When the conversation turns to "male birth control," most people think about a male version of the Pill, imagining that birth control for men will mimic the popular contraceptive for women.  In reality, the most likely candidates for male contraception are not in a pill form.  There have been a few candidate compounds for oral contraceptive use, but many of these have undesirable side effects, are ineffective, and in some cases researchers still lack a fundamental understanding of how they work. 

But other mechanisms are more successful: currently, researchers are utilizing multiple approaches to provide male contraception.  Researchers are working on interfering with sperm-egg binding and preventing sperm from successfully entering the female reproductive tract, but one of the most promising avenues for research is to arrest sperm production (spermatogenesis). 

With advancements in medical research, scientists can develop more targeted approaches to arrest sperm production, with fewer side effects than female birth control.  Current female hormonal birth control includes the oral contraceptive pill, the NuvaRing, and the Ortha Evra patch.  Even with diverse delivery methods, female hormonal birth control options all work the same way:  blocking ovulation through combinations of hormones. 

Male birth control is different.  Studies are being conducted using both hormonal and non-hormonal methods to reversibly disrupt spermatogenesis.  It is well known that women normally ovulate once a month, have a finite amount of eggs, and that the quality of a woman's eggs decrease with age.   Men, however, produce millions of sperm continuously throughout their lives.  It takes about 90 days for a mature sperm cell to be produced; therefore, an approach that would stop sperm production would be effective for a lengthy period of time.  A few research studies have reached clinical trial status, which is promising in the search of male birth control.

Hormonal Methods Alter Testosterone Levels

Analogous to female hormonal methods, one approach to blocking spermatogenesis is to alter testosterone levels in men.  By administering testosterone, the body stops producing the hormone in the testes (the site of spermatogenesis), thereby dramatically reducing sperm production.  Initial studies (sponsored by the World Health Organization) of weekly testosterone injections showed a reversible block in sperm production, with contraceptive efficacy comparable to female hormonal methods.  But the need for frequent injections, and minor side effects, including weight gain and acne, made this approach less than ideal.  To overcome these pitfalls, researchers combined testosterone and progestin to decrease injection frequency and minor side effects.  With this approach, multiple researchers have been able to effectively block sperm production, and reverse this block in 5-6 months by simply stopping hormone administration.  One study used both testosterone implants (every 4-6 months) with progestin injections (every 3 months), while another study found efficacy with separate injections of both testosterone and progestin in eight week intervals. 

Unfortunately testosterone cannot be orally dispensed due to the "first-pass effect" (i.e. processing by the liver), which leaves low amounts of the hormone needed to block sperm production.  To date, testosterone delivery requires either intramuscular injections and/or implants.  However, alternatives to injected testosterone are being studied.  With minor side effects and a high success rate, the only downfall to currently-studied male hormonal contraceptives includes a wide variation in response to treatment between individuals, particularly across ethnic backgrounds. 

Non-Hormonal Methods Promise Fewer Side Effects

Targeted non-hormonal methods are advantageous due to the promise of fewer side effects.  These include approaches that act upon molecules found only at the site of sperm production and treatments that are locally applied to the testes.  It has been known for many years that application of heat to the testis will disrupt spermatogenesis.  Therefore, heating the testis can provide a simple and affordable means of contraception.  Anatomically, the testes are kept cooler than the rest of the body.  Individuals with undescended testes (cryptochordism) suffer from low sperm counts due to the increase in testicular heat from the body.  A recent study confirmed that spending too much time in hot tubs or jacuzzis also leads to infertility.  Studies of heat-induced infertility may help in understanding the mechanism of action. 

There are many advantages to heat-based contraception methods.  Direct administration to the testis is easy:  internal heat by suspensories, external wet heat through hot water, or heat applied through a few minutes of ultrasound.  Studies in men demonstrated reduced sperm counts and diminished sperm motility using all of these approaches.  Dosage and contraceptive effectiveness of external wet heat and ultrasound has not been analyzed, however, results from trials using internal heat were dramatic with a 100% success rate.  Despite the ease of reversibility (simply stop the treatment), the amount of time required to regain normal sperm production varies between individuals, and would require a secondary measurement of fertility (see SpermCheck Vasectomy below).  Despite the ease, efficacy, and reversibility of heat-based contraceptive methods, there have not been enough studies performed to confirm safety.  Completion of the necessary clinical trials depends upon interest from government or non-profit groups.  The private sector is uninterested in pursuing heat-based contraceptives since administration is simple and cheap, therefore not profitable.

One pharmaceutical approach that could spark interest in the private sector involves the use of Adjudin, an analog of an anti-cancer drug (Lonidamine).  Adjudin works by disrupting the connections between immature sperm cells and the cells that help them to properly mature (Sertoli cells).  This ultimately leads to the production of immature sperm unable to fertilize an egg.  Studies in rats have shown that oral administration of Adjudin at doses required for contraception is toxic to the liver and muscles.  This problem was overcome by an innovative solution to target delivery of Adjudin.  Researchers artificially linked Adjudin to a modified hormone (FSH) that is normally delivered to the site of immature sperm cell and Sertoli cell contact, effectively hijacking the body's delivery system.  While Adjudin as a reversible male contraceptive is hopeful, there are still two major obstacles that remain:  optimization of delivery methods and completion of human clinical trials.

Confirming Lack of Sperm Production 

Since it takes just one sperm to fertilize an egg, it is extremely important to confirm a lack of sperm production using any of the aforementioned male contraceptives.   A product approved by the FDA last year will help to measure the effectiveness of male contraceptives which block spermatogenesis.  SpermCheck Vasectomy offers patients an at home method of measuring their sperm levels post-vasectomy.  It is easy to imagine that this product could also be used to measure the efficacy of reversible male contraceptives; in fact, SpermCheck Contraception is in the works. 

Arresting sperm production in males is analogous to disrupting ovulation in females.  However, this is not the only approach.  Male birth control options can also include methods which prevent sperm from entering the female reproductive tract and interfere with sperm-egg binding.  In my next article I will explore the results of these studies and report the effectiveness of these methods in terms of providing a safe, reversible male contraceptive. 

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