Familial aggregation of circulating c-reactive protein in polycystic ovary syndrome. Sasidevi A et al. STUDY QUESTION: What is the heritability of C-reactive protein (CRP) levels in women with polycystic ovary syndrome (PCOS) and their first-degree relatives? SUMMARY ANSWER: Women with PCOS and their siblings are more likely to have elevated CRP levels when both of their parents have elevated CRP. This PCOS family-based study indicates that CRP levels are likely a heritable trait. WHAT IS KNOWN ALREADY: Previous studies have established that an elevated blood level of CRP is variably present in women with PCOS, and may be present independent of metabolic status. STUDY DESIGN, SIZE AND DURATION: A familial based phenotyping study consisting of 81 families comprised of PCOS patients and their first-degree relatives for 305 subjects. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Study conducted at an academic health center. An elevated CRP level was defined as >28.6 nmol/l. To account for familial clustering, generalized estimating equations with a logit link were used to model the association between elevated CRP levels in patients with PCOS and their siblings with their parental group (A = neither parent with elevated CRP; B = one parent with elevated CRP; C= both parents with elevated CRP), adjusting for gender, age and BMI of the offspring. We did additional heritability analyses by using a variance component estimation method for CRP levels, adjusting for sex, age and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We observed elevated CRP levels in 94% of the offspring in group C, 45% in group B and 10% in group A after adjusting for age, gender and BMI of the offspring. The median BMI of the offspring in group A, B and C were 30.0, 28.7 and 31.2 kg/m(2), respectively. Heritability estimates of CRP levels ranged from 0.75 to 0.83 and remained significant after excluding for type 2 diabetes mellitus. Our small sample size increases the possibility of a type 1 error. LIMITATIONS, REASONS FOR CAUTION: This is a single report in an adequately powered but limited sample size study identifying the strong heritability of CRP levels. Replication in other large family cohorts is necessary. WIDER IMPLICATION OF THE FINDINGS: These findings support the concept that there is an increased cardiovascular disease risk profile in families of women with PCOS. STUDY FUNDING/COMPETING INTEREST: This research was supported by National Institutes of Health grants U54HD-034449 and P50 HD044405 (A.D.). Priyathama Vellanki is supported in part by NIH/NIDDK Training Grant T32 DK007169.
Increased C-Reactive Protein Levels in the Polycystic Ovary Syndrome: A Marker of Cardiovascular Disease.
Boulman N, et al .
The polycystic ovary syndrome (PCOS), one of the most common reproductive abnormalities, shares some components of the metabolic cardiovascular syndrome. Therefore, PCOS patients may represent the largest group of women at high risk for the development of early-onset cardiovascular disease (CVD) and/or diabetes. C-reactive protein (CRP) is a strong independent predictor of future CVD and/or stroke. Only one small published study has looked for such an association (17 PCOS patients vs. 15 controls). The objective of this study was to compare the levels of CRP and other risk factors of CVD in a large group of PCOS patients and controls. CRP measurements were undertaken in 116 PCOS patients and 94 body mass index-matched controls with regular menstrual cycles. Whereas 36.8% of the PCOS patients had CRP levels above 5 mg/liter, only 9.6% of the controls exhibited high CRP levels (P < 0.001). The mean +/- SD was 5.46 +/- 7.0 in the PCOS group vs. 2.04 +/- 1.9 mg/liter in the control (P < 0.001). The body mass index, white blood cell count, TSH, glucose, cholesterol, and homocysteine levels were not significantly different between the two groups. CRP levels are elevated in patients with PCOS and may be a marker of early cardiovascular risk in these patients. High CRP levels may explain why some PCOS women may possibly be at an increased risk for the development of early-onset CVD. Consequently, whether treatment regimens directed toward lowering CVD risk factors should be more aggressive for those PCOS women with increased CRP levels, awaits further clinical experience.
NCBI Summary:
The protein encoded by this gene belongs to the pentaxin family. It is involved in several host defense related functions based on its ability to recognize foreign pathogens and damaged cells of the host and to initiate their elimination by interacting with humoral and cellular effector systems in the blood. Consequently, the level of this protein in plasma increases greatly during acute phase response to tissue injury, infection, or other inflammatory stimuli. [provided by RefSeq, Sep 2009]
General function
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Cellular localization
Secreted
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Ovarian function
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Serum High-Sensitivity C-Reactive Protein and Homocysteine Changes During Hormonal Therapy in Women With Polycystic Ovary Syndrome: A Prospective, Matched Study. Makedos A et al. The study evaluated the effect of 5 hormonal regimes on serum levels of high-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) in women with polycystic ovary syndrome (PCOS). Women with PCOS received (1) conjugated estrogens and cyproterone acetate (n = 22), (2) 17beta-estradiol and cyproterone acetate (n = 17), (3) ethinyl-estradiol and cyproterone acetate (high dose; n = 20), (4) ethinyl-estradiol plus cyproterone acetate (low dose; n = 12), or (5) ethinyl-estradiol plus desogetrel (n = 12). Both hsCRP and Hcy levels were measured at baseline and after 4, 7, and 12 months. The 17beta-estradiol/cyproterone acetate regime resulted in significant reduction of both hsCRP and Hcy levels (P < .001). The other 4 regimes only resulted in a reduction of Hcy levels (P < .001). In conclusion, the 17beta-estradiol/cyproterone acetate regime had the most favorable effects in women with PCOS regarding serum levels of hsCRP and Hcy.
Expression regulated by
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Ovarian localization
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Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles. Capobianco G et al. PURPOSE: To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle. METHODS: Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2-3), periovulatory phase (days 12-13), and luteal phase (days 23-24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE). RESULTS: In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles. CONCLUSIONS: There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon.
Follicle stages
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Impact of metformin on C-reactive protein levels in women with polycystic ovary syndrome: a meta-analysis. Chen Y et al. (2017) The impact of the recommended first-line treatment with metformin on C-reactive protein (CRP) levels in patients with polycystic ovary syndrome (PCOS) is still controversial. We conducted a meta-analysis of studies reporting the impact of metformin on serum CRP levels in women with PCOS. The weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs) were used to assesse the effects. GRADE approach was used to assesse the quality of the evidence. A total of 20 studies that included 433 women with PCOS were analyzed. CRP levels significantly decreased after metformin treatment (WMD = -1.23mg/L, 95%CI: -1.65 to -0.81, I2 = 93% and P < 0.001 for heterogeneity). The decreased levels of CRP were observed both in lean (BMI<25 kg/m2) and obese (BMI>25 kg/m2) patients. Interestingly, the degree of decreased CRP levels was not depended on metformin dosage, but more significantly in patients treated beyond 6 months (WMD≥6months = -1.47mg/L vs. WMD<6months = -0.94 mg/L). Decreased CRP levels are not associated with the status of IR and androgen in patients with PCOS. However, the quality of evidence was very low because of the limitations and inconsistency of the included studies. Therefore, metformin shows the potential effects on CRP levels in women with PCOS. However, considering the very low quality of evidence for the analysis, the effect of metformin on CRP levels are still very uncertain, and large-scale randomized-controlled study is needed to ascertain the long-term effects of metformin in PCOS.//////////////////
Increased serum C-reactive protein levels in normal weight women with polycystic ovary syndrome. Makedos A 2014 et al.
Background: The clinical spectrum of polycystic ovary syndrome (PCOS) includes components of the metabolic syndrome, such as central obesity, insulin resistance, dyslipidemia, arterial hypertension and, even, disturbances of the clotting mechanism. All these disorders are epidemiologically related to cardiovascular disease, most probably through low-grade intravascular chronic inflammation. The aim of this study was to evaluate the serum concentrations of high sensitivity C-reactive protein (hsCRP), a non-specific marker of low-grade inflammation and a predictive marker for cardiovascular disease, in normal weight women with (PCOS). Patients and Methods: One hundred and eighty-eight (188) normal weight [body mass index (BMI) < 25 kg/m(2)] women with PCOS were included in the study. Forty-three (43) normal weight women without PCOS (normal ovulation without clinical or biochemical hyperandrogenemia) served as controls. Serum samples for luteinizing hormone, folliclestimulating hormone, prolactin, total testosterone, ?4-androstenedione, 17a-hydroxy-progesterone, sex hormone-binding globulin (SHBG), insulin, glucose and hsCRP were collected in early follicular phase (third to sixth day) of a menstrual cycle in the control group or during a spontaneous bleeding episode in the PCOS group. Results: Normal weight women with PCOS had higher concentrations of serum hsCRP as compared to normal weight women without PCOS (mean standard error of the mean 0.55 0.08 versus 0.27 0.08 mg/dL, p = 0.001). Conclusions: As normal weight women with PCOS are characterized by elevated serum concentrations of hsCRP, they have to be considered as carrying at least one marker of low-grade inflammation.
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