The use of progestin-only injectable contraceptives may be linked to an increased risk of chlamydial or gonococcal infection (hazard ratio, 3.6), according to data from women attending two clinics in the eastern United States.1 In contrast to several existing studies, this study did not find a statistically significant association between oral contraceptive use and the risk of acquiring a cervical infection.
Participants were recruited at one reproductive health clinic in the suburbs of Baltimore, Maryland, and one in the inner city from 1996 to 1999. The sample comprised 819 women aged 15-45 who had not used hormonal contraceptives during their last menstrual cycle or the injectable during the last four months, were not currently pregnant or planning to become pregnant in the next year, and tested negative for chlamydia and gonorrhea at enrollment or after treatment. At baseline and at three-, six- and 12-month follow-up visits, researchers conducted standardized interviews to collect information on participants' demographic characteristics, reproductive history, sexual behavior and contraceptive use. Standardized pelvic examinations were performed to evaluate signs of possible infection: abnormal discharge, a vaginal pH of 5.0 or greater, cervical friability (i.e., easily induced bleeding) and cervical ectopy (i.e., growth of tissue from the cervical lining out onto the uterus). In addition, specimens were collected for chlamydial and gonococcal testing.
At baseline, women were classified according to whether they chose to initiate the injectable, oral contraceptives or no hormonal method. To examine relationships between the use of each method and women's risk of infection, the researchers conducted chi-square tests and Cox regression analyses using data collected from 1,988 intervals of contraceptive use accumulated over the course of the study.
Roughly one-half of participants came from the inner-city clinic; 52% were white, and 43% were black. At baseline, the majority were younger than 25, single and nulliparous, and had graduated from high school. Roughly half had had six or more partners, and about three-quarters had used condoms in the last three months. Two-thirds had ever used oral contraceptives, and roughly one in 10 women had used the injectable. Five percent tested positive for chlamydia or gonorrhea at enrollment.
At baseline, higher proportions of women who initiated the injectable than of those who initiated oral contraceptives attended the inner-city clinic (56% vs. 30%); were nonwhite (55% vs. 30%), living with a partner (25% vs. 13%) and aged 25 or older (47% vs. 34%); had a high school education or less (47% vs. 34%); had been pregnant in the past 12 months (25% vs. 10%); and had ever had a child (40% vs. 11%). Injectable users reported several risk behaviors in higher proportions than oral contraceptive users: sex with a partner of positive or unknown STI status in the past year (14% vs. 6%), vaginal douching in the last 12 months (44% vs. 25%) and a coital frequency of five or more times per month during the past three months (63% vs. 60%). Abnormal vaginal discharge, high vaginal pH, cervical friability and diagnosis of chlamydia at baseline were also more common among injectable users than among oral contraceptive users (9-47% vs. 3-34%). Among women who chose neither method (controls), 15% had been pregnant in the past 12 months and 35% had ever given birth; 14% had had sex with a partner of positive or unknown STI status, 46% had douched within the last year and 46% reported a coital frequency of five or more times per month. Proportions with abnormal discharge (28%) and cervical friability (34%) were higher than among hormonal contraceptive users, while chlamydial infection was 6% at enrollment.
At follow-up interviews, risk behaviors in the past three months and clinical signs of possible infection tended to be most common among controls, but so was condom use. Differences were also identified between contraceptive use groups: Higher proportions of injectable users than of oral contraceptive users reported having douched (35% vs. 12%) and having had sex with a partner of positive or unknown STI status (8% vs. 6%); lower proportions reported having had two or more partners (9% vs. 11%), a coital frequency of five or more times per month (61% vs. 71%), sex with a new partner (12% vs. 17%) and having used condoms inconsistently (32% vs. 40%). The proportion of women who had abnormal vaginal discharge at follow-up visits was higher among injectable users than among oral contraceptive users (13% vs. 10%), as were the proportions with high vaginal pH (33% vs. 26%) and cervical friability (21% vs. 11%). However, 83% of women who relied on oral contraceptives had at least .04 cm of ectopy, compared with 77% of injectable users.
Bivariate analyses revealed that injectable users had a significantly higher risk of chlamydial or gonococcal infection than did controls (hazard ratio, 2.8). The risk was also significantly elevated among 15-17-year-olds, women who had a high school education or less, nonwhites, inner-city clinic attendees and participants who had been pregnant in the last year (1.6-6.3). Vaginal douching, multiple sex partners in the past three months and inconsistent condom use were significantly associated with an increased risk of infection (2.1-3.5), as were abnormal discharge, high vaginal pH and cervical friability (2.3-2.9).
The relationship between injectable use and women's risk of infection persisted in multivariate analyses (hazard ratio, 3.6). Participants who were aged 15-17, nonwhite and from the inner-city clinic also had a significantly elevated risk of infection (2.7-4.0). The only behavior significantly associated with an increased risk of acquiring chlamydia or gonorrhea was having had multiple partners in the past three months (2.6). The extent of cervical ectopy did not mediate the relationship between injectable use and women's risk of infection. Neither bivariate nor multivariate analyses revealed a significant association between oral contraceptive use and cervical infection.
The researchers acknowledge that their study is limited because they could not randomly assign women to use specific methods and could not ensure follow-up. Although they can only speculate as to how the hormonal injectable may affect women's susceptibility to cervical infection, they say their findings highlight the "need to counsel all women who use hormonal contraception and are not in a mutually monogamous relationship to use condoms consistently and correctly." Moreover, they point out, if further research corroborates their results, counseling for hormonal contraceptive users in settings where STIs are common "might need to be adjusted to reflect these findings."
1. Morrison CS et al., Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections, Sexually Transmitted Diseases, 2004, 31(9):561-567.