Male Birth Control Gel Provides New Contraceptive Options for Men

The Importance of Comprehensive Reproductive Healthcare

According to data from the National Survey of Family Growth, between 2015 and 2017, 63.3% of pregnancies among women ages 15–49 were unintended, only dropping by 1.3% between 2017 and 2019.

While statistics may vary depending on the source and data collection method, most sources estimate that roughly 45% of pregnancies in the United States are unintended. A 2022 BMC Public Health study revealed that the following factors increase the risk of unintended pregnancy:

• Young age
• Migration background
• Lower educational level
• Lower household income
• Financial difficulties
• Being single
• Reduced cognitive abilities
• History of drug use
• Multiple sexual partners
• History of abortion

“We have an epidemic of unplanned pregnancy globally and nationally that, while there have been lots of efforts to curb, continues to be of epidemic proportions,” said Stephanie Page, MD, PhD, Co-Director of the University of Washington Medicine Diabetes Institute in Seattle, WA, Robert B. McMillen Professor of Medicine in Lipid Research and head of the Division of Metabolism, Endocrinology and Nutrition.

Roughly 40–45% of pregnancies in the US and internationally are unplanned, despite the plethora of well-researched female contraceptives, including hormonal birth control pills, intrauterine devices (IUD), and more. Unfortunately, barriers to access, availability, and education are standing in the way of effective contraceptive use.

The effect of unplanned pregnancies carries beyond the pregnancy term, impacting mental health, emotional health, and economic well-being.

Male Birth Control Methods

Although many men have shown interest in new male contraceptive options, there are only two widely available and approved forms of male birth control: condoms or vasectomies.

While condom use is generally effective, data from the National Institute of Child Health and Human Development (NICHD), a subset of the NIH, notes that condoms have an 11–16% failure rate. Additional insights reveal that while vasectomies are relatively effective, with a failure rate under 1%, this form of birth control is widely misunderstood.

Most of the rhetoric in vasectomy discussions implies that traditional vasectomies are reversible; however, data from Planned Parenthood reveals that only 85% of vasectomy reversals are successful, leaving the remaining 15% who want to reverse the procedure struggling with male infertility.

“We have an untapped population who have grown increasingly interested in being part of the contraceptive equation, controlling male fertility, limiting their own fertility, as well as sharing in the burden of contraception,” said Page.

The Bill and Melinda Gates Foundation and Male Contraceptive Initiative recently sponsored a survey to assess men’s willingness to participate in contraception. According to an article published by the American Chemical Society (ACS), the survey data showed that 39% of men in the US and 76% of men in Nigeria and Bangladesh are interested in new forms of male contraception.

“Roughly 25–30% of contraception is done by men and with a combination of vasectomy and condom use,” noted Page. “Men are participating in contraception, and the data shows they are interested and willing to do more.”

NES/T Gel

Understanding the need for more options, Page, the Population Council, Eunice Kennedy Shriver NICHD, Los Angeles Biomedical Research Institute, and other researchers at the University of Washington School of Medicine have been exploring alternatives, including a new hormonal birth control gel for men: NES/T gel.

“Nestorone Testosterone gel, or NES/T gel as we call it, is a combination of hormones. The goal is to develop male hormonal contraceptives like female hormonal contraceptives, which include contraceptive patches, the birth control pill, and various other hormonal methods,” began Page.

She explained that progestin, a synthetic form of progesterone, is combined with testosterone for male hormonal contraception. For the NES/T gel, the chosen progestin is nestorone. Comparatively, female hormonal birth control combines progestin and estrogen.

“By giving men a combination of these two hormones, it blocks the signals from the brain to the testis — the same signals that regulate the menstrual cycle in women. By blocking those signals, the testicle stops testosterone production. Without that high testosterone level, the sperm in the testicle failed to mature,” noted Page.

It’s important to note that male hormonal contraceptives suppress sperm production while ensuring enough testosterone is available for typical sex characteristics, like libido.

“This particular product is a gel that's the consistency of hand sanitizer,” explained Page. “Men put it on daily; they must apply it daily to be maximally effective. Then they must wash their hands and not shower for four hours for maximal absorption.”

The gel is applied on men’s shoulders and upper arms and absorbed through the skin.

“The NES/T gel is very similar in concept to some testosterone gels that are on the market to treat male testosterone deficiency, but we have added this progestin component, which helps to make it a more effective contraceptive,” she continued.

Clinical Trials

“The male contraceptive gel has undergone a six-month trial in men where the outcome instead of preventing pregnancy was measuring the sperm output,” she noted. “We know that for it to be effective, the suppression of sperm production must reach a certain low threshold.”

According to her, 90–95% of the men who used the product for six months as directed met the required sperm threshold.  

Regarding side effects and adverse reactions, Page noted, “We looked at cholesterol levels, blood counts, and other things we know testosterone can impact. We saw that the product was very well tolerated.”

Beyond those factors that impact sperm count, Page and other researchers also evaluated mood swings and sex drive, finding minimal impacts. One side effect some patients reported was 1–2 kgs of weight gain; however, there was no evaluation of the weight, so there was no way to know if it was muscle or fat mass.

“The gel is very effective if it's used daily and very well tolerated,” she noted. “Nestorone gel is currently in a phase 2B efficacy study. This is a study that couples enroll in. It tests the ability of the gel to work as a contraceptive to prevent pregnancy.”

Although the study does not have results yet, the enrollment period has concluded, and researchers are hopeful about getting results soon. Page and her team have enrolled 450 couples to assess the effectiveness of the contraceptive gel in preventing pregnancy.

Page discussed how the team ensures efficacy across all patient populations by conducting diverse clinical trials.

“This is a huge problem in research, and the tools and strategies we've had to address it have been suboptimal,” noted Page. “In this study, we have 17 sites across the globe, some of which have much more diverse populations to recruit than others. That is specifically why they were chosen.”

Page noted that they also added new sites throughout the trial to improve the overall participant diversity. As the first male contraceptive trial with study sites in Africa, the NES/T gel is involved in clinical research in Kenya and Zimbabwe.

Through this site, the researchers are assessing diversity beyond racial and ethnic differences, accounting for varying resources and environments that may impact the efficacy and utility of this form of contraception.  

Other Male Birth Control Research

Page and her team are also working toward other versions of male birth control. She told LifeSciencesIntelligence that all male hormonal birth control functions through a similar mechanism of action, blocking sperm development using hormones. However, there may be different delivery methods. Just as there are many options for female birth control, the possibilities for male birth control depend on preference.

Although the hormonal forms of male birth control are farther ahead than most other forms, other non-hormonal forms are being explored. For example, some researchers are working on a reversible t alternative to vasectomy. Rather than cutting the connection between the testicle and the penis, clinicians can inject silicon or another gel into that connection that interjects the plumbing circuitry. Later the gel may dissolve, or a physician can inject a dissolving agent to reverse the procedure.

Beyond the reversible vasectomy alternative, some hormonal male birth control options, such as the male pill, have been evaluated in men but have not been tested for efficacy using couples.

Additionally, she noted that recent investigations have been working on an on-demand contraceptive.

“It’s a pill that a man would take between three and six hours before intercourse,” said Page. “Instead of targeting sperm production, the agent targets the movement of sperm.”

For sperm to reach the egg, specific molecules, proteins, and enzymes allow sperm to swim hyperactively.

“These on-demand contraceptives target hyperactive swimming. Non-hormonal methods target different parts of sperm maturation or function, but all the hormonal methods work by that same mechanism of action and vary mostly in their delivery form,” she explained.

Moving Forward

Throughout the discussion with LifeSciencesIntelligence, Page emphasized the importance of diverse, effective, and available contraceptive options.

“Whatever people feel about abortion, contraception is not a replacement for access to safe abortion, but it is probably our best tool for preventing the need for abortion,” explained Page. “Especially in this time in America, when women's human rights and reproductive rights are eroding, it's more important than ever to develop novel contraceptives and ensure that they're used so every pregnancy becomes a planned pregnancy.”

Despite the critical need for male contraception, the high risk, unclear definitions of responsibility by the FDA and other regulatory organizations, and limited incentives have held back product development and launch.

“One thing that is needed to move the field forward, whether it's this gel or any other method, is a review by regulatory agencies about not just the risk–benefit of contraceptives and how we get one of these approved for men, but also what the responsibility is for producers if there is a pregnancy,” shared Page.

She told LifeSciencesIntelligence that there are legal implications surrounding this kind of technology that may make companies unwilling to invest in them. Male contraceptive options are unlikely to reach the market without incentives for investment.

“At a minimum, we're hoping that governmental agencies will help us help to define a regulatory pathway that will allow a first agent, whatever that may be, to become available,” added Page.

Much like female contraceptives, researchers, medical professionals, and public health experts expect the uptake of these products to be significant, potentially altering behaviors as well.

“Getting something to the market will help elevate the conversation and allow men to show that they can take more responsibility,” she shared. “Without better options for men, we're unable to engage them in the way they might want to be. There needs to be some central movement behind this to get at least one product to the market, demonstrating that this is a worthy thing to invest in.”