MALE BIRTH CONTROL

STORY / JAMES GRAHAM, PH.D.

At a global population of over seven billion people and rising, a UN report in 2013 suggests that by 2050 this figure will be 9.6 billion.

Finite resources cannot match population growth and the implementation of effective family planning is fast becoming a serious economic, health, climate and social welfare issue.

For centuries, contraception has been an important method of voluntary population control that if properly adapted could help relieve the pressure that the human population is putting on the earth.

As early as 3500BC, the Egyptians were using lemon and honey as a contraceptive due to their spermicidal qualities. In the 15th century, condoms made of animal skin or intestines were used until rubber made an appearance in the 20th century.

On the whole, however, birth control is viewed mainly as a woman’s responsibility and this is mirrored by the birth control choices available today. At present, the only readily available options for men are condoms or vasectomy.

There has been a lot of research over the last four decades to develop a male hormonal contraceptive in the form either of an injection, implant, pill or transdermal gel. However, the progress and prospects of male contraceptives has been poor and finding a safe, reversible and effective male contraceptive has remained agonisingly elusive.

Male contraception of today

Condoms are a safe, effective, cheap and easily available choice of family planning that has the added benefit of preventing the spread of STIs.
However, conception rates when using condoms are actually notoriously high.

This is due to long-term compliance issues as well as condom failure, improper use, and slippage. Moreover, latex allergies and decreased sexual pleasure are common issues that impact a condom’s ability to be a uniform and long-term regimen for family planning.

In men, vasectomy is a viable alternative to condoms and involves a relatively straightforward and simple surgical procedure. In brief, the vas deferens is isolated and ligated and is a safe outpatient procedure carried out around the world.

When carried out by a competent medical professional, it can be performed under local anesthetic with little blood loss and low rates of infection. In theory it is a reversible technique however this is not guaranteed.

Ideally, male contraceptives should be easy to use, have few side effects, not affect libido, and be reversible. Many studies have shown that although most men were agreeable to male birth control, there are many cultural, religious and educational barriers to overcome.

This has meant that many in the pharmaceutical industry are unwilling to support research even though a 2012 study suggested that the market value of a new male contraceptive could be anywhere between 40 to 200 billion dollars.

The future of male contraception

Clinical studies using testosterone treatment for birth control have demonstrated a degree of promise. The hormone therapy method uses testosterone in combination with a progestin component to prevent the secretion and production of gonadotropins.

Gonadotropin suppression reduces testicular testosterone and stops spermatogenesis (process of producing sperm cells). Sexual function and male characteristics are unaffected by hormone therapy because the testosterone component of the contraceptive therapy maintains masculinity.

A recent safety and efficacy trial of an injectable contraceptive was published in the Journal of Clinical Endocrinology and Metabolism. The World Health Organization (WHO), in collaboration with the Contraceptive Research and Development Program (CONRAD), performed the trial, which was published in 2016.

This trial involved 320 men who received intramuscular injections every eight weeks of testosterone undecanoate and norethisterone enanthate (progestin component). Male subjects were monitored for spermatogenesis, reversibility of treatment, safety, and tolerability.

In the 56-week study, the pregnancy rate was reduced to 1.57 pregnancies per 100 patients and this was due to the effective lowering of sperm levels to less than one million per millilitre within 24 weeks. It was also reported to be effective in 98.4 per cent of men enrolled in the trial.

Although the researchers reported that the injections led to an almost complete and reversible suppression of sperm production, the frequency of adverse events were unacceptably high.

The trial’s safety endpoints showed that 20 men dropped out due to study related side effects. In addition, around 46 per cent of men developed acne, 17 per cent reported a mood disorder, and in five percent of men their sperm count did not recover one year after the study.

The mood disorders that were reported included one man developing major depressive disorder and another trying to commit suicide.

When making a statistical assessment based on whether the injections were responsible for these adverse events, the researchers said they were probably or possibly related.

The risk-benefit analysis

As such, this phase-II trial was prevented from being advanced further after two independent reviews found that the side effects were too great. Although the decision to cancel this trial has sparked controversy and ire, there is a different risk-benefit analysis when considering men and women.

In women it is a balance between drug risk and pregnancy whereas in men there are no direct health risks to getting a woman pregnant. Furthermore, after half a century of the administration of the female oral contraceptive pill, the balance of risks and benefits is clear and evident.

It is understandable that many of the available female contraceptive options also come with significant side effects. Certainly, the side effects reported in this study are similar, although not exact, to what women experience with the birth control pill.

But, the occurrence of two individuals developing severe mental health issues is an unacceptable exception. Regardless of the study drug, or study subjects, any trial with these adverse events would be prevented from being advanced to the next stage.

Will men use a hormonal contraceptive?

If a male contraceptive were to become available then one study showed that up to 72 per cent of men would show willingness to use it. Studies also show that up to 83 per cent of men would prefer the option of a pill rather than an injectable birth control drug.

Interestingly, although men and women were equally positive about the idea of a male contraceptive, it was shown that women actually did not trust their partners to remember to use a contraceptive such as this.

Although the 2016 WHO and CONRAD trial resulted in many adverse events, the majority of men that did not drop out of the study said that they and their partners would be happy to continue the therapy if it became available.

Given this positive reception for a male hormonal contraceptive, research is to be
continued and it is hoped that future trials will re-address the balance in a risk versus benefit analysis of male birth control.