Changes in mucosal immunity of the adolescent genital tract throughout the menstrual cycle

Abstract

BACKGROUND: Females may be most susceptible to STDs during menses and the follicular phase of the menstrual cycle. Research in adults has shown that genital tract immunity is most suppressed as unopposed estrogen peaks at ovulation; adolescents may be more responsive to estrogen, resulting in greater local immunosuppression and higher risk of STD. Study objectives were to (1) characterize mucosal immunity of the adolescent genital tract during the cycle and (2) determine if adolescents have more suppressed immunoglobulin (Ig) levels in the follicular phase than adults.METHODS: Girls age 15-17 years were eligible if they were ≥ 2 years post-menarche, had regular cycles, had had sex, and had a recent normal Pap smear. Daily from cycle day 9 until ovulation, then every other day until menses, cervical secretions for IgA, IgG, and cytokines were collected via Weck-cel sponge and serum for luteinizing hormone (LH), estradiol (E), and progesterone was obtained. To control for individual differences in cycle length and time of ovulation, each visit was converted to relative day (RD) to ovulation. From adult data, representative RDs for each cycle phase were identified: RD −4 (follicular), RD 0 (ovulation), RD +8 (luteal). Igs and cytokines were compared among the phases using the Friedman matched samples test. Spearman correlation coefficients (ρ) were used to correlate E levels with Ig and cytokine levels for each phase. Curves were fitted to the data using locally weighted regression (loess) smoothing. Rates of change in IgA and IgG were determined by the slope (β) from linear regressions for the follicular and luteal phases. Mean βs were compared with historical data on 13 adults, using t tests.RESULTS: Three girls (mean age 16.8 years) completed 49 visits (13-23 each). Mean IgA levels varied from 455 μg/mL (RD −4) to 140 μg/mL (RD 0) to 863 μg/mL (RD +8) (p = 0.05), as did mean levels of interleukin (IL)-6 (1756 to 262 to 6200 pg/mL, p = 0.05) and IL-8 (34 to 4 to 59 ng/mL, p = 0.05). Mean IgG levels followed a similar pattern, although the differences were not significant. Loess curves showed that IgA, IgG, IL-2, and IL-8 reached their lowest levels within 1 day of ovulation. In the follicular phase, E levels were negatively correlated with IgA (ρ = −0.62, p = 0.008), IL-2 (ρ = −0.52, p = 0.04), and IL-10 (ρ = −0.70, p = 0.002). Compared with adults, adolescents had a greater drop in IgG in the follicular phase (mean β −953 vs. −269 μg/mL/day, p = 0.045), but a similar rate of rise in IgG in the luteal phase (mean β + 118 vs. +100 μg/mL/day, p = 0.252). Rates of change in IgA did not differ between adolescents and adults for either phase.CONCLUSIONS: Cervical Ig and cytokine levels vary during the menstrual cycle in adolescents, reaching their nadir at ovulation. Adolescents have a steeper decline in follicular IgG than adults, suggesting that adolescents are more immunosuppressed when exposed to unopposed estrogen. Replicating and expanding these findings with a larger sample will be important to develop effective immunoprotection against STDs for this vulnerable population.