Chlamydial infection. Most recent studies find an association between use of OCs and infection with Chlamydia trachomatis, the most common STI (2, 4, 17, 35, 37, 97, 244, 284, 285, 331, 553). Older studies found a two- to threefold increase in risk of chlamydia among OC users (506). Some recent studies have found less increase, about 70% more than nonusers, and others have found no increase in risk (347, 374, 394, 509).

Greater risk of chlamydial infection among pill users could be due largely to cervical ectopy. Cervical ectopy is the extension of sensitive columnar epithelial cells from the cervical canal to the vaginal surface of the cervix. It is known to occur in OC users (219). Cervical ectopy may make columnar cells easier targets for C. trachomatis (17, 30, 94, 392). Several studies confirm a link between ectopy and chlamydial infection (284, 347, 374). These studies, however, could not determine which came first—ectopy or infection—and so it is not clear whether ectopy leads to infection or infection leads to ectopy. Similarly, in studies of chlamydial infection and OCs, it is possible that ectopy simply makes it easier to detect the infection (17, 505).

Chlamydial pelvic inflammatory disease (PID). For more than 10 years there has been considerable speculation about whether or not OCs actually offer some protection against PID caused by the ascent of chlamydial infection from the cervix into the fallopian tubes. Although OC users seem more susceptible to chlamydial infection than other women do, they are less likely to experience symptomatic chlamydial PID. For example, two recent studies found that pill users faced 20% to 30% as much risk of chlamydial PID as women using nonhormonal methods (242, 439).

How would OCs help protect against chlamydial PID? Possible explanations include reduced penetrability of cervical mucus, reduced uterine contractions during menses, and alteration of immunological response (36). Whether any of these mechanisms apply, however, is not certain.

Furthermore, most studies of PID have involved only women hospitalized for PID, which accounts for less than one-quarter of cases (439). Women hospitalized for PID are not representative of all women who have PID. Chlamydial PID, moreover, is less likely to lead to hospitalization than other forms of PID because chlamydial PID tends to be milder and less often noticed (340).

Other reproductive tract infections. Possible associations between OCs and other RTIs have also been studied, although not as extensively as OCs and chlamydial infection. The use of OCs has been reported to increase the risk of gonorrheal infection by 70% (284, 392) and the risk of candidiasis, a common yeast infection that is not usually sexually transmitted, by 50% to 80% (67, 392). Findings on OCs and bacterial vaginosis are conflicting. One study found a significant increase in risk (67); some have found a significant decrease (310, 424); and another found no relationship between OC use and risk of bacterial vaginosis (176). There is some evidence that OCs help protect against Trichomonas vaginalis, a common cause of vaginitis (22), although not all studies have found a protective effect (331).

Human immunodeficiency virus (HIV). Studies fail to show clear and consistent associations between OC use and HIV infection. Studies of the risk factors for HIV infection vary widely in quality and methodology and are difficult to compare directly. For many, OC use was only one of a number of variables that were examined, and the potential relationship between OC use and HIV was not the focus of the study. Individual studies often show elevated, although not statistically significant, risk of HIV infection among OC users. A recent analysis that pooled the results of 28 studies published or presented between 1985 and 1999 found a significant association between use of OCs and the incidence or prevalence of HIV infection. Based on the eight studies considered methodologically most sound, OC use was associated with a 60% increase in risk (504). Studies of OCs and HIV may not be suitable for a pooled analysis, however. One recent review of the literature on the association between OCs and HIV infection concludes that studies to date suffer from methodological limitations that make them inappropriate for combined statistical analysis (445).

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Several recent studies have found a significant association between OCs and HIV among various subgroups after adjusting for a variety of confounding factors. A prospective study of 435 HIV-negative Kenyan sex workers found that over a one-year period OC users were 2.6 times more likely to become HIV positive than women not using OCs (291). Another found a link only among poor women, after taking account of condom use, number of partners, and husband having multiple sexual contacts (202). In contrast, a study of women attending a Nairobi antenatal clinic—a group considered at low risk of HIV infection—found that OC users were 3.5 times more likely to be infected with HIV than women using other methods of contraception or no contraception at all. The association persisted after adjustment for variables such as frequency of intercourse, number of partners, and history of STI symptoms. Few of these women used condoms (428).

A cross-sectional study in Nairobi suggests that OC use increases the risk of HIV infection only among women with genital ulcers. OC use alone did not increase HIV risk. Women who had used OCs longer than 12 months and had genital ulcer disease, however, were 25 times more likely to be infected with HIV than women who did not use OCs and did not have genital ulcers. This finding was based on 16 women who were long-term OC users and had genital ulcer disease, 80% of whom were infected with HIV (362).

Some evidence has led to speculation that HIV-infected OC users could infect their partners more readily than other HIV-infected women. In Kenyan women HIV DNA was found more often in the cervical and vaginal secretions of HIV-infected OC users than in other HIV-infected women. The higher the OC dose, the more likely that HIV DNA was present (315). Another study found that HIV-infected OC users shed significantly more HIV DNA in cervical cells than did other HIV-infected women (77). Not all studies have found a link between OCs and HIV DNA levels, however (249).

The presence of another STI increases the risk of HIV infection by two- to sixfold (56, 91, 108, 114, 205, 232, 238, 256, 303, 339, 363). Bacterial vaginosis, which is often but not always sexually transmitted (201), also has been linked to increased HIV risk (414, 451, 507). If other STIs make women more susceptible to HIV infection, and OCs make women more susceptible to other STIs, then OCs might indirectly increase HIV risk (66, 217).

Studies of OCs and HIV are particularly difficult to carry out and to interpret. As in all studies of family planning methods, ethics prevent randomly assigning women to use various contraceptive methods. Differences in sexual behavior associated with choice of methods then make it difficult to compare users of different methods. Furthermore, all study participants at risk for STIs must be encouraged to use condoms and instructed in their use, making it difficult to study the effects of OCs among women who do not use condoms. Also, uncertainty about when a woman became infected with HIV can make it hard to know if a woman was using OCs at the time of infection. Finally, differences in classifications of OC use patterns make comparisons among studies difficult.