Ovarian-adrenal cross-talk in polycystic ovary syndrome: evidence from wedge resection

Abstract

Objective: To determine whether the ovary in¯uences adrenal androgen secretion in women with polycystic ovary syndrome (PCOS). Design: Six PCOS-affected patients with clomiphene resistance and gonadotrophin hyperresponsivity, and six controls with regular ovulatory cycles, matched for age and body mass index. Methods: Bilateral ovarian wedge resection was performed to induce ovulation surgically for these refractory women with PCOS. The adrenal androgen secretions were evaluated in PCOS patients before and again 6 months after this surgery, and in the controls, using an ACTH stimulation test (0.25 mg synthetic ACTH(1±24)). Results: Biochemically, basal levels and the maximum net increases (D) of 17-hydroxyprogesterone (17-OHP) and androstenedione, D17-OHP/Dprogesterone and Dandrostenedione/D17-OHP ratios in response to exogenous ACTH were signi®cantly higher in PCOS patients before operation than those of controls. This purely ovarian surgery in women with PCOS was found to signi®cantly reduce their basal androstenedione, testosterone and LH levels, insulin/glucose ratio, and post-corticotrophic D17-OHP, Dandrostenedione, D17-OHP/Dprogesterone and Dandrostenedione/D17-OHP, without obvious changes in FSH, oestradiol, sex hormone-binding globulin, Ddehydroepiandrosterone, Ddehydroepiandrosterone sulphate, Daldosterone and Dcortisol values. Conclusions: Ovarian hyperandrogenicity from polycystic ovary may contribute to the enhanced adrenal P450c17a activity and subsequent D 4 androgen reserve revealed by the pharmacological corticotrophin stimulation in our special PCOS cases.

High DHEAS/free testosterone ratio is related to better metabolic parameters in women with PCOS

“…Adrenal androgen secretion is not controlled solely by ACTH, an extra-adrenal mechanism other than ACTH is most probably involved additionally [14]. An ovarian messenger was suggested to mediate the crosstalk between adrenals and ovaries [15,16]. Suppression of the ovarian activity with GnRH agonist decreases DHEAS, but the messenger regulating this cross-talk between the ovaries and adrenal glands is unknown [17,18].…”

Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity

“…It is already known that hyperandrogenism, the main clinical feature of PCOS (14), correlates positively with hyperinsulinemia (15,17,63) and that adrenal gland androgens contribute to PCOS (127,199). In women, a rare 11␤-HSD1 polymorphism leading to lower 11␤-HSD1 activity is associated with enhanced cortisol clearance and reduced negative feedback suppression of ACTH secretion.…”

Different phenotypes of polycystic ovary syndrome by Rotterdam criteria are differently steroidogenic but similarly insulin resistant

“…Blood samples from all patients were collected just before the injection (basal, 0 hours), and at 3, 8, 12, 18, and 24 hours after OST. Glucose concentrations and all hormones were analyzed as previously reported elsewhere (8,9). To evaluate the functional state of ovarian enzymes acting in steroidogenesis, product/precursor ratios of absolute levels at time points before and after OST were employed as appropriate (9,10).…”

“…Glucose concentrations and all hormones were analyzed as previously reported elsewhere (8,9). To evaluate the functional state of ovarian enzymes acting in steroidogenesis, product/precursor ratios of absolute levels at time points before and after OST were employed as appropriate (9,10). We also use the ratios of the net product increment from baseline values versus basal precursors to evaluate the functional activity of these enzymes (9,10).…”

“…To evaluate the functional state of ovarian enzymes acting in steroidogenesis, product/precursor ratios of absolute levels at time points before and after OST were employed as appropriate (9,10). We also use the ratios of the net product increment from baseline values versus basal precursors to evaluate the functional activity of these enzymes (9,10). The methods for the multiple comparisons were analysis of variance (ANOVA) and analysis of covariance (ANCOVA) to identify group differences, with the Bonferroni correction when appropriate.…”