Contraception: when will the pill for men finally be available?

Prof. Michael Zitzmann is an andrologist and researches new contraceptives for men. In an interview, he explains how far the research is, at which hormonal hurdles one fails and why the pill would no longer be approved for women in its original form today.

BARBARA: Hello Professor Zitzmann. You are an andrologist. While most of us have some idea of ​​what a urologist is, most of us are probably not that familiar with andrologists. What are you doing?

Prof. Zitzmann: An andrologist is a doctor for men. Andrology is, so to speak, saddled on top of the training to become a urologist or internal endocrinologist.

Endocrinologists look at the hormones, right?

Yes, exactly. I’m an endocrinologist, so actually a hormone doctor. I’ve treated thyroid patients and diabetes patients. And of course the testicles have something to do with hormones too. So this is not so strange to me, but of course I still had to acquire urological expertise.

How do the patients come to you?

It depends on age: guys come to me who have puberty problems. Young men come here who have cancer and want to cryopreserve their sperm, couples who want to have children, older men with sexual problems and also trans-identical people come here. Therefore, the profession of andrologist is quite diverse. Some are also engaged in research, including research on the pill for men.

What is the current state of research?

There was the WHO study on birth control syringes for men in 2009, which we conducted with other centers around the world. It was a success in terms of effectiveness, but not a success in terms of side effects, so the WHO, i.e. the expert panel, stopped the study. Maybe for good reason as far as men were concerned. Compared to women, there are 10 to 15 percent side effects even with birth control pills. When you look at it in its entirety, you can ask yourself why it was stopped for men who have the same rate of side effects as women, while they can still buy their product freely.

Why is that?

I cannot resolve the dilemma either. The WHO made the decision back then – by the way, gynecologists were.

But would you say that birth control pills would still be approved for women today?

So the pill for women, as it was approved at the time, definitely not. In the meantime, more participants are needed in order to be able to carry out such a study and many more safety parameters have to be met. So I don’t think that it would be approved again in that form. But the new pills are on top of that. They don’t start completely as a new drug. You can already see how things went with the AstraZeneca vaccine and the associated thromboses, which are much rarer than the pill for women. The aim of the vaccine is to prevent a dangerous disease. Pregnancy is not a disease at first …

No, but of course it could also be very existential …

Yes, that’s right. It can also have drastic effects on women. That is why many also use contraceptives. And that goes for men too. But it is still not a drug that is supposed to prevent life-threatening diseases. A healthy man takes the birth control injection to prevent something in himself so that someone else does not get pregnant, which is not a disease per se. Therefore, such a drug should be free of side effects. Or people need to be informed exactly what is happening as a result.

But can freedom from side effects even be achieved if one uses hormones?

It can be achieved if you only worked with testosterone, the normal dose that a man would produce anyway. Then the sperm formation would also be stopped – but only in 75 percent of all cases. And a contraceptive that works three-quarters won’t work at all. Therefore, progestogens must be added, which in turn are synthetic and cause all the problems in men – mood swings, loss of libido, etc. That is what we know from gestagens in women. Testosterone was already approved as a drug to treat testosterone deficiency. There were no side effects either, but in combination with progestin there were. It was known that problems could arise there.

But is there still great interest among men in alternative contraceptives?

Yes, it goes up every now and then, then it goes down again. Many also say that they don’t want to take it. But overall the interest is great and at that time – the injection for the man was more than 10 years ago – a lot, especially couples, got in touch.

The syringe was not approved, but what is currently being researched?

A gel that is applied to the shoulders is currently being developed. It contains testosterone and a new progestin, which at least so far has shown no side effects, so it has a fairly neutral effect. Both are supposed to prevent the production of the hormones LH and FSH in the pituitary gland so that the testes are not stimulated to produce sperm and testosterone. And this gel, which is currently being tested in the USA, seems to be very effective and does not cause any problems.

Is that simply because progestin is not an endogenous hormone that men make?

Yes, exactly. A pill for men is still at the very beginning. There is a synthetic substance (DMAU) that can be swallowed and that binds both to the androgenic receptor, i.e. where the testosterone is bound, and to the gestagen receptor, so that noneGonadotropins (i.e. LH and FSH) are released, but so far this has only been tested in phase 1 studies, so this is far from being that far.

The mode of action is the same for all of them: The production of sperm should be inhibited, right?

Exactly by telling the pituitary gland that there is enough testosterone and the testes no longer have to produce testosterone, the control hormones LH and FSH are no longer released. However, FSH is responsible for the formation of sperm, which means that they are no longer produced. Basically, it works like the pill for the woman, she will then no longer ovulate.

With the exception of the gel, there is currently only the alternative vasectomy for men, i.e. the severing of the vas deferens …

… Yes, although the vasectomy can possibly also be reversed. But as soon as you operate on the spermatic duct, you don’t know for sure whether antibodies against sperm are not being produced.

Above all through the debate that has recently arisen due to the thrombosis cases caused by the AstraZeneca vaccine, many women have also drawn attention to the side effects of the pill in this context. The contraceptive pill is already 60 years old and apart from the condom there is still no equivalent for men, but there are few other contraceptive alternatives. Is that due to a lack of pharmaceutical interest?

Exactly, the pill works. At the moment there is not so much interest in researching alternatives. It used to be different. At the end of the 90s there were meetings with the WHO and pharmaceutical manufacturers who also carried out studies on this from time to time and the idea for the large WHO study was born. At that time the interest was there. But when the small ones were bought by the really big corporations, that was no longer an issue. For them it’s just a very small thing on the fringes, with which you may or may not make money. Perhaps that will destroy the market for the pill for women. Why should you disturb something that is actually going very well? That’s why they withdrew very quickly.

But wouldn’t it be the best option to find something that doesn’t work with hormones?

Yes, that would of course be good, but if you think about what it could be, you also end up with synthetic substances that restrict sperm mobility or formation. There are also ideas, but it has always been shown that these drugs are quite toxic. You never got any further at this point. Except with barrier methods. For example, there is a valve that you can insert into the vas deferens. But it has to be cut open and then the immune system automatically comes into play, which recognizes the sperm and forms antibodies. The question then arises again as to whether this valve, which has a contraceptive effect, will ultimately be reversible again or whether it will stay that way.

That means that the valve works like a vasectomy and then artificial insemination is only possible if you want to have children?

That could actually be the case, no one has yet investigated whether the man is capable of fertilization again if the valve is opened again.

Michael-Zitzmann

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Prof. Dr. Michael Zitzmann is a specialist in internal medicine, endocrinology and andrology, diabetology and sexual medicine at the Center for Reproductive Medicine and Andrology at the University Hospital Münster. In 2009 he was part of the research team for the WHO study on syringes for men.

Barbara