Among the uncertainties surrounding the etiology of polycystic ovary syndrome (PCOS) the role of increased peripheral cortisol metabolism has become interesting, particularly in relationship to the pathogenesis of adrenal hyperandrogenism. The patways of cortisol metabolism include irreversible inactivation of cortisol by 5α- and 5β-reductase. To evaluate the association of 5α- and 5β-reductase activity with adrenal hyperandrogenism in PCOS, we recruited 90 PCOS women (age range: 1845 years) classified into three groups accordingly to the responsiveness of androstenedione (A) and DHEA to 124ACTH: group of low responders (LR) (n=27), defined by A and DHEA responsiveness to 124ACTH within 2 SD of mean of a group of controls; group of medium responders (MR) (n=43), defined by A or DHEA responsiveness to 124ACTH over 2 SD; group of high responders (HR) (n=20), defined by A and DHEA responsiveness to 124ACTH over 2 SD. Excretion of cortisol and its metabolites was measured by electron impact gas chromatography-mass spectrometry in a 24-h urine collection. Relative 5α- and 5β-reduction of cortisol was assessed by 5α-tetrahydrocortisol (5α-THF)/cortisol, and 5β-THF/cortisol and 5β-tetrahydrocortisone (THE)/cortisone, respectively. The three groups were similar for age, body weight and body fat distribution. Testosterone, A and 17OH-progesterone basal levels were also similar among the three groups, whereas DHEA-S was significantly higher in MR (P<0.05) and more in HR (P<0.01) respect to NR. HR presented also basal cortisol levels significantly lower and cortisol responsiveness to 124ACTH significantly higher than MR (P<0.01) and NR (P<0.001, P<0.05). 5β-THF/cortisol and 5β-THE/cortisone were significantly higher in HR respect to MR and NR (P<0.05). No differences in 5α-THF/cortisol were observed among the three groups. These data open up the intriguing possibility of 5 β-reductase hyperfunction as a new pathogenetic mechanism of adrenal hyperandrogenism in a subgroup of PCOS women.
28 Apr - 02 May 2007
European Society of Endocrinology