YCT-529 Male Birth Control Pill Offers Men a Non-Hormonal Option for Pregnancy Prevention

A non-hormonal contraceptive pill for men, identified as YCT-529, has successfully completed its first human safety trial, heralding a potential paradigm shift in reproductive health.

The trial’s findings, published in Nature, confirm the pill's safety for human use, with no reported adverse side effects. This development offers a promising alternative to the limited range of male birth control options currently available. The Phase 1a trial, conducted by YourChoice Therapeutics in conjunction with Quotient Sciences at their Nottingham facility, signifies the inaugural clinical evaluation of a non-hormonal oral contraceptive for men.

The timing of this innovation coincides with escalating calls for a more equitable distribution of contraceptive responsibility between partners, particularly in regions where women disproportionately bear the burden of family planning. Boniface Njuguna, a trader from Thika, Kenya, views this development as personally significant. His partner has experienced challenges with intrauterine devices, including discomfort and complications.

"This is actually good news because my woman has issues with things like coils and reacts to them badly," Njuguna said. "It makes her so uncomfortable, so the fact that I can play a part in making our sex life healthier by taking a pill is very good.”

Historically, male contraceptive options have been restricted to condoms and vasectomy. Condoms offer inconsistent protection, while vasectomy involves a permanent surgical procedure. Previous efforts to broaden male birth control options encountered obstacles, exemplified by the World Health Organisation’s (WHO) 2016 trial of a hormonal injection. Although the injection demonstrated a 96 percent effectiveness rate, it was discontinued due to severe side effects, including mood disorders and depression.

YCT-529 marks a departure from hormonal methodologies. The pill is designed to temporarily and reversibly suppress sperm production without altering testosterone levels, mitigating the hormonal complications that have previously impeded progress in this field. Nadja Mannowetz, co-founder and chief science officer at YourChoice Therapeutics, emphasises the innovative nature of their approach: "This is the first time anyone has clinically trialled a non-hormonal male contraceptive pill."

The Phase 1a trial involved 16 healthy, vasectomised men, aged 32 to 59, with body mass indexes ranging from 21.9 to 31.1 kg/m². The inclusion of vasectomised participants was a precautionary measure to eliminate the potential for long-term fertility disruption. Participants were divided into two dosing cohorts, receiving either 10mg followed by 30mg, or 90mg followed by 180mg of YCT-529, with matching placebos administered to control groups. A subset of participants also received a third dose after a high-fat meal to assess the drug’s interaction with food intake.

Throughout the study, participants were required to abstain from alcohol, grapefruit juice, and other medications to ensure the accuracy of the results. The compound was manufactured under Good Manufacturing Practices in Alnwick and encapsulated in Swedish orange size 0 hard gelatin capsules. The trial received ethical approval from the Riverside Research Ethics Committee and regulatory clearance from the Medicines and Healthcare Products Regulatory Agency. It is registered under clinical trial number NCT06094283.

While the trial successfully confirmed the pill’s safety and tolerability, it did not assess its efficacy in reducing sperm production. This remains a crucial next step in determining its contraceptive potential. Researchers are currently conducting extended trials to evaluate sperm suppression over 28- and 90-day periods. If these trials are successful, YCT-529 could become the first widely available oral contraceptive for men that operates without hormonal interference.

The implications of such a development are substantial. Globally, nearly half of all pregnancies are unintended, highlighting the pressing need for more diverse and effective contraceptive options. In Kenya, hormonal contraceptives, such as Marvelon, Microgynon, and Cerazette, are widely used among women, despite frequent reports of side effects, including mood swings and weight gain. Emergency contraception, such as Postinor 2, is also prevalent, often as a last resort.

The introduction of a male pill could help rebalance the gendered dynamics of reproductive responsibility. Margaret Wekesa, a hotelier in Nairobi, welcomes the news as a move towards equality. "Women have for a long time been made to bear the ‘safe sex’ burden," she says. "We need to share the birth control journey together in equal measure. I am glad that a pill will soon be available for men.”

However, not all reactions have been unequivocally positive. Joram Ateya, a communications consultant, expresses scepticism regarding the long-term effects. "We are being told that it is safe and non-hormonal, but what if I end up with side effects like weight gain, acne, mood changes, and changes in libido, then cease to function as a man?" he queried.

Such concerns reflect broader anxieties about male contraceptive research, which has historically lagged behind female-focused innovations. The hesitancy to invest in male birth control has often been attributed to perceived market disinterest and the complexities of safely suppressing sperm without disrupting hormonal balance. YCT-529's non-hormonal mechanism may offer a resolution to this long-standing challenge.

Crucially, the pill does not offer protection against sexually transmitted infections (STIs), meaning that barrier methods, such as condoms, will still be necessary for disease prevention. Nevertheless, its potential to prevent pregnancy without permanent intervention or hormonal side effects represents a notable advancement in reproductive health.