Androgen Therapy Improves Insulin Sensitivity and Decreases Leptin Level in Healthy Adult Men With Low Plasma Total Testosterone
A 3-month randomized placebo-controlled trial
- Dominique Simon, MD, PHD12,
- Marie-Aline Charles, MD12,
- Najiba Lahlou, MD3,
- Khalil Nahoul, MD4,
- Jean-Michel Oppert, MD, PHD5,
- Michèle Gouault-Heilmann, MD6,
- Nicole Lemort, BSC7,
- Nadine Thibult, BSC1,
- Evelyne Joubert, MD8,
- Beverley Balkau, PHD1 and
- Eveline Eschwege, MD1
- 1INSERM U 21/U 258, Paris XI University, Villejuif, France
- 2Department of Endocrinology, Henri Mondor Hospital, Créteil, France
- 3Department of Hormonal Biochemistry, Saint-Vincent-de-Paul Hospital, Paris, France
- 4Claude Lévy Laboratory, Ivry, France
- 5Department of Nutrition, Hotel-Dieu Hospital, Paris, France
- 6Department of Biological Hematology, Henri Mondor Hospital, France
- 7INSERM U 468, Paris XII University, Créteil, France
- 8Besins-Iscovesco Laboratories, Paris, France
In men, an association between lower plasma total testosterone (PTT) and insulin resistance has been found in cross-sectional studies (1,2) and in one nested case-control study (3) without any possible conclusion in terms of causality or direction of the relationship. Indeed, to obtain such information, randomized controlled trials are needed. Until now, only one clinical trial has suggested that testosterone therapy improves insulin sensitivity in obese men (4). Cross-sectional studies concerning leptin regulation by androgens have provided no definitive conclusions as to whether the negative association between androgens and leptin level is independent (5) or dependent (6). This randomized controlled trial was designed to assess the role of androgens on insulin sensitivity and leptin regulation in healthy adult men.
This study was a randomized, double-blind, unicentric, controlled, clinical trial. Three treatments (testosterone, dihydrotestosterone [DHT], and placebo) were compared in parallel groups during a 3-month period. All of the examinations were performed by only two physicians, using a standardized protocol. Blood was drawn between 8:00 a.m. and 9:30 a.m. after an overnight fast to determine fasting plasma glucose, insulin, leptin, sex hormones, lipids, coagulation and fibrinolysis parameters, hepatic enzymes, and prostate-specific antigen (PSA) and blood cell count. Then, a standard 75-g oral glucose tolerance test and a digital rectal examination were performed. In addition, between days 10 and 20, all of the subjects were monitored to measure sex hormones in order to adapt the treatment dose. The study protocol was approved by the Henri Mondor Hospital Ethics Committee. All of the included subjects gave written informed consent.
Men with low levels of PTT (confirmed by two measurements) were selected from a large occupation-based population. The inclusion criteria were as follows: 1) either PTT ≤3.4 ng/ml [5th percentile value of PTT distribution in the 1,718 men of the TELECOM …
