Do Hormonals Affect STI Risks?

Several counseling options are likely if further research suggests an increased STI risk from hormonal methods.

Network: 2001, Vol. 20, No. 4

Do hormonal contraceptives affect the acquisition and transmission of sexually transmitted infections (STIs), including HIV? If so, what are the implications for the provision of these methods, which are among the world's most widely used contraceptives?

Research is conflicting, largely due to study design difficulties. However, it is clear that hormonal contraceptives do not protect against HIV or other STIs. Thus, providers should counsel women at high risk of HIV/STIs to use a condom during each act of intercourse, even if they are already using a hormonal method.

In the absence of conclusive research that use of hormonal contraception increases STI risks, providers should also continue to promote hormonal contraception when it is appropriate for family planning. The World Health Organization's contraceptive eligibility guidelines place no restrictions on the use of any hormonal method by women who are at increased risk of HIV or other STIs.¹

If further research shows hormonal contraception increases STI risks, providers likely will have several counseling options, says Dr. Charles Morrison, an FHI epidemiologist and principal investigator for a large study in Zimbabwe, Thailand and Uganda of the impact of oral contraceptive and injectable depot-medroxyprogesterone acetate (DMPA) use on HIV acquisition.

"First, women not exposed to HIV/STIs could continue to use any form of hormonal contraception that is appropriate for their family planning needs," he says. "Second, if a strong association were found between one of the hormonal methods and HIV (but not between another hormonal method and HIV), clients in countries with high HIV prevalence could obviously be counseled to use the method that does not present an increased risk."

If a strong association were found between HIV and both the pill and DMPA, women could be counseled to consider other effective contraceptives, such as intrauterine devices. For a woman still choosing hormonal contraception, it would be essential to counsel condom use for disease protection in addition to use of the hormonal method. Also, any risk associated with hormonal contraception would have to be carefully weighed against the risks of rejecting reliable contraception, and the risks associated with pregnancy itself, says Dr. Morrison.

Widely used methods

The most widely used hormonal contraceptives are oral contraceptives (which use a progestin alone or a combination of a progestin and an estrogen) and progestin-only injectables, primarily DMPA. Oral contraceptives, used by more than 100 million women worldwide in 2000,² are the most common modern contraceptive method used in sub-Saharan Africa, where rates of new HIV infections are high even among "low-risk" family planning clients. In Southeast Asia and India -- where the HIV epidemic is growing -- a quarter and a half, respectively, of those women using a modern contraceptive method use the pill.³ Progestin-only injectables are used by some 12 million women worldwide.⁴

Theoretically, these hormonal contraceptives have the potential to increase the risk of STI acquisition in a number of ways, since both estrogen and progestins affect the female genital tract. Oral contraceptives can cause cervical ectopy, a condition in which a specific type of cell that lines the inside of the cervical canal extends onto the outer surface of the cervix, where exposure to sexually transmitted pathogens is greater. Cervical ectopy appears to increase vulnerability to some STIs,⁵ which, in turn, increases a woman's risk of HIV infection.⁶ Hormones in the pill and injectables have been associated with changes in the immune system and, theoretically, could weaken it.⁷ Also, use of progestins alone thins the lining of the vagina, possibly leaving it more susceptible to tears or abrasions through which STI pathogens could enter the body. Finally, while progestins alone may inhibit infection by thickening cervical mucus,⁸they can decrease vaginal acidity, a condition that facilitates infection.

Research suggests that oral contraceptive users are more likely to become infected with chlamydia than are non-users.⁹ Whether cervical ectopy is directly associated with chlamydial infection, however, is unknown. Data also are conflicting as to whether hormonal contraception enhances infection with other STIs, such as gonorrhea. To address such gaps in knowledge, FHI is conducting among 1,000 U.S. women a prospective study of the association between DMPA or pill use, the development of cervical ectopy, and subsequent chlamydial and gonococcal infection. Results are expected in 2001.

Using the pill appears to reduce symptoms, as well as the incidence, of pelvic inflammatory disease (PID), caused by untreated gonococcal and chlamydial infection. But asymptomatic PID still may damage a woman's fallopian tubes, leaving her at risk for infertility.

Nearly all of some 30 studies of the association between hormonal contraception and HIV had major limitations, a team from FHI and the University of Washington, Seattle, WA, USA, concluded in 1998. A British researcher who reviewed the data from many of the same studies reached the same conclusion, noting that "no clear or consistent patterns emerge from these studies."¹⁰ However, a significant association between pill use and increased HIV risk was found by University of Washington researchers when they analyzed 28 studies grouped by methodologic quality. When six of the eight best studies detected the association, researchers concluded that "for women at risk of HIV infection, oral contraceptive use for prevention of pregnancy should be accompanied by condom use for prevention of HIV infection."¹¹

Data from studies of progestin-only injectables and HIV/STI risks also are conflicting, and no published studies are available on the impact of Norplant, a progestin-only implant, on HIV acquisition. A 1996 study found an eight-fold increase in simian immunodeficiency virus (SIV) infection in SIV-exposed monkeys receiving implants that maintained high progestin levels in their blood, compared to a group of placebo control monkeys exposed to SIV at a stage of their menstrual cycle when natural progesterone levels were low. Researchers noted that enhanced HIV infection was strikingly correlated with progesterone-related thinning of the monkeys' vaginal lining.¹²However, monkeys exposed to SIV throughout the entire menstrual cycle had a much lower risk of infection, an important observation since women at risk for HIV infection probably are exposed to the virus throughout most of the menstrual cycle.¹³

In a recent study of the effect of one DMPA injection, women did not experience at one or three months the dramatic vaginal thinning previously seen in monkeys.¹⁴Another recent study showed that DMPA use among 20 women for two to three years did not affect the thickness of the vaginal lining.¹⁵

At a 1996 meeting, experts reviewed human study data and concluded that an association between hormonal contraceptive use and HIV infection was questionable. Obtaining more definitive information requires a large, prospective study of the impact of oral contraceptive and DMPA use on HIV infection among women in a low-risk, general population, concluded a 1996 National Institute of Child Health and Human Development (NICHD) panel.

The study that FHI is coordinating in Zimbabwe, Thailand and Uganda has been carefully designed to avoid many of the methodological pitfalls of earlier studies. Sponsored by NICHD and expected to be completed in 2003, the study will follow for 15 to 24 months about 6,000 low-risk, HIV-negative women seen at family planning, maternal/child health, and STI clinics. Ancillary studies will investigate whether hormonal contraception affects acquisition of herpes simplex virus (HSV), human papilloma virus (HPV) and bacterial vaginosis, and the role of these infections in HIV acquisition. In addition, FHI will investigate the role of hormonal contraception and HIV subtype on genital shedding of HIV among women who become infected during the study.

Use of the pill, use of DMPA, and pregnancy are all associated with greater cervical shedding of HSV, according to a recent study of 273 women in Mombasa, Kenya, who were infected with both HIV and HSV. "The increased frequency of HSV shedding in hormonal contraceptive users and pregnant women may reflect direct effects of the hormones on virus replication or effects on the immune system's ability to control virus reactivation," noted the study's authors.¹⁶ However, results of studies of the association between hormonal contraception and cervical shedding of HIV are limited and inconclusive.

-- Kim Best

References

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