The male contraceptive regimen of testosterone and levonorgestrel significantly increases lean mass in healthy young men in 4 weeks, but attenuates a decrease in fat mass induced by testosterone alone.
In hypogonadal men, testosterone (T) in replacement dosages is known to increase fat-free mass (lean mass) and decrease fat mass. In young eugonadal men, similar dosages of T increase lean mass, but much higher dosages of T are required to decrease total body fat mass. Current T-based male hormonal contraceptive regimens include a second agent, such as a progestin, to maximize inhibition of pituitary gonadotropins and improve efficacy. To study the effect of such combinations on body composition, we randomized healthy, young, eugonadal men into four combinations of exogenous T and the progestin, levonorgestrel (LNG): 1) 100 mg T enanthate, im, weekly plus 125 micro g LNG, orally, daily (T+LNG); 2) T plus placebo LNG (T alone); 3) placebo T plus LNG (LNG alone); and 4) placebo T plus placebo LNG (placebo). We then analyzed body composition by dual energy x-ray absorptiometry after 4 and 8 wk of treatment. T+LNG significantly increased total lean mass after 4 and 8 wk of treatment (3.5 +/- 0.9% and 4.2 +/- 1.2%, respectively; P < 0.05) and truncal lean mass after 4 and 8 wk of treatment (4.7 +/- 0.9% and 5.0 +/- 0.9%, respectively; P < 0.05) compared with baseline and placebo. T alone also increased total and truncal lean mass significantly compared with placebo after 4 wk of treatment, but not compared with baseline (3.3 +/- 1.4% and 3.2 +/- 2.3%, respectively; P < 0.05 vs. placebo), suggesting an additive effect of T and LNG to increase lean mass. Fat mass significantly decreased in the abdomen in men administered T alone compared with LNG alone (-4.9 +/- 2.8%; P < 0.05). Fat mass significantly increased in the abdomen with LNG alone (4.1 +/- 1.0%; P < 0.05) compared with baseline and was unchanged with the combination of T+LNG, suggesting that LNG attenuates the decrease in fat mass seen with T alone. There was no change in weight or body mass index in any group during the study. This study shows that in young eugonadal men 1) T alone rapidly increases lean mass and decreases fat mass in 4-8 wk; 2) T+LNG rapidly increases lean mass, but has no effect on fat mass; and 3) LNG alone increases fat mass. The favorable profile on body composition by T is, therefore, partially attenuated by the progestin, LNG. These findings suggest that androgen-based male hormonal contraceptives might have favorable effects on body composition. The impact of these changes on cardiovascular risk in normal men needs further study.
Herbst
Karen L
KL
Population Center for Research in Reproduction, Department of Medicine, University of Washington, Seattle, Washington 98195, USA. kaherbst@cdrewu.edu.
Anawalt
Bradley D
BD
Amory
John K
JK
Matsumoto
Alvin M
AM
Bremner
William J
WJ
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D003272:Contraceptive Agents, Male / Q000008:administration & dosage*; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000008:administration & dosage* / Q000494:pharmacology
D003272:Contraceptive Agents, Male; D013739:Testosterone; D004958:Estradiol; D016912:Levonorgestrel; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone