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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

Population Center for Research in Reproduction, Department of Medicine, University of Washington (K.L.H., B.D.A., J.K.A., A.M.M., W.J.B.); Geriatric Research, Education and Clinical Center (A.M.M.); and Medical Service, Department of Veteran Affairs, Puget Sound Health Care System (B.D.A., A.M.M.), Seattle, Washington 98195

Address all correspondence and requests for reprints to: Karen L. Herbst, M.D., Ph.D., Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University, Room 3069 Third Floor, 1731 East 120th Street, Los Angeles, California 90059. E-mail: kaherbst{at}cdrewu.edu.

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 µg 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.

This work was supported by V.A. Merit Review Research Funds, the NICHHD, NIH through Cooperative Agreement U54-HD-12629 as part of the Specialized Cooperative Centers Program in Reproduction Research, and NIDDK Metabolism Training Grant T32-DK-O7247 (to K.L.H.).

Abbreviations: BMI, Body mass index; CT, computed tomography; DEXA, dual energy x-ray absorptiometry; E₂, estradiol; LNG, levonorgestrel; MRI, magnetic resonance imaging; T, testosterone.

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