Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility

Abstract

Objective: To evaluate the secondary impact of a prototype androgen contraceptive regimen on physical, metabolic and behavioral variables.

Design: Prospective, open, noncomparative contraceptive efficacy study.

Setting: International multicenter study comprising 10 centers in seven countries.

Subjects: Two hundred seventy-one healthy men, age 31.8 +/- 5.4 years (mean +/- SD), range 21 to 45 years.

Interventions: Weekly IM injections of 200 mg T enanthate.

Main outcome measures: Adverse effects and discontinuations; biochemical and hematologic changes and interpopulation differences.

Results: Chinese subjects were shorter and lighter and their baseline hemoglobin, plasma lipid, and liver enzyme levels were lower than in non-Chinese subjects. The most common side effects were painful injections, acne, fatigue, and weight gain. Gynecomastia and prostate problems were detected in 24 and 9 men, respectively, though no men stopped injections for such reasons. Testosterone enanthate increased body weight, hemoglobin, and urea but decreased testicular volume and creatinine. Plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol were unchanged; high-density lipoprotein cholesterol decreased by 14% to 18% in non-Chinese but was unchanged in Chinese men. Liver transaminases were increased by 36% to 51% in Chinese but were unchanged in non-Chinese subjects. These T enanthate-induced effects were reversible within 6 months of stopping injections and were not related to the duration of T exposure.

Conclusions: Testosterone enanthate administration in a contraceptive trial produced significant but reversible effects on skin, muscle, liver, lipid metabolism, and hemopoietic functions that varied between population groups. These effects reflect the relatively high peak levels and fluctuations of plasma T produced by the weekly T enanthate regimen rather than an inherent feature of hormonal male contraception. The results highlight the need for long-acting preparations of T with more stable delivery kinetics.

PIP: At 10 centers in 7 countries, researchers conducted a clinical trial of weekly intramuscular injections of 200 mg testosterone (T) enanthate in 271 healthy fertile men, 21-45 years old, to evaluate the secondary impact of this prototype male contraceptive regimen on various physical, metabolic, and behavioral variables. They also focused on the differences between Chinese men and non-Chinese men as well as their similarities. At baseline, Chinese men were shorter, weighed less, and had lower levels of hemoglobin, plasma lipids, and liver enzymes than non-Chinese men (p 0.05). The overall leading side effects were acne (80), fatigue (22), painful injections (15), and weight gain (12). 24 men, all of whom were non-Chinese men, experienced excessive development of the male mammary glands (gynecomastia). Nine men (1 Chinese, 8 non-Chinese) had prostate problems. No man discontinued T enanthate injections for gynecomastia or prostate problems, however. T enanthate contributed to an increased body weight (by 5% at 360 days) and increased levels of hemoglobin (by 7.6% at 360 days) and creatinine while it contributed to a decrease in testicular volume (by 26.2% at 360 days) and in urea level. T enanthate appeared to have no effect on plasma triglyceride, cholesterol, and low density lipoprotein (HDL) cholesterol. It was associated with a decrease of 14-18% in HDL-cholesterol in non-Chinese men but it had no effect on HDL-cholesterol in Chinese men. T enanthate increased liver transaminase by 36-51% in Chinese men but it had no effect on these enzymes in non-Chinese men. Regardless of length of exposure to T enanthate, the T enanthate-induced changes were reversible within 6 months. These findings suggest that T enanthate produced significant but reversible metabolic and physical effects that differed between Chinese and non-Chinese men. These effects are a result of the relatively high peak levels and fluctuations of plasma T produced by the weekly injections rather than an inherent feature of hormonal male contraception.