Steroidogenic alterations and adrenal androgen excess in PCOS

This cross-sectional study was undertaken to improve our understanding of the steroidogenic alterations leading to adrenal hyperandrogenism in polycystic ovarian syndrome (PCOS). Two-hundred and thirty-four women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. We used the androstenedione/DHEAS ratio as a surrogate for the level of ovarian 3βHSD activity. We then selected the 90th percentile for the ratio in those with elevated DHEAS (>9 μmol/l) as the cut-off level beyond which excess DHEAS production will be minimized by excess ovarian 3βHSD activity. This cut-off level was at a ratio of 1.5 and all PCOS women were then divided into two groups, the higher (>1.5) being the group with excess ovarian 3βHSD activity. We hypothesized that women with a high ratio would be unlikely to have DHEAS excess due to the rapid conversion of DHEA to androstenedione. Those with a low ratio (concordant ovarian and adrenal steroidogenesis) could then either have high DHEAS or normal DHEAS, depending on whether CYP17 activity was higher or lower respectively. Insulin resistance was found to be associated with decreased CYP17 activity while irregular cycles and neuroendocrine dysfunction were determined to be associated with higher ovarian 3βHSD activity. Adrenal androgen excess in PCOS seems to be related to insulin sensitivity as well as decreased activity of 3βHSD, the latter being preferentially present in those women with regular cycles or without neuroendocrine dysfunction.