Cited by 163Stress Responses and CortisolAdrenal Hormones and DisordersHormonal and reproductive studies

Testosterone suppression of CRH-stimulated cortisol in men

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Rubinow, David R, Roca, Catherine A, Schmidt, Peter J, Danaceau, Merry A, Putnam, Karen, Cizza, Giovanni, Chrousos, George, Nieman, Lynnette·2005·Neuropsychopharmacology

Abstract

Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (p<0.05, 0.005, and 0.01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (p<0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (p<0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (p<0.1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

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Crossref · 10.1038/sj.npp.1300742

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  • Testosterone replacement lowers cortisol levels and cortisol excursion after CRH stimulation tests.

    “On the other side, testosterone replacement has lowered cortisol levels and cortisol excursion after corticotropin-releasing hormone (CRH) stimulation tests [88].”

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Authors
Rubinow, D. R., Roca, C. A., Schmidt, P. J., Danaceau, M. A., Putnam, K., Cizza, G., Chrousos, G., & Nieman, L.
Affiliations
  • National Institutes of Health (US)
  • National Institute of Mental Health (US)
  • National Institute of Diabetes and Digestive and Kidney Diseases (US)
Corresponding author
Rubinow, David R
Venue
Neuropsychopharmacology
Published
2005-04-20
Volume
30
Issue
10
Pages
1906-1912
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W2072154896
Cited by
163
References
53
Citations by year
2026: 5 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 12 · 2020: 11 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 5 · 2015: 12 · 2014: 11 · 2013: 7 · 2012: 9
FWCI
2.09
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1z01mh002765-05)
  • National Institute of Mental Health (Z01 MH002765-09)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
testosterone, hypothalamic-pituitary-adrenal axis, corticotropin-releasing hormone stimulation test, cortisol, ACTH, androgens, GnRH agonist, leuprolide, testosterone replacement therapy, adrenal sensitivity, sexual dimorphism, men
MeSH terms
Adolescent, Adrenocorticotropic Hormone, Adult, Corticotropin-Releasing Hormone, Double-Blind Method, Drug Administration Schedule, Drug Interactions, Humans, Hydrocortisone, Male, Middle Aged, Radioimmunoassay, Testosterone, Time Factors, Leuprolide, Area Under Curve

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