By Melinda Young
Post-exposure prophylaxis (PEP) of doxycycline is recommended by the Centers for Disease Control and Prevention (CDC) for prevention of chlamydia, syphilis, and gonorrhea infections for men who have sex with men (MSM) and transgender women who have had a bacterial sexually transmitted infection (STI) within the past year, according to a new paper on doxycycline-PEP.1 But it also is a strategy that may work well for cisgender women who have a similar risk profile.
Called doxy-PEP, it worked well with MSM and transgender women in a randomized trial. Participants took a single dose of 200 mg of doxycycline within 72 hours, although around 24 hours post-exposure after condomless sex is ideal.1 “They encourage you to take doxy-PEP on the day after with plenty of food and water. If they don’t take food and water, they can get nausea and stomach upset,” says Eric. A. Meyerowitz, MD, an assistant professor in the department of medicine at Montefiore Medical Center in Bronx, NY.
This strategy was shown to decrease the rates of chlamydia and syphilis, and it decreased rates of gonorrhea to a lesser extent, he says. The CDC’s guidelines in June 2024 endorsed doxy-PEP for MSM and trans women because it shows efficacy, but they also said you can use a shared-decision making model for other populations, he says.
“So, they’re not making recommendations against it or making recommendations for it — for other populations — because there is not the same data showing efficacy yet,” Meyerowitz explains. “It is something that is appropriate for some people even in populations where there’s not efficacy data.”
There was only one study of doxy-PEP with cisgender women, enrolling 449 women in Kenya, and that study showed no benefit. But investigators concluded that poor adherence may explain the findings, since only 29% of participants in the doxycycline arm had evidence of doxycycline in hair samples, which may or may not be a suitable measure of adherence.1-3
“The key is to figure out who benefits from this,” Meyerowitz says. “In the initial study, you needed to have a bacterial STI within the last year, and that’s the specific population where the CDC guidelines recommend this strategy for.”
If doxy-PEP is used in a low-risk population, clinicians should think about their sex practices, number of sex partners, and history of STIs. If there has been no STI in the last year, then the chance of this having a benefit is lower than if someone had one or more recent bacterial STIs, he explains.
If a patient is pregnant, then doxycycline is not recommended because it can cause teeth staining to an exposed fetus.
“But if you have cisgender women with one or more STIs, it’s very reasonable to think about this with them,” Meyerowitz says. “And while the guidelines don’t fully endorse it, they definitely allow for this sort of shared decision-making.”
So, if a patient has had a recent bacterial infection, and this is something they would like to try, it is very reasonable to prescribe that, he adds. “There’s no reason from a biological perspective or having to do with blood levels of the medication to think it wouldn’t work with other populations,” he adds.
The added benefit to cisgender women using doxy-PEP is that it may help prevent syphilis in pregnancy, which has become a big problem in the past five years. “Preventing syphilis infections before pregnancy is extremely important, and this is potentially a tool in the toolbox to prevent it,” Meyerowitz says. “Even though the efficacy data is specific to one group at this time, I think it’s very reasonable to be thinking about it broadly.” Plus, there are some ongoing studies that are looking at the use of doxy-PEP in cisgender female patients.
The CDC’s recent endorsement and research in its use by MSM and transgender women suggest doxy-PEP could be a transformational prevention strategy that is widely implemented in sexual health clinics. It could have a big impact on curtailing bacterial STI infections.1
The new study’s authors recommend that more funding be directed to studying doxy-PEP in cisgender women to reduce gender disparities. They also recommend that implementation strategies for doxy-PEP be rooted in equity and designed to increase access to comprehensive sexual health services.1
Another benefit of this prevention strategy is its simplicity. Here is how it works:
- Shared decision-making: When a patient reports having had a bacterial STI within the previous 12 months, providers may consider discussing doxy-PEP. The provider and patient can engage in shared-decision making, with the provider discussing doxy-PEP, what it is, and how it has uncertain but potential benefit for cisgender women in preventing infection of chlamydia, syphilis, and possibly even gonorrhea.
- Prescription: The physician prescribes 200 mg of any formulation of doxycycline to patients who have heard about doxy-PEP and request it, if there is reason to believe it would benefit them. Or the physician discusses its use for patients who have a risk profile where it may be of some benefit, including those with a recent history of bacterial STIs. The amount prescribed typically is 30 pills.
- How to use it: It is important that patients know they need to use doxy-PEP 24 hours after the unprotected sexual encounter. If they forget it the next day, it could still be useful if taken on day 2 or at least within 72 hours of unprotected sex. They also need to make sure they take the pill with food and water to avoid side effects.
“Adherence is up to the person,” Meyerowitz notes. “Some people feel like they want to take it after every condomless sexual encounter, and others take it after specific encounters, where they have concerns about an infection.”
Since it is prescribed in advance, people can keep a bottle of doxy-PEP in their bedroom or bathroom. They just need to be reminded to wait 24 hours before taking the pill. Patients also need to know that if they already have symptoms of an STI, doxy-PEP is not going to be useful in treating their STI. It is prevention — not treatment, Meyerowitz says. “Doxy-PEP is used after a sexual encounter if they’re asymptomatic. If they have symptoms, they potentially could have an undiagnosed STI, and this is not the right strategy,” he adds.
There are no data to suggest that prophylactic use of doxycycline for this purpose could increase drug resistance. “There is no clinically significant resistance to syphilis and chlamydia to doxy,” Meyerowitz says.
“The other question is will there be an impact on doxy resistance to non-STI infections, things that normally live in the gut,” he adds. “One thing I tell my patients is there’s a long history of people using doxy, including using it for a long time, months, or years, and it seems to be quite safe in those settings. So, the question about how much people are going to use it is an open question, and it’s still being studied.”
OB/GYNs and other reproductive healthcare providers could think of doxy-PEP as being like Plan B for their patients, except its effect is not preventing pregnancy but trying to prevent bacterially transmitted infections, Meyerowitz says.
References
- Meyerowitz EA, Liang E, Bishop D, Mullis CE. Put a little doxy-PEP in your step: Using doxycycline to prevent chlamydia, syphilis, and gonorrhea infections. PLoS Pathog. 2024;20(9):1012575.
- Stewart J, Oware K, Donnell D, et al. Doxycycline prophylaxis to prevent sexually transmitted infections in women. N Engl J Med. 2023;389(25):2331-2340.
- Kojima N, Klausner JD. Doxycycline to prevent sexually transmitted infections in women. N Engl J Med. 2024;390(13):1248-1249.
Melinda Young has been a healthcare and medical writer for 30 years. She currently writes about contraceptive technology.
