Article

Endogenous Reproductive Hormones and C-reactive Protein Across the Menstrual Cycle: The BioCycle Study

Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
American journal of epidemiology (Impact Factor: 5.23). 03/2012; 175(5):423-31. DOI: 10.1093/aje/kwr343
Source: PubMed

ABSTRACT

C-reactive protein (CRP) is one of the most commonly used markers of acute phase reaction in clinical settings and predictors of cardiovascular risk in healthy women; however, data on its physiologic regulation in premenopausal women are sparse. The objective of this study was to evaluate the association between endogenous reproductive hormones and CRP in the BioCycle Study (2005-2007). Women aged 18-44 years from western New York were followed prospectively for up to 2 menstrual cycles (n = 259). Serum levels of CRP, estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to 8 times per cycle, timed by fertility monitors. CRP levels varied significantly across the cycle (P < 0.001). More women were classified as being at elevated risk of cardiovascular disease (CRP, >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%; P < 0.001). A 10-fold increase in estradiol was associated with a 24.3% decrease in CRP (95% confidence interval: 19.3, 29.0). A 10-fold increase in luteal progesterone was associated with a 19.4% increase in CRP (95% confidence interval: 8.4, 31.5). These results support the hypothesis that endogenous estradiol might have antiinflammatory effects and highlight the need for standardization of CRP measurement to menstrual cycle phase in reproductive-aged women.

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    • "However, follicular and luteal CRP concentrations were not different in this sample, and so CRP was not necessarily suppressed in the luteal phase in these participants. A recent study of industrialized women in western New York found that CRP increased through the luteal phase in spontaneous nonconceptive cycles (Gaskins et al., 2012), which suggests that systemic inflammatory activity is not necessarily lower through the luteal phase. "
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    ABSTRACT: Objectives: To test the hypothesis that life history trade-offs between maintenance and reproductive effort would be evident through inverse associations between levels of a biomarker of inflammation [C-reactive protein (CRP)], and ovarian hormones. Associations between CRP and age at menarche were also explored. Methods: Urinary CRP, salivary progesterone, and estradiol were measured over one menstrual cycle from rural Polish women (n=25), representing a natural fertility sample. Age of menarche was assessed through interview recall methods. We used minimum second-order Akaike Information Criteria as a means of multiple regression model selection, and repeated measures ANOVA to test cycle-dependent hypotheses. Results: Comparisons of individuals in high and low CRP tertiles revealed that those with high CRP had significantly lower progesterone (luteal P=0.03, mid luteal P=0.007) but not estradiol (follicular P=0.21, luteal P=0.15) concentrations through the menstrual cycle. However, when the age at menarche was included in the analysis, both age at menarche and urinary CRP were negatively associated with estradiol (R2=0.44, P=0.0007). Age at menarche and estradiol were the strongest negative predictors of CRP (R20=52, P=0.0001). Conclusions: Inflammation itself may suppress ovarian function, or indicate immune challenges that lead to ovarian suppression. The timing of menarche may also influence adult inflammatory sensitivity and ovarian hormone concentrations. This lends support to existing models of trade-offs between maintenance and reproduction in women.
    Full-text · Article · Aug 2013 · American Journal of Human Biology
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    • "Previous researchers have reported a rise in CRP at the time of menses [46], [50], more specifically a 50% increase in the variance in CRP concentrations at menses compared to other phases of the cycle [50]. This rise was attributed to endometrial cell turnover at the time of menses. "
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    ABSTRACT: Ovarian processes and the timing of ovulation are important predictors of both female fertility and reproductive pathology. Multiple waves of antral follicular development have been documented during the menstrual cycle in women. However, the mechanisms underlying the development of follicular waves and their clinical significance are not fully understood. The objective of this study was to examine the relationship between C-reactive protein (CRP) and follicular waves in healthy women. We wanted to determine whether follicular wave dynamics influence systemic inflammation, as ovarian activity increases local inflammatory processes and blood flow. We tested the hypothesis that women with 3 follicular waves would have higher CRP concentrations than those with 2 waves. We further hypothesized that a greater number of major waves (those with a dominant follicle) would be positively associated with CRP. Thirty-nine healthy women underwent daily transvaginal ultrasound examinations for one interovulatory interval, as part of an earlier study. Serum was collected every 3 days during the interovulatory interval (IOI). Enzyme-linked immunosorbent assays were conducted to quantify serum CRP concentrations. Women with 3 waves had higher average log CRP concentrations (n = 14, -0.43±0.35) over the IOI than those with 2 waves (n = 25, -0.82±0.47, p = 02). Average log CRP concentrations were greater in women with 3 (0.30±0.31) versus 1 (-0.71±0.55) or 2 (-0.91±0.47) major waves (p = 0.03). Greater average CRP over the IOI was attributed to greater CRP in the follicular, but not the luteal phase, of the IOI. A greater number of total antral follicular waves, in particular major waves, corresponded to greater serum concentrations of CRP. These findings suggest that women with a greater number of follicular waves exhibit greater tissue remodeling and therefore greater local and systemic inflammation.
    Full-text · Article · May 2013 · PLoS ONE
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    • "However, follicular and luteal CRP concentrations were not different in this sample, and so CRP was not necessarily suppressed in the luteal phase in these participants. A recent study of industrialized women in western New York found that CRP increased through the luteal phase in spontaneous nonconceptive cycles (Gaskins et al., 2012), which suggests that systemic inflammatory activity is not necessarily lower through the luteal phase. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To test the hypothesis that life history trade-offs between maintenance and reproductive effort would be evident through inverse associations between levels of a biomarker of inflammation [C-reactive protein (CRP)], and ovarian hormones. Associations between CRP and age at menarche were also explored. Urinary CRP, salivary progesterone, and estradiol were measured over one menstrual cycle from rural Polish women (n = 25), representing a natural fertility sample. Age of menarche was assessed through interview recall methods. We used minimum second-order Akaike Information Criteria as a means of multiple regression model selection, and repeated measures ANOVA to test cycle-dependent hypotheses. Comparisons of individuals in high and low CRP tertiles revealed that those with high CRP had significantly lower progesterone (luteal P = 0.03, mid luteal P = 0.007) but not estradiol (follicular P = 0.21, luteal P = 0.15) concentrations through the menstrual cycle. However, when the age at menarche was included in the analysis, both age at menarche and urinary CRP were negatively associated with estradiol (R(2) = 0.44, P = 0.0007). Age at menarche and estradiol were the strongest negative predictors of CRP (R(2) = 0.52, P = 0.0001). Inflammation itself may suppress ovarian function, or indicate immune challenges that lead to ovarian suppression. The timing of menarche may also influence adult inflammatory sensitivity and ovarian hormone concentrations. This lends support to existing models of trade-offs between maintenance and reproduction in women. Am. J. Hum. Biol. 25:389-398, 2013. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · May 2013 · American Journal of Human Biology
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