Hormonal-Free Male Contraceptive Passes First Safety Test

A potential new male contraceptive drug has passed its first human trials. The results provide the first indication that the drug, which does not use artificial hormones and does not interfere with testosterone production in the testicles, may be safe for humans.

There have been previous attempts to develop a male contraceptive, but most failed clinical trials due to unacceptable side effects. However, this new contraceptive works differently than previous attempts, meaning it does not require surgery and is far less likely to cause hormonal side effects – the very issues that have prevented previous drugs from reaching the market.

The study found that the drug was well tolerated in a small group of healthy young men and did not appear to cause serious side effects at the doses used. However, further research is needed to determine exactly how effective it is as a contraceptive.

The new method uses a specially designed chemical compound called YCT-529, which targets a specific cell receptor in the testicles called the alpha retinoic acid receptor.

Similar but less specific compounds had previously been shown to reduce sperm production in humans. However, they also had unwanted side effects – such as feeling sick when drinking alcohol, changing blood salt levels, and failing to fully restore fertility in some men. This made them unsuitable for use as a contraceptive.

But in animal studies, YCT-529 caused completely reversible and temporary infertility with no serious side effects. A study in mice also found that animals that fathered babies after stopping the drug produced normal, healthy offspring.

Based on these results, the drug has moved on to phase I human clinical trials. This is the first stage of human testing, where a small group of healthy volunteers are involved in testing for safety, tolerability, and possible side effects.

The small trial involved 16 male volunteers who took the drug twice in increasing doses — from 10 mg to 30 mg or from 90 mg to 180 mg. Some men were given a placebo for comparison.

Participants were monitored for 15 days for effects on hormone levels, inflammation (signs of cell damage), kidney and liver function, heart rhythm disturbances, sex drive and mood.

There were no changes in the body's natural hormone levels. There were no long-term liver or kidney dysfunctions or signs of cell damage. There were no dangerous heart rhythm abnormalities, and the participants reported no changes in mood or sex drive.

However, the participants only took two doses of the drug and were followed for only 15 days. The authors of the article indicate that a second phase study has already begun, in which the drug will be tested on a larger number of men.

Then a phase III trial involving hundreds of men is planned to assess the drug's efficacy, reversibility and long-term side effects - steps that have previously hampered the commercialization of other approaches.

Why Previous Male Contraceptives Failed

There are currently no commercially available methods of contraception for men that are safe, effective at preventing pregnancy, and allow control of sperm production (turn it on and off at will).

• Condoms have few side effects and are used voluntarily, but they have a relatively high failure rate (pregnancy occurs in about 12–18% of cases with typical use).
• Vasectomy, which cuts the tube that connects the testicles to the rest of the reproductive organs, is very effective (over 99%) and safe, but it is difficult to reverse and requires surgery.

There have been previous attempts (and some are still ongoing) to create a reversible method of contraception for men. Some approaches have been effective in stopping sperm production or preventing sperm from entering the reproductive tract. However, they have not been commercialized, often due to side effects.

There were two main approaches:

1. An injection of a substance into the vas deferens that filters and damages sperm during ejaculation. This substance can be removed with a small procedure if a man wants to become fertile again. The downside is an injection into the scrotum and the need for a subsequent procedure to restore it.
2. Stopping sperm production entirely by suppressing the hormones that trigger sperm production in the testicles. The most successful of these approaches involved injecting progestin, a synthetic analogue of progesterone, which signals the brain to stop producing FSH and LH, the hormones that control spermatogenesis and testosterone production.

But suppressing LH also turned off testosterone in the testicles, which is essential for normal male functioning. To compensate for the loss of testosterone, additional testosterone was needed - in tablets or gel form.

However, a large trial of the treatment was stopped early due to side effects including mood swings, acne and changes in sex drive.

There is a long way to go before the new drug can be considered suitable for use. But the new approach looks promising because it does not disrupt hormone balance and is taken orally rather than requiring invasive procedures.