Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues.
OBJECTIVE
This pilot investigation was conducted to explore the relationship between androgens and glucose tolerance in obese men and to select an optimal mode for androgen treatment.


METHODS
For exploratory purposes, testosterone (T) or dihydrotestosterone (DHT) were given in different doses and preparations for different periods of time to obese, middle-aged men. The administration forms were selected in order to by-pass the liver. In the first two studies T was given as a single intramuscular injection of 250 or 500 mg and the results evaluated after 1 week. In two subsequent studies testosterone was administered in moderate doses either as oral T undecanoate or a T and DHT in preparations applied on the skin for transdermal absorption for 6 weeks and 3 months respectively. Before and after treatment the following examinations were performed: glucose tolerance tests with insulin determinations or euglycemic clamps at submaximal insulin levels. Anthropometric measurements including the waist/hip circumference ratio and estimations of body fat and lean body mass (from measurements of whole body potassium content) were performed. Plasma triglyceride and cholesterol concentrations, liver function tests and blood pressure were followed. Physical examination including the prostate was performed before and after study. Muscle function, glycogen synthase and morphology were examined in the 3-month study.


RESULTS
Administration of T was followed by moderate increases of circulating T concentrations in all studies, except after injection of 500 mg, where large increases were seen. Follicle stimulating hormone and luteinizing hormone levels decreased consistently. Injection of 500 mg T resulted in a decreased glucose tolerance. In the other treatment groups, plasma insulin decreased or glucose disappearance rate increased in clamp measurements, suggesting improved insulin sensitivity. This was most pronounced in men with relative hypogonadism from the outset. In the study of 3 months duration, a decrease in the waist/hip ratio, without a change in body fat mass, was also seen. Plasma lipids, liver function tests and blood pressure did not change. Muscle strength, the fractional velocity of glycogen synthase as well as the percentage and diameter of type IIB fibres increased after T treatment. No adverse effects were seen. 17 -beta oestradiol concentrations were unaltered and DHT administration was less effective than T, suggesting that T rather than derivatives of this hormone was mainly responsible for the effects observed.


CONCLUSIONS
The results suggest that T administration to middle-aged, obese man may have beneficial effects.
Mårin
P
P
Department of Medicine I, Sahlgren's Hospital, University of Göteborg, Sweden.
Krotkiewski
M
M
Björntorp
P
P
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D001706:Biopsy; D001823:Body Composition / Q000187:drug effects; D013196:Dihydrotestosterone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives*
D007328:Insulin; D013196:Dihydrotestosterone; D013739:Testosterone; C004648:testosterone enanthate; C010792:testosterone undecanoate