Sex steroids and bone health in men.
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ABSTRACT:
SUBMITTER: Ohlsson C
PROVIDER: S-EPMC3705992 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:IntroductionThe mechanism(s) by which sex steroids regulate bone turnover in humans are unclear, and recent studies have suggested that follicle-stimulating hormone (FSH) may play an important role in regulating bone resorption.Materials and methodsFifty-nine men (median age, 69 yr) underwent suppression of sex steroids using a gonadotropin-releasing hormone (GnRH) agonist and aromatase blocker and were replaced with testosterone (T; 5 mg/d) and estradiol (E; 37.5 microg/d). After assessment of bone resorption markers (serum C-terminal telopeptide of type I collagen [CTX] and TRACP5b), they were randomized to sex steroid deficiency (-T, -E), E alone (-T, +E), T alone (+T, -E), or both (+T, +E) and restudied 3 wk later. Bone marrow aspirates were obtained to isolate osteoblastic, T, and monocytic cells using magnetic-activated cell sorting.ResultsSerum CTX and TRACP5b increased significantly (by 71% and 15%, p < 0.01 and < 0.001, respectively) in the -T, -E group, and these increases occurred despite a 60% suppression of serum FSH levels (p < 0.001) caused by the GnRH agonist. There were significant E (but not T) effects on preventing increases in serum CTx and TRACP levels. There was a nonsignificant trend (p = 0.122) for E to suppress RANKL mRNA levels in bone marrow osteoblastic cells. Changes in mRNA levels for other cytokines (TNF-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1ra, IFN-gamma) in bone marrow cells were not significant.ConclusionsE has greater suppressive effects on bone resorption than T, and increased bone resorption after sex steroid deficiency can occur independently of changes in FSH secretion. E effects on bone resorption may be mediated by regulation of RANKL production by osteoblastic cells, although further studies using more highly purified cells may reduce the variability of the mRNA measurements and allow for clearer definition of the mediators of sex steroid action in vivo.
| S-EPMC2674543 | biostudies-literature
Project description:Sex steroids have a significant effect on skeletal biology in men, with reduced levels being associated with lower skeletal bone mass and cortical thickness. The purpose of this study was to determine if sex steroids are associated with periodontitis and tooth loss in a cohort of 1210 older dentate men followed for 3 years. Periodontal measures included attachment loss, pocket depth, gingival bleeding, and number of teeth. Baseline serum testosterone and estradiol were measured by radioimmunoassay. Severe periodontitis was common at baseline (38%), and progression occurred in 32% of the cohort. Incident tooth loss occurred in 22% of the cohort. Testosterone, estradiol, and sex hormone binding globulin (SHBG) concentrations were not related to baseline periodontal status or number of teeth. Moreover, there was no relationship between sex steroid levels and periodontitis progression or incident tooth loss. Although periodontitis, progression of periodontitis, and tooth loss are common in older men, they were not associated with sex steroids.
| S-EPMC2841022 | biostudies-literature
Project description:Male hypogonadism results in changes in body composition characterized by increases in fat mass. Resident immune cells influence energy metabolism in adipose tissue and could promote increased adiposity through paracrine effects. We hypothesized that manipulation of circulating sex steroid levels in healthy men would alter adipose tissue immune cell populations. Subjects (n = 44 men, 19-55 yr of age) received 4 wk of treatment with the gonadotropin-releasing hormone receptor antagonist acyline with daily administration of 1) placebo gel, 2) 1.25 g testosterone gel (1.62%), 3) 5 g testosterone gel, or 4) 5 g testosterone gel with an aromatase inhibitor. Subcutaneous adipose tissue biopsies were performed at baseline and end-of-treatment, and adipose tissue immune cells, gene expression, and intra-adipose estrogen levels were quantified. Change in serum total testosterone level correlated inversely with change in the number of CD3+ (β = -0.36, P = 0.04), CD4+ (β = -0.34, P = 0.04), and CD8+ (β = -0.33, P = 0.05) T cells within adipose tissue. Change in serum 17β-estradiol level correlated inversely with change in the number of adipose tissue macrophages (ATMs) (β = -0.34, P = 0.05). A negative association also was found between change in serum testosterone and change in CD11c+ ATMs (β = -0.41, P = 0.01). Overall, sex steroid deprivation was associated with increases in adipose tissue T cells and ATMs. No associations were found between changes in serum sex steroid levels and changes in adipose tissue gene expression. Circulating sex steroid levels may regulate adipose tissue immune cell populations. These exploratory findings highlight a possible novel mechanism that could contribute to increased metabolic risk in hypogonadal men.
| S-EPMC5792144 | biostudies-literature
Project description:BACKGROUND:Exogenous testosterone decreases serum concentrations of high-density lipoprotein cholesterol (HDL-C) in men, but whether this alters cardiovascular risk is uncertain. OBJECTIVE:To investigate the effects of testosterone and estradiol on HDL particle concentration (HDL-Pima) and metrics of HDL function. METHODS:We enrolled 53 healthy men, 19 to 55 years of age, in a double-blinded, placebo-controlled, randomized trial. Subjects were rendered medically castrate using the GnRH receptor antagonist acyline and administered either (1) placebo gel, (2) low-dose transdermal testosterone gel (1.62%, 1.25 g), (3) full replacement dose testosterone gel (1.62%, 5 g) or (4) full replacement dose testosterone gel together with an aromatase inhibitor for 4 weeks. At baseline and end of treatment, serum HDL total macrophage and ABCA1-specific cholesterol efflux capacity (CEC), HDL-Pima and size, and HDL protein composition were determined. RESULTS:Significant differences in serum HDL-C were observed with treatment across groups (P = .01 in overall repeated measures ANOVA), with increases in HDL-C seen after both complete and partial testosterone deprivation. Medical castration increased total HDL-Pima (median [interquartile range] 19.1 [1.8] nmol/L at baseline vs 21.3 [3.1] nmol/L at week 4, P = .006). However, corresponding changes in total macrophage CEC and ABCA1-specific CEC were not observed. Change in serum 17β-estradiol concentration correlated with change in total macrophage CEC (β = 0.33 per 10 pg/mL change in serum 17β-estradiol, P = .03). CONCLUSIONS:Testosterone deprivation in healthy men leads to a dissociation between changes in serum HDL-C and HDL CEC. Changes in serum HDL-C specifically due to testosterone exposure may not reflect changes in HDL function.
| S-EPMC6064653 | biostudies-literature
Project description:Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations. To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men. 177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls). Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire. Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL. Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed.
| S-EPMC7337183 | biostudies-literature
Project description:Backgroundfrailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health.Methodsmen aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre.Resultsin total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05).Conclusionsoptimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.
| S-EPMC5859977 | biostudies-literature
Project description:Low serum concentrations of sex steroids and gonadotropins in men have been associated with increased cardiometabolic risk and mortality, but the clinical correlates of these hormones in men over late adulthood are less clearly understood. We analysed up to five serial measurements of total testosterone (TT), dehydroepiandrosterone sulphate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH) and total estradiol (EST) in older men in the original cohort of the Framingham Heart Study to determine the short- (2-years; 1,165 person-observations in 528 individuals) and long-term (up to 10-years follow-up; 2520 person-observations in 835 individuals with mean baseline age: 71.2 years) clinical correlates of these sex steroids and gonadotropins using multilevel modelling and Generalized Estimating Equations. Age, body mass index and pre-existing type 2 diabetes were inversely related to long-term TT concentrations, whereas higher systolic blood pressure showed a positive association. Furthermore, age and pre-existing cardiovascular disease (CVD) were inversely associated and HDL cholesterol concentrations positively associated with long-term DHEAS concentrations respectively. Analyses of short-term changes revealed age was inversely related to DHEAS, but positively related to FSH and LH concentrations. Our community-based study identified modifiable correlates of decreasing TT and DHEAS concentrations in elderly men, suggesting that maintenance of a low CVD risk factor burden may mitigate the age-related decline of these hormones over the late adulthood.
| S-EPMC3434249 | biostudies-literature
Project description:Homelessness is associated with increased prevalence of mental health disorders, substance use disorders and mental health/substance use disorder comorbidity in the United States of America. Gay, bisexual and other men who have sex with men (MSM) living in the United States are at increased risk for homelessness, and have also evidenced elevated mental health and substance use disorder prevalence relative to their non-MSM male counterparts.Secondary analysis of data from a randomised controlled trial estimating the diagnostic prevalence of substance use/mental health disorder comorbidity among a sample of homeless, substance-dependent MSM (DSM-IV verified; n?=?131).The most prevalent substance use/mental health disorder comorbidities were stimulant dependence comorbid with at least one depressive disorder (28%), alcohol dependence comorbid with at least one depressive disorder (26%) and stimulant dependence comorbid with antisocial personality disorder (25%).Diagnostic depression and antisocial personality disorder both demonstrated high rates of prevalence among homeless, substance-dependent (particularly stimulant and alcohol dependent) MSM. [Fletcher JB, Reback CJ. Mental health disorders among homeless, substance-dependent men who have sex with men. Drug Alcohol Rev 2016;36:555-559].
| S-EPMC5303689 | biostudies-literature
Project description:ContextThe effect of bariatric surgery on the reproductive function of obese men is not entirely elucidated.ObjectiveThe aim of the study was to define the effect of Roux-En-Y gastric bypass surgery on the reproductive hormones and sexual function in obese men.Design and settingThe cohort was followed for 2 yr at a clinical research center.PatientsSixty-four severely obese men (22 who had gastric bypass surgery and 42 controls) participated in the study.Intervention(s)Anthropometrics [weight, body mass index (BMI), and percentage body fat] and reproductive hormones were measured. The sexual quality of life was assessed using the Impact of Weight on the Quality Of Life-Lite questionnaire.Main outcome measure(s)Reproductive hormones and sexual quality of life were measured.ResultsThe mean age was 48.9 +/- 1.2 yr. At baseline, mean weight was 333.0 +/- 7.1 lb, BMI was 46.2 +/- 0.9 kg/m(2), and total testosterone was 339.9 +/- 21.32 ng/dl. BMI correlated positively with estradiol and negatively with total and free testosterone. Indices of dissatisfaction with sexual quality of life correlated positively with measures of obesity. Difficult sexual performance and low sexual desire correlated negatively with free and total testosterone (r = -0.273, P = 0.038; and r = -0.267, P = 0.042, respectively). After 2 yr, the gastric bypass surgery group had a significant decrease in BMI (-16.6 +/- 1.2 vs. -0.46 +/- 0.51 kg/m(2)) and estradiol (-8.1 +/- 2.4 vs. 1.6 +/- 1.4 pg/ml) and had an increase in total testosterone (310.8 +/- 47.6 vs. 14.2 +/- 15.3 ng/dl) and free testosterone (45.2 +/- 5.1 vs. -0.4 +/- 3.0 pg/ml). Sexual quality of life was improved after gastric bypass surgery.ConclusionHormonal alterations and diminished sexual quality of life among obese men are related to degree of obesity, and both are improved after gastric bypass surgery.
| S-EPMC2682482 | biostudies-literature
Project description:IntroductionHuman papillomavirus (HPV) infection is transmitted through skin-to-skin contact, and vaginal and anal sex are the most common transmission routes. Sex workers and men who have sex with men (MSM) are more exposed to the virus, and therefore, a higher frequency of this infection would be expected. The prevalence of HPV infection types and the forms and factors of transmission must be investigated to control infection-related outcomes. This protocol study will be the first nationwide study with a uniform methodology to evaluate HPV prevalence of and infection types among sex workers and MSM in Brazil.Methods and analysisThis multicentre cross-sectional study will be conducted with a respondent-driven sampling method to recruit 1174 sex workers and 1198 MSM from all regions of Brazil. The study will consist of preliminary interviews to verify the eligibility criteria and characterise the network size as well as a second questionnaire to obtain sociodemographic, behavioural and sexual information. Specimens from the oral cavity and anal and cervical or penile/scrotal sites will be collected. All HPV samples will be processed in a certified central laboratory. Other sexually transmitted infections will be evaluated by interview and by rapid testing for HIV and syphilis. Strict quality control will be conducted using different procedures, including the training and certification of the health professionals responsible for acquiring data and monitoring visits.Ethics and disseminationThe project was approved by the research ethics committee of the main institution and the corresponding ethics committees of the recruitment sites. Due to the literature gap on the sexual health of sex workers and MSM and the intense stigma surrounding these populations, a critical analysis of the study results will contribute to epidemiological knowledge and will be useful for the development of strategies against virus morbidities.
| S-EPMC6886941 | biostudies-literature