What’s going on with male contraception? Is it the future?

Posted on

By: Emily Gerson, Undergraduate Student at George Washington University and Research Assistant at the Maternal Health Task Force

Disclaimer: While we recognize that not all people with male sex organs identify as men, we will be using the terms “men/male” to refer to people with penises and “women/female” to refer to people with uteri. We apologize for the cis- and heteronormativity that this promotes.

Although it is impossible to become pregnant without contribution from a man, the contraception industry has virtually ignored their role in procreation, leaving their options stagnant in condom use, vasectomies, and the withdrawal method. Men who have female partners are frequently involved in conversations regarding birth control, but a man educating himself and encouraging his partner’s usage is wildly different from actual willingness to subject himself to the arduous administration methods and unpredictable side effects that come to be expected with contraceptives.

Research has demonstrated that men are not opposed to using contraception if it means safer sex and a shared burden between partners. Male contraception could revolutionize family planning; combining it with female contraception could relieve worry from partners where a woman uses the pill, or similar contraceptives with high user error rates. Still, a lack of knowledge and research holds back progress, and attitudes towards male contraception vary based on location and contraceptive.[1][2][3][5] For instance, 44% of men in Hong Kong expressed willingness to try a male pill compared to 83% of white men in Cape Town, and 32% of men in Edinburgh expressed willingness to try an injectable compared with 62% of white men in Cape Town.[4]

This is not to say that research has not been done on this regard. In fact, international research into the idea of male contraception began in the 1970s,[1] and there are numerous male contraception options in very early stages of development, with several drawing more attention than others.

So, what are some of the products being tested? From injectables to thermal underwear, methods with varying amounts of hormones (as well as non-hormonal methods) have demonstrated effectiveness, with the drawbacks mainly being unpleasant side effects and demanding means of execution.[2][5]

Hormonal methods

Male hormonal contraceptives work by suppressing gonadotropins (hormones which stimulate the activity of the gonads) release from the pituitary, inducing the suppression of spermatogenesis (the development of mature sperm cells).[6] Thousands of healthy men have enrolled in clinical trials of male hormonal contraceptives with a nearly universal return of steroid production and spermatogenesis function once the contraceptives are stopped.[6]

Large, international studies have demonstrated testosterone’s efficiency in suppressing sperm concentrations, while further research has found that testosterone alone is not as efficient as testosterone plus a progestin, both in the rate and extent of suppression of spermatogenesis.[5][6]

Testosterone clears quickly from the system when taken orally, and multiple doses per day is impractical, thus rendering the implementation of a male pill improbable.[2] Hormonal injections are among the most widely researched male contraceptive options, and have been found to be extremely effective, with sperm function returning to normal after discontinuation.[5] In a trial evaluating a testosterone injectable, 61% of the 44 participants who completed the 1-year exposure period rated the injectable as excellent or good and 79% indicated that they would use it if it were available.[3]The World Health Organization (WHO) and the Contraceptive Research And Development Program (CONRAD) analyzed testosterone undecanoate (TU) and norethisterone enanthate (NETE) in a large efficacy study, however after mild to moderate mood changes were noted in some of the participants, an external safety review committee recommended stopping further injections before the planned end of the study.[5]  The most common mood change, found in 16.9% of participants, was categorized as “emotional disorder,” with 63 participants ranking the disorder as “mild,” two ranking it as “moderate” and zero as “severe.” The next most common mood change was mood swings, found in 4.7% of participants, with 16 participants ranking the mood swings as “mild,” three ranking them as “moderate” and zero as “severe.” [12] Although the side effects seem tame when quantified like this, one participant is thought to have taken their own life and another attempted to do so during the trial.[13] WHO and CONRAD will not be moving forward in clinical trials, as there is no more funding available to retest another formulation.[9]

Other methods of delivery are also being tested. Nestorone, a transdermal testosterone gel, showed effective suppression of gonadotropins when used for 20 days.[6] With no injections necessary, the gel would be widely accepted, and an encouraging trial showed that most failure was due to inconsistent or nonuse of products, not failure of product’s effectiveness.[2] Nestorone is currently in Phase 2 clinical trials.[10]

Non-hormonal methods

Perhaps the most recognizable non-hormonal method is RISUG, an injectable form of long acting reversible contraception (LARC) that began development in India in the early 1980s.[6] RISUG has been in clinical trials for decades, with Phase 1 and Phase 2 published in 1993 and 1997, and Phase 3 in 2003. The longest duration of the RISUG bearer was over 13 years.[7]

Intellectual property rights to RISUG were acquired by NGO Parsemus Foundation in 2010.[5] Parsemus used the RISUG technology to create Vasalgel, which claims to have a different polymer and formulation than RISUG. Parsemus has performed preclinical studies in rabbits and monkeys, and intends to begin trials in humans in 2020, although human trial start dates had previously been projected for 2018 and 2019.[2] According to the Parsemus website, “The procedure is similar to a no-scalpel vasectomy, except a gel is injected into the vas deferens (the tube the sperm swim through), rather than cutting the vas (as is done in vasectomy). If a man wishes to restore flow of sperm, whether after months or years, the polymer would be dissolved and flushed out.”[8] However, until drug companies choose to allocate funds to and put priority on testing Vasalgel, progress will be extremely difficult.

Another fascinating non-hormonal option is thermal contraception. This is based on the notion that in human males, testicular temperature is 2-5 degrees Celsius lower than core body temperature, so when testicular temperature is increased, sperm output is reduced. Specific thermal underwear lifts testes closer to the body and warms them by 2 degrees Celsius.[1] A French study found that males enjoyed that the underwear was natural and non-invasive but expressed concern over the need to wear it continuously.[1]

So, what’s stopping progress?

Researchers have been playing around with the idea of male contraception for decades, but a lack of urgency surrounds the issue. Regardless of ample enthusiasm for the idea, the fact remains that pursuing male contraceptives like the ones described above would involve significant effort on the part of both male volunteers and the male-led pharmaceutical industry. Myriad hormonal and non-hormonal methods have been studied at least partially, but these studies receive little funding and almost no media attention, and abandonment and incompletion are rampant.[9] Public access to male contraception requires completed and successful clinical trials, which in turn require significant funds and far more participants. Pharmaceutical companies have expressed little interest in male contraception, presumably because the complex drug would not become profitable for many years.[15]

Clinical trials that managed to amass the funding and subjects have been cut short due to side effects, such as mood swings, that are frequently associated with female hormonal contraception methods that millions use every day. Should men have to deal with the same side effects women do for the sake of family planning? Well, the flaws in female contraception, despite their use as an argument for leniency in male contraception development, also detract from funding towards male birth control, as better, more effective female contraception is also a public health goal. Sure, women endure severe adverse effects in the name of family planning, but they also have far more at stake, leaving them more likely to deem the side effects worth the risk.

Organizations that fund contraception research and promotion are unlikely to divert all of their focus away from women’s health and onto men’s when there is still so much work to be done in achieving access to the family planning options already on the market. Yet, the Bill and Melinda Gates Foundation and the David and Lucile Packard Foundation have both directed funds towards male contraception research. It’s important to note, though, that female contraception and its role in empowering women from low resource areas continues to be of higher priority.[14][16]

Further, male contraception would not eliminate, or even necessarily reduce, the need for female contraception. Even in a hypothetical near future where male birth control is cheap, safe, and accessible, for men to become the sole bearer of contraceptive responsibility the hypothetical future would also need to be one where women can trust the intentions of all men that they are sexually intimate with. Unfortunately, the latter concept proves to be elusive. It is impossible to tell if a potential partner has a long acting reversible contraceptive (LARC), like Vasalgel, and a pill would be easy to lie about having taken. With their bodies, finances, and futures on the line, women might not trust that men are telling the truth. With the prevalence of “stealthing,” the act of secretly removing the condom without the knowledge of the partner, this is not an unfounded fear.[10] Research has shown that men generally desire larger families than women do, and in many cultures women are left out of reproductive decisions.[17] “Stealthing” is rooted in the patriarchal notion that man’s pleasure and his “right” to extend his bloodline justify violating a woman’s bodily autonomy.[18] Covert male contraception could make the abusive behavior even easier. Men are not the only perpetrators of reproductive manipulation, however. Male contraception would grant agency to men who fear being coerced into fatherhood by a deceptive partner. They would not have to carry the child, but fatherhood is itself far too heavy of a responsibility to risk if one is not fully prepared.

Though male birth control would not replace its female counterpart, significant interest has been gauged due to the anticipated benefits. While male contraception is unlikely to be publicly available any time soon, it is not yet a lost cause. Nestorone transdermal gel’s clinical trial is estimated to complete by 2021,[11] and Parsemus is currently accepting donations to fund its research.[8] Very recently, the Bill and Melinda Gates Foundation allotted a grant of about $900,000 (£716,670) to Dundee University in Scotland for research into a male pill.[14] The progress may be slow, but the science is there, and it is promising.

 

[1] Are men ready to use thermal male contraception? Acceptability in two French populations: New fathers and new providers

[2] Male Contraceptive Development: Update on Novel Hormonal and Nonhormonal Methods

[3] Modeling the impact of novel male contraceptive methods on reductions in unintended pregnancies in Nigeria, South Africa, and the United States

[4] Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations

[5] Update on male hormonal contraception

[6] Beyond the Condom: Frontiers in Male Contraception

[7] RISUG: An instravasal injectable male contraceptive

[8] https://www.parsemus.org/projects/vasalgel/

[9] Why We Still Don’t Have Birth Control Drugs for Men

[10] Stealthing: What You Need to Know

[11]https://clinicaltrials.gov/ct2/show/NCT03452111

[12] Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men

[13] https://arstechnica.com/features/2018/02/more-than-half-a-century-later-wheres-the-male-pill/

[14] Dundee University researchers start work on male pill

[15] Male contraception: Another holy grail

[16] https://www.packard.org/grants-and-investments/grants-database/parsemus-foundation/

[17] Reproductive Motivation and Family-Size Preferences among Nigerian Men

[18] ‘Rape-Adjacent’: Imagining Legal Responses to Nonconsensual Condom Removal