Contraception and sexually transmitted infections: risks and benefits, hypotheses and evidence
Authors: Jared M Baeten, Renee Heffron
Journal: The Lancet Global Health (2015)

Women bear most of the worldwide burden of sexually transmitted infections (STIs) and their resultant morbidity and mortality.1Robinson N Stoffel C Haider S Global women's health is more than maternal health: a review of gynecology care needs in low-resource settings.Obstet Gynecol Surv. 2015; 70: 211-222Crossref PubMed Scopus (8) Google Scholar However, STIs are only one adverse health threat borne disproportionately by women, who also face important risks related to reproductive health, violence and trauma, economic instability, and other areas. Interventions that aim to mitigate these risks can have substantial public health success, but occasionally interventions inadvertently generate new risks as well. Hormonal forms of contraception, including oral contraceptive pills, progestin-only injectables such as depo-medroxyprogesterone acetate (DMPA), and hormone-containing technologies (implants, intrauterine devices, patches, and rings) are used by more than 150 million women worldwide, and worldwide implementation of safe and effective contraception has had substantial public health effect on prevention of unintended pregnancy and maternal morbidity.2Ahmed S Li Q Liu L Tsui AO Maternal deaths averted by contraceptive use: an analysis of 172 countries.Lancet. 2012; 380: 111-125Summary Full Text Full Text PDF PubMed Scopus (398) Google Scholar Contraceptives, though, are not without risk, and some methods have been associated with increased likelihood of complications, such as thromboembolic disease.3Food and Drug Administration Office of Surveillance and EpidemiologyCombined hormonal contraceptives (CHCs) and the risk of cardiovascular disease endpoints.http://www.fda.gov/downloads/Drugs/DrugSafety/UCM277384.pdfGoogle Scholar Still, when weighed against the substantial health and economic benefits afforded by prevention of unintended pregnancy, the public health balance favours widespread access to a diverse assortment of safe and effective contraceptive methods as a public health imperative. In The Lancet Global Health, Grabowski and colleagues4Grabowski MK Gray RH Makumbi F Use of injectable hormonal contraception and women's risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda.Lancet Glob Health. 2015; (published online June 18.)http://dx.doi.org/10.1016/S2214-109X(15)00086-8PubMed Google Scholar report that women consistently using DMPA were at nearly double the risk of acquiring herpes simplex virus type 2 (HSV2) compared with those using no contraception; in a sensitivity analysis limited to those whose main partner had HSV2, the risk increased by six times. HSV2, the cause of genital herpes, is prevalent in populations worldwide, including in Africa, and is a common cause of morbidity related to genital ulcer disease and of rare serious morbidity in infants with neonatal infection; it is also an important risk factor for HIV acquisition in adults.5Barnabas RV Celum C Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: new insights and interventions.Curr HIV Res. 2012; 10: 228-237Crossref PubMed Scopus (77) Google Scholar The results from Grabowski and colleagues build on a large and contentious body of evidence suggesting that DMPA might increase HIV risk,6Polis CB Phillips SJ Curtis KM et al.Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence.Contraception. 2014; 9: 360-390Summary Full Text Full Text PDF Scopus (71) Google Scholar and a smaller number of studies exploring associations of contraceptives with other STIs. Although we have contributed to this discussion with observational data showing increased HIV risk associated with DMPA,7Heffron R Donnell D Rees H et al.Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study.Lancet Infect Dis. 2012; 12: 19-26Summary Full Text Full Text PDF PubMed Scopus (349) Google Scholar we acknowledge that results across studies have been inconsistent and the answer is still unclear. Authors of meta-analyses8Morrison CS Chen PL Kwok C et al.Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.PLoS Med. 2015; 12: e1001778Crossref PubMed Scopus (149) Google Scholar, 9Ralph LJ McCoy SI Shiu K Padian NS Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies.Lancet Infect Dis. 2015; 15: 181-189Summary Full Text Full Text PDF PubMed Scopus (110) Google Scholar have noted increased risk estimates for an association between DMPA and HIV association, but those results are only as strong as the observational data from which they derive, and important criticisms of the observational scientific literature in this discipline have been raised,10Polis CB Westreich D Balkus JE Heffron R for the participants of the 2013 HC-HIV Observational Analysis MeetingAssessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and recommended analytic approaches.AIDS. 2013; 27: S35-S43Crossref PubMed Scopus (37) Google Scholar including small sample sizes, reliance on self-reported contraceptive exposures, infrequent ascertainment of HIV and other STI outcomes, and inconsistent methods and findings, persisting even into recent studies.11Wall KM Kilembe W Vwalika B et al.Hormonal contraception does not increase women's HIV acquisition risk in Zambian discordant couples, 1994-2012.Contraception. 2015; (published online Feb 21.)https://doi.org/10.1016/j.contraception.2015.02.004Summary Full Text Full Text PDF Scopus (25) Google Scholar Notably, the Rakai Program previously identified no increased HIV risk related to DMPA in the population from which the present HSV2 risk was noted,12Lutalo T Musoke R Kong X et al.Effects of hormonal contraceptive use on HIV acquisition and transmission among HIV-discordant couples.AIDS. 2013; 27: S27-S34Crossref PubMed Scopus (23) Google Scholar and the only other cohort to explore DMPA's effects on HIV and HSV2 came to the opposite conclusion—increased HIV risk with no increase in HSV2 acquisition.13Baeten JM Benki S Chohan V et al.Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women.AIDS. 2007; 21: 1771-1777Crossref PubMed Scopus (133) Google Scholar, 14Chohan V Baeten JM Benki S et al.A prospective study of risk factors for herpes simplex virus type 2 acquisition among high-risk HIV-1 seronegative women in Kenya.Sex Transm Infect. 2009; 85: 489-492Crossref PubMed Scopus (37) Google Scholar We and others have argued that rigorous studies, with sufficient samples sizes and robust measurement of contraceptive exposures, infection outcomes, and behavioural confounders, including the potential for a randomised trial,15Cates W for the Evidence for Contraceptive Options and HIV Outcomes (ECHO) ConsortiumResearch on hormonal contraception and HIV.Lancet. 2014; 383: 303-304Summary Full Text Full Text PDF PubMed Scopus (15) Google Scholar are essential now to address outstanding questions related to contraceptives and HIV and STIs. The HSV2 results from Grabowski and colleagues' study rest on just nine incident HSV2 cases of those using DMPA and infrequent annual assessments of contraceptive exposure, HSV2 outcome, and confounding factors, so we therefore agree with Grabowski and colleagues that the results are hypothesis-generating but not definitive evidence. For such a topic that intersects at two priority areas of global health—STIs and reproductive health—to have more hypotheses than clear evidence is frustrating—and sends a message to women that is complex and confusing. Importantly, potential infectious risks (HSV2, other STIs, and HIV) that might increase with use of some contraceptives should be weighed carefully because infections are not the only risks. Some have called for removal of DMPA from settings with high HIV and STI risks, but in Rakai, like in many other parts of Africa, DMPA is the dominant contraceptive chosen by women, showing desire for its effectiveness, ease of use, and ability to be used discretely, and its ease of delivery by health systems. Efforts to expand contraceptive method options by introduction of long-acting effective methods such as implants and intrauterine devices in settings like Rakai are sorely needed, but acceptability, deliverability, and STI and HIV risks of new contraceptive methods are outstanding issues, leaving open the potential for risks that are as yet unanticipated. Ultimately, attention to inter-relations between contraceptive options and STI and HIV outcomes is a strong reminder of the priority for integrated sexual and reproductive health research, grounded in evidence as it emerges and weighing risks and benefits that are crucial to health-care programming and delivery. We declare no competing interests. Use of injectable hormonal contraception and women's risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, UgandaConsistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa. Full-Text PDF Open Access