Hormonal contraception and STIs: researchers continue to investigate a possible relationship.

The possible impact of hormonal contraceptive use on the acquisition or transmission of sexually transmitted infections (STIs), including HIV, remains an important research question. However, current knowledge of a potential relationship is insufficient to change family planning practices.

According to the World Health Organization medical eligibility criteria for contraceptive use, no restriction exists for the use of any hormonal contraceptive method for individuals with a current STI, at increased risk of STIs (for example, having multiple partners or a partner who has multiple partners), at high risk of HIV, who are HIV-positive, or who have AIDS. (1) Yet, hormonal contraceptives do not appear to protect against HIV or other STIs. Thus, while continuing to promote hormonal contraception for family planning when appropriate, providers should counsel hormonal contraceptive users who are also at high risk of HIV/STIs to use a condom during each act of intercourse.

A review of issues related to hormonal contraceptive use by women who are infected with HIV or are at risk of infection was held in Washington, DC, USA, in January. 2003. Sponsored by the U.S. National Institute for Child Health and Human Development (NICHD), the meeting was organized to address HIV-infected and at-risk women's need for guidance regarding pregnancy prevention, fertility regulation, and hormone use. The meeting identified the need to better understand:

* Possible interactions between hormonal contraception and antiretroviral therapy;

* Any relationships between hormonal contraception and HW-disease progression;

* Possible effects of hormonal contraception on HIV-positive women's infectivity; and

* Appropriateness of nonhormonal methods for HIV-infected or at-risk women.

Meanwhile, research has focused on the following potential areas of risk:

Hormonal use and HIV acquisition: Two thorough reviews of numerous studies of the risk of HIV acquisition among women who use hormonal contraceptives have been conducted. One found a relationship between use of oral contraceptives (OCs) and HIV acquisition, (2) while the other did not. (3) Authors of the reviews, however, noted that the quality of such studies was generally poor (4) and their results inconsistent. (5)

Few studies of hormonal contraceptive use and HIV acquisition have been prospective (which would reduce the chance of bias), and most have had methodological flaws. However, a large prospective study of the relationship between the use of combined OCs or depot-medroxyprogesterone acetate (DMPA) and HIV acquisition is being conducted by FHI researchers and collaborating institutions, and should yield results in 2004. The study, funded by NICHD, is being conducted in Uganda, Thailand, and Zimbabwe among some 6,200 HIV-negative, 18- to 35-year-old users of combined OCs, users of DMPA, and women not using hormonal contraception. Study participants are tested for HIV every 12 weeks until they have become infected or have been followed for 15 to 24 months. The study is also designed to determine if the presence of STIs other than HIV affects the rate of HIV acquisition among hormonal contraceptive users compared with non-users.

Hormonal use and acquisition of other STIs: Researchers are investigating the effect of hormonal contraceptive use on the acquisition of STIs (other than HIV), which can have major health consequences such as infertility, certain cancers, and other chronic diseases. Infection with STIs (particularly those that cause genital ulcers) also increases both infectivity of and susceptibility to HIV. (6) A prospective cohort study involving 948 Kenyan sex workers found that use of oral or injectable hormonal contraception was associated with susceptibility to STIs: Users of OCs were at greater risk of acquiring chlamydial infection and vaginal candidiasis than women not using hormonal contraception, while women using DMPA had a significantly increased risk of chlamydial infection. (7)

Meanwhile, in a prospective study among some 1,000 U.S. women (484 OC users, 151 DMPA users, and 368 controls), FHI researchers and collaborating institutions found that use of DMPA--but not OCs--was significantly associated with the risk of chlamydial and gonococcal infection. (8) A substudy of this larger investigation found that DMPA use was associated with the risk of acquiring oncogenic human papilloma virus (HPV). OC use, in contrast, was associated with a decrease in the persistence of oncogenic HPV infection. (9) Oncogenic HPV infection is of concern because it is associated with increased rates of cervical cancer.

OC users also had a significantly lower incidence of HPV infection than non-users in a prospective study that included, at study entry, 105 HPV-negative, 13- to 21-year-old U.S. women attending family planning clinics. (10) However, once a persistent HPV infection is established OCs appear to provide no protection against, and may even facilitate, progression to cervical cancer. (11) A pooled analysis of data from eight case control studies conducted by the International Agency for Research on Cancer showed that prolonged use of OCs (from five to nine years) among HPV-infected women was associated with up to a threefold increased risk of cervical cancer. Use for 10 years or longer was associated with up to a fourfold increased risk of cervical cancer. (12)

Hormonal use and HIV transmission: A theoretical concern exists that hormonal contraceptive use by HIV-infected women might increase shedding of HIV and thus increase transmission to uninfected partners. A cross-sectional study evaluating cervical and vaginal secretions of 318 HIV-infected women attending STI clinics in Mombasa, Kenya, found that cervical shedding of HIV-infected cells was significantly associated with use of DMPA and with both low-dose and high-dose OCs. (13) But a prospective study among HW-positive women attending a family planning clinic in Mombasa (101 of whom chose to use DMPA; 52, low-dose combined OCs; seven, high-dose combined OCs; and 50, progestin-only OCs) detected no increase in cervical shedding of HIV-infected cells or free virus one and two months after initiation of hormonal contraception, compared with the period before initiation. (14)

To further clarify the matter, FHI researchers are conducting a prospective study in Zimbabwe and Uganda, funded by NICHD, of the effect of combined OC or DMPA use on HIV genital shedding among 140 women with acute or early HIV infection. The women, who will be compared with HIV-infected women not using hormonal contraception, are being followed every 12 weeks for up to four years. Preliminary results are expected in 2004.

Whether hormonal contraceptive use near the time of HIV infection affects disease progression is also of concern. One study among 115 HIV-infected Kenyan sex workers found that those using hormonal contraceptives near the time of HIV acquisition were more likely to be infected with multiple strains of the virus than women not using hormones. Infection with multiple strains may be associated with faster HIV progression. (15) Similarly, in a prospective cohort study of HW acquisition among 1,337 sex workers in Mombasa--230 of whom acquired HIV during follow-up--the use of DMPA and presence of genital ulcer disease at the time of HIV infection were associated with a higher viral load set point (the blood level at which the HIV virus settles about six months after initial infection). The higher the viral load set point, the faster HIV-related deterioration of the immune system occurs. Thus, this research finding suggests that DMPA use and genital ulcer disease may hasten the natural course of HIV infection. (16)

REFERENCES

(1.) World Health Organization. Improving Access to Quality Care in Family Planning. Medical Eligibility Criteria for Contraceptive Use. Geneva, Switzerland: World Health Organization, 2002.

(2.) Wang CC, Kreiss JK, Reilly M. Risk of H1V infection in oral contraceptive pill users: a meta-analysis. J Acq Immune Defic Syndr 1999; 21(1):51-58.

(3.) Stephenson JM. Systematic review of hormonal contraception and risk of HIV transmission: when to resist meta-analysis. AIDS 1998;12(6):545-53.

(4.) Stephenson.

(5.) Stephenson; Wang.

(6.) Eng TR, Butler WT, eds. The Hidden Epidemic. Confronting Sexually Transmitted Diseases. Washington, DC: National Academy Press, 1997.

(7.) 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.

(8.) Morrison CS, Bright P, Wong E, et al. Hormonal contraception, cervical ectopy and the acquisition of cervical infections. 14th Meeting of the International Society for Sexually Transmitted Diseases Research, Berlin, Germany, June 24-27, 2001.

(9.) Morrison C, Nanda K, Wong E, et al. Hormonal contraception and incidence and persistence of high-risk HPV infection. 20th International Papillomavirus Coherence, Paris, France, October 4-9, 2002.

(10.) Moscicki A-B, 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.

(11.) Brabin L. Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression. AIDS Patient Care STDS 2002;16(5):211-21.

(12.) Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359(9312): 1085-92.

(13.) Mostad SB, Overbaugh J, DeVange DM, et al. Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HW-1 infected cells from the cervix and vagina. Lancet 1997;350(9082):922-27.

(14.) McClelland RS, Wang CC, Overbaugh J, et al. The effect of hormonal contraception on genital shedding of human immunodeficiency virus type-1. The XIV International Conference on HIV/AIDS, Barcelona, Spain, July 7-12, 2002.

(15.) Sagar M, Lavreys L, Baeten J, et al. Correlates of viral diversity in primary HIV-1 infection in women. The Ninth Conference on Retroviruses and Opportunistic Injections, Seattle, WA, February 24-28, 2002.

(16.) Lavreys L, Baeten JM, Kreiss JK, et al. Natural history and covariates of HIV-1 viremia among women in Mombasa, Kenya. The XIV International Conference on HIV/AIDS, Barcelona, Spain, July 7-12, 2002.