The Real Male Pill Part 2

Soumya Vemuganti

Part II in a series on male birth control: With advancements in medical research, scientists can develop more targeted approaches to arrest sperm production, with fewer side effects than female birth control.

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
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

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
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

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Hormonal Methods Alter Testosterone Levels

Analogous to female hormonal methods,
one approach to blocking spermatogenesis is to alter testosterone levels
in men.  By administering
, 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

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
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
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
is in the

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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