Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11 beta-hydroxysteroid dehydrogenase.
BACKGROUND
Hyperandrogenemia is the hallmark of the polycystic ovary syndrome, yet the relative contributions of the adrenal cortex and ovary to the overproduction of androgen remain unclear. To identify possible causes of adrenocortical overactivity, we studied the metabolism of adrenal and ovarian steroid hormones in women with this disorder.


METHODS
We measured 24-hour urinary excretion of steroid hormone metabolites by high-resolution capillary gas chromatography in 65 women with the polycystic ovary syndrome and 45 normal women matched for body-mass index.


RESULTS
After adjustment for body-mass index, the urinary excretion of testosterone and androstenedione metabolites was 1.9 times higher in the women with the syndrome than in the normal women, and the excretion of dehydroepiandosterone metabolites (C19 steroid sulfates) and cortisol metabolites was 1.5 and 1.3 times higher, respectively (P < 0.01 for all comparisons). The affected women also had significantly higher ratios of 11-oxo (oxygenated) metabolites to 11-hydroxy metabolites of cortisol (1.4 times higher, P < 0.001) and of 11-oxo to 11-hydroxy metabolites of corticosterone (1.8 times higher, P < 0.001). In the group with the polycystic ovary syndrome, 55 percent of the nonobese women and 24 percent of the obese women had ratios above the upper limit of normal; the ratios in the obese women did not differ significantly from those in the nonobese women.


CONCLUSIONS
Adrenal secretion of cortisol and androgens is increased in women with the polycystic ovary syndrome. The increases may be explained by dysregulation of 11 beta-hydroxysteroid dehydrogenase causing increased oxidation of cortisol to cortisone, which cannot be accounted for by obesity.
Rodin
A
A
Division of Biochemical Medicine, St. George's Hospital Medical School, London, United Kingdom.
Thakkar
H
H
Taylor
N
N
Clayton
R
R
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D005260:Female; D006728:Hormones / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000652:urine; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism* / Q000652:urine; D017588:Hyperandrogenism / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000652:urine
D006728:Hormones; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone