DoxyPEP: Your Complete Guide

A Modern, Evidence-Based Approach to Preventing Bacterial STIs

Doxycycline post-exposure prophylaxis, known as DoxyPEP, is one of the most important tools in modern sexual health. It offers a reliable, real-world way to prevent bacterial sexually transmitted infections by using a single dose of doxycycline within seventy-two hours after sexual exposure.

DoxyPEP is simple, practical, and highly effective for the bacterial STIs people are most likely to encounter. And unlike many traditional prevention strategies, DoxyPEP aligns with how people actually have sex.

Most bacterial STIs today spread through unprotected oral sex.

Very few people use condoms for oral sex.

Dental dams exist almost exclusively in pamphlets, not bedrooms.

This is why infections such as chlamydia, gonorrhea, and syphilis continue to circulate widely, even among people who believe they are being careful. DoxyPEP fills that gap. It prevents real infections that occur through real behaviors.

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What DoxyPEP Is

DoxyPEP is not daily antibiotics and it is not ongoing therapy. It is a one-time dose of doxycycline taken after sex. The medication works during the early window before bacteria multiply and establish an infection in the body.

Doxycycline has an exceptional safety record spanning more than fifty years. In the context of DoxyPEP, the medication is used briefly, at the precise moment when it is most effective.

This is post-exposure prophylaxis, not chronic antibiotic use.

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How Well DoxyPEP Works

Across multiple large studies in the United States, France, and Japan, DoxyPEP has shown consistent and meaningful reductions in:

• chlamydia
• syphilis
• gonorrhea
• and, in many cases, Mycoplasma genitalium

The reductions are substantial.

Many studies show fifty to eighty percent fewer infections depending on the organism.

In Tokyo, among female sex workers who actually took the medication, the reductions were dramatic:

• sixty-four percent fewer chlamydia infections
• sixty-one percent fewer gonorrhea infections
• one hundred percent fewer syphilis infections

This is exactly what high-quality prevention looks like.

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Does DoxyPEP Work for Women?

Yes.

There is no biological reason DoxyPEP would not work in women.

The only study suggesting otherwise was the Kenya trial, where adherence was extremely low and many participants reported taking the medication despite hair-sample testing showing otherwise. The medication simply was not taken. The study cannot be interpreted as evidence of ineffectiveness.

When women take DoxyPEP, as shown in the Tokyo data, it works.

At Shameless Care, we prescribe DoxyPEP to women every day.

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Antibiotic Resistance: What We Know and What We Are Still Learning

Resistance is always an important part of antibiotic stewardship. The key is understanding where the risk truly lies.

For the bacteria DoxyPEP is designed to prevent:

Gonorrhea

Neisseria gonorrhoeae has had tetracycline resistance for decades. DoxyPEP did not create it. This resistance predates the concept of DoxyPEP entirely.

Syphilis

Treponema pallidum has no documented clinically significant resistance to doxycycline after decades of use.

Chlamydia

Chlamydia trachomatis has not shown meaningful doxycycline resistance in clinical practice.

This does not guarantee that resistance will never occur, but the biological likelihood is low for these organisms.

The main unanswered questions are not about STIs.

They are about the gut microbiome.

Doxycycline is broad spectrum. It will shift gut bacteria temporarily, especially in people who use it often. Researchers are studying whether these shifts matter long term, and how frequently they occur. It is appropriate to monitor this closely, and recommendations may evolve as data accumulate.

DoxyPEP is highly effective now, and it prevents many infections that would otherwise require full treatment courses. But resistance and microbiome effects are long-term considerations that continue to be studied.

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Where DoxyPEP Fits in a Modern Sexual Health Strategy

Modern prevention must reflect modern sexual behavior.

Condoms protect against HIV and reduce risk for some types of intercourse.

But they do not meaningfully reduce oral STI transmission because almost no one uses them for oral sex.

Most bacterial STIs spread through exactly this route.

DoxyPEP strengthens sexual health by preventing the infections that condoms realistically do not address.

A comprehensive sexual health approach includes:

• routine multi-site STI testing
• PrEP for HIV where appropriate
• DoxyPEP for bacterial STI prevention
• shame-free, honest communication
• a modern understanding of how infections actually spread

DoxyPEP is not supplemental.

It is one of the primary tools of effective STI prevention today.

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Explore the Full Guide

Below are the four detailed Learning Center articles that expand every part of the DoxyPEP picture.

DoxyPEP Effectiveness

A deeper look at the major studies, the numbers, and what people can expect in real life.

DoxyPEP for Women

Why the early narrative was misleading and what the data actually show.

DoxyPEP and Mycoplasma genitalium

Understanding how DoxyPEP affects Mgen risk and why prevention matters.