Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism.
BACKGROUND
Evidence suggests that testosterone (T) influences insulin sensitivity in men. The mechanism of this effect is unclear but is thought to involve changes in body composition.


OBJECTIVE
The aim of this study was to determine whether acute sex steroid withdrawal decreases insulin sensitivity in young, healthy men with idiopathic hypogonadotropic hypogonadism (IHH).


METHODS
This was a 2-wk prospective study.


METHODS
The study was conducted at a General Clinical Research Center.


METHODS
Twelve men with IHH (age 40.8 +/- 2.8 yr) were studied: 1) on hormone replacement with normal T levels and 2) 2 wk after discontinuing therapy.


METHODS
Each evaluation comprised a 75-g oral glucose tolerance test with assessment of insulin sensitivity (fasting insulin levels, homeostatic model assessment for insulin resistance, and Matsuda insulin sensitivity index) and insulin secretion (corrected insulin response). Serum cortisol, leptin, adiponectin, free fatty acids, IL-6, C-reactive protein, and TNF-alpha levels were also measured.


RESULTS
Body mass index was unchanged (27.1 +/- 1.1 to 27.2 +/- 1.1 kg/m(2)). Serum T levels decreased from 529 +/- 65 to 28 +/- 8 ng/dl (P < 0.00005). Fasting insulin levels increased from 4.9 +/- 0.7 to 6.2 +/- 0.6 microU/ml (P = 0.005), homeostatic model assessment of insulin resistance increased from 1.07 +/- 0.2 to 1.4 +/- 1.01 (P < 0.005), and insulin sensitivity index decreased from 11.0 +/- 2.3 to 7.5 +/- 0.7 (P < 0.05). There was a trend for fasting glucose levels to increase, 86.7 +/- 1.3 to 90.8 +/- 1.7 mg/dl (P = 0.09). IL-6 levels increased from 1.2 +/- 0.2 to 2.4 +/- 0.5 pg/ml (P < 0.01), whereas TNF-alpha levels decreased from 1.0 +/- 0.1 to 0.6 +/- 0.1 pg/ml (P < 0.05). No other significant changes were observed.


CONCLUSIONS
1) Acute sex steroid withdrawal reduces insulin sensitivity in young healthy IHH men. 2) The acuity of the hypogonadism and absence of changes in body mass index or leptin levels suggest that sex steroids modulate insulin sensitivity in the absence of apparent or detectable changes in body composition.
Yialamas
Maria A
MA
Reproductive Endocrine Unit of the Department of Medicine , Massachusetts General Hospital, Bartlett Hall Extension 511, Boston, Massachusetts 02114, USA.
Dwyer
Andrew A
AA
Hanley
Erin
E
Lee
Hang
H
Pitteloud
Nelly
N
Hayes
Frances J
FJ
D054392:Adipokines / Q000378:metabolism; D000328:Adult; D000368:Aged; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000009:adverse effects*; D006062:Gonadotropins / Q000172:deficiency*; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood / Q000172:deficiency
D054392:Adipokines; D016207:Cytokines; D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D013739:Testosterone