Doxycycline is an antibiotic that can be taken within 72 hours of unprotected sex to help prevent common bacterial STDs (sexually transmitted diseases). When doxycycline is used in this way it is called Doxy PEP (postexposure prophylaxis).

Doxy PEP significantly protects against 3 STDs, syphilis, chlamydia, and gonorrhea, in high-risk, sexually active adults. STDs may also be called sexually transmitted infections or STIs.

What is Doxy PEP?

Doxy PEP is a prevention strategy where people at high risk for bacterial STIs take 200 mg of doxycycline within 72 hours (3 days) after unprotected sex to reduce their chances of getting chlamydia, gonorrhea, and syphilis infections. It will not protect against other common STIs, such as HIV, monkeypox, or herpes.

Clinical trials have reported a 73% reduced risk in high-risk individuals of contracting a bacterial STD when Doxy PEP is taken within 72 hours of having sex without a condom.

Doxy PEP contains doxycycline, which is a broad-spectrum antibiotic from the tetracycline family that is effective against a wide range of different types of bacteria.

PEP stands for postexposure prophylaxis.

Who should take Doxy PEP?

Doxy PEP is recommended by the CDC for gay and bisexual men, men who have sex with men (MSM), and transgender women (TGW) who have had chlamydia, syphilis, or gonorrhea in the last 12 months, and are at high risk of reinfection.

The benefits of Doxy PEP may also extend to those who have not had a bacterial STI in the past year, but who will be participating in risky sexual activities. Talk to your healthcare provider about this.

There is not enough evidence to determine the effectiveness of Doxy PEP in other populations, such as heterosexual men and women, or people who have never had an STD.

Doxycycline for STD dosage

The recommended dosage is doxycycline 200 mg taken as a single dose.

• Doses should be taken as soon after sex as possible, but no later than 72 hours.
• Do not take more than 200 mg of doxycycline per 24 hours.
• Take doxycycline exactly as prescribed by your healthcare provider and only for its intended purpose. Do not share your doxycycline.
• Ask your healthcare provider to provide you with enough doses of doxycycline to last until your next visit.

How should I take doxycycline for STDs?

Take Doxy PEP with food and a glass of water.

• This will help reduce side effects such as nausea, indigestion, or irritation of your esophagus.
• Do not lie down for one hour after taking doxycycline to prevent esophagitis (an irritation to the lining of your esophagus).
• Most doxycycline brands, except the Oracea brand, can be taken with milk or food, which can help if the medication upsets your stomach. The Oracea brand should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal, since food can reduce its absorption and effectiveness.
• Do not take doxycycline within 2 hours of antacids or supplements containing iron, calcium, or magnesium.
• Ask your doctor if any medications you take interact with doxycycline. There have been no clinically relevant interactions between doxycycline and gender-affirming hormonal therapy reported.
• Wear sunscreen, stay in the shade, or cover up to stay protected from the sun while taking doxycycline.

If you are engaging in high risk sexual behavior, you should be tested for STIs and HIV every 3 to 6 months. During these visits to your healthcare provider, you can reassess if there is an ongoing need for Doxy PEP.

Doxy PEP side effects

The most common side effects of Doxy PEP are:

• An upset stomach, with symptoms such as nausea or stomach pain
• Esophagitis (throat irritation)
• A skin rash
• Sensitivity to the sun, meaning you sunburn more easily.

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How effective is doxycycline for STDs?

The effectiveness of Doxy PEP is highest for chlamydia and syphilis (80-90% reduction) and moderate for gonorrhea (50-55% reduction) in men who have sex with men and transgender women populations. Overall, a two-thirds reduction in bacterial STD incidence was reported in the main Doxy PEP trial (NCT03980223). This study included participants living with HIV or on pre-exposure prophylaxis (PrEP).

Results were less favorable in a randomized open-label trial that investigated Doxy PEP for women (n=449 cisgender Kenyan women), with no significant between group difference in incidence of STDs (relative risk, 0.88; 95% confidence interval, 0.60 to 1.29; P=0.51).

• However, hair studies detected doxycycline in only 29% of participants, suggesting nonadherence or biological differences may be a factor in the result.

How often should you test for STDs?

Many STDs often show no symptoms, which is why the CDC recommends regular screening for all sexually active individuals. The recommended screening frequencies for specific infections are:

HIV:

• At least once a year for everyone aged 13-64.

Gonorrhea and chlamydia:

• Annually for sexually active women under 25.
• Annually for women 25 and older with risk factors (e.g., new or multiple partners).

During pregnancy:

• Early in pregnancy testing for syphilis, HIV, hepatitis B, and C.
• Additional testing for chlamydia and gonorrhea if at risk.

Gay/Bisexual Men, MSM, and TGW:

• Syphilis, chlamydia, and gonorrhea at least once a year; every 3-6 months if there are multiple or anonymous partners or on HIV PrEP.
• HIV at least once a year; more frequently if needed.
• Hepatitis C annually if living with HIV.

Injection Drug Users:

• HIV at least once a year.

How do you test for STDs?

STD testing involves a sample of body fluid to check for infections and may include swab tests, blood tests, or urine tests. Your healthcare provider will select the right test for you based on your sexual behavior, symptoms, history of STDs, and overall risk assessment.

• Different tests may be needed based on whether you've had vaginal, anal, or oral sex. For example, oral swab tests are appropriate for oral sex-related risks.
• If you have symptoms like sores or unusual discharge, a swab test from the affected area may be necessary.

Swab tests

• Purpose: Detects infections in the genital, throat, anus, or sores.
• Commonly detects: Chlamydia, gonorrhea.
• Procedure: Samples are taken from the affected area using a sterile swab.
• Advantages: Higher accuracy for oral and anal infections compared to urine tests.

Blood tests

• Purpose: Identifies diseases such as HIV, syphilis, and hepatitis.
• Procedure: Blood is drawn from a vein and analyzed in a lab.
• Advantages: Can detect infections even without symptoms and identify antibodies.

Urine tests

• Purpose: Detects diseases like chlamydia and gonorrhea.
• Procedure: A urine sample is collected and analyzed.
• Advantages: Non-invasive and easy to perform.
• Limitations: May not detect infections in the throat or rectum, which require swab tests for accurate diagnosis.

References

• Preventing STIs with Doxy PEP. Sexually Transmitted Infections (STIs). CDC. https://www.cdc.gov/sti/prevention/doxy-pep.html
• Bachmann LH, Barbee LA, Chan P, et al. CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024. MMWR Recomm Rep 2024;73(No. RR-2):1–8. DOI: http://dx.doi.org/10.15585/mmwr.rr7302a1
• Doxycycline. Drugs.com https://www.drugs.com/doxycycline.html
• Stewart, J., Oware, K., Donnell, D., et al. (2023). Doxycycline prophylaxis to prevent sexually transmitted infections in women. New England Journal of Medicine, 389(25), 2331-2340. https://doi.org/10.1056/NEJMoa2304007
• Szondy, I., et al. (2024). Doxycycline prophylaxis for the prevention of sexually transmitted infections: A systematic review and meta-analysis of randomized controlled trials. International Journal of Infectious Diseases, 147, 107186.
• Molina JM, Bercot B, Assoumou L, Rubenstein E, Algarte-Genin M, Pialoux G, Katlama C, Surgers L, Bébéar C, Dupin N, Ouattara M, Slama L, Pavie J, Duvivier C, Loze B, Goldwirt L, Gibowski S, Ollivier M, Ghosn J, Costagliola D; ANRS 174 DOXYVAC Study Group. Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design. Lancet Infect Dis. 2024 Oct;24(10):1093-1104. doi: 10.1016/S1473-3099(24)00236-6. Epub 2024 May 23. PMID: 38797183.
• Luetkemeyer AF, Donnell D, Cohen SE, Dombrowski JC, Grabow C, Haser G, Brown C, Cannon C, Malinski C, Perkins R, Nasser M, Lopez C, Suchland RJ, Vittinghoff E, Buchbinder SP, Scott H, Charlebois ED, Havlir DV, Soge OO, Celum C. Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension. Lancet Infect Dis. 2025 Mar 24:S1473-3099(25)00085-4. doi: 10.1016/S1473-3099(25)00085-4. Epub ahead of print. PMID: 40147465.

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