April 22, 2011
A contraceptive effectiveness trial of a hormone-based method for male contraception will be ending early, based on the recommendation made as part of the standard annual research project review process at the World Health Organization (WHO). This Phase II study is a collaboration between WHO and CONRAD and was designed to evaluate whether the combination of a long-acting progestin, norethisterone enantate (NET-EN), and a long-acting androgen, testosterone undecanoate (TU), represents a safe and effective method of male fertility regulation.
The review panel’s recommendations to discontinue injections and transition participants to the recovery phase were made based on their determination that the risks of possible side effects may outweigh the potential benefits to the male study participants. Participants are currently being transitioned off the study medication and placed into the recovery phase in which the participants are followed until sperm levels return to levels generally considered fertile.
The two drugs are approved and marketed for other purposes. The Panel recognized that their recommendation applies to this particular combination at the dosage and frequencies administered, not necessarily to the drugs used alone in their approved indications and dosing regimens or in other combinations. This study involves ten sites in eight countries and was the first study designed to demonstrate the effectiveness of the combination as a male contraceptive.
As of the end of March 2011, 110 couples had completed the 12-month efficacy phase of the study and as of April 5th, another 103 couples are in the suppression and efficacy phase. The study design consists of a sperm suppression phase in which the male participant began to receive injections of the two drugs every 8 weeks and couples were counseled to continue using other forms of birth control, followed by an efficacy phase of approximately 56 weeks during which the male participant continued to receive injections and couples were asked to rely on the study regimen for their only method of contraception, and ending with the recovery phase.
Earlier, small-scale trials provided promising results in terms of sperm suppression, with no major side effects. Although side effects of androgen and progestin administration were expected (e.g., acne, increased libido, injection site pain, weight gain, mood changes, and others), several side effects, particularly depression and other mood changes as well as increased libido, were reported at a higher frequency than anticipated for this combination and not commonly seen with the products when used in their approved indications and dosing regimens. Based primarily on these issues, WHO panel members expressed concern whether the drug combination could be successfully developed and marketed as a male contraceptive method.
CONRAD and WHO have supported research in male contraception for the past several decades and are disappointed that this TU/Net-En trial will not proceed to completion as planned. Although this drug combination will not move forward as a contraceptive method, significant information will be obtained about the feasibility and acceptability of a combination hormone-based method to provide contraception. This data will provide the field of reproductive health with valuable information. There is a strong rationale for developing a male contraceptive and WHO-supported research has shown a high degree of acceptability for this method in Italy and China.
We fully recognize that this trial could not have been implemented without the willingness of the participants to take part in furthering development of a novel contraceptive method for all men, and the dedication and hard work of the principal investigators and study team.
For more information, please contact: Annette Larkin, firstname.lastname@example.org, +1 703.772.6427