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The male pill

A novel type of male contraceptive that momentarily halts sperm cells in their tracks and prevents pregnancies in preclinical models could prove to be a game changer, writes Dr Vasan S S
Last Updated : 23 April 2023, 02:41 IST

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Male contraception has long been a source of discussion. The findings of the researchers at Weill Cornell Medicine in the United States who have developed an experimental contraceptive drug candidate that could result in a new type of male contraceptive have come as a good alternative to the limited options like physical barriers or condoms and surgical options like a vasectomy. The potential medication functions by exploiting a molecular switch to temporarily stop sperm from reaching an egg by shocking them for two hours. This finding may lead to the development of a male contraceptive tablet that is comparable to the contraceptive pill currently available for women. The high rate of sperm production in males and unfavourable side effects of existing contraceptives present a number of obstacles to the development of male contraceptives, nevertheless.

Due to their negative effects, many reliable and efficient male contraceptive treatments have been abandoned, while others are still in the development stage. Male contraceptives have a tough time being accepted because of men’s worries about potential infertility and unidentified side effects, as well as the risk-averse character of males, ethics committees, and pharmaceutical businesses.

A molecular switch stuns sperm

The chemical switch that the contraception uses can stun sperm for up to two hours, essentially stopping them from reaching an egg. This finding may lead to the development of a male contraceptive tablet that is comparable to the contraceptive pill currently available for women.

Male birth control options

At the moment, the only methods available for male birth control are physical ones like condoms, and surgical ones like vasectomy, withdrawal, and spermicide. But, the creation of a male contraceptive pill may provide men with another choice.

The challenges

The high rate of sperm production in men is one of the main obstacles to the development of male contraceptives. It is challenging to stop every single sperm that men create from reaching an egg and resulting in pregnancy because they produce millions of them every day.

History of male contraception

Male contraception has a rich history that includes a variety of techniques, such as ceasing ejaculation. Thioridazine, which was first used to treat schizophrenia, is one example of this. The medicine was found to have the unexpected side effect of inducing dry orgasms, which were neither pleasurable nor regular.

Another illustration is the usage of the blood pressure medicine phenoxybenzamine, which, like thioridazine, also has an ejaculation-suppressing action, but was not always desirable and successful. Male contraceptive treatments can be safe and effective, but many have been ignored because of unfavourable side effects.

Suppression of hormonal axis

Researchers tested the impact on sperm production in the 1970s by giving testosterone injections to participants once a week for a few months. Although it wasn’t completely infallible, one of the early experiments revealed that this approach was very effective, resulting in only five pregnancies. Subsequent trials looked into whether adding a second hormone, like progestin, a synthetic form of the female reproductive hormone progesterone, could boost effectiveness. The use of hormone therapy, however, created a challenge because it frequently causes a variety of side effects, many of which are typical for women taking contraceptive tablets. For instance, testosterone use alone might result in weight gain, greasy skin, and acne, among other problems, which led to the early termination of some trials.

Many non-hormonal contraception alternatives for males have also been suggested, despite these difficulties. They include a temporary vasectomy known as Reversible Inhibition of Sperm Under Supervision and a vaccination that targets a protein involved in sperm development (RISUG). In order to stop sperm from leaving the testes, RISUG entails injecting a synthetic polymer into the vas deferens, which is the tube that does this. It was initially created to sterilise water pipes, but it was later modified so that it could be used safely inside the human body. In India, RISUG is presently undergoing Phase III clinical trials, the last phase of testing before a medication is authorised.

On-demand male contraception

In clinical tests, hormonal methods of male contraception achieved overall effectiveness rates of 94% in preventing sperm production by interfering with spermatogenesis. Nevertheless, these initiatives were given up because of unfavourable side effects. The most advanced male contraception currently under development uses a topically applied nestorone-testosterone gel in ongoing global clinical research.

Non-hormonal strategies focus on gene disruption technologies targeting essential factors for spermatogenesis. Small molecule inhibitors against bromodomain testes-specific protein and retinoic acid receptor antagonists show promise in reversibly suppressing sperm production, but there are concerns about their selectivity and potential side effects.

Two other efforts involve blocking sperm functions using Triptonide, a herb originally identified from Chinese folklore, an inhibitor of the epididymal peptidase inhibitor (EPPIN).

However, all of these hormonal and non-hormonal strategies require months of continuous treatment before they become effective and demand a similar time upon cessation of treatment to be fully reversible. As a result, an on-demand approach for male contraception remains a challenge for the contraceptive development landscape.

Men’s concerns

“Men are worried about future fertility and about unknown side effects that may only become known years after using a product,” says Walker. “They’re worried about the effect on their performance, how they feel about sex,” he adds.

There are several charities working tirelessly to fund research into male contraceptives, but it is speculated that pharmaceutical companies may have less incentive to develop them when female contraceptive methods are so effective. “I think people are more risk-averse in the world of male contraception,” believes Walker. “Men are more risk-averse, ethics panels are more risk-averse, and possibly pharmacy companies are more risk-averse. Each method seems to face the hurdle of acceptability.”

A learning

Modern versions of the combined contraceptive pill are generally considered safe for most women, although they can lead to high blood pressure and blood clots in rare cases. However, they can also cause a range of less serious side effects, such as mood swings, nausea, headaches, and breast tenderness. There is also some evidence to suggest that they can alter a woman’s body shape.

Stringent research

Male contraceptive pills are held to a higher set of standards — both in terms of acceptable side effects and safety more generally — because men (except transgender men) cannot get pregnant.

(The author is a uroandrologist with a leading hospital in Bengaluru.)

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Published 22 April 2023, 18:40 IST

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