Wednesday, November 30, 2022

Birth control for men. Finally?

Men have been waiting for it since about 1960 when the first oral birth control pill was approved and marketed! How many times since then have we seen reports about this subject!

This is a very long article covering several different, new, and promising approaches!

Of course, the obligatory and absurd propaganda and demagoguery had to be included by the American Chemical Society:
"Note: Contraception is an issue that affects people of all genders. Although most people who can become pregnant are cisgender women, many transgender men and nonbinary and intersex people can as well. Similarly, “male contraception” would benefit not only cisgender men but also many transgender women and nonbinary and intersex people. Historically, gender diversity has not been considered in contraception development or research, and this article is limited by this trend."

"IN BRIEF
For decades, researchers have been working on what has popularly been called “male birth control”—and surveys show there is demand for it. But concerns about side effects, efficacy, and more have kept such options from getting to market. In June, the US Supreme Court ruled that the US Constitution does not confer a right to abortion, and that decision has renewed calls for new birth control options. [????] Several drug candidates are getting close. Is a pharmaceutical contraceptive that can be marketed to men finally on the horizon?"

"... are one of thousands of couples around the globe participating in a Phase 2 trial for the NES/T gel, a topical contraceptive that combines Nestorone—a synthetic progestin—and testosterone. Together, these hormones suppress sperm production. Efficacy has been much higher than expected ...
the gel may have a lower failure rate than that of birth control pills with typical use. But hormonal birth control that targets sperm has gotten to Phase 2 trials before. Despite decades of research, no method has made it to market. ...
Past impediments included concerns about side effects and efficacy. But the NES/T trial differs from past ones in significant ways. NES/T is not an injection, and it’s self-administered. The trial also has checks in place for mental health. Side effects so far have been minimal. ...
And the recent US Supreme Court decision that the US Constitution does not confer the right to abortion has renewed those calls. [????] ...
Researchers see an opportunity to create birth control that uses nonhormonal methods to target molecules involved in the production or function of sperm. Some candidates target proteins that play key roles in generating sperm. Others target proteins that are important later in the sperm’s journey, like those that enable sperm to swim properly. YourChoice’s lead candidate targets a protein called retinoic acid receptor (RAR-α), which is involved in sperm production.
RAR-α is part of the vitamin A pathway. Certain cells in the body convert vitamin A (also known as retinol) from food into retinoic acid, which is involved in cell growth, differentiation, and more.
Normally, retinoic acid binds to RAR-α, which results in the expression of some genes related to sperm production. YourChoice’s drug, YCT-529, binds to RAR-α so that retinoic acid can’t. As a consequence, some genes needed for sperm production don’t get expressed.
... works on sperm ion channels, is taking another approach by zeroing in on a target that affects how sperm swim. ... Sperm gain this quality, called hyperactivated motility, after ejaculation as they progress toward the egg.
... targeting a protein called CatSper, a calcium ion channel in the sperm flagellum that is key to hyperactivated motility. In animal models such as mice, editing out the gene that encodes CatSper prevents sperm from attaining hyperactivated motility, so they swim only symmetrically ... Even if sperm could somehow get to an egg with their faulty swimming, CatSper is also important for other processes key to conception, like the reaction that allows sperm to penetrate the egg coating. Without CatSper, that step is blocked.
Eppin Pharma also has a drug in the works that interferes with sperm function. The small molecule, EP055, binds to EPPIN (epididymal protease inhibitor), a protein on the sperm surface. In binding, it prevents steps that make the sperm functional, like a rise in pH, an influx of calcium ions in the sperm cell, and hyperactivation of sperm motility.
The structure of Eppin Pharma's drug candidate EP055.
Targeting sperm motility has a potential advantage: such drugs would take effect more quickly than drugs that cut off sperm production from the start, which take months to achieve a contraceptive effect.
... a contraceptive that can be taken on demand and halt fertility almost immediately. Their compound would target an enzyme called soluble adenylyl cyclase (sAC), which catalyzes the creation of cyclic adenosine monophosphate (cAMP), a messenger molecule needed for sperm motility. Their drug candidate would inhibit sAC, preventing cAMP from being produced, and stopping sperm from swimming altogether.
They envision that people will take the compound as needed, like the erectile dysfunction drug Viagra. It might be taken around 30 min before sex, and it could last a few hours, a day, or even a weekend. But users wouldn’t need to take it every day. ..."

Birth control for men The demand for birth control that targets sperm is high. Can the drugs in development overcome the obstacles that have hampered earlier attempts?

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