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.

Context:Normocalcemic primary hyperparathyroidism is typically identified after referral to a specialty clinic. At diagnosis, patients demonstrate features seen in hypercalcemic primary hyperparathyroidism. Normocalcemic hypoparathyroidism has been discovered after hypocalcemia unmasked after bisphosphonate administration.Objective: We hypothesized that screening unselected, nonreferral populations, such as The Osteoporotic Fractures in Men (MrOS) study and Dallas Heart Study (DHS), would identify asymptomatic subjects with normocalcemic hyperparathyroidism and hypoparathyroidism.Methods: Normocalcemic hyperparathyroidism was defined as serum PTH greater than the upper reference range with normal albumin-adjusted serum calcium, excluding common secondary causes (renal failure [estimated glomerular filtration rate Ͻ60 mL/min], 25-hydroxyvitamin D Ͻ20 ng/mL, and thiazide use), and normocalcemic hypoparathyroidism as PTH below the reference range with normocalcemia. Crosssectional data were obtained from MrOS, and longitudinal data (baseline and 8 years) from DHS. Results:In 2364 men from MrOS, we identified 9 with normocalcemic hyperparathyroidism (prevalence 0.4%) and 26 with normocalcemic hypoparathyroidism (1.1%). In 3450 men and women from DHS, we identified 108 with normocalcemic hyperparathyroidism (3.1%) and 68 with normocalcemic hypoparathyroidism (1.9%). Of the 108 normocalcemic hyperparathyroid subjects, 64 had follow-up data. Hypercalcemic primary hyperparathyroidism developed in 1 subject whereas 13 (0.6% of the follow-up cohort) showed persistently elevated PTH levels with normocalcemia. Of the 26 normocalcemic hypoparathyroid subjects with follow-up data, none developed overt hypoparathyroidism and 2 (0.09%) had persistent evidence of normocalcemic hypoparathyroidism. Conclusions:This study documents normocalcemic primary hyperparathyroidism and hypoparathyroidism identified among community-dwelling individuals. Larger studies are needed to determine the true prevalence and natural history of these parathyroid disorders. (J Clin Endocrinol Metab 98: 2734 -2741, 2013) P rimary hyperparathyroidism, a common endocrine disorder, is traditionally defined by hypercalcemia and an elevated or inappropriately normal PTH concentration. A newer presentation of primary hyperparathyroidism has been described in which serum calcium is normal and PTH is elevated in the absence of secondary causes of hyperparathyroidism, such as renal disease or vitamin D deficiency (1-6). Recognition of this phenotype of pri-

Design and MethodsSkeletal muscle adipose tissue (AT) infiltration (myosteatosis) increases with aging and may contribute to the development of type 2 diabetes mellitus (T2DM). It remains unclear if myosteatosis is associated to glucose and insulin homeostasis independent of total and central adiposity. We evaluated the association between intermuscular AT (IMAT) in the abdominal skeletal muscles (total, paraspinal and psoas) and fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 393 non-diabetic Caucasian men aged 65+. Abdominal IMAT, visceral (VAT) and subcutaneous (SAT) AT (cm3) were measured by quantitative computed tomography at the L4-L5 intervertebral space.ResultsIn age, study site, height and muscle volume adjusted regression analyses, total abdominal and psoas (but not paraspinal) IMAT were positively associated with glucose, insulin and HOMA-IR (all P < 0.003). The associations between total abdominal and psoas IMAT and insulin and HOMA-IR remained significant after further adjusting for lifestyle factors, as well as DXA total body fat, VAT or SAT in separate models (all P <0.009).ConclusionsOur study indicates a previously unreported, independent association between abdominal myosteatosis and hyperinsulinemia and insulin resistance among older Caucasian men. These associations may be specific for particular abdominal muscle depots, illustrating the potential importance of separately studying specific muscle groups.

SummaryObjective To examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men. Design Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men of 65 years or older. Patients One thousand six hundred and two men were chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and twenty-three MrOS participants with sex steroids measured using RIA were also examined. Measurements Baseline and follow-up (4AE5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and oestradiol were measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analysed using linear regression. Results Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (P = 0AE03) and 3MS performance (P = 0AE02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance. Conclusions Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or oestradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.

Higher endogenous testosterone is associated with reduced loss of lean mass and lower extremity function in older men losing weight. Endogenous testosterone may contribute to healthy aging.

Purpose Progression of lower urinary tract symptoms (LUTS) among community dwelling older men is not well described. Materials and Methods We evaluated 5,697 participants in MrOS, a prospective cohort study of community dwelling men aged 65 years and older. We characterized LUTS utilizing the American Urological Symptom Index (AUA-SI) at two time points: study entry and 2-year follow-up. Progression was examined in the overall cohort and within strata of baseline symptoms (AUA-SI ≤ 7 points and ≥8 points) using descriptive statistics. Results At baseline, the mean (SD) age was 73.5 (5.8) years and mean (SD) AUA-SI score was 8.3 (6.3). Mean (SD) and median total AUA-SI increased during follow-up by 1.1 (5.0) and 1.0 points, respectively. Of the 3092 men with AUA-SI ≤ 7 at baseline, 883 (29%) reported LUTS progression (AUA-SI ≥8 points) at follow-up. The frequency of LUTS progression increased with advancing baseline age. Of the 2605 men with AUA-SI ≥ 8 at baseline, 622 (24%) reported progression of at least 4 AUA-SI points at follow-up. Among the 2200 men with baseline AUA-SI ≤7 and no prior history of BPH or LUTS treatments, 94% remained untreated, 2% reported BPH surgery, and 4% reported medication use at follow-up. Conclusions Up to 29% of community dwelling older men with no or mild LUTS will develop clinically significant LUTS within 2 years. These data help elucidate the natural history of LUTS in the community and provide useful data for designing clinical trials of LUTS prevention.

Background Data describing urinary health in elderly, community-dwelling prostate cancer (PCa) survivors are limited. Objective To elucidate the prevalence of lower urinary tract symptoms, urinary bother, and incontinence in elderly PCa survivors compared with peers without PCa. Design, setting, and participants A cross-sectional analysis of 5990 participants in the Osteoporotic Fractures in Men Research Group, a cohort study of community-dwelling men ≥65 yr. Outcome measurements and statistical analysis We characterized urinary health using self-reported urinary incontinence and the American Urological Association Symptom Index (AUA-SI). We compared urinary health measures according to type of PCa treatment in men with PCa and men without PCa using multivariate log-binomial regression to generate prevalence ratios (PRs). Results and limitations At baseline, 706 men (12%) reported a history of PCa, with a median time since diagnosis of 6.3 yr. Of these men, 426 (60%) reported urinary incontinence. In adjusted analyses, observation (PR: 1.92; 95% confidence interval [CI], 1.15–3.21; p = 0.01), surgery (PR: 4.68; 95% CI, 4.11–5.32; p < 0.0001), radiation therapy (PR: 1.64; 95% CI, 1.20– 2.23; p = 0.002), and androgen-deprivation therapy (ADT) (PR: 2.01; 95% CI, 1.35–2.99; p = 0.0006) were each associated with daily incontinence. Daily incontinence risk increased with time since diagnosis independently of age. Observation (PR: 1.33; 95% CI, 1.00–1.78; p = 0.05), surgery (PR: 1.25; 95% CI, 1.10–1.42; p = 0.0008), and ADT (PR: 1.50; 95% CI, 1.26–1.79; p < 0.0001) were associated with increased AUA-SI bother scores. Cancer stage and use of adjuvant or salvage therapies were not available for analysis. Conclusions Compared with their peers without PCa, elderly PCa survivors had a two-fold to five-fold greater prevalence of urinary incontinence, which rose with increasing survivorship duration. Observation, surgery, and ADT were each associated with increased urinary bother. These data suggest a substantially greater burden of urinary health problems among elderly PCa survivors than previously recognized.

Measurement of serum testosterone (T) levels is recommended in the evaluation of osteoporosis in older men and estradiol (E2) and sex hormone binding globulin (SHBG) levels are associated with the rate of bone loss and fractures, but the clinical utility of sex steroid and SHBG measurements for the evaluation of osteoporosis in men has not been examined. To evaluate whether measurements of T, E2 and/or SHBG are useful for the prediction of fracture risk or the rate of bone loss in older men, we analyzed longitudinal data from 5487 community-based men participating in the MrOS Study in the US, Sweden and Hong Kong. Serum T, E2 and SHBG levels were assessed at baseline; incident fractures were self-reported at 4 month intervals with radiographic verification (US), or ascertained via national health records (Sweden, Hong Kong). Rate of bone loss was assessed by serial measures of hip BMD. We used receiver operating characteristic (ROC) curves, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to assess improvement in prediction. Mean age at baseline was 72-75 years and the prevalence of low T levels (<300 ng/dL) was 7.6-21.3% in the three cohorts. There were 619 incident major osteoporotic and 266 hip fractures during follow up of approximately 10 years. Based on ROC curves, there were no improvements in fracture risk discrimination for any biochemical measure when added to models, including FRAX with BMD. Although minor improvements in NRI were observed for the dichotomous parameters low BioE2 (<11.4 pg/ml) and high SHBG (>59.1 nM), neither sex steroids nor SHBG provided clinically useful improvement in fracture risk discrimination. Similarly, they did not contribute to the prediction of BMD change. In conclusion, there is limited clinical utility of serum E2, T and SHBG measures for the evaluation of osteoporosis risk in elderly men.