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
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.

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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
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. 

Related Content

Commentary Politics

Four Facts Nancy Pelosi—and All ‘Pro-Choice’ Democrats—Should Know About Abortion

Jodi Jacobson

House Minority Leader Nancy Pelosi could not articulate a vigorous, unapologetic, and evidence-based response on abortion to questions posed in an interview this week by Roll Call's Melinda Henneberger.

Just a week or so after Democratic National Committee Chairwoman Rep. Debbie Wasserman Schultz (D-FL) blamed voters for being “complacent” about abortion, House Minority Leader Nancy Pelosi illustrated why, despite being the nominally pro-choice party, Democrats continuously fail to lead on the issue of reproductive health care.

Pelosi could not articulate a vigorous, unapologetic, and evidence-based response on abortion to questions posed in an interview this week by Roll Call‘s Melinda Henneberger. In fact, Pelosi expressed discomfort with using the word “abortion,” underscoring how deeply abortion stigma has permeated the discourse of even the female leader of the Democratic Party, one of the most powerful women in the United States.

It is more than clear that abortion will continue to be politicized through the 2016 election and beyond. But Democrats persist in stumbling when asked about it. So here are some facts that any politician claiming to be pro-choice—and otherwise charged with protecting the interests, rights, and health of the voters who put them in office—must master and assert without apology.

Access to safe abortion care is fundamentally a matter of public health. In countries where access to abortion is limited either by law or in practice, women face high rates of maternal mortality and morbidity. In other words, they die and are injured, sometimes permanently, at far higher rates than in countries or regions where access to safe abortion care is guaranteed. This was indeed the case in the United States before Roe v. Wade.

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Today, according to conservative estimates, more than 300,000 women worldwide die each year from complications from pregnancy, childbirth, and unsafe abortion. That’s 830 women each and every day. These are women in their teens to their late 40s, who are most likely to be raising children and earning critical income for their families. Many times the number who die from unsafe abortion suffer long-term illness and disability instead.

In Uganda, for example, due to lack of access to contraception among other factors, more than four in ten births are unplanned, and women say they have far larger families than they want. In their struggle to have fewer children, they often resort to abortion. Abortion is, however, illegal in Uganda, and access to safe abortion is only available to the wealthy. Not surprisingly, Uganda has one of the world’s highest rates of maternal death, and estimates indicate that if rates of clandestine abortion continue, half of all women in Uganda will need treatment for complications of unsafe abortion at some point in their lives.

By contrast, as was the case for the United States, rates of maternal deaths and illnesses from unsafe abortion declined dramatically in both Nepal and in South Africa after those two countries legalized and increased access to abortion care.

The deaths of women should be reason enough to address the need for safe abortion, but families also suffer. When a mother dies, her children, especially those under 5, are more likely to suffer malnutrition, neglect, and death. As I first wrote more than 25 years ago, history has long shown that politically or religiously motivated laws will never eliminate abortion; they only make it more costly in terms of women’s health, and the health and well-being of their families. The fact of abortion as a public health issue should be the first talking point in any informed conversation led by pro-choice politicians.

Abortion is a matter of fundamental human rights. Every person on earth has the right to determine whether or not to become a parent, and when and with whom to have a child, although clearly too many people are as yet unable to exercise these rights.

Furthermore, the international community has long recognized the broader fundamental human rights of women. According to the 1993 Vienna Declaration on Human Rights:

The human rights of women and of the girl-child are an inalienable, integral and indivisible part of universal human rights. The full and equal participation of women in political, civil, economic, social and cultural life, at the national, regional and international levels, and the eradication of all forms of discrimination on grounds of sex are priority objectives of the international community.

Choice in childbearing, childbirth, and parenting are fundamental to women’s ability to make decisions about their participation in society, on their own terms. Women, however, cannot exercise these fundamental human rights without unfettered access to contraception and abortion. Yet too many governments, politicians, and religious leaders appear willing to abrogate access to these basic health interventions, ironically on the basis of a “pro-life” agenda—albeit one that ignores the value of women’s lives. Any politician who calls themselves pro-choice should understand the need to protect and promote the human rights of living, breathing women, and be able to articulate them.

Abortion is a fundamental economic issue. Access to both contraception and abortion play a major role in women’s economic lives. There have been innumerable academic studies carried out and policy papers written over the past several decades about the connections between access to abortion and women’s economic status throughout the world, and all of them come to the same conclusions: The ability to control reproduction is essential to women’s abilities to support themselves and their families, and is essential to long-term economic growth.

Having a child or children is a major lifetime economic investment for anyone; the U.S. Department of Agriculture has estimated that it now costs more than $245,000 to raise a child in this country, not including the costs of college tuition. A study by the Economic Policy Institute shows that child care alone outpaces the cost of rent in 500 of 618 municipalities examined. Given these and other considerations, such as low wages and the cost of health insurance, transportation, food, clothing, and other necessities, unintended pregnancy can throw a family into economic crisis. Studies show that most women seeking abortion are already struggling financially, cannot afford an additional child, or want to continue their education to create a better future for themselves and their families.

The Turnaway Study, a multi-faceted research project on abortion conducted by researchers at the University of California, San Francisco’s Advancing New Standards in Reproductive Health program, examined the relationship between abortion, reproductive control, and poverty, among other things. As noted in a policy brief by the Reproductive Health Technologies Project about the economics of abortion and women’s lives, the Turnaway Study found that women denied an abortion in the United States had three times greater odds of ending up below the federal poverty line two years later than did women in similar economic circumstances who were able to obtain an abortion, adjusting for any previous differences between the two groups.

Smaller family size and educational attainment are among two of the most critical factors in the economic success of families and communities. Women and their partners know what it means to bring a child into the world and what it takes to raise children, and only they are equipped to make decisions about whether they have the financial and emotional means to make that commitment. Access to abortion is therefore fundamentally about personal and family economics. Abortion is about what women want for their future, and the future of any children now and later.

Access to abortion also has wider social and economic implications. According to the World Health Organization’sSafe abortion care: the public health and human rights rationale:”

Safe abortion is cost saving. The cost to health systems of treating the complications of unsafe abortion is overwhelming, especially in poor countries. The overall average cost per case that governments incur is estimated (in 2006 US dollars) at US$ 114 for Africa and US$ 130 for Latin America. The economic costs of unsafe abortion to a country’s health system, however, go beyond the direct costs of providing post-abortion services. A recent study estimated an annual cost of US$ 23 million for treating minor complications from unsafe abortion at the primary health-care level; US$ 6 billion for treating post-abortion infertility; and US$ 200 million each year for the out-of-pocket expenses of individuals and households in sub-Saharan Africa for the treatment of post-abortion complications. In addition, US$ 930 million is the estimated annual expenditure by individuals and their societies for lost income from death or long-term disability due to chronic health consequences of unsafe abortion.

Unintended pregnancies also have other cost implications. Researchers at the Brookings Institute found that the United States spends $12 billion each year to cover medical care for women who experience unintended pregnancies and on infants who were conceived unintentionally.

In short, it is a fact that providing people with the means needed to make choices in childbearing is economically beneficial at all levels of society. In a country otherwise obsessed with individual economic choices, this should be a clear argument.

Abortion is an individual health issue. Yes, abortion is an individual health issue, related to but separate from its broader role in public health. Anyone who has had—or knows someone who has had—a difficult pregnancy, a miscarriage, an emergency c-section, a stillbirth, or any number of other complications is aware, pregnancy and childbirth can be wonderful and can be life-threatening, and the reality of either is a roll of the dice.

There are any number of contraindications for pregnancy that would result in the need for an abortion and any number of complications that can arise during a pregnancy, threatening the life or health of the pregnant person, the fetus, or both. The potential for very serious complications rises later in pregnancy, or after 20 weeks, the magic number alighted on by anti-choice zealots as somehow being a rational point after which abortion should be banned.

Any number of complications compromising the health of a pregnant person can occur, or fetal anomalies can be found, at or after 20 weeks of pregnancy, potentially causing even the most wanted pregnancy to go awry. Henneberger, now editor in chief at Roll Call, has frequently advocated for 20-week abortion bans, either not understanding or not caring that such a ban would dramatically limit access to medical care for untold numbers of women who face complications. Pelosi should have been able to more forcefully tell her why this is dangerous.

The United States is sliding backward on many fronts, including on access to contraception and abortion, two public health interventions for which the cost-benefit analyses are clear.

Politicians who claim to be pro-choice and raise money from citizens who support public health, human rights, and choice in childbearing must be able to articulate, embrace, and defend their positions. For too long, Democrats have come across as inept and apologetic when talking about abortion, even though the facts are clear and indisputable.

It’s time for this to stop.

Analysis Sexuality

Male Birth Control Pill Is Still ‘Right Around the Corner,’ Like It Has Been for Years

Martha Kempner

We regularly learn about how research is progressing toward creating alternative forms of reversible contraception for men that include pills, shots, or other devices. Despite the flurry of excitement these news pieces generate, it seems we are still quite far from mass-marketed male birth control.

Seemingly every year, we learn about how research is progressing toward creating alternative forms of reversible contraception for men that include pills, shots, or other devices. Despite the flurry of excitement these news pieces generate, it seems we are still quite far from mass-marketed male birth control. This month’s advance—a trial that successfully rendered mice temporarily infertile—is cut from the same cloth: It is a valid proof of concept, but likely quite a few years away from being realistically accessible on pharmacy shelves.

The new study, published in the journal Science, showed that researchers in Japan were able to block a specific protein necessary in the production of sperm—and more importantly for human men seeking a non-permanent contraception, it showed that normal sperm production resumed soon after the mice were taken off the drugs.

Specifically, scientists were examining a protein called calcineurin, which they have long suspected was instrumental in male fertility. To test this part of their theory, they genetically engineered mice that could not fully produce calcineurin and found, as suspected, these mice were infertile because the sperm they produced were not flexible enough to fertilize eggs.

Once they had tested that hypothesis, they moved on to trying to block the calcineurin in normal mice. They did this using two existing drugs—the antibiotic cyclosporine and tacrolimus, an anti-rejection drug given to patients who have had organ transplants. (Interestingly, infertility in humans is not listed as a side effect for either medication.) Within four to five days of receiving the drugs, the mice became unable to impregnate their female companions. And, within a week of being taken off the drugs, fertility returned.

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As reported by HealthDay, researcher Masahito Ikawa of Osaka University said, “It is important that we find an effective and reversible contraceptive option to allow men more control over their own reproductive futures. … The findings of this study may be a key step to giving men that control.”

Others agree that these results are exciting. Patricia Morris, director of biomedical research at the Population Council, said that this was an interesting approach because it did not involve hormones. She told Live Science, “Approaches to male contraception that target hormones can affect sex drive and thus are less desirable as contraceptives.” She added that this approach was exciting because it was so specific—targeting just one protein—and therefore, less likely to have side effects elsewhere in the body.

But in some ways this study is just a proof of concept. The researchers aren’t suggesting that the two drugs they used in mice be used in men for contraception, because both suppress the immune system, leaving a person more at risk for illness and infection. Both drugs also increase the risk of lymphoma and skin cancer. So before these findings can be translated into a monthly birth control pack for guys, researchers must first see if the effects of blocking calcineurin are the same in humans—findings in mice are often replicated in humans, but not always. Then they have to find a less toxic way to block the protein.

As Rewire has reported, there are many other attempts under way to create and perfect male birth control. For example, last year, scientists were able to render three baboons infertile by using something called Vasalgel, which is injected into the vas deferens and blocks sperm from coming out during ejaculation. This is same principle used for a vasectomy, but that procedure is permanent and severs the vas deferens. Vasalgel, which is currently undergoing testing, is intended to be reversible. It can be flushed out of the vas deferens with a second injection if a man decides he wants to be fertile again. A similar product called RISUG (reversible inhibition of sperm under guidance) is being developed in India.

As scientists continue their quest to find a new male birth control method, it remains unclear how excited most men are for these products. A survey reported in U.S. News and World Report found that 66 percent of men might be interested in a pill, 44 percent might try a shot, and 36 percent were interested in an implant.

Of course, such surveys are based mostly on hypotheticals for now. The men surveyed, for example, might not have known that some of the shots in development are intended to be administered directly into the testicles, which may have affected their reactions. And regardless, it will be many more years of studies on primates, mice, and men before anyone we know will really have to decide whether that’s something he’s willing to undergo in order to take control of his own fertility.