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Oral Progestogen Combined with Testosterone as a Potential Male Contraceptive: Additive Effects between Desogestrel and Testosterone Enanthate in Suppression of Spermatogenesis, Pituitary-Testicular Axis, and Lipid Metabolism¹

Department of Medicine, Manchester Royal Infirmary, University of Manchester, United Kingdom M13 9WL; and the Medical Research and Development Unit, N.V. Organon, Oss, The Netherlands

Address all correspondence and requests for reprints to: Dr. F. C. W. Wu, Department of Endocrinology, Manchester Royal Infirmary, Oxford Road, Manchester, United Kingdom M13 9WL. E-mail: frederick.wu{at}man.ac.uk

The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 ± 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 µg DSG orally daily and 100 mg T enanthate, im, weekly; 2) 300 µg DSG and 50 mg T enanthate; or 3) 150 µg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 µg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 µg DSG/100 mg T enanthate group, but was not different from that in the 150 µg DSG/100 mg T enanthate group. DSG (300 or 150 µg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 µg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 ± 1.7%, 10.3 ± 2.6%, and 7.7 ± 2.8%, respectively, during treatment with DSG alone with no difference between 300 and 150 µg. Addition of T enanthate (both 50 and 100 mg weekly) induced a further fall only in high density lipoprotein cholesterol to 22.6 ± 3.7% from the baseline. In summary, the combined actions of oral DSG with low doses of T enanthate were highly effective in suppressing pituitary-testicular functions in adult men. The optimal regimen for inducing azoospermia was 300 µg DSG daily with 50 mg T enanthate weekly. Oral DSG exerted discernible effects on lipid metabolism. We conclude that the combination of oral progestogens with low dose T is a promising approach to achieve effective reversible male contraception.

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