We analyzed whether chlamydial infection was more prevalent among females with larger amounts of ectopy or T zone, and among females using OCs or DMPA. Analyses were adjusted for potential confounders such as age, sexual partners, sexual frequency, condom use, douching, and reproductive or gynecologic history (menarche, parity, past sexually transmitted diseases).
Univariate analysis. We analyzed the frequency and percent of chlamydial infection by strata of the risk factor or potential confounder. Differences among levels were evaluated with the Fisher exact test. Unadjusted odds ratios and 95% CIs of infection between strata were obtained from simple logistic regression. All analyses were performed with SAS version 6.11 (SAS Institute, Cary, NC).
Multivariate analysis. We used multivariate logistic regression to calculate the adjusted odds of chlamydial infection by the amount of cervical ectopy (area or percent), the amount of T zone (area or percent), and by hormonal contraceptive use (OC, DMPA). Potential confounders were examined in multivariate models if they were associated with the risk factor and chlamydial infection on univariate analysis, or if they were predictors of chlamydia in the documented literature. The final models each contain only three variables because of small numbers. Variables that were not significantly associated with chlamydia are indicated at the bottom of the multivariate tables.
Categorization of Variables
The areas and percent of ectopy and T zone were divided into approximate tertiles. Ectopy was not normally distributed (25% of participants had no ectopy). All categories were established before data analysis based on biology and previous literature, when available.15 The categories were (1) area of ectopy: none (0 mm2), mild (<22 mm2), and moderate (>22 mm2); (2) percent ectopy: none (0%), mild (0.01‐8%), and moderate (>8%); (3) T zone area: small (<129 mm2), moderate (129‐198 mm2), and extensive (>199 mm2); and (4) percent T zone: mild (<31%), moderate (31‐46%), and extensive (>47%). Age and sexual and reproductive history were categorized by the median, tertile, or average ages of reproductive or sexual events obtained from the literature.1
Cervical specimens were tested for chlamydia by PCR using the Amplicor system (Roche Molecular Diagnostics, Branchburg, NJ) according to the manufacturer's instructions.13,14
Description of Population
Although cervical photographs were taken in 97 patients, nine photographs were unreadable because the cervix was not adequately visualized. These nine participants who were subsequently excluded from the analysis of ectopy and T zone did not differ by demographic, reproductive, or gynecologic histories.
The median age of this predominantly black (91%) sample was 17 years (Table 1), and sexual debut occurred at a median of 14.0 years. Half of the participants had been sexually active for > 3 years and 41% had been pregnant. At study enrollment, 12 females (12%) were using OCs, 15 (15%) were using DMPA, 2 (2%) were using Norplant, and 64 (66%) were not using any form of hormonal contraception.
Cervical measures and cervical maturation. Sixty of 88 participants (74%) had ectopy. C trachomatis was detected by polymerase chain reaction in 15 of 97 females (15%) (Table 1). Chlamydia prevalence was not significantly different among the three ectopy strata (Table 2). Adolescents with moderate ectopy (27.3 percent) tended to have a greater rate of infection than adolescents with mild ectopy (11.1%, P = 0.08) on univariate analysis only. Neither T zone area nor T zone percent was significantly associated with chlamydia.
Hormonal contraception. Chlamydial infection was associated with current DMPA use. Forty percent of current DMPA users had chlamydia, compared with 8% of OC users and 12% of nonhormone users (P = 0.03) (Table 3). Use of DMPA for more than 3 months conferred the greatest risk of infection compared with use for 1 to 3 months or with nonhormone use (P < 0.001). Duration of OC use was not associated with chlamydial infection.
Sexual history and sexually transmitted diseases. In contrast to previous studies, chlamydial infection was more common in women with fewer lifetime partners (32% versus 10%, P < 0.001) (Table 3). The prevalence of chlamydia did not differ significantly by type of partner, sexual frequency, or condom use. There was a nonsignificant trend for higher prevalence of chlamydia in persons without a history of gonorrhea or trichomoniasis.
Association between hormonal contraception and other covariates. DMPA users were generally similar to OC users and nonhormonal contraceptive users in terms of demographics and behavioral and gynecologic history; however, DMPA users were more likely to be monogamous and to have more frequent sex than OC users. However, these variables are unlikely to be confounders because they were associated with hormonal contraceptive use (the risk factor), but not with chlamydial infection (the outcome).
We evaluated the independent contribution of cervical ectopy and T zone and hormonal contraceptives to chlamydial infection adjusted for covariates (Table 4). Chlamydia was not independently associated with any amount of cervical ectopy even after adjustment (model 1).
Chlamydial infection was more likely in DMPA users compared with nonhormone users (adjusted OR, 5.44; 95% CI, 1.25‐23.6) even when adjusted for age and lifetime number of partners (model 2). The strength of the association between DMPA and chlamydia diminished when adjusted for age and T zone size (adjusted OR, 3.6; 95% CI, 0.72‐17.68) (model 3). Oral contraceptive users did not have an increased likelihood of chlamydial infection in this study (adjusted OR, 0.92; 95% CI, 0.10‐8.78), adjusted for age and number of partners (model 2), or for age and T zone size (model 3).
Paradoxically, chlamydia was somewhat less likely with more lifetime partners (adjusted OR, 0.31; 95% CI, 0.08‐1.17) when adjusted for age and current contraceptive use (models 1 and 2). No other variables were associated with chlamydial infection, including age, number of partners during the past 6 months, condom use, frequency of sex during the past 6 months, reproductive history, past hormonal contraceptive use, or history of gonorrhea or trichomoniasis.
Using a standardized, reproducible measurement technique for cervical ectopy, we examined two chlamydia risk factors that are especially relevant to young women: cervical ectopy and hormonal contraception. We found that carefully measured ectopy was not associated with prevalence of chlamydia.
After adjusting for age and number of sexual partners, DMPA users were more likely to be infected with chlamydia compared with nonhormone users. Although this relation was no longer significant after adjustment for T zone size, we think that this decrease is explained by the strong association between DMPA and T zone size rather than by confounding by T zone. No independent relation between T zone and chlamydia was found. OC users did not have an elevated prevalence of chlamydial infection compared with DMPA or nonhormone users.
Our results contrast with most previous cross‐sectional studies in adolescents that found a relation between ectopy and chlamydial infection.9,16,17 Our results coincide with one previous longitudinal study that did not find an elevated risk of infection with greater amounts of ectopy.7 We think that previous studies may have used less‐sensitive measurements with the potential misclassification of T zone and inflammation as ectopy.7 It easier to distinguish between the areas of ectopy and T zone using cervical photographs after acetic acid application because the T zone may appear red with unaided visual assessment. Computerized planimetry allowed for the reliable quantification of the different cervical zones and the detection of small areas of ectopy not seen by unaided visual assessment. These techniques also improved measurement reliability.11
To assay for chlamydia, we used PCR techniques that increases sensitivity by 20‐30% compared with culture.18 With culture techniques, ectopy may improve detection of the organism because the columnar cells are exposed to the vaginal environment. Use of PCR may reduce this detection bias because fewer organisms are needed to detect an infection.
The relation between OCs and chlamydia has been debated.7–9,19–21 A second controversy relates to the contribution of estrogen or progesterone components. Our data suggest that progesterone (e.g., DMPA) is more likely than estrogen to increase the risk of chlamydial infection. Few other studies have evaluated DMPA as a risk factor for chlamydial infection.22
The inconsistent results among previous studies on the relation between OC use and chlamydia risk may be due to multiple factors, including varying duration of hormone exposure8 or behavior changes in women using different contraceptive methods. Adolescents frequently change or discontinue contraception, have variable compliance, and change the frequency of intercourse.1 For example, one study found a higher prevalence of chlamydia among adolescents using OCs for more than 6 months.8 Similarly, in our study no person currently using OCs or DMPA for less than 4 months was infected. Finally, although dose of estrogen or progesterone in OCs has not been associated with an increased rate of chlamydia,5,23 our study may differ because current OC preparations have less estradiol and progestin, are less androgenic, and are are more similar to each other than past OC preparations.
The mechanism by which progesterone might elevate the risk of chlamydial infection is not well known. Progesterone might alter attachment or growth of chlamydia24 and stimulate hyperplasia of columnar cells, thereby increasing the number of target cells24 or maintain the number of columnar cells by inhibiting metaplasia. DMPA may directly affect the T zone because progesterone alone inhibits complete maturation of squamous epithelium.25 Although OCs, which contain estrogen and progesterone, are thought to elevate chlamydial risk primarily by producing ectopy, it is unlikely that progesterone alone promotes infection by ectopy. In another study, we found no association between DMPA or OCs and ectopy.26
Because of our small sample size and cross‐sectional design, we were limited in our ability to detect small differences in infection rates, to adjust for multiple confounders, to test for interaction between ectopy and hormone use, or to derive more precise odds estimates.
Cervicography was well tolerated and less subject to observer bias than previous techniques. Applying these methods in a large prospective study will improve our understanding of the complex relation between DMPA, OC use, cervical development, and the risks of infection with chlamydia. It will be important to obtain baseline measurements of ectopy and T zone before hormonal contraceptive use. Because DMPA use is increasing worldwide, it is important to gain a better understanding of the potential risk of DMPA use, which may increase reproductive sequelae among young women.
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© Copyright 2000 American Sexually Transmitted Diseases Association
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