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This version published online on February 15, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2190
A more recent version of this article appeared on May 1, 2005
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*Compound via MeSH
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*TESTOSTERONE

Submitted on November 9, 2004
Accepted on February 7, 2005

INCREASING INSULIN RESISTANCE IS ASSOCIATED WITH A DECREASE IN LEYDIG CELL TESTOSTERONE SECRETION IN MEN

Nelly Pitteloud, Megan Hardin, Andrew A. Dwyer, Elena Valassi, Maria Yialamas, Dariush Elahi, and Frances J Hayes*

Reproductive Endocrine Unit of the Dept. of Medicine, Massachusetts General Hospital, Boston, MA.; Dept. of Medicine, Massachusetts General Hospital, Boston and the Dept. of Surgery, University of Massachusetts Medical Center, Worcester, MA

* To whom correspondence should be addressed. E-mail: fhayes{at}partners.org.

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 (HPG) axis in men with a spectrum of insulin sensitivity.

Twenty-one men (age 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 (mg· kgP-1P· minP-1P), 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 gonadotropin-releasing hormone (GnRH) antagonist followed by sequential stimulation testing with GnRH (750 ng/kg IV) and human chorionic gonadotropin (hCG) (I,000 IU IM) to assess pituitary and testicular responsiveness, respectively.

Nine subjects had normal glucose tolerance, 9 had impaired glucose tolerance and 3 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 post hCG (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. Further studies are required to determine the mechanism of this effect.
Key words: insulin resistance • hypothalamic-pituitary-gonadal axis • testosterone • men




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eLetters:

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Letter to the Editor
Andrea M. Isidori, et al.
JCEM Online, 20 Oct 2005 [Full text]
Response to Letter to the Editor
Frances Hayes, et al.
JCEM Online, 20 Oct 2005 [Full text]

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