There's an effective morning-after pill for STIs but it's not clear it works in women

There's a treatment that works like a morning-after pill for sexually transmitted infections – an antibiotic taken in the hours after unprotected sex. And it can significantly lower the chance of developing common STIs like chlamydia and syphilis.

In fact, the approach has proven effective enough that federal guidelines are now being finalized so that more doctors and public health departments can offer it to those who're at high risk of STIs.

Except so far, "doxy-PEP" – short for doxycycline post-exposure prophylaxis (PEP) – is only recommended for men who have sex with men and transgender women.

"There's enthusiasm for doxy-PEP and you're seeing a lot of places rolling it out, but not for cisgender women," says Dr. Jenell Stewart, an infectious disease specialist at Hennepin Healthcare and the University of Minnesota.

And for the time being, it's likely to stay that way, given the results of a study published on Wednesday in the New England Journal of Medicine. It represents the first clinical trial to test whether doxy-PEP can be effective in this population.

"Unfortunately, it didn't work in our study – we didn't see any reduction of new STIs," says Stewart, one of the study's authors.

The results seem to cast doubt on hopes that doxy-PEP can work in a broader population and help solve the troubling rise in STI rates. Research shows women are more likely to have certain STIs and to suffer from serious complications.

But the topline results are not necessarily the final word.

"I think it's premature to discard this intervention," says Dr. Jeanne Marrazzo, who directs the National Institute of Allergy and Infectious Diseases and was not involved in the study. "There is biological plausibility, and such an urgent need to control these infections in women."

So why exactly did doxy-PEP fall short?

The year-long study followed nearly 450 women in Kenya who were mostly in their 20s and already taking HIV PrEP, an indication that they're at heightened risk of STIs.

The trial design was similar to a previous study that found doxy-PEP was effective at reducing bacterial STIs among men who have sex with men.

Recent data suggest that despite biological differences between cisgender men and cisgender women, doxycycline should still be protective against bacterial STIs.

The levels of doxycycline in rectal and vaginal fluids are similar and high enough to inhibit infections from chlamydia and syphilis, says Dr. Connie Celum, professor of global health and medicine at the University of Washington in Seattle

"I don't think there's a reason to suspect it wouldn't work," she says, "I really do think adherence appears to be the major factor in this study."

This is what Dr. Stewart also suspects based on hair samples collected from a subset of the participants.

Even though a majority of the women said they were taking doxycycline regularly after sex, their analysis shows the numbers were, in reality, much lower. Only about a third of the samples had doxycycline present.

The discrepancy isn't necessarily all that surprising to Marrazzo, who wrote an editorial that accompanied the study.

She points out that people are often eager to tell their doctor they're following instructions and taking care of their health.

"It's similar in clinical trials, right? Participants want to stay in the studies," she says.

Stewart says they're gathering more data to understand why many women ended up not taking doxycycline, and she plans to launch a new trial in the U.S.

"While this is disappointing and we have a delay in giving this potential intervention to cisgender women, it also gives me optimism," says Stewart. "We just didn't have enough participants taking the medicine to see an impact, so I think the question is still on the table."

Awareness of STI risk may be lower in Kenya and that could partially explain the lack of adherence in the study. STI testing is not widely available and most infections are asymptomatic. That's in contrast to Western countries where testing is a regular part of HIV PrEP programs.

"Men who have sex with men and trans women in the U.S. and Europe are much more aware of STIs than women in Africa for whom testing is not available," says Celum, "They may not have perceived themselves to need this."

Other factors could be at play, too. There's less antibiotic resistance in gonorrhea in the U.S. compared to Kenya. The women in the trial were also having fewer sexual partners than those enrolled in the previous trials and therefore they were taking the medication less often.

Marrazzo says future clinical trials need to take into account why adherence was low so that researchers and doctors can get a clear picture of whether doxy-PEP is a viable option for women.

This situation reminds her of when guidance on oral HIV PrEP was first rolled out, which was based largely on data from men who have sex with men and transgender women.

"This is like deja vu," she says, noting that there just isn't good enough data on doxy-PEP's effect in women. "What is so disheartening about these results and the current state of the CDC guidelines is that, once again, women are not going to be included with definitive data."