Meta-analysis finds doxycycline prophylaxis reduces STI risk in MSM and transgender women

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Sexual health Published April 12, 2026 Medically reviewed May 25, 2026 Study authors: Zhao Peipei, Zou Qian, Tucker Joseph, Fitzpatrick Tomas, Tang Weiming PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider doxycycline prophylaxis for STI prevention in MSM/TGW, but note safety data are unreported.

This systematic review and meta-analysis pooled data from 14 eligible studies to evaluate doxycycline prophylaxis (both pre-exposure and post-exposure) for preventing sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW). The primary outcome was the risk of acquiring any STI, with secondary outcomes focusing on chlamydia, gonorrhoea, and syphilis.

The analysis found doxycycline prophylaxis was associated with a 60% reduction in the risk of acquiring any STI (relative risk 0.40, 95% confidence interval 0.30 to 0.52). For specific infections, the overall reductions were substantial: chlamydia (RR 0.18, 95% CI 0.11-0.28), gonorrhoea (RR 0.61, 95% CI 0.44-0.86), and syphilis (RR 0.20, 95% CI 0.12-0.33). The effect was consistent in randomized controlled trials, showing a 76% decrease for chlamydia, 33% for gonorrhoea, and 78% for syphilis.

Safety and tolerability data were not reported in the meta-analysis, representing a significant evidence gap. Key limitations include the lack of reported safety outcomes and the heterogeneity of included studies regarding doxycycline dosing regimens and follow-up periods. The practice relevance is that these findings contribute to the evidence base for integrating doxycycline prophylaxis into STI prevention strategies for MSM and TGW, but the absence of safety data necessitates caution.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedApr 2026

PMID41800911

View Original Abstract ↓

BACKGROUND: Recent systematic reviews have demonstrated the efficacy of doxycycline prophylaxis in preventing bacterial sexually transmitted infections (STIs) in randomised controlled trials (RCTs). In this review, we updated evidence from RCTs and non-RCTs and compared the effectiveness of doxycycline as pre- (doxy PrEP) and post-prophylaxis (doxy PEP) across different groups. METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library, and two conference abstract archives for publications from January 2010 to April 2025. Eligible RCT and non-RCT studies on doxy PrEP and doxy PEP to prevent STIs were included in the analysis. Pooled risk ratios were calculated using fixed-effects and random-effects models. This study was registered with PROSPERO (CRD42024568934). RESULTS: Fourteen eligible studies (4 doxy PrEP, 10 doxy PEP) were included for analysis. Participants were primarily men who have sex with men (MSM) and transgender women (TGW). Doxycycline (either PrEP or PEP) reduced the risk of acquiring any STIs by 60% (risk ratio (RR), 0.40; 95% CI, 0.30-0.52) in RCT and non-RCT trials. Doxycycline was associated with fewer incidences of chlamydia (RR, 0.18; 95% CI, 0.11-0.28), gonorrhoea (RR, 0.61; 95% CI: 0.44-0.86), and syphilis (RR, 0.20; 95% CI; 0.12-0.33). Meta-analysis of seven RCTs showed 76% decrease on chlamydia (RR: 0.24; 95% CI: 0.13-0.45), 33% decrease on gonorrhoea (RR, 0.67; 95% CI; 0.45-0.98), and 78% decrease on syphilis (RR, 0.22; 95% CI; 0.14-0.36). HIV-positive and HIV-negative people benefited from using doxy PrEP and PEP regimens prevented bacterial STIs. CONCLUSIONS: RCT and non-RCT data demonstrated the effectiveness of doxy PrEP and doxy PEP in reducing STIs among MSM/TGW. Integrating doxy PrEP or doxy PEP as a biomedical tool into STI prevention strategies should be considered.