Primary Ovarian Insufficiency due to Steroidogenic Cell Autoimmunity Is Associated with a Preserved Pool of Functioning Follicles

Mother-Infant Department, Section of Obstetrics and Gynecology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 08/2009; 94(10):3816-23. DOI: 10.1210/jc.2009-0817
Source: PubMed


Primary ovarian insufficiency (POI) is defined as hypergonadotropic amenorrhea before the age of 40 yr. In 4-5% of patients with POI, an ovarian autoimmune process is present.
Serum concentrations of antimüllerian hormone (AMH) have been determined in 26 women with POI due to steroidogenic cell autoimmunity (SCA-POI), 66 with nonautoimmune idiopathic POI (iPOI), 40 postmenopausal women (PMW), and 44 healthy fertile women (HW). SCA-POI was diagnosed according to presence of steroidogenic enzyme autoantibodies (17alpha-hydroxylase, side chain cleavage, and 21-hydroxylase autoantibodies).
AMH concentrations were significantly higher in women with SCA-POI than women with iPOI (P = 0.018) or PMW (P = 0.03) but significantly lower than HW (P < 0.0001). AMH was detected in 11 of 26 women with SCA-POI (42%) and seven of 66 with iPOI (11%) (P = 0.002). Serum concentrations above the fifth percentile of the normal range (0.6 ng/ml) were detected in nine of 26 women with SCA-POI (35%) and four of 66 with iPOI (6%) (P = 0.001). Eight of 12 women with SCA-POI with less than 5 yr (67%) and one of 14 with longer disease duration (7%) had AMH concentrations within the normal range (P = 0.003). AMH concentrations correlated inversely with disease duration in women with SCA-POI (rho = -0.563, P = 0.003) but not women with iPOI. AMH correlated inversely with FSH serum concentrations in HW (rho = -0.584, P < 0.001) but not PMW or women with POI.
Two thirds of women with recent-onset SCA-POI had normal AMH concentrations. Women with SCA-POI, differently from those with iPOI, present a preserved ovarian follicle pool for several years after diagnosis of ovarian insufficiency.

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    • "In contrast, AMH levels are undetectable in the great majority of women diagnosed with primary ovarian insufficiency (POI) (WHO group 3) suggesting premature follicle pool exhaustion (Knauff et al., 2009). Moreover, AMH may provide useful information regarding the extent of follicle pool depletion in various POI-like conditions, such as incipient ovarian failure (Knauff et al., 2009), ovarian failure due to autoimmunity (La Marca et al., 2009) or FSH receptor loss of function mutation (Kallio et al., 2012). In this context, it should be noted that current criteria used to define POI (such as FSH concentrations .40 "
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    ABSTRACT: BACKGROUND In women, anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells of ovarian follicles during the early stages of follicle development. After an initial increase until early adulthood, AMH concentrations slowly decrease with increasing age until becoming undetectable ∼5 years before menopause when the stock of primordial follicles is exhausted. However, major individual variability exists in the pace of follicle pool depletion and the initial size of the follicle pool, reflected by a wide range of age at menopause. Individual AMH serum concentration does accurately reflect the size of the pool of antral follicles, representing the quantity of the remaining primordial follicles. Accordingly, AMH levels may vary significantly in women of the same chronological age, allowing AMH to predict the remaining length of a woman's reproductive lifespan.
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    • "We recently documented normal serum AMH concentrations in two-thirds of women with recently diagnosed autoimmune POI (La Marca et al, 2009), which provides the first demonstration of the existence of a subgroup of women with POI with a preserved ovarian follicle pool for several years. Since AMH is the best biochemical marker of residual follicle pool, the results of our study (La Marca et al, 2009) are highly relevant for the future planning of clinical trials of immunotherapy aimed at preserving the residual functional tissue and/or delay the progression of the destructive ovarian autoimmune process in women with autoimmune POI. "

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    • "Even POF/POI, and in physiologic menopause ovaries still contain substantial numbers of NGFs. A form of POF/POI, characterized by steroidogenic cell autoimmunity, demonstrates almost uniformly preserved follicle pools on ultrasound [28]. Indeed, in the past considered a rare finding, follicles can be seen on ultrasound in over a third of POF/POI cases [42]. "
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