Male contraception: where are we now?

24 Jul 2020

More than 50 years after the arrival of the contraceptive pill, men still have only two contraceptives: the condom and the vasectomy
While today’s women have an arsenal of effective contraceptives to control their fertility, men, on the other hand, are in dire need. They can choose a condom or a vasectomy. But none of these options is ideal. Condom, effective in only 85% of cases, is often perceived as binding and can cause allergies. As for vasectomy, its main disadvantage is that it is not always reversible. Therefore, it is better to be sure of your decision because it could be final. As for the so-called “natural” methods, we can cite abstinence (or interrupted intercourse), but this is far from reliable. As a result, contraception is primarily a women’s business.

Go below the million sperm mark

So how can we explain that, more than fifty years after the arrival of the pill, there is still no male equivalent available? A first element of response is based on the biological differences between the reproductive system of men and that of women. Spermatogenesis, that is, sperm production, is a continuous process that is reversibly more difficult to prevent than the release of an egg once a month.

The goal is to obtain an ejaculation that contains less than a million sperm per milliliter, compared to 15 to 150 million in normal times. However, since the 1970s, the scientific community has ingeniously competed to overcome this obstacle. The goal is to obtain an ejaculation that contains less than a million sperm per milliliter, compared to 15 to 150 million in normal times. Below this threshold, the risk of unwanted pregnancy is considered very close to zero.

Another important detail: this phenomenon must, of course, be reversible. To do this, several levers can be operated. Either it is blocking the path to sperm, that is what we already do with condoms and vasectomy, or it is avoiding or drastically reducing the production of sperm by hormonal or thermal means, or it is good to denature the sperm so that they do not work. Paralyzing sperm is the last solution that American scientists have chosen. The researchers managed to block the mobility of the sperm from 4 macaques thanks to the injection of a compound called EP055. And in that way, sperm cannot reach the egg if the opportunity arises. In addition, primate sperm regained their initial freedom of movement 18 days after injection. Furthermore, no short and long-term side effects have been observed. It remains to be seen if this method would give such good results in humans.

Non-hormonal contraception

Non-hormonal contraception, that is, targeting sperm without altering the hormones that control their manufacture, is the path that most attracts researchers. Partly because it would avoid the possible side effects of hormonal disruption. Many doors opened in this direction … and immediately closed, mainly due to adverse effects. So far, only one non-hormonal method of contraception has been tried in humans, without success. It is a molecule capable of blocking the synthesis of vitamin A in the testicles. This vitamin is essential for sperm production. The first clinical trials took place in the 1960s. However, they were later abandoned due to the appearance of significant adverse effects related to concomitant alcohol consumption. Since then, researchers are looking to develop a safer molecule.

Testosterone kit to prevent sperm production

Perhaps this is the approach of hormonal methods in which clinical trials are the most prolific. Since the early 1990s, no fewer than 8 major studies have been conducted on nearly 2,700 volunteers. And for each of them, the principle is the same: administer in the form of injections or applications of creams that contain hormones that will induce a decrease in the concentration of testosterone in the testicles. Without testosterone, there is no sperm.

However, many of these studies, if they led to satisfactory results, had to be abandoned for several reasons: lack of efficacy, undesirable effects, fear of long-term consequences (in particular for the prostate and liver)

Testosterone is the hormone of life, it reduces bad cholesterol, it increases good cholesterol, it has a protective action against cardiovascular diseases and acts on mood. Playing with it can put men at serious risk.

Two main routes are currently being studied: the first is a hormone-based gel that must be applied daily to the skin. Tested in 2012 for 6 months, this gel made it possible to reduce sperm concentration below the fertility threshold in 88% of the 56 participants. As for the second, the male equivalent of the pill, it has been tested in 100 men. The findings are encouraging, according to the researchers, although side effects (weight gain, decreased “good” cholesterol) have appeared.

Male contraception, a plumbing issue?

What if the answer to this dilemma was mechanical and not biological? This is the gamble made by India, where research teams have been working since the early 1990s on a method of contraception. The principle is simple: prevent sperm from coming out, blocking your way. The Indian process, called RISUG (for “reversible sperm inhibition under guidance”), involves injecting into the two vas deferens (tubes connecting the testes to the prostate) a gel that forms a semipermeable barrier. Sperm, too large to pass through, become blocked and recycled by the body.

In addition to the fact that this treatment does not modify ejaculation in any way, animal studies have shown that it is reversible in a few months, thanks to the injection of a product intended to dissolve the gel. In humans, there is insufficient data. A clinical trial should bring new elements in the coming years.

 

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