Can the pill be side-effect free and taken on demand?

Preventing pregnancy is largely viewed as the responsibility of anyone who can become pregnant. It’s a burden that can hold significant emotional, financial and physical weight (not just the bathroom scale kind).

Since the introduction of the contraceptive pill in Australia in 1961, there are now more than a dozen hormonal and non-hormonal contraception options for women, yet the list of potential side effects is ever-present.

We’re talking irregular bleeding, nausea, headaches, breast tenderness, bloating, weight gain, mood swings, libido loss, cramps—the list goes on.

It raises the question: Can contraception be side-effect free?

First the pills need to be in male hands.

Contraception options for men are limited to condoms and non-reversible vasectomies. End of list. But it’s not the end of the story.

Multiple new male contraceptives are in development. Some are well into clinical trials, and initial results look promising.

Some of these new drugs are non-hormonal, effectively eradicating hormonal side effects.

Men could have control over their fertility while maintaining their libido, weight, sexual function and mood. This is also the case for their female counterparts. However, these methods still come with other side effects such as painful periods (in the case of the copper IUD).

Pass the pill

Sarcastic gifs and 65 years of side effects aside—we arrive at YCT-529.

This drug is turning heads with its non-hormonal, side-effect free, sperm-nuking potential. It’s an oral pill taken daily (like the OG) but boasts no nasties.

Male animals deprived of vitamin A become infertile. This is because the retinoic acid receptor alpha (RAR-α)—where vitamin A binds in our bodies—is essential for normal sperm production, making it an ideal drug target.

YCT-529 stops vitamin A binding in cells, leading to a dramatic decrease in sperm count.

YCT-529 was 99% effective and 100% reversible when tested on mice. In primates, sperm count fell below fertile level within 2 weeks of daily dosing.

The contraceptive compound successfully completed a human phase 1a clinical trial and is now in a phase 2b trial where researchers hope to better understand dosing and safety.

Slow down, little swimmers

Another male contraceptive pill in development can be taken on demand—like Viagra, but for a different purpose.

Soluble adenylyl cyclase (sAC) is an enzyme with many responsibilities. One is to act as a starting pistol for sperm—without which they won’t swim.

Some males can be born with mutations in the genes that influence sAC function, rendering them infertile but otherwise healthy, making it another ideal contraceptive drug target.

TDI-11861 is an oral contraceptive pill that interferes with sAC function for a short time—about 2–3 hours.

During this time, sperm remains immobile, making conception nearly impossible.

Repeat mouse studies have shown that, after the effects of TDI-11861 have worn off, unused sperm returns to normal.

A larger consequence of TDI-11861’s unique modus operandi is that it could also be developed into an on-demand, side-effect free female contraceptive—the contraceptive equity we’re all waiting for.

Either way, it leaves plenty of time for foreplay while you wait for TDI-11861 to do its thing.

Did someone say clinical trials?

TDI-11861 is still awaiting human trials, but other male contraception options are closer to market.

Beyond oral pills, we have Contraline’s NES/T and ADAM 2.0. (Not exactly the sexiest names, Contraline.)

NES/T is a hormonal gel applied daily to a male’s shoulders, suppressing sperm production for months while maintaining libido without side effects. NES/T is lubing up for phase 3 clinical trials.

Another “not a pill” option is ADAM 2.0—a 21st-century vasectomy.

A non-hormonal hydrogel is injected into the vas deferens to block sperm flow. Unlike the traditional vasectomy, it’s easily reversible.

This simple 15-minute procedure has demonstrated it can block sperm release for up to 24 months. ADAM 2.0 is currently undergoing phase 2 clinical trials.

With these new drugs in development, it’s only a matter of time before the burden of contraception is equally shared among all sexually active humans.

But for how much longer will the burden of side effects continue to be one-sided?

This article first appeared on Particle, a science news website based at Scitech, Perth, Australia. Read the original article.