High serum inhibin concentration discriminates autoimmune oophoritis from other forms of primary ovarian insufficiency.
ABSTRACT Primary ovarian insufficiency (POI) is defined by hypergonadotropic amenorrhea occurring before the age of 40 yr. In 4-5% of women with POI, an ovarian autoimmune process can be demonstrated.
We have determined the serum concentrations of total inhibin and inhibin B by sensitive ELISAs in 22 women with autoimmune POI (aPOI), 71 women with non-autoimmune idiopathic POI (iPOI), 77 postmenopausal women, and 90 healthy, fertile women (HW). Diagnosis of aPOI was made according to the presence of steroid cell autoantibodies and/or 17alpha-hydroxylase autoantibodies and/or cytochrome P450 side-chain cleavage autoantibodies. All aPOI patients were also positive for adrenal autoantibodies.
Total inhibin levels were significantly higher in women with aPOI (median, 281 pg/ml) than in women with iPOI (median, 74 pg/ml) or HW (median, 133.5 pg/ml) (P < 0.001). Levels of inhibin B were also significantly higher in women with aPOI (median, 109 pg/ml) than in women with iPOI (median, 18 pg/ml) (P < 0.001) or HW (median, 39 pg/ml) (P < 0.05). Serum concentrations of total inhibin and inhibin B were significantly higher in women with POI than in postmenopausal women (P < 0.001), irrespective of the presence/absence of autoantibodies. At receiver-operating characteristic analysis, cutoff values of 133 pg/ml for total inhibin and 60.5 pg/ml for inhibin B ensured 86.4% sensitivity and 81-84.5% specificity for aPOI vs. iPOI.
We conclude that a variable degree of ovarian function is preserved in women with POI and that aPOI is characterized by increased inhibin production resulting from a selective theca cell destruction, with initial preservation of granulosa cells.
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ABSTRACT: The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models.Cellular & Molecular Immunology advance online publication, 20 October 2014; doi:10.1038/cmi.2014.97.Cellular & molecular immunology 10/2014; DOI:10.1038/cmi.2014.97 · 4.19 Impact Factor
Article: Biology of ovarian aging[Show abstract] [Hide abstract]
ABSTRACT: The woman's reproductive system ages much faster than other systems of the body. Menopause is the last step in the process of ovarian aging. Studies on the biological clock stops more and more often attract the attention of many researchers. This is related to the increase in life expectancy, but also increasingly making decisions about motherhood later on and the increasing number of infertile couples. Neuroendocrine and uterine factors are contributing to a reduction in fertility with age, the ovary is the main authority responsible for this phenomenon. Aging of the ovary is dominated by a progressive reduction in the number of follicles. And the number and quality of follicle - ovarian reserve - are linked to the age of the woman. Research helpful in the determination of the ovarian reserve involves the measurement of the number of antral follicles during transvaginal ultrasound and blood levels of follicle-stimulating hormone between the 2nd and 4th day of the cycle, inhibin B, estradiol and anti-Mullerian hormone. A strategy based on the use of stem cells to regenerate the ovary is proposed as future therapies for the treatment of female infertility. In this article, we report factors affecting aging of the ovaries and changes accompanying this phenomenon.Menopausal Review 06/2013; 3(3):231-234. DOI:10.5114/pm.2013.36589 · 0.38 Impact Factor
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ABSTRACT: Abstract There is an increased incidence of autoimmune thyroid disease (AITD) in women with infertility. We hypothesized that serum anti-Müllerian hormone (AMH) levels will be lower in premenopausal women with AITD than controls. We evaluated ovarian reserve in women with AITD (n = 85) and healthy controls (n = 80), all <40 years old. Detailed data on reproductive history were obtained. Gonadotrophins, steroids, AMH, and inhibin B levels were measured during the follicular phase. The number of pregnancies as well as live births was lower in women with AITD (p < 0.01). No difference was observed in terms of FSH, estradiol, and inhibin B. AMH levels were lower in AITD women than in controls (1.16 + 0.17 versus 1.28 + 0.25 ng/ml, mean + SD, p = 0.001). According to the multiple regression analysis, even after age adjustment, AITD was significantly and independently affected AMH levels (t = 2.674, p = 0.008). Women with AITD seem to have a diminished ovarian follicular reserve and measurement of serum AMH level has the potential to be used to predict this comorbidity.Gynecological Endocrinology 10/2014; 31(2):1-4. DOI:10.3109/09513590.2014.973391 · 1.14 Impact Factor