Evidence for the Acceptability of an Injectable Hormonal Method for Men. (Special Report).

The search for a safe, effective and reversible hormonal method of fertility regulation for men has been under way for more than 20 years. Several publicly supported and international biomedical research organizations, including the World Health Organization (WHO), The Population Council, the Contraceptive Research and Development Program, Family Health International and the National Institutes of Health, have conducted or supported research in this area in developed and developing countries. As a result, a variety of hormonal compounds and contraceptive delivery systems, including injections, pills, implants and patches, are currently under investigation.

Many factors, however, including limited funding and a lack of commercial interest in male fertility regulation, have slowed progress. Pharmaceutical companies reportedly doubt that a market exists for hormonal contraceptives for men and fear the potential for litigation. (1)

Nonetheless, clinical trials of a hormonal method, supported by WHO, have shown encouraging results. Between 1986 and 1990, 10 centers in seven countries (Australia, China, Finland, France, Sweden, the United Kingdom and the United States) completed a clinical trial demonstrating the contraceptive efficacy of azoospermia (or the absence of sperm) induced by testosterone enanthate, a drug long used to treat hypogonadal men. In that trial, 271 healthy fertile men aged 21-45 who were in stable relationships received weekly injections of 200 mg of testosterone enanthate. Those who became azoospermic (65%) continued with weekly injections for a period of 12 months, during which the contraceptive efficacy of the method was assessed. Azoospermia was associated with near-perfect contraceptive efficacy (just 0.8 conceptions per 100 person-years). (2)

A second study investigated whether this state of complete azoospermia was necessary for contraceptive efficacy. Between 1990 and 1994, 15 centers in nine countries (Australia, China, France, Hungary, Singapore, Sweden, Thailand, the United Kingdom and the United States) participated in a study in which men received weekly injections of 200 mg of testosterone enanthate, but the 12-month contraceptive efficacy assessment stage was initiated sooner--when men reached a state of oligozoospermia (less than three million sperm/ml). The vast majority (97%) of the 289 men who remained in the study for six months achieved this level of subfertility, and their subsequent experience demonstrated that complete azoospermia was unnecessary to achieve an acceptable level of contraceptive efficacy. (3)

While testosterone enanthate has been valuable in establishing the viability of a hormonal agent for male contraception, it has several drawbacks, including the need for frequent injections and for a relatively long period (3-4 months, on average) to achieve oligozoospermia; it also has a pharmacokinetic profile that produces above-normal testosterone levels immediately following each injection. Thus, in future trials, testosterone enanthate will be combined with another hormone (such as DMPA) to shorten the time needed to achieve a contraceptive effect, or a new formulation (such as testosterone buciclate, which requires less frequent injections and does not produce a physiological peak (4)) will be used instead.

Researchers believe that with a full-scale effort, a newly formulated product could be ready for introductory trials by the turn of the century. (5) No studies have examined the important question of whether the method will find acceptors, but the attitudes and opinions of men who participated in the clinical trials may provide helpful insights.

This report presents information gleaned from focus group discussions and questionnaires completed by men who volunteered for the trials. The shortcomings of the present formulation and the plans to address them are important factors to keep in mind when assessing the observations of the early clinical trial participants. Nonetheless, the findings add to an extremely limited body of evidence indicating that there may be a niche among contraceptive users for a hormonal method for men.