies. Women with positive adrenal antibodies will require referral to a medical endocrinologist for additional evaluation and long-term follow-up of their adrenal function.