High levels of serum allopregnanolone in women with premature ovarian failure

Abstract

The endocrine characteristics of patients with premature ovarian failure (POF) have not been fully elucidated. The aim of the present study was to evaluate whether steroidogenic activity in women with POF is different with respect to fertile and postmenopausal subjects. In particular, circulating levels of allopregnanolone, a neuroactive steroid involved in modulation of reproductive function in rats, have been evaluated and correlated with serum levels of delta 4 precursor (dehydroepiandrosterone sulfate (DHEAS)), delta 5 intermediates (androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone) and final products (estradiol and testosterone) of androgens. Levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were also determined. In all cases specific radioimmunological assays were used. Women with POF showed statistically significantly lower concentrations of 17-OHP, androstenedione and testosterone when compared to fertile controls, while no differences were found between women with POF and postmenopausal women. Serum DHEAS levels were similar in POF patients and in fertile controls and higher with respect to postmenopausal women. Serum allopregnanolone levels were significantly higher in women with POF than in postmenopausal and in fertile women. A significant inverse correlation between allopregnanolone levels and menopausal age in patients with POF was observed while no significant correlation was found between allopregnanolone and progesterone, androstenedione, 17-OHP and testosterone levels. In conclusion, allopregnanolone is scarcely influenced by the reduction of ovarian and adrenal activity observed in POF.

Does Interrelationship of Allopregnanolone and Tetrahydrodeoxycorticosterone during Pregnancy and Postpartum Depression Exist? A Review of the Current Evidence

“…Similar results of delayed follicular phase with THDOC enhancement are present in rats [13] but no effect in primates [46]. These results can be correlated with human where elevated levels of ALP may induce premature ovarian failure [47].…”

Assessment of androgen concentration in women: liquid chromatography–tandem mass spectrometry and extraction RIA show comparable results

“…In this group, testosterone and DHEA concentrations were similar as female controls, while AD concentrations were significantly lower. In the existing literature, it is debated whether POI is associated with decreased androgen concentrations (14,(29)(30)(31)(32)(33), and only one study presented with results similar to ours (34). As previous studies only applied direct RIA, chemiluminescence immunoassays, and extraction RIA, conflicting findings most probably resulted from lower sensitivity, lack of specificity, or lower accuracy of these assays (10).…”

Ovarian Autoimmune Disease and Ovarian Autoantibodies

“…[73][74][75] Endocrine markers of ovarian function, such as sex steroid hormones, do not appear to be differentially altered in POF. [76][77][78][79][80] Autoimmune and nonautoimmune ovarian failure are not readily differentiated by endocrine profiles.…”