Male Contraceptives : A 2021 Update I Bench to Bedside

When you talk about contraception. In many cases women are at the forefront of discussions and while there have been huge strides in medical advancements there haven't been many around male contraceptives. Women have many options but you cannot say the same for men. This unfortunately leaves the burden of preventing pregnancy mainly on women. In this post, i’ll focus on two review papers that discuss the current findings in relation to male contraceptives. A review paper is a document that summarises key scientific findings within a specific research area.

What are the main options for men?

There are only two methods of contraceptives for men

1. Condoms

2. Vasectomy

To fully understand the difficulty in making male contraceptives or the delay in the production of male contraceptives we have to understand what makes a good contraceptive. Simply put a good contraceptive will stop sperm being present in the semen. The active agent for child production is sperm so therefore we need a contraceptive that leads to lower or no sperm production. The scientific term for this is Azoospermia !

Azoospermia is the medical condition of a man whose semen contains no sperm.

How have the developments in male contraceptive methods achieved this?

Review 1: Reversible Inhibition of Sperm under guidance ( RISUG)

Date published: 2020

Bench to bedside scale: closer to the use in the clinic. In phase 3 trials and waiting for approval in India. Single country study, therefore limited but its success could change things globally!

Overview: In 1979 Prof Guha a well known surgeon developed a method called Reversible Inhibition of Sperm under Guidance (RISUG). The procedure has been in the process of development and implementation for close to 40 years. During the procedure a liquid( insert name) is injected with the aim to block sperm movement. The authors describe the process as follows

“RISUG® forms electrically charged precipitates in the lumen and further layers the lumen wall and inner walls of vas deferens. Precipitates are dominated with positive charge creating an acidic environment. Passing through the RISUG® injected vas deferens, sperms suffer ionic and pH stress, causing acrosomal damage, rendering them unable to fertilize oocytes”

In a very simplified form, the vas deferens is a tube like structure that carries the sperm. Like many process in our bodies, there are optimal conditions and this means that changes to these processes can affect the outcome. The RISUG method changes the environment of the sperm thereby damaging them and making then unable to ferilize “eggs”. It doens’t change how future sperm will be produced but only sperm that is on its way through the tube ( vas deferens).

Vas deferens: serves to transport sperm cells

RISUG was developed by Prof Guha. In India, sterilisation is a commonly used method of contraceptive. Sterilization is usually done to women, leaving men with little responsibility. In an aim to level the playing field the RISUG clinical trials in India serve as huge strides and in the field of contraceptives.

Now we’ve had a looked at how it works and why it was developed. Let’s dig a little deeper into the process and real world evidence of the procedure.

Clinical trials as we have all seen due to covid follow a pattern. It initially starts with proof of concept, showing the treatments works in animal species. Common animal models include: mice, rats, rabbits and pigs. In the trails of RISUG rats, rabbits and monkeys were used.

Following animal trials and proof that the procedure is safe, small scale human trials were conducted to further prove safety. In the RISUG trial, phase 1 trials the participants underwent the procedure and were then followed up for two years post procedure for any clinical complications. Where participants had partners both were confirmed to be sterilised.

What is sterlisation?

Sterilisation is a permanent method of contraception, for people who don't want more children, or any children. It works by stopping sperm from meeting an egg

After proof of safety, proof that it works and actually prevents pregnancy was done in phase 2 studies, alongside studies to determine the appropriate dose. In Phase 2 studies, 12 men were given the treatment and women were not sterilized or on any form of birth control. In this study, only a single pregnancy was reported. The child was healthy and following that success phase 3 trials were conducted ! The Phase 3 studies were proven to be very effective with a failure rate of 0.98%. Participants also reported no side effects and benefits from the treatment were 92.6% effective after 2 months and increased to 96.7% six months post-procedure.

Review 2: Male Contraceptives: Where are we going and where have we been

Bench to bedside scale: Phase 2 clinical trials ( small group size before expansion to phase 3 studies)

So we’ve had a look at a minimally invasive procedure as a contraceptive now lets move on to hormones. The previous method - RISUG looks at targeting the transport of sperm cells. This paper published in the BMJ focuses on hormonal methods of contraception but I will specifically look at the gel based method that got a bit of press in 2016.

This is a gel and was talked about quite a bit on the press in 2016. The gel is now in phase 2 trials which is the actual effectiveness stage.This method focuses on the hormonal conditions that are needed for sperm to be produced, by changing these conditions, Azoospermia is achieved.

Azoospermia is the medical condition of a man whose semen contains no sperm.

So what happened in clincial trials. The results showed a decrease in sperm concentration. This approach focuses more on the targeting specific pathways in sperm production to achieve azoospermia.

The authors summarised their findings as follows

“ A nestorone-testosterone gel (NES/T) has recently entered an international phase IIb clinical trial -> There was a significant decrease in sperm concentrations in the NES/T group despite the duration of treatment being only 4 weeks, and no differences in psychosexual measures between groups or from baseline. “

In summary, the gel did work in the small group it was tested on with encouraging results although the study had a short treatment period of only one month.

In terms of side effects. It was successful with relatively few side effects and common to those women usually complain about and no effect on men suxual desires from baseline. The most common adverse event was acne (21% of subjects, mild in 16%, moderate in 5%) without differences among treatment groups. Changes in sexual function were reported by four subjects (4%). Subjective depressed mood was reported in one, depression in two, altered mood in one, and mood swings in three subjects. Insomnia was reported in 6% of subjects. Headaches, reported in 17% of subjects, were high

Finally, How do men actually feel about this. Agenda aside, men from surveys held were pretty receptive to the idea of more contraceptive option. So even with the positive attitude, pharmaceuticals are still walking the fine line in developing a product that has adequate demand.

So to end will you consider either of these contraceptive methods?

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