By Charles Morrison, PhD Senior Epidemiologist, Clinical Research Division, Family Health International
Dr. Morrison is an epidemiologist who, for more than a decade, has directed research and published on the relationship between contraception and sexually transmitted infections, including HIV.
Do hormonal contraceptive methods increase women's risk of acquiring sexually transmitted infections (STIs) other than HIV? This question is of critical concern, given that more than 100 million women worldwide use these methods.1 Decreasing STI incidence by identifying and addressing any factors contributing to it is a major public health priority since untreated STIs in women cause important, long-term health consequences. Bacterial STIs — such as chlamydial and gonococcal infection — are associated with pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, and infertility. Also, STIs in women may increase the risk of HIV acquisition2 and transmission to sexual partners.3
Existing research on the relationship between hormonal contraceptive use and STIs is limited, and many studies suffer from serious methodological problems.4 Further high-quality, prospective research is needed to reach informed conclusions about individual contraceptive methods and the risk of acquiring specific STIs. However, based on a review in 2005 of evidence on the topic, the World Health Organization concluded that its existing guidance was appropriate. That guidance places no restrictions on the use of combined oral contraceptives (COCs) or depot-medroxyprogesterone acetate (DMPA) by women at risk of acquiring an STI.5
A review of peer-reviewed articles describing research on contraception and STI risk published between January 1966 and December 2004 helps to clarify the matter.6 The review, conducted by FHI and collaborating institutions,* focused largely on prospective studies that assessed contraceptive use prior to infection status. Cross-sectional studies were included but de-emphasized, since such studies cannot determine the sequence of contraceptive exposure and STI outcome, making it impossible to clearly establish the nature of any association. The review found:
a possible increased risk of acquiring chlamydial infection associated with both the use of COCs7 and the use of DMPA injections8
no convincing evidence that either COC or DMPA use is associated with the acquisition of gonococcal infection9
insufficient or inconclusive evidence regarding the associations between COC or DMPA use and the risk of acquiring trichomoniasis,10 human papillomavirus (HPV),11 herpes simplex virus (HSV),12 or syphilis13
To further clarify the matter, FHI researchers and colleagues are conducting ancillary studies to their recently published prospective study of hormonal contraceptive use and HIV acquisition. These ancillary studies and secondary analyses will investigate whether hormonal contraception affects acquisition of HSV, bacterial vaginosis (BV), chlamydial and gonoccocal infection, trichomoniasis, and HPV. They will also assess the role of HSV, BV, and trichomoniasis in HIV acquisition.
No published studies report on STI risk among users of other progestin-only methods including progestin-only pills, the injectable norethisterone enanthate (NET-EN), or the implant Implanon. Likewise, STI risk among users of newer combined hormonal methods such as the patch (Ortho Evra), the ring (NuvaRing), or the combined injectables Cyclofem and Mesigyna has not been evaluated.
Possible mechanisms of action
Although further, high-quality research is needed to determine whether hormonal contraceptive use is associated with STI acquisition, such a relationship is plausible for both biological and behavioral reasons. Possible biological mechanisms include:
increased cervical ectopy (a condition in which the lining usually found inside the cervical canal extends onto the cervix's outer surface, where exposure to sexually transmitted pathogens is greater) associated with OC use14
changes in the body's immune system associated with the use of steroids15
direct influence of sex hormones on pathogen virulence, resulting in enhanced susceptibility to infection16
a hypo-estrogenic effect associated with DMPA use, resulting in changes in the vaginal microbial flora or in the vaginal epithelium17
In terms of behavioral factors, women choosing various methods of contraception may differ from one another in the sexual risks they take. Their sexual risk-taking may also change after they begin taking contraceptives.
Public health, clinical implications
If a given contraceptive method is shown more conclusively to increase the risk of acquiring certain STIs, counseling strategies should ensure that women understand the association between method use and infection. Until methods that are highly protective against both pregnancy and STIs are available, women at risk of infection should continue to be encouraged to use highly effective contraception to prevent unintended pregnancy together with condoms to help prevent STIs.
However, care should be taken not to cause unwarranted concern about risks associated with contraceptive use. Suggesting an increase in STI risk that has not been shown to exist could result in women stopping a particular contraceptive method without plans to adopt another. This could result in surges in pregnancies that are both unintended and may have serious health consequences. Pregnancy can result in serious maternal harm or death, especially in some resource-poor settings where childbirth is unsafe or women lack access to safe abortions.
The risks and benefits associated with the use of any contraceptive method need to be carefully evaluated by contraceptive providers and users. For many women, increased susceptibility to STIs may be of little concern since their lifestyles, low STI incidence where they live, and other factors may put them at low risk for such infections. Indeed, potential increases in STI risk associated with specific contraceptive methods may not be relevant for large segments of the population in many settings. On the other hand, many women either do not understand that they are at risk of acquiring STIs or do not accurately assess their risks. Thus, for sexually active women not in mutually monogamous relationships with uninfected partners, contraceptive counseling should continue to emphasize the need for condom use and frequent STI screening in addition to highly effective contraception.
* Institutions collaborating in this review were Family Health International, Durham, NC, USA; University of North Carolina, Chapel Hill, NC, USA; Centers for Disease Control and Prevention, Atlanta, GA, USA; and Johns Hopkins University, Baltimore, MD, USA.
Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999;75(1):3-17; Cohen MS. Sexually transmitted diseases enhance HIV transmission: no longer a hypothesis. Lancet 1998;351(Suppl 3):5-7; Corbett EL, Steketee RW, ter Kuile FO, et al. HIV-1/AIDS and the control of other infectious diseases in Africa. Lancet 2002;359(9324):2177-87.
Wang CC, McClelland RS, Reilly M, et al. The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. J Infect Dis 2001;183(7):1017-22; Ghys PD, Fransen K, Diallo MO, et al. The associations between cervicovaginal HIV shedding, sexually transmitted diseases and immunosuppression in female sex workers in Abidjan, Côte d'Ivoire. AIDS 1997;11(12):F85-93; Mostad SB, Overbaugh J, DeVange DM, et al. Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1-infected cells from the cervix and vagina. Lancet 1997;350(9082):922-27; Sha BE, Zariffard MR, Wang QJ, et al. Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis. J Infect Dis 2005;191(1):25-32.
Mohllajee A, Curtis K, Martins S, et al. Hormonal contraceptive use and risk of sexually transmitted infections: a systematic review. Contraception 2006;73(2):154-65.
Morrison CS, Turner AN, Curtis K, et al. Highly-effective contraception and sexually transmitted infections in the Western European context. In Glasier A, Wellings K, Critchley H, eds. Contraception and Contraceptive Use. London, UK: RCOG Press, 2005.
Louv WC, Austin H, Perlman J, et al. Oral contraceptive use and the risk of chlamydial and gonococcal infections. Am J Obstet Gynecol 1989;160(2):396-402; Avonts D, Sercu M, Heyerick P, et al. Incidence of uncomplicated genital infections in women using oral contraception or an intrauterine device: a prospective study. Sex Transm Dis 1990;17(1):23-29; Baeten JM, Nyange PM, Richardson BA, et al. Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study. Am J Obstet Gynecol 2001;185(2):380-85; Morrison CS, Bright P, Wong EL, et al. Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections. Sex Transm Dis 2004;31(9):561-67; Cottingham J, Hunter D. Chlamydia trachomatis and oral contraceptive use: a quantitative review. Genitourin Med 1992;68(4):209-16.
Baeten; Morrison, Bright, Wong, et al; Lavreys L, Chohan V, Overbaugh J, et al. Hormonal contraception and risk of cervical infections among HIV-1-seropositive Kenyan women. AIDS 2004;18(16):2179-84.
Louv; Baeten; Morrison, Bright, Wong, et al; Lavreys.
Baeten; Avonts; Barbone F, Austin H, Louv WC, et al. A follow-up study of methods of contraception, sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis. Am J Obstet Gynecol 1990;163(2):510-14.
Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003;157(3):218-26; Moscicki AB, Hills N, Shiboski S, et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA 2001;285(23):2995-3002; Sellors JW, Karwalajtys TL, Kaczorowski J, et al. Incidence, clearance and predictors of human papillomavirus infection in women. CMAJ 2003;168(4):421-25; Rousseau MC, Franco EL, Villa LL, et al. A cumulative case-control study of risk factor profiles for oncogenic and nononcogenic cervical human papillomavirus infections. Cancer Epidemiol Biomarkers Prev 2001;9(5):469-76; Green J, Berrington de Gonzalez A, Smith JS, et al. Human papillomavirus infection and use of oral contraceptives. Br J Cancer 2003;88(11):1713-20; Giuliano AR, Papenfuss M, Abrahamsen M, et al. Human papillomavirus infection at the United States-Mexico border: implications for cervical cancer prevention and control. Cancer Epidemiol Biomarkers Prev 2001;10(11):1129-36.
Lavreys L, Chohan B, Ashley R, et al. Human herpesvirus 8: seroprevalence and correlates in prostitutes in Mombasa, Kenya. J Infect Dis 2003;187(3):359-63; Smith JS, Herrero R, Munoz N, et al. Prevalence and risk factors for herpes simplex virus type 2 infection among middle-age women in Brazil and the Philippines. Sex Transm Dis 2001;28(4):187-94; Willmott FE, Mair HJ. Genital herpesvirus infection in women attending a venereal diseases clinic. Br J Vener Dis 1978;54(5):341-43; Evans BA, Kell PD, Bond RA, et al. Predictors of seropositivity to herpes simplex virus type 2 in women. Int J STD AIDS 2003;14(1):30-36; Wolinska WH, Melamed MR. Herpes genitalis in women attending Planned Parenthood of New York City. Acta Cytol 1970;14(5):239-42.
Baeten.
Louv; Bright PL. A longitudinal investigation of cervical ectopy [dissertation]. University of North Carolina at Chapel Hill, 2003.
Sonnex C. Influence of ovarian hormones on urogenital infection. Sex Transm Infect 1998;74(1):11-19.
Sonnex.
Miller L, Patton DL, Meier A, et al. Depomedroxy-progesterone-induced hypoestrogenism and changes in vaginal flora and epithelium. Obstet Gynecol 2000;96(3):431-39.
