HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.
Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.
Dr. Niloufar Ilani
Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.
Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.
Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.
Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.
Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.
After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.
No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.
Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.
Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.
Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.
Patient and sperm characteristics were similar between groups at the start of the study.
Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.