Ask a woman any day about contraception and I swear she would do anything not to have to take it, fiddle around with it, inject it, or have a procedure to insert it. Every time there is a hint of some scientific advance towards an effective pharmaceutical candidate for male contraception, we wait and hold our breath. However, nothing has come to the table yet. So what is the issue? Why is it so difficult to find an effective mechanism or drug for males?

The truth is that female hormones and their regulation of the menstrual cycle have proven much easier to control than little ‘swimmers’ produced by males or the hormones that control them. But arguably there is a need for another method of male contraception rather than the condom. It’s estimated that more than half of men would be willing to take an oral contraceptive if it were available. Pharma has been working on various mechanisms to impact male fertility including the use of hormones to affect motility and the ability to fertilize the egg. Both these treatments would require the man to take a pill. If both the male and female were to take oral contraception the chances of them both missing a pill on the same day must be lower than the risk of a woman forgetting by herself.

Gendarussa, which is a non-hormonal pill derived from the plant Justicia gendarussa has been investigated in Phase II clinical trials by Indonesian scientists. It isn’t fully understood how gendarussa works but it is thought to effect enzymes at the head of the sperm and reduces the ability for the sperm to enter into the egg. Airlangga University in Indonesia has provided extracts of the plant to Indofarma, an Indonesian pharma company who are investigating stability and the possibility of mass production. In addition, as this is an herbal preparation there is the potential that the product may be marketed in Indonesia in the not-too-distant future. Outside the country, for it to be taken forward as a potential contraceptive solution, there would need to be massive investment in research studies to investigate pharmacokinetics and further, larger clinical efficacy studies before even contemplating continuing to the level of FDA approval.

The other area of research into oral contraceptives for men comes in the form of an Epididymal Protease Inhibitor (Eppin). Eppin works on the sperm cell by inhibiting mobility by modulating prostate-specific antigen activity and binding to semenogelin, the protein found in semen. It has been successfully studied in macaques using a method of immunization, which resulted in effective and reversible contraception. Eppin is also lacking trial data and is a long ways away from being moved forward for any licensing approval. So where does that leave us?

In December 2016 a trial initiated at Edinburgh University using a hormone-based injection was halted due to adverse events and side effects. The injection consisted of a long-acting progestogen norethisterone enanthate (200mg) combined with testosterone undecanoate (1000mg) due to the inhibitory effect of the medication on testosterone production. It works by acting on the pituitary gland in order to reduce sperm production and proved to be almost 100% effective (96%) in the 320 men who took part. However, there were significant issues with depression, mood issues, and other unwanted side effects, which led to a 6.3% drop out rate. The numbers and severity of problems were high enough for an external review panel to deem that the risks outweighed the benefits. So while it was a seemingly effective treatment, it is one that requires further investigation for tolerability and toxicity issues.

However, there is one line of investigation, which may well provide a solution for the male contraception hopefuls. Vasalgel has been in development by the U.S.-based Parsemus Foundation for some time now. Vasalgel is not a pill but a gel which is injected into the vas deferens in a similar fashion to that which a vasectomy takes place. It requires a local anesthetic and the gel is injected into the lumen and works on the same basis as Reversible Inhibition of Sperm Under Guidance (RISUG). RISUG is a technique that has been developed in India using a combination of the copolymer styrene/maleic anhydride (SMA) with the solvent dimethyl sulfoxide. Upon injection into the vas deferens the gel amply coats the lumen and seems to effectively prevent the sperm from passing through. The action isn’t completely understood as it was initially thought to be a change in pH that ruptured the sperm. However, it’s since been suggested that it’s the effect of the presence of both negative and positive charges on the surface of the polymer that causes the breakdown of the membrane. RISUG is only available in trial conditions locally in India, but has been investigated using the same principals in the U.S.

In February 2017 the Parsemus Foundation published trial data in the journal Basics and Clinical Andrology claiming that the non-drug-based gel had successfully induced reliable and long-term contraception in Rhesus monkeys. This follows on from research published in 2016 suggesting that this was also the case in rabbit models but this also showed that the effect on sperm production was reversible by use of ultrasound and flushing out of the gel. The developers seem to be comparing the procedure to vasectomy, the only current permanent solution for male contraception. However, due to the fact this it is done without the need for a scalpel and is also potentially much easier to reverse, it seems to have more attractive aspects than the alternative. The Foundation is suggesting that a realistic time frame for FDA approval of the technique could be as soon as 2018-2020 depending on funding of further clinical trials. They are currently still ‘crowd funding’ on their own website in order to take developments further.

Although we aren’t out of the woods yet, and we still don’t have an approved pill, injection or technique, over 40 years of sourcing drug candidates and research may well be near to achieving a positive result for male contraception in the not too distant future.