Increasing Insulin Resistance Is Associated with a Decrease in Leydig Cell Testosterone Secretion in Men
Abstract
Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.
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Insulin sensitivity may improve within a few days of testosterone administration.
“Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3–12 months.”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [49]
Stimulation of endogenous testosterone increases insulin sensitivity within 48 h.
“And indeed, in an experimental study, stimulation of endogenous testosterone was shown to increase insulin sensitivity within 48 h (49).”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [49]
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- Authors
- Pitteloud, N., Hardin, M., Dwyer, A. A., Valassi, E., Yialamas, M., Elahi, D., & Hayes, F. J.
- Affiliations
- Massachusetts General Hospital (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Hayes, Frances J.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-05
- Volume
- 90
- Issue
- 5
- Pages
- 2636-2641
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2063561693
- Semantic Scholar
- 738d1a656688d0d9a6a3097ce2a0727ec901d554
- Cited by
- 525
- References
- 60
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 18 · 2023: 23 · 2022: 21 · 2021: 34 · 2020: 27 · 2019: 22 · 2018: 29 · 2017: 21 · 2016: 16 · 2015: 24 · 2014: 25 · 2013: 31 · 2012: 34
- FWCI
- 12.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- National Institutes of Health (5k23dk002858-04, 5r03dk064276-02)
- U.S. Public Health Service (NIA-0059)
- National Institute of Diabetes and Digestive and Kidney Diseases (R03-DK064276-01, K23 DK 02858-04)
- National Center for Research Resources (M01RR001066)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- insulin resistance, testosterone, hypothalamic-pituitary-gonadal axis, luteinizing hormone pulsatility, impaired glucose tolerance, diabetes mellitus, hyperinsulinemic-euglycemic clamp, GnRH stimulation test, hypogonadism
- MeSH terms
- Adult, Aged, Humans, Insulin Resistance, Leydig Cells, Luteinizing Hormone, Male, Middle Aged, Sex Hormone-Binding Globulin, Testosterone, Leptin, Waist-Hip Ratio
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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