Although, in this study, even though the prevalence of T2D and hypertension increased during follow-up time, the association remained statistically significant (data not shown). Another strength of the study was the standardized sampling of blood specimens in the morning after fasting according to EAU guidelines, avoiding diurnal changes in the levels of sex hormones (5, 6, 37, 38). Although a large part of the cohort could not participate in this study due to loss-to-follow-up, sensitivity analyses showed similar characteristics between participants and non-participants at the second visit. In a cross-sectional study on Finnish non-diabetic men (1896 participants), results suggested metabolic syndrome as a great contributor to the high CRP–low testosterone relationship (21). Moreover, our data indicate that CRP, a marker of inflammation, per se can predict the development of biochemical hypogonadism regardless of anthropometric measures such as WHR and BMI. The magnitude of the effect was observed to be lower when adjusting for BMI in all fully adjusted models although the same direction in the association was observed (data not shown). When assessing the relationship between hsCRP levels and biochemical hypogonadism, similar models were used (Table 3). However, comparison of sociodemographic and health-related variables from BACH with other large regional (Boston Behavioral Risk Factor Surveillance System) and national (National Health Interview Survey) surveys have shown that the BACH estimates are comparable to national trends on key health related variables. History of comorbid conditions was assessed by self-report with the potential for reporting and/or recall bias; however, previous research has demonstrated the reliability and validity of self-report for heart disease, diabetes, and hypertension.30 The BACH study was limited geographically to the Boston area. However, a full analysis of the potential influence of medication use in general on CRP levels is beyond the scope of this paper. Thus, we cannot exclude the alternative hypothesis that low androgen levels may be a consequence of inflammation. All assays were previously approved by the Food and Drug Administration for clinical use. Additionally, participants were asked separately if they were taking medications for specific indications, such as high cholesterol and high blood pressure. BACH participants were asked to gather all prescription, over-the-counter and alternative medications in the home used by them over the past 4 weeks for recording of the label information by the interviewer. Two blood pressure measurements were obtained during the interview and were averaged. A venous blood sample (20 ml) was obtained and height, weight, and hip and waist circumference were measured along with self-reported information on medical and reproductive history, major comorbidities, lifestyle and psychosocial factors, and symptoms of urogynecological conditions. The objective of this analysis was to investigate the association between sex hormone levels and C-reactive protein (CRP) in a population-based sample of men. We studied the effects of normalisation of plasma testosterone levels in an open, nonrandomised study. Therefore, we were only able to observe biochemical hypogonadism in the longitudinal analyses. To the best of our knowledge, no studies have examined a longitudinal association between high CRP concentration and the development of hypogonadism. It has previously been observed that testosterone, through its androgen receptors, regulates the expression of cytokines, providing a modulating role in the inflammatory response (2, 7). Testosterone concentration decreases with aging, and if reaching hypogonadic levels in adulthood, this is defined as late-onset hypogonadism (LOH), according to the European Association of Urology (EAU) (5). Serum concentrations of testosterone and C-reactive protein (CRP) were measured at both visits. Non-fasting blood samples were collected close to waking time (median time since awakening 3 h 38 min) to control for diurnal variation in hormone levels. Interviews were completed with 63.3% of eligible subjects, resulting in a total sample of 5504 adults (2301 men, 3203 women, 1767 Black, 1877 Hispanic, 1859 White respondents). Detailed methods have been described elsewhere.9 In brief, BACH used a multi-stage stratified random sample to recruit approximately equal numbers of subjects according to age (30–39, 40–49, 50–59, 60–79 years), gender, and race/ethnic group (African American (Black), Hispanic, and Caucasian (White)). The BACH survey is a population-based epidemiologic survey of a broad range of urologic symptoms and risk factors in a randomly selected sample. A positive trend between estradiol (total and free) and CRP levels was not statistically significant.
