Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Controlled Clinical Trial
. 2009 Mar;32(3):210-8.
doi: 10.1007/BF03346454.

Increased clearance of cortisol by 5beta-reductase in a subgroup of women with adrenal hyperandrogenism in polycystic ovary syndrome

A Gambineri  1 , G Forlani, A Munarini, F Tomassoni, G E Cognigni, W Ciampaglia, U Pagotto, B R Walker, R Pasquali
Affiliations
Controlled Clinical Trial

Increased clearance of cortisol by 5beta-reductase in a subgroup of women with adrenal hyperandrogenism in polycystic ovary syndrome

A Gambineri et al. J Endocrinol Invest. 2009 Mar.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Response of androgens and cortisol to ACTH1-24 (Δ(60-0)) in PCOS normal responders-NR, intermediate responders-IR and high responders-HR, and in controls shown as individual values (scatter plot) and means ± SD. P< 0.001 for comparison in androstenedione and DHEA, P= 0.025 for comparison in 17OH-Progesterone, and P= 0.001 for comparison in cortisol among the three groups of PCOS (NR, IR, HR) by one-way ANOVA. To convert to SI units, multiply DHEA by 3.467 (result in nmol/L) and cortisol by 27.59 (result in nmol/L).
Figure 2
Figure 2
Fasting plasma DHEA-S and cortisol levels in PCOS normal responders-NR, intermediate responders-IR and high responders-HR, and in controls. Data are means ± SD. P= 0.004 for comparison in DHEA-S and P= 0.003 for comparison in cortisol among the three groups of PCOS (NR, IR, HR) by one-way ANOVA. To convert to SI units, multiply DHEA-S by 2.741 (result in μmol/L).
Figure 3
Figure 3
Relative 5β- (5βTHF/cortisol, 5βTHE/cortisone) and 5α- (5αTHF/cortisol) reduction of cortisol and the balance of 5β- and 5α-reductases (5βTHF/5αTHF) in PCOS normal responders-NR, intermediate responders-IR and high responders-HR, and in controls. Data are means ± SD. P= 0.049, P= 0.053, P= 0.825, and P= 0.044 for comparison in 5βTHF/cortisol, 5βTHE/cortisone, 5αTHF/cortisol, and 5βTHF/5αTHF levels, respectively, among the three groups of PCOS (NR, IR, HR) by one-way ANOVA.
Figure 4
Figure 4
Relationship between androstenedione or DHEA response to ACTH1-24 and fasting plasma cortisol levels.
See this image and copyright information in PMC

References

    1. Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol. 1992;167:1807–1812. - PubMed
    1. Wild RA, Umstot ED, Andersen RN, Ranney GB, Givens JR. Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol. 1983;146:602–605. - PubMed
    1. Hoffman DI, Klove K, Lobo RA. The prevalence and significance of elevated dehydroepiandrosterone sulfate levels in anovulatory women. Fertil Steril. 1984;42:76–81. - PubMed
    1. Azziz R, Black V, Hines GA, Fox LM, Boots LR. Adrenal androgen excess in the polycystic ovary syndrome: sensitivity and responsivity of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. 1998;83:2317–2323. - PubMed
    1. Walker BR. Activation of the hypothalamic-pituitary-adrenal axis: cause or consequence? GH & IGF Res. 2001;11(Suppl A):S91–95. - PubMed

Publication types

MeSH terms