Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity.


OBJECTIVE
The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls.


METHODS
We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers.


METHODS
A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study.


METHODS
The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test.


METHODS
We measured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5 alpha-reductase, and 11 beta-hydroxysteroid dehydrogenase types 1 and 2. We also measured circulating levels of glucose, insulin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone and calculated homeostasis model assessment.


RESULTS
Total androgen metabolites were higher in PCOS patients compared to BMI-matched controls (4,105 +/- 2,047 vs. 2,532 +/- 1,610 microg/24 h for the nonobese; 5,547 +/- 2,911 vs. 2,468 +/- 1,794 microg/24 h for the obese; both P < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10,786 +/- 3,852 vs. 8,834 +/- 4,487 microg/24 h; P = 0.001). 5 alpha-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5 alpha-reductase activity than controls (all P < 0.05). 11 beta-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls.


CONCLUSIONS
PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
Vassiliadi
Dimitra A
DA
Centre for Endocrinology, Diabetes & Metabolism, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Barber
Thomas M
TM
Hughes
Beverly A
BA
McCarthy
Mark I
MI
Wass
John A H
JA
Franks
Stephen
S
Nightingale
Peter
P
Tomlinson
Jeremy W
JW
Arlt
Wiebke
W
Stewart
Paul M
PM
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000378:metabolism; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005938:Glucocorticoids / Q000096:biosynthesis; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*
D000728:Androgens; D005938:Glucocorticoids; D042944:Cholestenone 5 alpha-Reductase; D006854:Hydrocortisone