The relationship between klotho, testosterone, and sexual health parameters among US adult men.

BACKGROUND: Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed. OBJECTIVE: Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone). METHODS: Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300 ng/dL). RESULTS: A positive association was observed between serum klotho and testosterone (ß = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statistically significant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (ß = 90.51, p = 0.001, ß = 106.93, p = 0.002, ß = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9 ng/dL, 390 ng/dL, 409.3 ng/dL, and 436.6 ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (ß = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (ß = - 2.28, p = 0.04, ß = - 2.22, p = 0.04, ß = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively). CONCLUSION: Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.

Investigating the prevalence of erectile dysfunction among men exposed to organophosphate insecticides.

INTRODUCTION: Erectile dysfunction (ED) poses a significant disease morbidity and contributor to male infertility, where an estimated 20-40% of men are affected annually. While several risk factors have been identified in the etiology of ED (e.g., aging, heart disease, diabetes, and obesity), the complete pathogenesis remains to be elucidated. Over the last few decades, the contribution of environmental exposures to the pathogenesis of ED has gained some attention, though population studies are limited and results are mixed. Among environmental contaminants, organophosphate (OP) insecticides represent one of the largest chemical classes, and chlorpyrifos is the most commonly used OP in the U.S. OP exposure has been implicated in driving biological processes, including inflammation, reactive oxygen species production, and endocrine and metabolism disruption, which have been demonstrated to adversely affect the hypothalamus and testes and may contribute to ED. Currently, studies evaluating the association between OPs and ED within the U.S. general population are sparse. METHODS: Data were leveraged from the National Health and Nutrition Examination Survey (NHANES), which is an annually conducted, population-based cross-sectional study. Urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of the most pervasive OP insecticide chlorpyrifos, were quantified as measures of OP exposure. ED was defined by responses to questionnaire data, where individuals who replied "sometimes able" or "never able" to achieve an erection were classified as ED. Chi-square, analysis of variance (ANOVA), and multivariable, weighted linear and logistic regression analyses were used to compare sociodemographic variables between quartiles of TCPy exposure, identify risk factors for TCPy exposure and ED, and to analyze the relationship between TCPy and ED. RESULTS: A total of 671 adult men were included in final analyses, representing 28,949,379 adults after survey weighting. Approximately 37% of our cohort had ED. Smoking, diabetes, aging, Mexican-American self-identification, and physical inactivity were associated with higher ED prevalence. Analysis of TCPy modeled as a continuous variable revealed nonsignificant associations with ED (OR = 1.02 95% CI [0.95, 1.09]). Stratification of total TCPy into quartiles revealed increased odds of ED among adults in the second and fourth quartiles, using the first quartile as the reference (OR = 2.04 95% CI [1.11, 3.72], OR = 1.51 95% CI [0.58, 3.93], OR = 2.62 95% CI [1.18, 5.79], for quartiles 2, 3, and 4, respectively). CONCLUSIONS: The results of our study suggest a potential role for chlorpyrifos and other OPs the pathogenesis of ED. Future studies are warranted to validate these findings, determine clinical significance, and to investigate potential mechanisms underlying these associations.

The association between 2,4-D and serum testosterone levels: NHANES 2013-2014.

BACKGROUND: Previous studies have investigated associations between herbicides such as 2,4-Dichlorophenoxyacetic acid (2,4-D) and dyshormonogenesis, specifically low testosterone, in human, rodent, and cell models, but results have been conflicting and inconclusive. METHODS: Using data from a cross-sectional study of 456 adult men in the 2013-2014 NHANES survey cycle, we examined the relationship between urinary concentrations of 2,4-D and serum testosterone levels. RESULTS: Multivariable regression models adjusting for potential confounders revealed a significant, negative association between urinary 2,4-D and mean serum testosterone among U.S. adult males (ß = - 11.4 ng/dL, p = 0.02). Multivariable logistic regression models using a cutoff defining abnormally low testosterone (i.e., serum testosterone < 300 ng/dL) revealed no significant associations between 2,4-D and the odds of low testosterone. CONCLUSION: These findings expand on previous literature implicating a role for 2,4-D in the etiology of low testosterone and dyshormonogenesis. Future studies are warranted to corroborate these findings, determine clinical significance, and to investigate the proposed potential biological mechanisms underlying this association.

Familial study of prostate cancer in Jamaica.

OBJECTIVES: Rates of prostate cancer in Kingston, Jamaica are extremely high (occurring in more than 300 men out of 100,000 in 1989 to 1993). This article addresses the familial aggregation of prostate cancer in Jamaica. Early evidence for familial prostate cancer was found in the Utah Mormon population. Increased risk of prostate cancer in men with a family history of prostate cancer has been consistently observed in subsequent studies. There have been few studies, however, involving black men, who are known to have an overall higher risk of developing prostate cancer. METHODS: Two hundred sixty-three patients with prostate cancer documented by histology were studied. Two hundred sixty-three age-matched control patients were used for comparison. Extensive pedigrees were obtained for both patients with cancer and controls. Data on other malignancies including lung, breast, colon, stomach, and uterine were also collected. RESULTS: The patients with cancer and the controls were comparable with respect to age and family size. Thirty patients with cancer had a first degree relative (ie, brother, father, or son) with prostate cancer compared to 15 controls. The odds ratio is 2.1 (95% confidence interval 1.1 to 4.4). Nine patients with cancer had a second degree relative (ie, grandfather, grandson, or uncle) affected compared to 3 controls. The odds ratio is 3.1 (95% confidence interval 0.8 to 17.8). There was no statistically significant difference in the rates of any of the other cancers studied. CONCLUSIONS: Familial aggregation of prostate cancer is clearly evident in black Jamaican men. A man with one first degree relative with prostate cancer is twice as likely as the general population to develop prostate cancer. In addition, there may be a statistical difference in the risk of developing prostate cancer if an individual has one second degree relative affected.

The epidemiology of prostate cancer in Jamaica.

PURPOSE: Before this study, the highest reported incidence of prostate cancer in the world was thought to be among United States black men. The age adjusted rates in 1992 for United States black and white men were 249 and 182/100,000 respectively. The epidemiology of prostate cancer in Jamaica, a country of 2.5 million people of primarily African descent, was studied and compared with that of white and black Americans. MATERIALS AND METHODS: The study included 1,121 cases of prostate cancer diagnosed from 1989 to 1994. Sources of information included the Jamaican Cancer Registry, government pathology laboratory, hospital and clinic records, and physician office records. Incidence rates were computed using data from the 1991 Jamaican census. Age adjustments were made using the 1970 United States standard population. RESULTS: The average age adjusted incidence of prostate cancer in Kingston, Jamaica was 304/100,000 men. Median patient age at diagnosis was 72 years. More than 80% of the cases were pathologically confirmed. Of the patients 30% presented with acute urinary retention, 16% presented with bone metastases, 15% had gross hematuria at the time of diagnosis and an abnormal rectal examination suspicious for cancer was noted in 42%. Prostate specific antigen was measured in only 7% of cases in 1989 but in 48% of cases by 1994. CONCLUSIONS: These data demonstrate that Jamaican men in Kingston have a high incidence of prostate cancer, much higher than even black Americans during a similar period. Furthermore, the cancers are more significant clinically with greater morbidity in Jamaica than in the United States.

Hypercalcaemia. Parathyroidectomy.

We have found the following points to have been to help in the surgery of these elusive glands: Working with a physician who has an interest in calcium metabolism Using methylene blue preoperatively Making the collar incision slightly lower than that for a thyroid operation Using a stitch in the lateral border of the thyroid gland to pull it forwards and medially Looking for the parathyroid glands in fat Assuming that the first operation is going to be the only operation.

Prognostic factors in children with rhabdomyosarcoma.

The characteristics of 554 evaluated patients entered into a clinical trial conducted by the Pediatric Intergroup Rhabdomyosarcoma Committee between November 1972 and September 1978 were examined for their relationship to prognosis. Prognosis was defined as disease-free time and overall survival time in clinical groups I and II and time on study and survival time in clinical groups III and IV; all times were measured from the start of treatment. The percentage of patients surviving 2 years differed significantly among the clinical groups: I, 92; II, 78; III, 64; and IV, 35. The percentage of patients free of disease at 2 years was significantly higher in group I than in group II (83 vs. 72%, respectively); P = 0.02. The patient characteristics of group I most related to disease-free and overall survival were histologic cell type (alveolar, unfavorable), lymphocyte count (low count, unfavorable), and primary site (disease in extremities, unfavorable). In group II, sex (male, favorable) and lymphocyte count (low count, unfavorable) were significantly related to disease-free and overall survival times. Patients in the clinical subgroup with both microscopic residual disease and lymph node metastasis had poorer survival than patients in other subgroups. Primary site of disease was the only characteristic of group III related to length of time on study and to survival. Orbit and the genitourinary system were favorable primary sites, whereas the retroperitoneal area and extremities were unfavorable. In group IV, primary site (genitourinary, favorable) was related to length of time on study and survival. Sex (male, favorable) was related to survival experience.

Antibodies to the glycoprotein antigen of bovine leukemia virus in the cattle population of five states.

A selected (non-random) serological survey of cattle for antibodies to the glycoprotein antigen of bovine leukemia virus has been conducted in five states by seven investigators. A total of 1,295 beef and dairy cattle from 74 herds were studied with attention to the following: type of production, number of animals per herd, previous history of bovine leukemia cases in the herd, age of the animal, and serological reaction in the bovine leukemia glycoprotein immunodiffusion test (BL-GID). It was concluded that herd size (1-50, or 50+ animals per herd) exercised no influence on the percent positive BL-GID reactions. However, a previous history of clinical bovine leukemia in the herd and the type of production (beef or dairy) had considerable influence on the percent positive BL-GID reactors. Animals from herds that had a history of bovine leukemia exhibited 52.0% positive BL-GID reactions as compared to 13.7% reactors in animals from herds with no herd history of bovine leukemia. Beef animals exhibited 2.6% positive BL-GID reactions, while dairy animals exhibited 28.2% positive BL-GID reactions. Data were insufficient to determine age trends.

The relationship between semen evaluation methods and fertility in the bull.

The results are presented of two experiments in which the quality of samples of bull semen was assessed by a number of laboratory tests and then correlated with the 112-day non-return percentage obtained by the use of those samples in A.I. The results reveal the inadequacy of the laboratory tests used as methods of predicting the fertility of semen samples but show that limits may be set outside which poor semen samples could be discarded.