Hormonal contraceptives—male

General information

The notion that an oral contraceptive closely similar to that used in women might be developed for men has been discussed for many years, but the concept has not found wide acceptance. Delays in putting the concept into practice have related variously to difficulties in finding an effective combination, complaints of reduced libido or potency, and the long delay between the start of treatment and the attainment of azoospermia.

Of the many possible formulations tested all have proved to have unacceptable facets, generally including a very slow onset of action, uncertain reliability, and undesirable effects on biochemistry, body weight, or sexual function. However, some progress has been made with the combination of oral desogestrel and intramuscular testosterone.

In a study of the effects of various combinations of desogestrel and testosterone, including a sequential pattern, the optimal dosage to induce azoospermia seemed to be desogestrel 300 micrograms/day by mouth and testosterone enanthate 50 mg weekly by intramuscular injection [ ]. Among 24 subjects, there were no withdrawals clearly related to the treatment. During weeks 1–3, adverse reactions were reduced sex drive (n = 4), tiredness (n = 1), and a sensation of depression (n = 1); during weeks 4–24 they included mild acne (n = 10), increased sexual interest (n = 3), emotional lability (n = 2), tiredness (n = 2), night sweats (n = 1), and headache (n = 1). However, laboratory studies showed that desogestrel had clear effects on lipid metabolism in dosages of 150 micrograms/day or more, with reductions in HDL cholesterol, apolipoprotein, A1 lipoprotein, sex hormone binding globulin, and to some extent total cholesterol and LDL cholesterol. If this approach is developed to provide a more convenient dosage scheme, these biochemical changes will be among those that need to be followed carefully.

A combination of oral desogestrel 150 or 300 micrograms + intramuscular testosterone 50 or 100 mg has been tested in 24 young men and compared with historical data from studies on a combination of oral levonorgestrel + intramuscular testosterone [ ]. All the doses tested achieved azoospermia. All the groups tended to gain weight compared with their baseline, but the weight gain was greatest (and statistically significant) in men who received the higher dose of testosterone. Adverse reactions were acceptably uncommon; acne occurred in occasional cases, but no one developed gynecomastia.

In a similar study limited to 8 weeks, the various formulations rapidly suppressed LH and FSH to a similar extent, irrespective of dosage, while testosterone concentrations fell slightly during treatment, with evidence of a linear dose–response relation [ ]. There were minor changes in plasma concentrations of inhibin B, but in seminal fluid it was suppressed, becoming undetectable in all the men who took desogestrel 300 micrograms/day. There were no significant changes in lipoproteins, fibrinogen, or sexual behavior during treatment, and only minor falls in hematocrit and hemoglobin concentration.