Male contraception, a long-standing and confidential research topic, is gaining momentum. Hormonal, non-hormonal and reversible surgical methods are advancing rapidly, reflecting the growing demand for shared responsibility in family planning, reports Medscape.
Recently, experts at the 41st Congress of the French Society of Endocrinology highlighted both the scientific progress and cultural challenges that remain in bringing these options to the market.
Geoffroy Robin, PhD, gynaecologist and andrologist at CHU Lille, Lille, France, highlighted shifting attitudes: “While female contraception has been a major social advance, it is now sometimes seen as a constraint by women who have not experienced or are not always aware of all the battles fought to obtain it.”
Public scepticism toward hormonal contraception, amplified by media coverage, has renewed calls for non-hormonal alternatives that expand contraceptive options and address safety concerns.
Within the broader push for gender equality, there is a growing demand for men to take a more active role in family planning and share contraceptive responsibility, he said.
Groups such as the Association for Research and Development of Male Contraception advocate the development of reliable, reversible and accessible male contraceptive methods, several of which could become available in the coming years.
Methods
Male hormonal contraception is currently one of the most advanced approaches in development, and evidence suggests that many men are willing to use it if it becomes available.
Studies have indicated that 44%-83% of men support male contraception. A transdermal gel combining nestorone (a potent progestin) with testosterone is currently in late-stage clinical trials and may become the first widely used male hormonal contraceptive.
“The progestin blocks sperm production, while testosterone is administered at a replacement dose to maintain normal functions. This avoids the side effects associated with high-dose testosterone, which has remained largely experimental because of tolerance issues and a delivery method that is difficult to use,” said Robin.
“Applied daily, the gel has proven more effective at inducing severe oligozoospermia than methods using high-dose testosterone alone and is generally well accepted,” he added.
The oral route remains limited because oral testosterone requires multiple daily doses with fatty meals to be effective.
Therefore, the development of oral male contraceptives is likely to focus on alternative molecules.
Some of these are steroid derivatives, such as 11-beta-MNTDC and dimethandrolone, while others target pathways outside the gonadotropic axis, notably by acting on retinoic acid.
“Many studies have shown that spermatogenesis is regulated by paracrine molecules, among which retinoic acid plays a significant role. Vitamin A deficiency blocks spermatogenesis in animals; therefore, the strategy is to use a retinoic acid antagonist,” said Robin.
The most advanced candidate for this oral, non-hormonal approach involves YCT-529, an oral selective retinoic acid receptor-alpha antagonist that disrupts spermatogenesis. Studies in non-human primates have demonstrated that it induces reversible seminiferous tubule hypoplasia, with fertility restored after discontinuation of treatment.
Hormonal methods often produce side effects similar to those seen in women, including acne, weight changes, altered libido, mood fluctuations, and hyperglobulinaemia. The risk of thromboembolism has not yet been established.
All of these approaches require approximately six months to become fully effective, allowing time for pre-existing sperm, particularly those stored in the seminal vesicles, to be cleared.
Until these methods are widely available, men currently have three options: withdrawal, which is highly unreliable; the male condom; or vasectomy.
Although permanent, vasectomy has grown increasingly popular: procedures in France rose by 491% between 2010 and 2018, with nearly 20 000 operations performed in 2018.
The procedure involves cutting both vas deferens under local and brief general anaesthesia. Because it is irreversible, it is strictly regulated by law, requiring a four-month reflection period and documented, informed consent.
Reversible methods
The development of reversible, non-surgical, and long-lasting methods could address this unmet need.
Vasalgel, a polymer gel injected into the vas deferens, provides contraception for approximately 14 months and can be reversed with sodium bicarbonate. However, reversibility is not always complete, as morphological alterations in sperm have been observed in some studies.
An alternative concept, the on-demand vasectomy, is currently under development. A German company is creating a microswitch implanted next to the vas deferens that can be activated or deactivated under the skin to block or allow sperm passage. This concept has been validated using animal models.
Thermal methods
Thermal approaches, which maintain the testicles at temperatures above 35 °C for approximately 16 hours a day using specialised briefs or jockstraps, can temporarily reduce sperm production, and remain of interest to men.
The Andro-switch ring is unavailable pending CE certification, and its return to the market will depend on the successful completion of the approval process.
Barriers
Despite these scientific advances, several major obstacles remain. Pharmaceutical interest is limited, and societal attitudes may hinder its adoption.
Questions persist: are men ready to take responsibility for contraception, and could doing so challenge traditional notions of masculinity? Are women prepared to trust men with contraception, accepting the potential consequences of user error or noncompliance?
This story was translated from Univadis France.
Medscape article – Vasectomy on demand? Future of male contraception emerges (Open access)
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