The birth control pill for men – both the male and female population of the planet has been dreaming about such a miracle pill for many years. However, progress in this area has only recently begun to appear. This article describes the difficult path that eventually led to the discovery of a non-hormonal drug that reversibly blocks spermatogenesis at the gene level without any serious side effects.
Today, due to the widespread use of female contraceptives (the birth control pill), the need for male contraceptives seems far-fetched. But a lot of problems are still not solved. The growth rate of the world’s population is gaining momentum (in some countries they are almost uncontrollable). A significant percentage of pregnancies remain unplanned, and this leads to a high frequency of abortions, especially among adolescents. An extensive range of contraceptive options invented for women (from barrier, surgically introduced, to hormonal drugs in various forms), unfortunately, is not available to everyone due to the high cost or physiological intolerance. So, the need for a male alternative is obvious.
The first birth control pills were male
To begin with, the first steps in the creation of birth control pill were taken precisely in the direction of male contraception. The fact is that before the appearance of hormonal female contraceptives in the early 60s, it was on the shoulders of men that all the responsibility for preventing unwanted pregnancies fell, so it is quite logical that scientists first rushed to help them in this difficult task.
So, in the late 50s, in the area of the city of Salem (Oregon, USA), scientists began testing a drug for birth control called WIN 18,446 on male prison inmates. And WIN 18,446 worked perfectly: the prisoners felt good and looked quite healthy, but at the same time they had fewer spermatozoa, and even those turned out to be stunted and infirm. It would seem that this is what we need. But, unfortunately, when clinical trials began to be conducted among the free population, an unpleasant side effect was discovered. Men after taking the drug began to show characteristic signs of poisoning: vomiting, sweating, headaches and blurry vision. Scientists have managed to find the reason for such a fiasco. It turned out that it was alcohol. Since the prisoners could not drink alcohol, during the first tests of WIN 18,446, it did not occur to anyone that it could go badly with drinking. Thus, the work on the male miracle pill was abandoned, and for the next 50 years, such experiments were not even started.
Why was it so difficult?
WIN 18,446 is a pretty vivid example of why creating a “male contraceptive pill”is extremely difficult. This drug had everything you needed: it blocked spermatogenesis in everyone who took it (that is, indiscriminately) and this effect was reversible — the number of spermatozoa returned to normal if the drug was stopped. But the case still failed, since no man would have wanted to give up drinking.
The requirements for male contraceptives are much higher than for female ones. For example, taking hormonal female contraceptives increases the risk of blood clots in the blood vessels. However, the risk of blood clots during pregnancy is 10 times higher, so this side effect of birth control pills can be ignored. In men, there are no risks associated with pregnancy, so there should simply be no side effects of drugs for men. Otherwise, who will agree to take the risk, especially since the drug will have to be taken constantly for a long time.
The main achievements in the field of male contraception
In fact, there is no shortage of approaches to male contraception, and since the invention of the condom (it seems, in the sixteenth century by a certain Charles Condom), many useful ideas have appeared.
Surgical methods (vasectomy, plugs in the seminal ducts). If you block the lumen of the seminal ducts (vas deferens) with the help of implanted plugs, this will prevent the movement of spermatozoa. Such plugs can then be surgically removed or dissolved. During vasectomy, a part of the vas deferens is surgically removed, and this is irreversible.
“Dry orgasm”. The promotion of sperm in vas deferens is facilitated by two types of muscle contractions — transverse and longitudinal. Certain drugs can fix a longitudinal contraction, from which the seminal duct will collapse, preventing ejaculation.
Temperature increase. A necessary condition for normal sperm production is a temperature several degrees below 37 °C. If, for example, you wear too tight underwear, then the testes will be in close proximity to the body, and this can disrupt spermatogenesis. Other methods of temperature exposure to the testes also work.
Hormonal drugs. Until recently, scientists tried to create a male contraceptive pill in the image and likeness of female hormonal contraceptives. Without going into tortuous biochemical details, it can be argued that artificially high testosterone levels suppress the level of other hormones necessary for sperm maturation. It works amazing — the number of spermatozoa falls crushingly almost instantly. However, such a powerful effect also affects other tissues of the body that respond subtly to the level of sex hormones, which causes many very unpleasant side effects. In addition, it was not so easy to deliver testosterone to the testes. Testosterone, taken orally, falls apart in the body so quickly that men would have to take several tablets a day to maintain a sufficiently high level of this hormone. Alternative methods-injections and gels-are infinitely inconvenient in everyday life. In addition, hormonal contraception does not work at all in 20% of men! And when the men who participated in the first clinical trials began to complain about such side effects as acne, obesity, sudden mood changes, decreased sexual desire and the disappearance of an erection, it became clear that this would be a failure in the pharmaceutical market. And the development was curtailed. Modern researchers are moving away from the furiously circulating hormones throughout the body and are betting on molecules specific only to the testes.
Attack on Sertoli cells. Scientists from the University of Kansas Medical Center have determined that gamendazole disrupts the work of Sertoli cells. Sertoli cells, in addition to feeding and protecting immature maturing sperms, also keep them from premature exit into the lumen of the seminal tubule. Gamendazole disrupts this inhibitory function of Sertoli cells, reducing the level of inhibin B, and immature sperm, unable to fertilize, are released and rush into the seminal ducts. The effect of gamendazole gains strength in just a few weeks and is reversible. Another advantage of this drug is that it does not need to overcome the hemato-testicular barrier, since Sertoli cells are accessible from its “blood” side. Despite the fact that gamendazole seems to be an ideal solution, scientists who have discovered its contraceptive effect have not been able to get permission for clinical trials for some years, mainly due to bureaucratic delays.
An attack on genes specific to the testes. By blocking the activity of genes that are expressed exclusively in the testes, it is possible to completely disrupt the production of spermatozoa or seriously weaken their mobility. This strategy is the most promising due to its sufficiently high efficiency combined with a narrow focus of action.
This will be discussed in more detail later.