The Endocrine Society's 94th Annual Meeting and Expo:
Combination Gel for Male Hormonal Contraception
At the 94th Annual Meeting of The Endocrine Society, research was presented on a possible new combination of testosterone and Nestorone ®. It is a transdermal gel, and it could be used for male hormonal contraception.1
Christine Wang, MD, principal investigator of the clinical trial, said, “This is the first time that testosterone and Nestorone have been applied to the skin together to deliver adequate amounts of hormones that suppress sperm production. Men can use transdermal gels at home—unlike the usual injections and implants, which must be given in a health care provider’s office.”
This study was a proof of concept study, and it involved 99 healthy male volunteers. They were randomized into 3 treatment groups:
- Group 1: 10 g testosterone + placebo (T alone)
- Group 2: 10 g testosterone + 8 mg Nestorone (T+NES 8 mg)
- Group 3: 10 g testosterone + 12 mg Nestorone (T+NES 12 mg)
All 3 groups applied 2 separate gels.
There were 2 outcomes studied in these groups: 1) the percentage who, by the end of 20-24 weeks of treatment had a sperm count of < 1 million/mL, and 2) how each treatment affected gonadotropins, sperm morphology, and motility.
Sperm Count Results after Gel Treatment
Of the 99 men who started the study, 56 men completed at least 20 weeks of the daily 2-gel application.
In the T alone group, the percentage of men with sperm concentration of < 1 million/mL was only 23%. However, in the T+NES 8 mg and T+NES 12 mg groups, it was significantly higher—89% (p < 0.0001) and 88% (p < 0.0002), respectively.
Additionally, 78% of men in the T+NES 8 mg group became azoospermic (p < 0.001), and 69% in the T+NES 12 mg group became azoospermic (p < 0.008). By comparison, just 23% of men in the T alone group achieved this complete absence of sperm.
Effect on Gonadotropins, Sperm Morphology, and Motility
Following the decrease in sperm concentration, sperm motility and normal sperm morphology also decreased.
T+NES 8 mg and T+NES 12 mg groups showed more suppression of serum luteinizing hormone and follicular stimulating hormone concentrations.
Of note: the median total and free testosterone levels remained within the normal adult male range in all treatment groups. Therefore, it appears that this treatment does not an effect on androgenic activity.
Sperm Concentrations Returned to Normal After Study
There was a recovery period in this study, and all subjects returned to a normal sperm concentration during that time.
Next Steps in the Male Hormonal Contraception Study
It must be seen if testosterone and Nestorone can be combined into one gel—as opposed to the 2 gels that were used in this preliminary study. After that, there will be a Phase III trial.