Carrie M. Nielson

The Human Papillomavirus Infection in Men Study: Human Papillomavirus Prevalence and Type Distribution among Men Residing in Brazil, Mexico, and the United States

Male sexual behavior influences the rates of cervical dysplasia and invasive cervical cancer, as well as male human papillomavirus (HPV) infection and disease. Unfortunately, little is known regarding male HPV type distribution by age and across countries. In samples combined from the coronal sulcus, glans penis, shaft, and scrotum of 1,160 men from Brazil, Mexico, and the United States, overall HPV prevalence was 65.2%, with 12.0% oncogenic types only, 20.7% nononcogenic types only, 17.8% both oncogenic and nononcogenic, and 14.7% unclassified infections. Multiple HPV types were detected in 25.7% of study participants. HPV prevalence was higher in Brazil (72.3%) than in the United States (61.3%) and Mexico (61.9%). HPV16 (6.5%), HPV51 (5.3%), and HPV59 (5.3%) were the most commonly detected oncogenic infections, and HPV84 (7.7%), HPV62 (7.3%), and HPV6 (6.6%) were the most commonly detected nononcogenic infections. Overall HPV prevalence was not associated with age. However, significant associations with age were observed when specific categories of HPV, nononcogenic, and unclassified HPV infections were considered. Studies of HPV type distribution among a broad age range of men from multiple countries is needed to fill the information gap internationally with respect to our knowledge of HPV infection in men. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2036–43)

Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts

CONTEXT Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. METHODS TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. RESULTS In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. CONCLUSION Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

Finite element analysis of the proximal femur and hip fracture risk in older men

Low areal BMD (aBMD) is associated with increased risk of hip fracture, but many hip fractures occur in persons without low aBMD. Finite element (FE) analysis of QCT scans provides a measure of hip strength. We studied the association of FE measures with risk of hip fracture in older men. A prospective case‐cohort study of all first hip fractures (n = 40) and a random sample (n = 210) of nonfracture cases from 3549 community‐dwelling men ≥65 yr of age used baseline QCT scans of the hip (mean follow‐up, 5.6 yr). Analyses included FE measures of strength and load‐to‐strength ratio and BMD by DXA. Hazard ratios (HRs) for hip fracture were estimated with proportional hazards regression. Both femoral strength (HR per SD change = 13.1; 95% CI: 3.9–43.5) and the load‐to‐strength ratio (HR = 4.0; 95% CI: 2.7–6.0) were strongly associated with hip fracture risk, as was aBMD as measured by DXA (HR = 5.1; 95% CI: 2.8–9.2). After adjusting for age, BMI, and study site, the associations remained significant (femoral strength HR = 6.5, 95% CI: 2.3–18.3; load‐to‐strength ratio HR = 4.3, 95% CI: 2.5–7.4; aBMD HR = 4.4, 95% CI: 2.1–9.1). When adjusted additionally for aBMD, the load‐to‐strength ratio remained significantly associated with fracture (HR = 3.1, 95% CI: 1.6–6.1). These results provide insight into hip fracture etiology and demonstrate the ability of FE‐based biomechanical analysis of QCT scans to prospectively predict hip fractures in men.

The Optimal Anatomic Sites for Sampling Heterosexual Men for Human Papillomavirus (HPV) Detection: The HPV Detection in Men Study

Background. Human papillomavirus (HPV) infection in men contributes to infection and cervical disease in women as well as to disease in men. This study aimed to determine the optimal anatomic site(s) for HPV detection in heterosexual men.Methods. A cross-sectional study of HPV infection was conducted in 463 men from 2003 to 2006. Urethral, glans penis/coronal sulcus, penile shaft/prepuce, scrotal, perianal, anal canal, semen, and urine samples were obtained. Samples were analyzed for sample adequacy and HPV DNA by polymerase chain reaction and genotyping. To determine the optimal sites for estimating HPV prevalence, site-specific prevalences were calculated and compared with the overall prevalence. Sites and combinations of sites were excluded until a recalculated prevalence was reduced by <5% from the overall prevalence.Results. The overall prevalence of HPV was 65.4%. HPV detection was highest at the penile shaft (49.9% for the full cohort and 47.9% for the subcohort of men with complete sampling), followed by the glans penis/coronal sulcus (35.8% and 32.8%) and scrotum (34.2% and 32.8%). Detection was lowest in urethra (10.1% and 10.2%) and semen (5.3% and 4.8%) samples. Exclusion of urethra, semen, and either perianal, scrotal, or anal samples resulted in a <5% reduction in prevalence.Conclusions. At a minimum, the penile shaft and the glans penis/coronal sulcus should be sampled in heterosexual men. A scrotal, perianal, or anal sample should also be included for optimal HPV detection.

Proximal Femoral Structure and the Prediction of Hip Fracture in Men: A Large Prospective Study Using QCT

The structure of the femoral neck contributes to hip strength, but the relationship of specific structural features of the hip to hip fracture risk is unclear. The objective of this study is to determine the contribution of structural features and volumetric density of both trabecular and cortical bone in the proximal femur to the prediction of hip fracture in older men. Baseline QCT scans of the hip were obtained in 3347 men ≥65 yr of age enrolled in the Osteoporotic Fractures in Men Study (MrOS). All men were followed prospectively for an average of 5.5 yr. Areal BMD (aBMD) by DXA was also assessed. We determined the associations between QCT‐derived measures of femoral neck structure, volumetric bone density, and hip fracture risk. Forty‐two men sustained incident hip fractures during follow‐up: an overall rate of 2.3/1000 person‐years. Multivariable analyses showed that, among the QCT‐derived measures, lower percent cortical volume (hazard ratio [HR] per SD decrease: 3.2; 95% CI: 2.2–4.6), smaller minimal cross‐sectional area (HR: 1.6; 95% CI: 1.2–2.1), and lower trabecular BMD (HR: 1.7; 95% CI: 1.2–2.4) were independently related to increased hip fracture risk. Femoral neck areal BMD was also strongly related to hip fracture risk (HR: 4.1; 95% CI: 2.7–6.4). In multivariable models, percent cortical volume and minimum cross‐sectional area remained significant predictors of hip fracture risk after adjustment for areal BMD, but overall prediction was not improved by adding QCT parameters to DXA. Specific structural features of the proximal femur were related to an increased risk of hip fracture. Whereas overall hip fracture prediction was not improved relative to aBMD, by adding QCT parameters, these results yield useful information concerning the causation of hip fracture, the evaluation of hip fracture risk, and potential targets for therapeutic intervention.

The Effects of Serum Testosterone, Estradiol, and Sex Hormone Binding Globulin Levels on Fracture Risk in Older Men

CONTEXT The relationship between sex steroids and fracture is poorly understood. OBJECTIVE The objective of the study was to examine associations between nonvertebral fracture risk and bioavailable estradiol (bioE2), bioavailable testosterone (bioT), and SHBG. DESIGN This was a case-cohort study. SETTING The Osteoporotic Fractures in Men Study (MrOS) was conducted in a prospective U.S. cohort in 5995 community-dwelling men 65 yr old or older. PARTICIPANTS Participants included a subcohort of 1436 randomly chosen white men plus all 446 minorities and all those with incident hip and other nonvertebral fractures. MAIN OUTCOME MEASURES Baseline testosterone and estradiol were measured by mass spectrometry (MS) and SHBG by RIA. RESULTS Men with the lowest bioE2 (<11.4 pg/ml) or highest SHBG (>59.1 nm) had greater risk of all nonvertebral fractures [adjusted hazard ratio (HR) [95% confidence interval]: 1.5 (1.2-1.9) and 1.4 (1.1-21.8), respectively]. Men with the lowest bioT (<163.5 ng/dl) had no increased fracture risk after adjustment for bioE2 [adjusted HR 1.16 (0.90-1.49)]. A significant interaction between SHBG and bioT (P = 0.03) resulted in men with low bioT and high SHBG having higher fracture risk [HR 2.1 (1.4-3.2)]. Men with low bioE2, low bioT, and high SHBG were at highest risk [HR 3.4 (2.2-5.3)]. CONCLUSIONS Older men with low bioE2 or high SHBG levels are at increased risk of nonvertebral fracture. When SHBG levels are high, men with low bioT levels have higher risk. The strongest association occurred when all measures were considered in combination.

Age-Specific Prevalence, Incidence, and Duration of Human Papillomavirus Infections in a Cohort of 290 US Men

BACKGROUND Human papillomavirus (HPV) infections cause disease in men and women, and male-to-female HPV transmission influences the risk of cancer in females. The purpose of the present study was to describe the overall and age-specific incidence and clearance of HPV infections in men. METHODS In a prospective cohort study of 290 men aged 18-44 years, participants were examined at baseline and every 6 months, with a mean duration of follow-up of 15.5 months. RESULTS The period prevalence was 52.8% for any, 31.7% for oncogenic, and 30.0% for nononcogenic HPV infection. The 12-month cumulative risk of acquiring a new HPV infection was 29.2%. Incidences of HPV types 6, 11, 16, and 18 were 2.8, 0.5, 4.8, and 0.8 per 1000 person-months, respectively. The median time to clearance of any HPV infection was 5.9 months (95% confidence interval, 5.7-6.1 months), with comparable times to clearance for oncogenic and nononcogenic infections. Approximately 75% of men tested negative for any HPV 12 months after initial HPV detection. Age was not significantly associated with HPV incidence or duration of infection in men. CONCLUSION HPV infection in men was common, with relatively rapid rates of acquisition and clearance.

BMI and fracture risk in older men: The osteoporotic fractures in men study (MrOS)

Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m2); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m2), 52% were overweight (25 to 29.9 kg/m2), 18% were obese I (30 to 34.9 kg/m2), and 3% were obese II (35 to 39.9 kg/m2). Overall, nonspine fracture incidence was 16.1 per 1000 person‐years, and hip fracture incidence was 3.1 per 1000 person‐years. In age‐, race‐, and BMD‐adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87–1.25] for overweight, 1.29 (95% CI 1.00–1.67) for obese I, and 1.94 (95% CI 1.25–3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84–1.23, for overweight; HR = 1.12, 95% CI 0.86–1.46, for obese I, and HR = 1.44, 95% CI 0.90–2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men.

Human Papillomavirus Prevalence and Type Distribution in Male Anogenital Sites and Semen

Background: Human papillomavirus (HPV) is sexually transmitted and causes cervical cancer. Although HPV can infect men and women, little is known about infection in men. Specifically, the prevalence of type-specific HPV infection and the distribution of infections by anogenital anatomic site in men are incompletely characterized. Methods: We tested 463 men ages 18 to 40 years for HPV at the glans/corona, penile shaft, scrotum, urethra, perianal area, anal canal, and in a semen sample. Eligible men acknowledged no history of genital warts and had sexual intercourse with a woman within the past year. HPV testing by PCR and reverse line blot genotyping for 37 types was conducted on each of the specimens from the seven sampling sites. Results: When HPV results from any sampling site were considered, 237 (51.2%) men were positive for at least one oncogenic or nononcogenic HPV type, and another 66 (14.3%) men were positive for an unclassified HPV type. The types with the highest prevalence were HPV-16 (11.4%) and 84 (10.6%). External genital samples (glans/corona, shaft, and scrotum) were more likely than anal samples to contain oncogenic HPV (25.1% versus 5.0%). HPV-positive penile shaft and glans/corona samples were also more likely to be infected with multiple HPV types than other sites. Conclusions: More complete anogenital sampling and sensitive detection for 37 HPV types resulted in a higher HPV prevalence in primarily asymptomatic men than reported previously. The penile shaft was the site most likely to be HPV positive and harbored the greatest proportion of multiple type and oncogenic infections. These results have implications for research of HPV among men and transmission between partners. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1107–14)

Obesity and fracture in men and women: An epidemiologic perspective

In Western societies, mean body weight has increased dramatically in older people, and a similar trend exists in Asia. Yet insufficient attention has been directed to the problem of osteoporotic fractures in the overweight and obese. Many, if not most, osteoporotic fractures occur in overweight or obese people, and obese men may be particularly susceptible. We discuss the potential implications of these findings, including the challenge of identifying individuals at highest risk, screening and treatment strategies, and future research directions.