IMPORTANCE Muscle pain, fatigue, and weakness are common adverse effects of statin medications and may decrease physical activity in older men. OBJECTIVE To determine whether statin use is associated ...with physical activity, longitudinally and cross-sectionally. DESIGN, SETTING, AND PARTICIPANTS Men participating in the Osteoporotic Fractures in Men Study (N = 5994), a multicenter prospective cohort study of community-living men 65 years and older, enrolled between March 2000 and April 2002. Follow-up was conducted through 2009. EXPOSURES Statin use as determined by an inventory of medications (taken within the last 30 days). In cross-sectional analyses (n = 4137), statin use categories were users and nonusers. In longitudinal analyses (n = 3039), categories were prevalent users (baseline use and throughout the study), new users (initiated use during the study), and nonusers (never used). MAIN OUTCOMES AND MEASURES Self-reported physical activity at baseline and 2 follow-up visits using the Physical Activity Scale for the Elderly (PASE). At the third visit, an accelerometer measured metabolic equivalents (METs kilocalories per kilogram per hour) and minutes of moderate activity (METs ≥3.0), vigorous activity (METs ≥6.0), and sedentary behavior (METs ≤1.5). RESULTS At baseline, 989 men (24%) were users and 3148 (76%) were nonusers. The adjusted difference in baseline PASE between users and nonusers was −5.8 points (95% CI, −10.9 to −0.7 points). A total of 3039 men met the inclusion criteria for longitudinal analysis: 727 (24%) prevalent users, 845 (28%) new users, and 1467 (48%) nonusers. PASE score declined by a mean (95% CI) of 2.5 (2.0 to 3.0) points per year for nonusers and 2.8 (2.1 to 3.5) points per year for prevalent users, a nonstatistical difference (0.3 −0.5 to 1.0 points). For new users, annual PASE score declined at a faster rate than nonusers (difference of 0.9 95% CI, 0.1 to 1.7 points). A total of 3071 men had adequate accelerometry data, 1542 (50%) were statin users. Statin users expended less METs (0.03 95% CI, 0.02-0.04 METs less) and engaged in less moderate physical activity (5.4 95% CI, 1.9-8.8 fewer minutes per day), less vigorous activity (0.6 95% CI, 0.1-1.1 fewer minutes per day), and more sedentary behavior (7.6 95% CI, 2.6-12.4 greater minutes per day). CONCLUSIONS AND RELEVANCE Statin use was associated with modestly lower physical activity among community-living men, even after accounting for medical history and other potentially confounding factors. The clinical significance of these findings deserves further investigation.
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.
The combination of a low bioavailable testosterone level, low estradiol level, and high sex hormone binding globulin level confers the highest risk of nonvertebral fracture in elderly men.
Background. Our understanding of factors associated with acquisition and clearance of human papillomavirus (HPV) in men has been limited. This study sought to determine factors associated with those ...aspects of HPV infection in a cohort of US men. Methods. A total of 285 men aged 18–44 years were monitored every 6 months for ∼18 months. Risk-factor information was obtained at each visit by use of a self-administered questionnaire. A continuous-time 2-state Markov model was applied. Results. Lifetime number of sex partners reported at enrollment was the most significant risk factor for acquisition of all types of HPV. Men reporting >16 lifetime sex partners were at significantly elevated risk of any HPV infection (adjusted hazard ratio AHR, 2.8 95% confidence interval {CI}, 1.1–7.1), oncogenicHPVinfection (AHR, 9.6 95% CI, 2.4–37.8), and nononcogenic HPV infection (AHR, 3.6 95% CI, 1.3–9.9), compared with those reporting 0–l4 partners. Circumcised men were 3 and 6 times more likely to clear infection with any and oncogenic HPV types, respectively. In addition, having had >16 lifetime sex partners was associated with greater likelihood of clearance of oncogenic HPV infection (AHR, 4.9 95% CI, 1.2–19.8). Conclusions. The key factor associated with acquisition of HPV was lifetime number of sex partners, whereas circumcision was the most significant determinant for clearance of any HPV infection and oncogenic HPV infection.
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)
Purpose
This narrative review describes the application of negative control outcome (NCO) methods to assess potential bias due to unmeasured or mismeasured confounders in non‐randomized comparisons ...of drug effectiveness and safety. An NCO is assumed to have no causal relationship with a treatment under study while subject to the same confounding structure as the treatment and outcome of interest; an association between treatment and NCO then reflects the potential for uncontrolled confounding between treatment and outcome.
Methods
We focus on two recently completed NCO studies that assessed the comparability of outcome risk for patients initiating different osteoporosis medications and lipid‐lowering therapies, illustrating several ways in which confounding may result. In these studies, NCO methods were implemented in claims‐based data sources, with the results used to guide the decision to proceed with comparative effectiveness or safety analyses.
Results
Based on this research, we provide recommendations for future NCO studies, including considerations for the identification of confounding mechanisms in the target patient population, the selection of NCOs expected to satisfy required assumptions, the interpretation of NCO effect estimates, and the mitigation of uncontrolled confounding detected in NCO analyses. We propose the use of NCO studies prior to initiating comparative effectiveness or safety research, providing information on the potential presence of uncontrolled confounding in those comparative analyses.
Conclusions
Given the increasing use of non‐randomized designs for regulatory decision‐making, the application of NCO methods will strengthen study design, analysis, and interpretation of real‐world data and the credibility of the resulting real‐world evidence.
Background: Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning ...variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men.
Methods: Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay.
Results: There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites.
Conclusions: On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.
A large international study of older men reveals evidence for substantial geographical and racial differences in sex steroid levels.
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