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Male birth control gel shows promise in US trial

The US National Institutes of Health (NIH) says a combination hormonal topical gel has shown promise by suppressing sperm production in a shorter amount of time than experimental products tested in other clinical trials.

The preliminary findings, described as “a milestone”, were presented recently at the Endocrine Society’s annual meeting in Boston, reports The Washington Post.

The study, in Phase 2b trials, included 222 men who completed at least three weeks of daily treatment with a gel made from the progestin medication segesterone acetate and testosterone.

The compound was developed by the Population Council, a non-profit organisation that focuses on reproductive health, in collaboration with the NIH.

In the trial, researchers conducted sperm count tests every four weeks to evaluate suppression of sperm. They aimed for a sperm count of 1m or fewer per millilitre for effective contraception. Normal sperm count is between 15m and 200m sperm per millilitre of semen. By Week 15, 86% of participants achieved the low threshold, with sperm production typically suppressed by the eighth week of treatment.

Diana Blithe, chief of the Contraceptive Development Programme at the NIH, said the findings marked a milestone and said she considers male contraception as much a men’s health issue as a women’s.

Blithe said women who participated in the clinical trials with their partners felt relieved when they were able to stop using hormonal birth control for the study’s duration.

“Many women have difficulties with various contraceptive methods, and one eye-opening aspect of the clinical trial has been hearing from them what it meant to be in the study, especially when they were able to stop using their birth control for a year,” she added.

The only effective forms of birth control on the market for men are vasectomies, which are not easily reversible, and condoms, which have a low acceptance rate.

Here’s what to know about the gel and the state of research into male contraception.

The 5ml hormonal gel is applied once daily and split between the shoulder blades. The gel’s segesterone acetate component, which is a synthetic progesterone, suppresses hormones needed to maintain testosterone concentrations in the testes, which is where sperm are made, thereby inhibiting sperm production.

The testosterone component in this two-part combination ensures that testosterone levels essential for male physiological processes and health are maintained at stable levels.

Testosterone plays a vital role in bodily activities beyond sperm production, such as sexual function and overall hormone regulation.

Health experts say expanding birth control options to men helps level the playing field in discussions surrounding birth control and alleviates the burden traditionally carried by women.

“Any form of male birth control is important in the scope of our reproductive health landscape,” said Jesse Mills, clinical professor of urology and director of the men’s clinic at UCLA. “It will allow us to have a much better dialogue when it comes to whose responsibility it is to prevent pregnancy.”

Because the gel is undergoing clinical trials, long-term safety and efficacy are still being examined. But preliminary findings show promise.

“At this stage, it’s about getting the dosing right and seeing if it’s effective and safe,” said Alexandra Joice Berger, a urologist at Brigham and Women’s Hospital in Boston.

Berger said that in earlier trials of male birth control products, it had taken months before sperm production declined to levels that would be effective at preventing pregnancy, and trial participants suffered side effects.

One of the biggest takeaways from the ongoing trial is that the drug seems to work faster than previous iterations of a male birth control, with fewer adverse effects.

Why isn’t there a hormonal male birth control?

Hormonal birth control trials for men have been ongoing since the 1970s, with approaches aimed at suppressing sperm production. One method involved using high doses of a testosterone pill to inhibit the brain’s release of hormones that stimulate the testes, thereby reducing sperm count. But that approach has significant side effects associated with the high doses, including liver toxicity, mood change, acne, weight gain and increased risk of cardiovascular problems.

Another option involved a combination of testosterone with progestins, commonly used in female contraception, to lower the dose of each hormone and minimise side effects. Examples of this combination include injections or implants.

While this approach showed some success in decreasing sperm counts, challenges included variability in effectiveness, the need for frequent administration, and side effects such as decreased libido and mood swings. Those issues hindered further development.

Cost has played a significant role in slowing development of a hormonal male birth control. Drug developments can range from $1bn to $2bn, according to the Congressional Budget Office.

“No pharmaceutical company is willing to put up money to develop a drug if there are not people who are going to take it,” Mills said. “It’s very concerning and, frankly, testimony to the sexism present in the drug development that it has taken so long to still not have an FDA-approved drug for male birth control.”

When might a male birth control be available?

The trial of the gel is expected to conclude by the end of this year, and the next step involves analysing the results. Blithe hopes this drug will keep showing positive results, but more funding is needed to progress, and right now, there is no commercial partner.

“We are encouraged by the results and the side effect profile so far, but more studies are needed to confirm that,” she added.

Study details

Time to Sperm Suppression With Daily Transdermal Use of Nestorone and Testosterone Combination Gel for Male Contraception Is Faster Than Expected

D. Gross, C. Wang, D. Blithe et al.

Presented at ENDO 2024

Background
The development of a safe, highly effective, and reliably reversible male contraceptive method is an unmet worldwide need. While studies have shown that some hormonal agents have potential efficacy for male contraception, the slow onset of spermatogenic suppression may be a limitation. Co-administration of a progestin with testosterone reduces time to sperm suppression compared to testosterone alone. Studies using injectable hormones showed an average of 12 or more weeks to reach sperm suppression to ≤1 million/mL, the goal for effective contraception. A Phase IIb Clinical Trial of daily Nestorone (Nes) (segesterone acetate) and Testosterone (T) combination gel is currently evaluating contraceptive efficacy, as well as safety, acceptability, reversibility, and timeline to sperm suppression. 

Objective
To assess the time to sperm suppression (concentration ≤1 million/mL) with daily self-administration of Nes 8 mg/T 74 mg combination gel in healthy males. 

Design
Couples were screened and enrolled into the study. The male partner began daily skin application of Nes 8 mg/T 74 mg gel/5 mL. We evaluated the time from the first gel application until the first observed sperm concentration reached ≤1 million/mL. In the original protocol, local site sperm concentration assessments were scheduled at 4-week intervals. The protocol was amended to add a visit at week 6 while the study was ongoing; however, some subjects had reached week 8 or 9 prior to full protocol approval to include the intervening visit. 

Results
Of 222 participants enrolled to use Nes 8 mg/T 74 mg gel and had a sperm assessment at ≥3 weeks after treatment began, 192 (86%) achieved suppression to ≤1 million/mL during treatment. At 5 weeks of treatment, 40 participants (21%) were suppressed to ≤1 million/mL. By 8 and 9 weeks, 100 (52%) and 122 (64%), respectively, were suppressed. Due to delays in local protocol amendment approval, 54 participants did not have a visit between week 5 and week 8 or 9. Of those, 21 subjects were suppressed at their first follow-up visit after week 5. Thus, they were assigned a suppression time at week 8 or 9 but may have been suppressed earlier. Overall, the median observed time to suppression for those who suppressed was 8 weeks, with 157 (82%) and 166 (86%) suppressed within 12 and 15 weeks, respectively, of initiating treatment. 

Conclusion
More than 80% of participants using this novel male hormonal contraceptive gel formulation containing Nestorone 8 mg and Testosterone 74 mg showed suppressed sperm output within 12 weeks, a rate that appears to be faster than prior studies with other hormonal regimens. In view of this timeline based on the available data, more complete early assessment at weeks 4, 5, and 6 may have revealed a faster average time to suppression. A more rapid time to suppression may increase the attractiveness and acceptability to potential users.

 

ENDO article – Time to Sperm Suppression With Daily Transdermal Use of Nestorone and Testosterone Combination Gel for Male Contraception Is Faster Than Expected (Open access)

 

The Washington Post article – Male birth control gel shows promise in early-stage clinical trials (Restricted access)

 

See more from MedicalBrief archives:

 

Second potential male birth control pill passes human safety tests

 

No-scalpel vasectomy raises hope as long-term male contraceptive

 

Most promising study to date on male contraceptive pill

 

 

 

 

 

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