By Melinda Young
Women are increasingly worried about side effects from hormonal contraception, leading to an increase in people using no contraception or relying on cycle tracking, according to new data. And this trend is not just in the United States. A British study found that the number of patients using no contraception at the time of conception increased by 14% over five years from 2018 to 2023. The number of people using fertility-awareness methods increased from 0.4% to 2.5% between 2018 and 2023.1
In the United States, the use of the birth control pill decreased, use of condoms increased, and use of withdrawal increased between the periods of 2006-2010 and 2015-2019.2 Nonhormonal contraception options, such as permanent contraception and use of condoms, withdrawal, and fertility-based awareness methods, are used by significant percentages of women ages 15-44 years.2
But these methods are lacking — reversibility in the case of surgical permanent contraception and high effectiveness with the others. So, some scientists have focused on finding a nonhormonal-based contraception option that would be effective and acceptable to people who want to stay away from hormones and their side effects.
“There is a [2013] study showing that any new contraception option that comes up will increase the number of contraceptive users by 4% to 8%, so the more the better,” says Wipawee Winuthayanon, PhD, an associate professor, OB/GYN and women’s health and an integrative physiology director of the Translational Biosciences Graduate Program in the School of Medicine at the University of Missouri in Columbia.3
“This is important,” she adds. “Even if we’re working on [a new contraceptive] right now, we don’t know if it will work. It may seem to be working in the dish, but once it’s in the body, does it work? I’m not discouraged by that.”
Winuthayanon maintains optimism for eventual success with a new contraceptive product she has been studying for eight years. The potential contraceptive would make semen ineffective. And it would be entirely and easily reversible, whether used by women or men. The research involves the prostate-specific antigen (PSA), which liquifies semen in the ejaculate, making it capable of fertilizing an ovum. If a contraceptive could prevent this action and keep semen in its gel-like form, it would prevent pregnancy.4,5
“Right after the ejaculate is deposited in the vagina, the consistency of the semen is gel-like. But inside the semen is PSA — the prostate-specific antigen, which is the same used for prostate cancer screening, made in the prostate gland,” Winuthayanon says.
“The prostate-specific antigen, once it’s mixed with semen, hydrolyzes the gel; it turns from gel-like to a watery consistency, and now sperm can swim up to fertilize the egg in the fallopian tubes,” she explains. “Our goal is to block this PSA activity so the semen stays gel-like and can be trapped in there.”
Some women with infertility have a natural PSA antibody that inhibits PSA activity, making it difficult to get pregnant. Some men have a mutation of the PSA enzyme that causes their semen to be hyper-viscous — thick and sticky, so they have infertility issues, as well.
For a contraceptive to work, it would need to keep the sperm in the gel. “We performed some drop screening and found there is a compound that can incubate PSA activity,” Winuthayanon says. “It was tested in human semen and makes semen hyper-viscous.” The compound inhibits PSA for more than eight hours.4 It would be possible to create either a male or female contraceptive that would block PSA action, but the female contraceptive would probably be developed first, Winuthayanon says.
A major challenge to bringing this contraceptive option to market is that its animal studies cannot include mice. “PSAs are only expressed in human and nonhuman primates, so we cannot test this in mice,” she explains.
“We collaborate with an investigator at the National Oregon Primate Center and are testing right now if we can use a vaginal film contraception to prevent pregnancy in the female monkey,” she says.
If it works, women could use the vaginal film contraceptive before having sexual intercourse. “It would be nonhormonal because it doesn’t interfere with ovulation. It acts locally in the vagina,” Winuthayanon says. This type of method might appeal to women who want an effective contraceptive that does not change their bodies’ estrogen and progestin levels and would not interfere with ovulation, she notes.
Until research progresses, scientists do not know whether the vaginal film would change the vaginal microbiome. If the microbiome changes, the contraceptive user could be more susceptible to infections, Winuthayanon says. “First, we’ll see if it works,” she adds.
To develop a male contraceptive that neutralizes PSA activity in men, researchers would need to develop an antibody injection. Theoretically, the male body would continue to make PSA, but it would not be active if the antibody was present, Winuthayanon says. “In theory, we would need to formulate it every 30 days or optimize it for every three months,” she adds.
It is a mode of action that has already been used to treat other conditions — like the antibody eye drops that treat dry eyes. Men would inject themselves.
Unfortunately, funding for creating this method as a male contraception is lacking. “I applied for a National Institutes of Health (NIH) grant three times for the male contraception, and we haven’t gotten the funding yet,” Winuthayanon says. Researchers will explore private funding options as well.
“It could be convenient for men. It would mostly be intravenous, but the subcutaneous route — like in the arm — is being explored,” she adds. “We have to find an antibody that works, first.”
This type of contraceptive in women could be administered in a way that is similar to the spermicidal gel, vaginal film, and any fast-dissolving insert. It would be applied locally and work right away, she says.
Winuthayanon has five years of funding from NIH to test the female contraceptive in monkeys as a proof of concept study. If it works in nonhuman primates, the next steps would include looking at toxicity and vaginal microbiome change and seeing if the product gets into the blood and has an effect on the body. Only after that work would it be ready to be tested in humans. Clinical trials would be at least five to 10 years in the future.
Another new nonhormonal contraceptive is available now for prescription. It was approved on Feb. 25, 2025, by the Food and Drug Administration (FDA). It is marketed as Miudella — the first hormone-free copper intrauterine system approved in the United States in more than four decades. It was called VeraCept when under development.6
The new intrauterine system contraceptive is an amazing product, says Anita Nelson, MD, a professor of obstetrics and gynecology at Western University of Health Sciences in Pomona, CA. She also is a professor emeritus at David Geffen School of Medicine at the University of California Los Angeles and medical director of research at Essential Access Health in Los Angeles. “It adjusts to the shape of any given uterus,” Nelson says. “We had a comparison study out of the Dominican Republic, and the copper is lower, the shape is different, and the study showed less bleeding.”7
The intrauterine device (IUD) also is more comfortable to insert than the only other copper IUD (Copper-T/Paragard) marketed in the United States, she adds. Miudella can prevent pregnancy for up to eight years. It is hormone-free and contains less than half the amount of copper of the four-decade-old copper IUD. The new IUD has a flexible frame made of nitinol, a material that has super-elastic properties, which make it easier to insert.6
Its IUD frame is the smallest hormone-free flexible IUD frame available in the United States. Of 1,620 participants receiving the contraceptive, 98.8% had successful IUD placements. Its most common adverse events — bleeding and pain — are similar to what has been observed in both copper and hormonal IUDs. About 15% of participants discontinued use of Miudella because of bleeding or pain.7,8
Expulsions occurred in 2.2% within one year and 3.9% within three years. Serious adverse events were rare, including five people with ectopic pregnancies and one instance each of uterine perforation, anemia, and uterine hemorrhage.7,8
Melinda Young has been a healthcare and medical writer for 30 years. She currently writes about contraceptive technology.
References
1. Gray C. Data shows 14% rise in women using no contraception at all. Women’s Health. Jan. 15, 2025. https://www.womenshealthmag.com/uk/health/sexual-health/a63429105/contraception-methods-changing/#the-study
2. Daniels K, Abma JC. Contraceptive methods women have ever used: United States, 2015-2019. National Health Statistics Reports 2023;195:1-17. https://www.cdc.gov/nchs/data/nhsr/nhsr195.pdf
3. Ross J, Stover J. Use of modern contraception increases when more methods become available: Analysis of evidence from 1982-2009. Glob Health Sci Pract. 2013;1(2):203-212.
4. Winuthayanon W. PSA inhibitors for contraception: Insights from prostate cancer. Trends Pharmacol Sci. 2025; Jun 4:S0165-6147(25)00095-1. [Online ahead of print].
5. Erickson JA, Jimmidi R, Anamthathmakula P, et al. Synthesis and optimization of small molecule inhibitors of prostate specific antigen. ACS Med Chem Lett. 2024;15:1526-1532.
6. FDA approves MIUDELLA, the first hormone-free copper intrauterine system (IUS) in the U.S. in over 40 years, from Sebela Women’s Health Inc. Sebela Pharmaceuticals Inc. Feb. 25, 2025. https://www.prnewswire.com/news-releases/fda-approves-miudella-the-first-hormone-free-copper-intrauterine-system-ius-in-the-us-in-over-40-years-from-sebela-womens-health-inc-302384684.html
7. Creinin MD, Gawron LM, Roe AH, et al. Three-year efficacy, safety, and tolerability outcomes from a phase 3 study of a low-dose copper intrauterine device. Contraception. 2025;143:110771.
8. McGovern G. FDA approves Miudella, first hormone-free, copper IUD in over 40 years. Pharmacy Times. Feb. 26, 2025. https://www.pharmacytimes.com/view/fda-approves-miudella-first-hormone-free-copper-iud-in-over-40-years
Some scientists have focused on finding a nonhormonal-based contraception option that would be effective and acceptable to people who want to stay away from hormones and their side effects.
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