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J Endocrinol Invest. 2009 Mar;32(3):210-8.
Increased clearance of cortisol by 5beta-reductase in a subgroup of
women with adrenal hyperandrogenism in polycystic ovary syndrome.
Gambineri A, Forlani G, Munarini A, Tomassoni F, Cognigni GE, Ciampaglia
W, Pagotto U, Walker BR, Pasquali R.
Division of Endocrinology, Department of Internal Medicine, and Centre
for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital,
University Alma Mater Studiorum of Bologna, Bologna, Italy.
OBJECTIVE: Increased peripheral metabolism of cortisol may explain
compensatory ACTH-dependent adrenal steroidogenesis and hence
hyperandrogenism in polycystic ovary syndrome (PCOS). Previous studies
have described an increased 5alpha-reduction of cortisol or impaired
regeneration of cortisol by 11beta-HSD1 in PCOS. However, these
observations may be confounded by obesity. Moreover, the relationship
between alterations in cortisol metabolism and the extent of adrenal
androgen hyper-secretion in response to ACTH has not been established.
This study aimed to examine the association between cortisol metabolism
and ACTH-dependent adrenal hyperandrogenism in PCOS, independently of
obesity. DESIGN: We compared 90 PCOS women (age 18-45 yr) stratified by
adrenal androgen responses to ACTH1-24 and 45 controls matched for age
and body weight. METHODS: PCOS women were stratified as normal
responders (NR), intermediate responders (IR), and high responders (HR)
to 250 microg ACTH1-24: NR (no.=27) had androstenedione and DHEA
responses within 2 SD of the mean in controls; IR (no.=43) had DHEA
responses >2 SD above controls; HR (no.=20) had both androstenedione and
DHEA responses >2 SD above controls. Results: All groups were similar
for age, body weight, and body fat distribution. Basal testosterone,
androstenedione, and 5alpha-dihydrotestosterone plasma levels were
similarly elevated among the 3 groups of PCOS compared with controls,
whereas basal DHEA-S was higher in HR (2.8+/-1.2 microg/ml) and IR
(2.4+/-1.1 microg/ml) than in NR (1.8+/-0.8 microg/ml) and controls
(1.7+/-0.6 microg/ml). The HR group had the lowest basal plasma cortisol
levels (101+/-36 ng/ml vs IR 135+/-42 ng/ml, NR 144+/-48 ng/ml, and
controls 165+/-48 ng/ml; all p<0.01), but the greatest cortisol response
to ACTH1-24 (Delta(60-0)cortisol 173+/-60 ng/ml vs IR 136+/-51 ng/ml, NR
114+/-50 ng/ml, and controls 127+/-50 ng/ml; all p<0.01), and the
highest urinary excretion of total and 5beta-reduced cortisol
metabolites (eg 5beta-tetrahydrocortisol/ cortisol ratio 25.2+/-15.3 vs
IR 18.8+/-10.7, NR 19.7+/-11.4, and controls 17.2+/-13.7; all p<0.05).
There were no differences in urinary excretion of 5alpha-reduced
cortisol metabolites or in 5alpha-dihydrotestosterone/testosterone ratio
between groups. CONCLUSIONS: Adrenal androgen excess in PCOS is
associated with increased inactivation of cortisol by 5beta-reductase
that may lower cortisol blood levels and stimulate ACTH-dependent
steroidogenesis.
Publication Types:
* Controlled Clinical Trial
* Research Support, Non-U.S. Gov't
PMID: 19542736 |
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