How a male contraceptive pill could work John Amory

When I tell people

that I’m trying to develop
a contraceptive pill for men,

the response usually varies
along gender lines.

Women say something like,

“Fantastic. It’s about time. When?”

(Laughter)

Men have one of two responses.

They either love the idea,

or they look at me a little warily

and wonder what exactly
I have in store for their testicles.

(Laughter)

So why does the world need a male pill?

Well, what if I told you

that of the six million pregnancies
annually in the United States,

three million of them are unintended?

That’s half.

That’s a really surprising number.

And those three million
unintended pregnancies

account for the vast majority
of the more than one million abortions

annually performed in the United States.

Happily, the rate of unintended pregnancy
has fallen in the last few years

by about 10 percent.

This is because more women
are using effective, long-acting,

reversible forms of contraception.

But we still have a long way to go.

One approach that’s finally
becoming a real possibility

is better contraceptive options for men.

Think about it.

We have over a dozen methods
of contraception for women:

pills, patches, IUDs,
shots, sponges, rings, etc.

For men, we’ve had the same two options

for more than a hundred years:

condoms and vasectomy.

Despite having only two options,

both of which have significant drawbacks,

men currently account
for 30 percent of all contraceptive use,

with 10 percent of couples
relying on vasectomy

and 20 percent of couples using condoms.

Why are 20 percent of couples
relying on condoms for contraception

when condoms have a one-year
failure rate of over 15 percent?

It’s because many women
can’t either safely take

currently available female contraceptives,
for reasons such as blood clots,

or they can’t tolerate the side effects.

So if we think a male contraceptive
would be useful, the next question is:

How do we go about developing one?

Well, there’s two general approaches.

The first approach is to try and interfere

with the way the sperm
swim towards or bind to the egg.

This approach turns out
to be really difficult,

because it’s hard to get enough medication
in the small volume of the ejaculate

and have it still work inside
the female reproductive tract.

This is why there’s been a lot more work
done on the second approach,

which is turning off
sperm production entirely.

This is also challenging.

Why? Turns out
that men make a lot of sperm.

(Laughter)

Men make a thousand sperm every second

and to have an effective contraceptive,

you need to get that level
of sperm production

down to one percent of its normal value.

The good news is, this is possible,

almost.

The most studied approach has been to use
hormones to suppress sperm production.

Testosterone and progesterone,
when administered together,

will suppress the signals from the brain
to the testes to make sperm,

and in about 90 percent of men,

sperm production after
three to four months will stop.

Unfortunately, 10 percent of men
don’t respond to these hormonal regimens

for reasons that aren’t understood.

For the last several years,
my colleagues and I

have been taking a different approach
to male contraceptive development,

one that doesn’t involve
the administration of hormones.

Specifically, we are looking to block
the function of vitamin A in the testes.

Why? Well, for over 90 years
it’s been known

that you need vitamin A to make sperm.

Animals who are deprived
of vitamin A in their diet

stop making sperm

and restart making sperm again
when the vitamin A is reintroduced.

The vitamin A that we ingest

is converted by a family of enzymes
to something called retinoic acid.

One of these enzymes
is found only in the testes.

It’s this enzyme
that we are attempting to block.

The blockade of this enzyme
should deprive the testes of retinoic acid

and stop sperm production

without affecting vitamin A’s functions
elsewhere in the body.

We’re testing this approach in animals

and hope to move to human testing soon.

Obviously, the impact
of such a male contraceptive

would go well beyond reproductive biology.

It’s interesting to speculate
about the effect that it would have

on relationships between men and women.

One intriguing possibility

is that a man could monitor
his contraceptive status over time.

In the last several years,

two groups have introduced
home sperm-testing devices

that are iPhone-based

and that are easy to use.

A man could test his sperm count
and share the result with his partner.

If the man’s sperm count were zero,

the man and his partner
would feel very comfortable

relying on his contraceptive.

A tool like this,
coupled with a male contraceptive,

could greatly increase the role for men
in preventing unintended pregnancy.

The researchers who are working
on male contraception

are trying to create
a better future for couples,

a future where contraception is no longer
considered just “a woman’s issue,”

rather an issue
for couples to decide together.

So why does the world need a male pill?

Well, I believe that a male pill

will help reduce the stubbornly high
rates of unintended pregnancy and abortion

and allow men to equally participate

in contraception.

Thank you.

(Applause)