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Introduction Thyroid hormone replacement in central hypothyroidism (CHT) is more difficult than in primary hypothyroidism (PHT), putting patients at risk for inappropriate substitution. In this study, we compared the dosage of thyroid hormone replacement in patients with CHT with that of patients with PHT. In addition, we explored and compared quality of life (QoL) between both groups, based on two questionnaires, the SF-36 health score and the thyroid-specific ThyPRO score. Methods This is a monocentric, cross-sectional study, performed at the Ghent University Hospital (Belgium). We included 82 patients in total, 41 patients with CHT and 41 patients with PHT. At the time of inclusion, all patients had to have a stable dose of levothyroxine over the past 6 months and patients with PHT needed to be euthyroid (defined as having a thyroid-stimulating hormone level within the reference range, 0.2–4.5 mU/L). All data were retrieved from medical files, and questionnaires on QoL were self-administered. Results The CHT and PHT groups were comparable regarding age and BMI. There was no significant difference between both groups regarding total daily dose of levothyroxine (100 (93.75–125.00) vs 107.14 (75.00–133.93) μg in CHT and PHT, respectively; P = 0.87) or daily dose of levothyroxine per kg body weight (1.34 (1.16–1.55) vs 1.55 (1.16–1.82) μg/kg, respectively; P = 0.13). Serum levels of fT4 (P = 0.20) and fT3 (P = 0.10) also did not differ between the two groups and both were in the normal (mid)range for the two groups. Regarding QoL, patients with CHT scored worse in terms of depressive and emotional symptoms, impaired daily and social life. Conclusion We could demonstrate a difference in QoL between patients with CHT and PHT. Although patients with CHT had a somewhat lower levothyroxine substitution dose than patients with PHT, this difference was also not significant and probably does not explain the difference in QoL.

Context: Osteoporosis is a major public health concern worldwide. Understanding the roles of diet and physical activity in ensuring adequate bone mass accrual during childhood and adolescence may help identify strategies to reduce the risk of osteoporotic fractures later in life. Objective: The present systematic review was conducted to provide an overview of the current knowledge of the combined effects of physical activity and diet on bone mass accrual in children and adolescents. Data Sources: Data were obtained via searches of the PubMed, EMBASE, SPORTDiscus, and ISI Web of Science databases. Study Selection: Studies published in English and Spanish between 1887 and August 2013 were eligible for inclusion. Two investigators evaluated the studies against the inclusion and exclusion criteria. A total of 14 studies (7 cross-sectional and 7 experimental) were included in the review. Data Extraction: The Pedro score and the Black and Down’s checklist were used to evaluate the methodological quality of the experimental and the cross-sectional studies, respectively. Study characteristics were summarized in accordance with the review's PICO criteria. Data Synthesis: Significant exercise-by-calcium interaction was detected at several different bone sites. Conclusions: Although the results of cross-sectional studies were inconsistent, the results of randomized controlled trials showed that exercise has the potential to improve bone health under conditions of adequate calcium intake.

In order to better understand and treat neuropathic pain, scientific study must use methods that can assess pain processing at the cortical level where pain is truly perceived. Operant behavior paradigms can accomplish this. We used an operant task to evaluate changes following chronic constriction injury to the trigeminal nerves. We also relate these behavioral changes to immunohistochemistry of transient receptor potential channels vanilloid 1 and melastatin 8 (TRPV1 and TRPM8) in the trigeminal ganglia. Following nerve injury, successful performance of the operant task was reduced and aversive behaviors were observed with 10 and 37 °C stimulation, indicating cold allodynia and mechanical allodynia respectively. In contrast, while aversive behaviors were observed with 48 °C stimulation, successful performance of the operant task was not substantially hindered following injury. These behavioral changes were accompanied by an increase in TRPV1 positive cells and an increased intensity of TRPM8 staining at 2 weeks post-injury, when cold allodynia is maximal. These findings suggest that the incorporation of operant behavioral assessment in the study of pain may provide insight into the relationship among peripheral changes, motivational drive, and pain. Understanding this relationship will allow us to better treat and prevent chronic neuropathic pain.

buysse h, de moor g, coorevits p, van maele g, kaufman j & ruige j (2011) Journal of Nursing and Healthcare of Chronic Illness 3, 456–468 Main characteristics of type 1 and type 2 diabetic patients interested in the use of a telemonitoring platform Aims and objectives. The main question addressed in this work, and to the best of our knowledge the first study focusing on this aspect, is whether diabetic patients – before they ever used a telemonitoring platform – are interested in using such a platform. In case they are interested, it is investigated whether characteristics of interested users could be distinguished. From a clinical perspective, special attention was drawn to metabolic control and to empowerment. Background. Diabetes is one of the most challenging health problems in the 21st century. The use of a telemonitoring platform could be an opportunity for persons with diabetes. However, until now, it has never been investigated if those persons are interested in using such a platform. Results. Of the 172 patients signing the informed consent, 137 (79·7%) patients filled in the questionnaires. Depending on the type of treatment, about 40–60% is interested in using a telemonitoring platform. Patients can easily be identified by the use of a computer or Internet, and interested patients log their treatment data. Most patients showing interest are on insulin treatment without having adequate metabolic control, or are on insulin and oral treatment with low empowerment scores, suggesting that implementation of a telemonitoring platform in these patients makes sense and can be used to improve metabolic control, e.g., by increasing empowerment. Conclusions. There is substantial interest in the use of a telemonitoring platform in insulin using (type 1/type 2) patients, and there is also a potential for improvement of metabolic control or empowerment in these patients. Implications for practice. Implementation of telemonitoring projects is potentially cost-effective in insulin using (type 1/type 2) patients already using a computer or the Internet.

OBJECTIVE Comprehensive proteomic profiling of the human adipocyte secretome identified dipeptidyl peptidase 4 (DPP4) as a novel adipokine. This study assessed the functional implications of the adipokine DPP4 and its association to the metabolic syndrome. RESEARCH DESIGN AND METHODS Human adipocytes and skeletal and smooth muscle cells were used to monitor DPP4 release and assess the effects of soluble DPP4 on insulin signaling. In lean and obese subjects, depot-specific expression of DPP4 and its release from adipose tissue explants were determined and correlated to parameters of the metabolic syndrome. RESULTS Fully differentiated adipocytes exhibit a substantially higher release of DPP4 compared with preadipocytes or macrophages. Direct addition of DPP4 to fat and skeletal and smooth muscle cells impairs insulin signaling. A fivefold higher level of DPP4 protein expression was seen in visceral compared with subcutaneous fat of obese patients, with no regional difference in lean subjects. DPP4 serum concentrations significantly correlated with adipocyte size. By using adipose tissue explants from lean and obese subjects, we observed a twofold increase in DPP4 release that strongly correlated with adipocyte volume and parameters of the metabolic syndrome and was decreased to the lean level after weight reduction. DPP4 released from adipose tissue correlated positively with an increasing risk score for the metabolic syndrome. CONCLUSIONS DPP4 is a novel adipokine that may impair insulin sensitivity in an autocrine and paracrine fashion. Furthermore, DPP4 release strongly correlates with adipocyte size, potentially representing an important source of DPP4 in obesity. Therefore, we suggest that DPP4 may be involved in linking adipose tissue and the metabolic syndrome.

Purpose Till now no validated instrument exists to measure the readiness and attitude of diabetic patients towards the use of telemonitoring. The purpose of the described study was to develop a Telemonitoring Attitude and Readiness Questionnaire and to check its validity and reliability. Methods After performing in-depth interviews in two separate sessions, the Telemonitoring Attitude and Readiness Questionnaire was completed by a convenience sample of 138 patients with type 1 and type 2 diabetes to determine internal consistency. Test–retest reliability was further evaluated with a subsample of 21 patients. Results Analysis supports the validity and reliability of the 13-item Telemonitoring Health Effect and Readiness Questionnaire (THERQ) with three subscales: Communication with peers or during holidays with a professional (Cronbach's α = 0.84), telemonitoring health effect (Cronbach's α = 0.87), and communication with a professional from home (Cronbach's α = 0.88). Test–retest reliability is satisfactory (intraclass correlation coefficients between 0.58 and 0.92). Conclusions The results of this study provide preliminary evidence that the Telemonitoring Health Effect and Readiness Questionnaire is a valid and reliable instrument to measure the readiness and subjective feelings of health effect towards the use of telemonitoring. The THERQ could be used before the implementation of telemonitoring to check if diabetic patients are interested in the use of it but it could also be used in (randomized) controlled trials as the questions are put in such a way that also patients not (yet) using telemonitoring can answer the questions.

SummaryAlthough the role of testosterone in the aetiology of social dominance is often suggested, surprisingly few studies have addressed the relationship between sex steroid hormones and dominance as a personality trait. In this paper, the relationship between testosterone and dominance is studied in a sample of adolescent boys and girls, taking into account the moderating role of gender ideology and same-sex peer group orientation. A direct association between free testosterone (FT) and dominance was found in girls but not in boys. In boys, masculine ideology moderated the relationship between FT and dominance, while in girls the relationship between FT and dominance was moderated by same-sex peer group affiliation.

This study examines the relationship between gender, control, and adolescent risk-taking in a sample of 599 adolescents and explores the relation of paternal and maternal direct and indirect control with adolescent risk-taking, controlling for potentially confounding effect of family-related stressors and differential association. Gender differences in levels and effects of direct and indirect control, in levels and effects of family-related strain and in differential association are found. Although the variables related to direct control had a larger explanatory power in girls than in boys—and were in part mediated by differential association—none of the variables explains a substantial part of the gender gap in aggressive and/or non-aggressive risk-taking.

ObjectiveThis study was designed to assess longitudinal changes in serum testosterone levels, explore relationships with aging, genetic-, health-, and lifestyle-related factors, and investigate predictors of changes in healthy elderly men.DesignPopulation-based, longitudinal, 4-year observational study in 221 community-dwelling men aged 71–86 years at baseline.MethodsHormone levels assessed by immunoassay, anthropometry, questionnaires on general health, and genetic polymorphisms. Predictors of changes in testosterone levels explored using linear mixed-effects modeling for longitudinal analyses.ResultsTotal testosterone (TT), free testosterone, and bioavailable testosterone (BioT) levels decreased with aging, decreases in BioT being most marked. No changes in sex hormone-binding globulin (SHBG) or estradiol (E2), while LH and FSH levels increased during follow-up. Subjects who gained weight displayed a greater decline in TT levels, mainly due to decreasing SHBG levels. However, baseline body composition was not predictive of subsequent changes in testosterone levels. Baseline E2 (P=0.023 to 0.004), LH (P=0.046 to 0.005), and FSH (PP=0.041–0.035). Carriers of a ‘TA’ haplotype of the estrogen receptor α gene (ERα) PvuII and XbaI polymorphisms displayed a slower decline of TT and BioT (P=0.041–0.007).ConclusionsIn elderly men with already low serum testosterone levels, a further decline was observed, independent of baseline age. The identification of FSH levels as a predictor of this decline appears to reflect the testicular mechanisms of aging-related changes in testosterone production, whereas associations with E2 and ERα polymorphisms are suggestive of estrogen-related processes, possibly related to changes in the neuroendocrine regulation of testosterone production.

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

PurposeTo assess the evolution of body composition and bone metabolism in trans men during the first year of cross-sex hormonal therapy.MethodsIn a prospective controlled study, we included 23 trans men (female-to-male trans persons) and 23 age-matched control women. In both groups, we examined grip strength (hand dynamometer), biochemical markers of bone turnover (C-terminal telopeptides of type 1 collagen (CTX) and procollagen 1 aminoterminal propeptide (P1NP)), total body fat and lean mass, and areal bone mineral density (aBMD) by dual-X-ray absorptiometry (DXA) and fat and muscle area at the forearm and calf, bone geometry, and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), before treatment and after 1 year of treatment with undecanoate (1000 mg i.m./12 weeks).ResultsBefore hormonal treatment, trans men had similar bone and body composition compared with control women. Testosterone treatment induced in trans men a gain in muscle mass (+10.4%) and strength and loss of fat mass (−9.7%) (allPPP=0.036 andP=0.001 respectively). None of these changes were observed in the control group.ConclusionsShort-term testosterone treatment in trans men increased muscle mass and bone turnover. The latter may rather reflect an anabolic effect of testosterone treatment rather than bone loss.

Background: Serum C-peptide concentrations reflect pancreatic function in different clinical and diagnostic settings; however, the utility of C-peptide testing is limited by the lack of standardized commercial immunoassays. Standardization can best be done by split-sample comparison with a hierarchically higher reference measurement procedure with a set of native sera. For serum peptides, isotope-dilution liquid chromatography–mass spectrometry (ID-LC/MS) is recommended as a reference measurement procedure. Methods: We evaluated the analytical performance characteristics of an ID-LC/tandem MS procedure for measurement of serum C-peptide after a 2-step solid-phase extraction. To investigate the feasibility of this procedure for use in standardization, we also performed a method comparison with 3 representative commercial assays. Results: The ID-LC/tandem MS procedure showed maximum within-run, between-run, and total CVs on dedicated sera (C-peptide concentrations, 1.6 and 4.0 μg/L) of 2.1%, 2.5%, and 2.9%, respectively; an accuracy of 94.6%–104.1%; a minimum trueness of 98.1% (95% confidence interval, 96.2%–100.0%), and limits of quantification and detection of 0.15 and 0.03 μg/L, respectively. Deming linear regression analysis of the method-comparison data showed that the immunoassays correlated well with ID-MS and were specific, but lacked intercomparability and trueness. We propose that the deficiencies can be resolved by recalibration on the basis of the method comparison. Conclusions: The ID-LC/tandem MS procedure is suitable for specific and accurate measurement of basal and stimulated serum concentrations of proinsulin C-peptide fragment 33–63 and is suitable for use in standardization of C-peptide immunoassays.

Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between "substitutive" and "pharmacological" androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of these men were not androgen deficient. Most consistent effects of treatment have been on body composition, but to date there is no evidence-based documentation of clinical benefits of androgen administration to elderly men with normal or moderately low serum testosterone in terms of diminished morbidity or of improved survival or quality of life. Until the long-term risk-benefit ratio for androgen administration to elderly is established in adequately powered trials of longer duration, androgen administration to elderly men should be reserved for the minority of elderly men who have both clear clinical symptoms of hypogonadism and frankly low serum testosterone levels.

Stimulation of luteinizing hormone (LH) secretion by N-methyl-D,L-aspartic acid (NMA), reported for several mammalian species, is generally accepted to be mediated through stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) release. In view of a previously reported unexpected inhibitory action of NMA on GnRH release from hypothalamic explant of intact male guinea-pigs, the aim of the present study was to assess the in vivo effects of NMA in the adult male guinea-pig. In the gonadally intact male, NMA (5 mg/animal) elicited a robust LH secretion, which was blocked by the N-methyl-D-asparte-receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5,12 mg/animal). In the castrated male, NMA elicited only a marginal and inconsistent LH secretion. Cetrorelix (CET), a GnRH receptor antagonist, administered intracardiacally 1 min or 45 min preceding bolus injection of NMA significantly reduced the LH response to NMA in the intact male. Surprisingly, following GnRH receptor blockade with CET, there still was a substantial residual serum LH response to NMA, while CET completely abolished the serum LH response to high dose (1 microg or 10 microg) guinea-pig GnRH (gpGnRH). These results indicate that NMA stimulates LH secretion in the gonadally intact male guinea-pig in vivo and that this effect is mediated in part through gpGnRH-independent mechanisms.

Following an information campaign through the media on the subject of 'andropause', 81 consecutive self-referred patients were evaluated. At presentation these patients had complaints possibly related to partial androgen deficiency in the aging male. Hormonal parameters were measured and specific aging male questionnaires, such as Androgen Deficiency in Aging Male (ADAM) and Aging Males' Symptoms (AMS) scale questionnaires were completed. The median age was 59 (range 53-66) and mean body mass index (BMI) was 26.4 ± 3.3 kg/m2. Mean testosterone was 479.8 ± 149.0 ng/dl and mean free testosterone was 10.0 ± 3.0 ng/dl. Only 7.1% of all patients were diagnosed with 'idiopathic' ADAM. The majority of patients presented with erectile dysfunction. A wide variety of conditions were diagnosed, including hemo chromatosis, micro- and macroprolactinoma, hypothyroidism, benign prostate hypertrophism and prostate carcinoma. The scores of AMS psychological, somatovegetative and sexual subscales were 12, 16 and 13, accord...

(2002). The effects of testosterone deficiency on male sexual function. The Aging Male: Vol. 5, No. 4, pp. 242-247.

The role of estrogens in male physiology has become more evident, as a consequence of the discovery of human models of estrogen deficiency such as estrogen resistance or aromatase deficiency. In ma...

The aim of the present study was to assess the progesterone (Pr) transforming 5 alpha-reductase (5 alpha-R) and 3 alpha-oxidoreductase (3 alpha-OR) activities in the hypothalamus of the male rat as a function of age and following castration and/or adrenalectomy performed at the sixth day of life. The hypothalamic activity of these enzymes was estimated from the sum of the 5 alpha- or 3 alpha-reduced metabolites produced from 14C-labeled Pr incubated "in vitro" with hypothalamic tissue. Plasma levels of testosterone (T), progesterone (Pr), estrone (E1), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured simultaneously. Special attention was paid to the GC/MS analysis of the endogenous content of the hypothalamic Pr-metabolites 3 alpha-hydroxy-pregn-4-en-20-one (3 alpha-Pr), 5 alpha-pregnane-3,20-dione (5 alpha-Pr) and 3 alpha-hydroxy-5 alpha-pregnan-20-one (5 alpha,3 alpha-Pr). The high 5 alpha-R and 3 alpha-OR activities estimated in the hypothalamus of prepubertal rats are not related to the action of gonadal or adrenal steroids. Substantial and comparable endogenous 3 alpha- and/or 5 alpha-Pr-metabolites were found in hypothalami from both prepubertal and mature rats. The results of the present study do not provide evidence for a contributory role of the 3 alpha-hydroxylated Pr derivative to the regulation of gonadotropin secretion in the male rat.

The diagnosis of hypoandrogenism in the aging male is still difficult, since the symptomatology is aspecific and multifactorial, and it is unknown whether the androgen requirements of elderly men are the same as those of young men. Indeed, there are arguments for decreased (increased androgen feed-back sensitivity) as well as for increased (decreased concentration of androgen receptors) requirements in elderly men. In the absence of a reliable, clinically useful, parameter of androgen activity, we have to rely on plasma androgen level, an indirect parameter. In the absence of convincing arguments for altered requirements with age, we consider that the normal range of (free) testosterone levels in young adults is also valid for elderly men, the lower normal limit being 11 nmol/l for total testosterone and 0.225 nmol/l for free testosterone. There are indirect, suggestive clinical arguments for accepting these limit values. The diagnosis of hypoandrogenism in elderly males requires both the presence of clinical symptoms and decreased (free) testosterone levels. The best methods for determining free or bioavailable testosterone, are equilibrium dialysis and ammonium sulfate precipitation, respectively. They are, however, time-consuming techniques which are not easily automated. Calculation of the free androgen index (testosterone/sex hormone binding globulin (SHBG)) is not a valid method for male serum. Calculation of free testosterone from total testosterone, SHBG and albumin concentration, yields values that are in good agreement with values obtained by dialysis or ammonium sulfate precipitation. Several conditions should, however, be fulfilled: reliable methods for the determination of testosterone and SHBG, SHBG measurement in serum and not in plasma, use of fresh serum (not repeatedly frozen and thawed), absence of (exogenous) steroids competing for binding sites on SHBG and blood samples taken between 08.00 and 10.00 in the fasting state. Under these conditions an excellent correlation with dialysis and bioavailable testosterone (ammonium sulfate precipitation) is generally obtained.

The DNA sequence of the encoding gene predicts a unique structure for guinea-pig gonadotropin-releasing hormone (GnRH). We assessed the immunoreactivity of synthetic mammalian GnRH, of a synthetic peptide with predicted guinea-pig GnRH structure, and of extracts from rat and guinea-pig hypothalami, using two different RIA systems. Whereas immunoreactivity of mammalian and guinea-pig GnRH was rather similar when using an antiserum with conformational specificity for mammalian GnRH (Root RR-5 antiserum), binding of both peptides to an antiserum with sequential specificity (Kelch R-13 antiserum) was markedly different. The findings for GnRH extracted from rat and guinea-pig hypothalami were similar to those for the corresponding synthetic peptides. Assessment of in-vivo biological activity of synthetic mammalian and guinea-pig GnRH in the intact male guinea-pig showed that both peptides stimulate LH secretion dose-dependently, the response to mammalian GnRH being slightly greater at low dose. This study confirms that the GnRH expressed in the brain of the adult guinea-pig differs from mammalian GnRH and indicates that mammalian and guinea-pig GnRH display conformational similarity and that both can stimulate guinea-pig luteinizing hormone secretion.

The importance of senile osteoporosis in men as a public health problem has long been underestimated. Elderly men are at substantial risk for fracture, and morbidity after osteoporotic fractures appears to be more serious and mortality more common in men than in women. Risk factors for osteoporotic fractures in men appear to be qualitatively similar to those in women, but there are quantitative differences. Low bone mineral density (BMD) is an important risk factor for fracture in men; however, further clarification of the relationship between BMD, bone geometry and fracture risk is needed before formulating definitive proposals on operational densitometric criteria for diagnosis of osteoporosis in men and the identification of men at high risk for fracture. Understanding of the mechanisms underlying senile bone loss and the pathogenesis of senile osteoporosis in men remains fragmentary with, in particular, the need for further clarification regarding the precise impact of hormonal status in elderly men o...

Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. Prior to CSH, trans women had lower aBMD at all measured sites (all p

The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index of bioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.

The aim of the present study was to assess the activities of the progesterone (Pr) transforming enzyme systems 3alpha-oxidoreductase (3alpha-OR), 5alpha-reductase (5alpha-R) and 20alpha-oxidoreductase (20alpha-OR) in the hypothalamus of the male rat, at different stages of sexual maturation and following castration and adrenalectomy. Special attention was paid to transformation to 3alpha-reduced compounds previously shown to inhibit FSH synthesis and secretion. Homogenates of hypothalamic tissue were incubated with 14C-progesterone. Pr-metabolites were isolated, identified by gas chromatography/mass-spectrometry (GC/MS) and measured by liquid scintillation counting (LSC). In adult rats a ratio of 6:2.5:1 for 5alpha-R:3alpha-OR:20alpha-OR enzyme- activities was found. The hypothalamic 5alpha-R and particularly 3alpha-OR activities were considerably higher before puberty (10-20 day old rats) than in adulthood. Adrenalectomy in adult rats resulted in an increased activity of the three enzyme systems. No significant changes were seen following castration. Among the isolated metabolites, 3alpha-hydroxy-pregn-4-en-20-one (3alpha-Pr) and 3alpha-hydroxy-5alpha-pregnane-20-one (5alpha,3alpha-Pr) were identified. Conversion to both these neurosteroids was considerably higher during prepuberty than in adulthood. The finding that before puberty the hypothalamus has a markedly increased capacity to convert Pr to 3alpha-reduced compounds, such as 3alpha-Pr, known to effectively inhibit FSH release, warrants further research into the mechanisms regulating the hypothalamic formation of biologically active Pr derivatives and their role in the regulation of gonadotropin secretion.

Aging in healthy men is accompanied by a progressive decline of gonadal function with, in particular, a decline of Leydig cell function and decreased testosterone production. Population means for total serum testosterone decrease by about 30% between the ages of 25 and 75 years. Over the same period, mean serum levels of free or bioavailable testosterone decrease by as much as 50%. The decline of Leydig cell function in aging is the consequence of primary testicular changes, with decreased numbers of Leydig cells, and alterations in neuroendocrine regulation of the pituitary secretion of luteinizing hormone (LH), with an inappropriately low LH drive in the face of a persistent relative hypoandrogenism. The changes in neuroendocrine regulation of LH secretion are situated primarily at the hypothalamic level with, in particular, an increased sensitivity to the negative feedback effects of sex steroids. The testicular changes and the altered regulation of LH secretion are accompanied by an independent, age-a...

In order to evaluate the role of sex hormones and aging on body composition in males, plasma testosterone, free testosterone, estradiol and sex hormone binding globulin as well as insulin-like growth factor I (IGF-I) and insulin levels were determined in a group of 372 ambulant males, aged 20–85 years. In addition, these parameters were correlated with aging and body composition. Muscle mass decreased and fat mass increased significantly with age. Both age and free testosterone were independent determinants of fat mass. Abdominal fat was by far the most important determinant of free testosterone levels, gluteal fat contributing little to the free testosterone levels. The decrease of fat free mass was essentially correlated with age, the contribution of free testosterone levels being marginal. The ratio of subcutaneous to visceral fat decreased with age, independent of body mass index, free testosterone or estradiol levels. This suggests that, at a similar degree of obesity, the health hazards are more pro...

Background: To assess and compare the predictive value of physical function measurements (PFMs) for all-cause mortality in older men and to evaluate the Timed Up and Go test (TUG) as a predictor in subjects with underlying comorbidity. Design: Observational study of a population-based sample of 352 ambulatory older men aged 7186 at study baseline. The Rapid disability rating scale-2, 36-Item short form health survey, Grip strength, Five times sit-to-stand test, Standing balance, and TUG were determined at baseline. Associations with all-cause mortality were assessed using Cox proportional hazard analyses. Age, Body mass index (BMI), smoking status, education, physical activity and cognitive status were included as confounders. Follow-up exceeded 15years. Comorbidity status was categorized into cardiovascular disease, chronic obstructive pulmonary disease (COPD) and diabetes mellitus. Results: All examined PFMs were associated with all-cause mortality. TUG was the best predictor (adjusted HR per SD increase=1 center dot 58, 95% CI=1 center dot 401 center dot 79, P

Several aspects of the regulation of androgen secretion and plasma levels in males remain controversial. Among these, we cite the problem of whether the age-related decrease in testosterone (T) levels is an intrinsic aging phenomenon or is a sequel of previous illness, the mechanisms underlying the increase in sex hormone-binding globulin (SHBG)-binding capacity in aging men and the supranormal capacity observed immediately after a weight-reducing diet, and the role of insulin in the age-associated decrease in dehydroepiandrosterone (sulfate) [DHEA (DHEAS)] levels. To gain further insight into these issues, we investigated the influence of age, smoking, body mass index (BMI), serum albumin, insulin, GH, and insulin-like growth factor I (IGF-I) levels, respectively, on androgen levels and SHBG-binding capacity in a nonobese healthy population (n = 250) as well as in an obese population (n = 50) before and after weight loss. The influence of GH supplementation on SHBG, DHEAS, DHEA, and insulin levels was studied in a small group of men (n = 8) with isolated GH deficiency. In nonobese healthy men, age was inversely correlated with serum levels of all androgens studied (although total T levels stayed relatively stable until age 55 yr) as well as with albumin, GH, and IGF-I levels and positively correlated with BMI, insulin levels, and SHBG-binding capacity. Nevertheless, SHBG levels were significantly negatively correlated with insulin levels (P0.001) as well as with mean 24-h GH and IGF-I levels. Among possible confounding factors affecting (free) T [(FT)] levels in healthy men, smoking appeared to be accompanied by higher (F)T levels than those in nonsmokers. BMI increased with age, but although BMI was negatively correlated with T, FT, and SHBG, respectively, the age-dependent decrease in T levels persisted after correction for BMI. Data not corrected for BMI may, nevertheless, overestimate the age-associated decrease in T levels. The albumin concentration decreased with age, and if FT is the feedback regulator of plasma T levels, albumin concentration might be a codeterminant (although, evidently, less important than SHBG) of T levels and contribute to the age-associated decrease in T levels. In any case, albumin concentration is a codeterminant of DHEAS concentration. T, DHEA, and DHEAS levels were significantly correlated, but this correlation disappeared after controlling for age; hence, there is no evidence for an adrenal-gonadal interaction in men. In obese men, T, FT, and SHBG levels were significantly lower than those in the nonobese men and inversely correlated with BMI; DHEAS levels were slightly lower than those in the nonobese controls, but no significant correlation between DHEA or DHEAS, and insulin levels was observed. After a weight-reducing, protein-rich diet, resulting in a mean weight loss of +/- 15 kg, SHBG-binding capacity increased to normal values notwithstanding the fact that the subjects were still obese and that the insulin levels remained higher than those in the nonobese controls. Considering that after weight loss, GH and IGF-I levels remained lower than those in the nonobese controls, that adult men with isolated GH deficiency presented with higher SHBG levels than normal controls, which decreased to normal levels during GH substitution, and that elderly men have elevated SHBG levels notwithstanding high insulin levels, we suggest that the low GH and/or IGF-I levels might play a role in the elevated SHBG levels observed in both elderly males and obese men after a weight-reducing diet. As weight loss did not influence DHEAS levels notwithstanding an important decrease in insulin levels, our data do not support a role of insulin in the regulation of plasma DHEAS levels.

This study aimed to examine the changes in RR interval and blood pressure (BP) variability and humoral factors during postural changes in borderline arterial hypertension. Twenty-nine patients (44 +/- 3 year; BP, 145 +/- 3/84 +/- 3 mm Hg) with borderline hypertension and a control group of 38 subjects (35 +/- 2 year; BP, 123 +/- 3/70 +/- 2 mm Hg) underwent power spectrum analysis of RR interval and BP (low frequency (LF), 0.05 to 0.15 Hz; high frequency (HF), 0.15 to 0.40 Hz) in the supine and standing positions. Concentrations of plasma renin activity, angiotensin II, and aldosterone in supine and standing positions had been determined in the hypertensive group. Borderline hypertensives are characterized by higher oscillations of systolic and diastolic BP, but not of RR interval in the supine position versus the control group. Low frequency and HF components of systolic and diastolic BP expressed as absolute data are also significantly higher in borderline hypertensives. Moreover, standing tended to increase the LF/HF ratio of both RR interval and BP variability compared to controls. The standing position was able to further activate the LF but not the HF component of BP variability. In borderline hypertension renin release during postural changes correlated well with the decrease in the power of the HF vagal component of RR interval variability (r = -0.70, P.001) and with the increase of the LF component of diastolic blood pressure variability (r = 0.43, P = .03). In conclusion, our results indicate that in borderline arterial hypertension, LF and HF oscillations of BP are already significantly increased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

In distinction to the course of reproductive ageing in women, men do not experience a rapid decline of Leydig cell function or irreversible arrest of reproductive capacity in old age. Hence, strictu sensu, the andropause does not exist. Nevertheless, both spermatogenesis and fertility as well as Leydig cell function do decline with age, as shown by a decrease of +/- 35% of total and of 50% of free testosterone levels between the age of 20 and 80 years. The origin of this decline of Leydig cell function resides on the one hand in the testes, and is essentially characterized by a decreased number of Leydig (and Sertoli) cells and on the other hand in the hypothalamo-pituitary complex characterized by a decreased luteinzing hormone (LH) pulse amplitude, LH pulse frequency being maintained. As the responsiveness of the gonadotrophs to gonadotropin-releasing hormone (GnRH) remains unimpaired, one may assume that the amount of GnRH released at each pulse is also reduced, possibly as the consequence of a reduction of the cellular mass of GnRH neurones. Plasma levels of testosterone below the lower normal limit occur, however, only in a minority of elderly men from 7% in the age group 40-60, to 20% in the age group 60-80 and 35% in the age group over 80 years old. Factors influencing testosterone levels in elderly men are multiple: hereditary, environmental (obesity, stress), psychosocial (depression, smoking, drugs) or socioeconomical (diet, hygiene). Whether these elderly men should be substituted with androgens remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between baseline Fracture Risk Assessment Tool (FRAX®) and treatment efficacy was evaluated using data from a pivotal phase 3 study. Relative risk of vertebral, nonvertebral, and all clinical fractures decreased with increasing probability of fracture for bazedoxifene (BZA) versus placebo but remained generally constant for raloxifene (RLX). To determine whether the FRAX® predicts osteoporosis treatment efficacy, we evaluated reductions in fracture incidence associated with BZA and RLX according to baseline fracture risk determined by FRAX® using data from a phase 3 osteoporosis treatment study. Hazard ratios (HRs) for effects of BZA and RLX versus placebo on incidence of vertebral, nonvertebral, and all clinical fractures were calculated using a Cox regression model. Cox regression analyses were performed in subgroups at or above 10-year fracture probability thresholds determined by FRAX®. HRs for the risk of vertebral, nonvertebral, and all clinical fractures versus placebo decreased with increasing 10-year fracture probability for BZA, while those for RLX remained stable. In all 10-year fracture probability subgroups, all BZA doses significantly reduced vertebral fracture risk versus placebo (HR = 0.22–0.66). BZA at 20, 40, and 20/40 mg significantly reduced risk of nonvertebral fractures (HR = 0.45, 0.44, and 0.45, respectively) and all clinical fractures (HR = 0.38, 0.41, and 0.40, respectively) for ≥20.0 % fracture probability. Vertebral fracture risk reductions for RLX 60 mg versus placebo were significant in subgroups at lower fracture probabilities (≥2.5– ≥ 10.0 %), but not higher (≥12.5 %), and in no subgroups for nonvertebral or all clinical fractures. The antifracture efficacy of BZA increased with increasing baseline FRAX® score, but there was no clear relationship between RLX and baseline FRAX®. These findings provide independent confirmation of current literature, suggesting that the relationship between FRAX® and treatment efficacy varies for different agents.

Endogenous opiates exert a tonic restraint on LH release, which is centrally mediated through inhibition of hypothalamic GnRH secretion. The aim of the present study was, using an in vitro superfusion approach, to perform a detailed study of the effects of opioid receptor activation and blockade on the dimensions of pulsatile GnRH release from the isolated medial basal hypothalamus of the adult male guinea pig. The mu-receptor antagonist naloxone at 10(-3) M (n = 12), 10(-6) M (n = 12), and 10(-9) M (n = 12), the opioid agonist morphine sulfate at the same concentrations (n = 14 for each concentration), or morphine and naloxone together at 10(-3) M (n = 14), was added to the medium alternately either during the first or the second of two consecutive 3-h observation periods. Five-minute fractions (750 microliters) were collected for measurement of GnRH by RIA. Morphine suppressed total GnRH output from the medial basal hypothalami (Por = 0.01 at 10(-3) M and 10(-6) M; P = NS at 10(-9) M), with mean pulse frequency, mean amplitude of all pulses, and mean sum of pulse amplitudes being significantly inhibited at all morphine concentrations, whether pulse analysis (Ultra pulse analysis algorithm) was performed at a two-coefficient of variation (2CV; Por = 0.05, Por = 0.01, and Por = 0.01, respectively) or a 3CV (Por = 0.05, Por = 0.05, and Por = 0.01, respectively) threshold. A different set of experiments (n = 14), with exposure to 10(-3) M morphine during the second of three consecutive 3-h observation periods, indicated that after morphine withdrawal a gradual recovery of GnRH output and pulse frequency to pretreatment values occurred, whereas pulse amplitude remained significantly suppressed during the posttreatment observation period. The inhibitory actions of 10(-3) M morphine were effectively prevented by the presence of 10(-3) M naloxone. Total GnRH output (Por = 0.05), mean pulse frequency (Por = 0.05), mean amplitude of all pulses (Por = 0.05), and mean of the sum of pulse amplitudes (Por = 0.01) were increased during opioid blockade with 10(-3) M and 10(-9) M naloxone (either 2CV or 3CV threshold for pulse analysis). A similar trend for 10(-6) M naloxone was only apparent after the exclusion of two outliers with unusually high basal GnRH release.(ABSTRACT TRUNCATED AT 400 WORDS)

In a group of 36 untreated patients with mild-to-moderate essential hypertension (office systolic blood pressure [SBP] 160 ± 3.4 mm Hg, office diastolic blood pressure [DBP], 102 ± 1.5 mm Hg), 24-hour ambulatory blood pressure monitoring, and determination of left ventricular (LV) mass index according to the formula of Devereux were performed. After an overnight fast, blood samples were taken for the determination of serum aldosterone levels and plasma renin activity. Urinary catecholamine concentrations were assayed from 24-hour urine collections. Left ventricular mass index (143.7 ± 8 g/m 2 ) did not correlate significantly with either office SBP or office DBP. The correlation of LV mass index with mean 24-hour SBP (145 ± 3 mm Hg) was statistically significant: r = 0.395, p = 0.026. However, the best correlation was obtained with mean 24-hour DBP (90 ± 3 mm Hg) with r = 0.499 (p = 0.004). Urinary catecholamine levels did not correlate with LV mass index. In addition, LV mass index correlated significantly with plasma renin activity (r = 0.346, p = 0.050) and serum aldosterone levels (r = 0.559, p = 0.0009). There was a strongly significant correlation between LV mass index and serum aldosterone levels even after adjustment for mean 24-hour SBP (r = 0.496, p = 0.005) and DBP (r = 0.514, p = 0.004). These results demonstrate that ambulatory blood pressure determinations but not office blood pressure parameters correlate well with left ventricular hypertrophy in essential hypertension. Nonhemodynamic factors are important determinants of left ventricular mass as well. Moreover, aldosterone seems to play an important rote in cardiac hypertrophy independent of its relation with arterial blood pressure.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p0.01) and QCT (5.7%, p0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p0.0001), total hip (10.8%, p0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p0.0001).Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

Nessuna funzione fisiologica rimane inalterata dal processo di invecchiamento, che determina ineluttabilmente una diminuzione della capacita funzionale e dell’efficacia dei meccanismi regolatori omeostatici. Tutti i sistemi ormonali vengono colpiti in gradi diversi dal fenomeno dell’invecchiamento e l’asse gonadico dell’uomo non fa eccezione, anche se le modificazioni sono progressive e di ampiezza modesta, se confrontate con la riduzione relativamente improvvisa della produzione degli ormoni ovarici che caratterizza la menopausa nella donna.

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1) and salmeterol 50 microg twice daily, in 32 patients with persistent asthma using a randomised double-blind, placebo-controlled, double-dummy, five-period crossover design. All patients exhibited a provocative concentration leading to a 20% decrease in forced expiratory volume in 1 s (PC(20)) methacholine

About one in three osteoporotic fractures occur in men, and the consequences of fractures are more severe in men. However, only too few men at high risk of fracture are detected and treated. There is no consensus definition of osteoporosis in men based on bone mineral density (BMD), and therapeutic decisions should be based on absolute fracture risk as estimated from age, BMD, fracture history, and additional clinical risk factors. In men, secondary osteoporosis deserves particular attention. Genetically determined alterations of bone mass acquisition during growth are involved in idiopathic osteoporosis in the young, whereas senile osteoporosis involves progressive bone loss throughout adult life. Estradiol appears to be the predominant sex steroid involved in regulation of bone maturation and metabolism. The evidence base for the long-term efficacy and safety of therapies for osteoporosis in men, including the bone-active agents (i.e. bisphosphonates and teriparatide), is limited, so that they should be applied with discernment based on clinical judgement and careful estimation of fracture risk.

Bone health is a parameter of interest in the daily follow-up of male-to-female (M --F) transsexual persons both before and after sex reassignment surgery (SRS) due to an intensely changing hormonal milieu. We have studied body composition, areal, geometric, and volumetric bone parameters, using DXA and peripheral quantitative computed tomography at different sites in 50 M --F transsexual persons, at least 3 yr after the start of the hormonal treatment and 1 yr after SRS. In this cross-sectional study, hormone levels and markers of bone metabolism were assessed using immunoassays. Prevalence of low bone mass as defined by a Z-scoreor = -2.0 according to DXA criteria was 26% at lumbar spine and 2% at the total hip. We found no major differences in hormonal parameters between participants with a Z-scoreor = or-2.0. Markers of bone turnover were comparable between subjects with or without low bone mass, indicating a stable bone turnover at the time of investigation. No significant differences in bone size or density were observed between patients on transdermal vs. oral estrogens. Low bone mass is not uncommon in M --F transsexual persons. Smaller bone size, and a strikingly lower muscle mass compared with men appear to underlie these findings.

Studies on 2d:4d, the ratio between the second and the fourth digit, as a possible indicator of prenatal androgen exposure, have failed to produce consistent results. This paper analyzes the relation between 2d:4d, sex steroids and well-documented sex differences in characteristics such as depression, dominance, and aggressive (ART) and non-aggressive adolescent risk-taking (NART) in a comparatively large sample of adolescent boys (N=301, mean age: 14.4 years) and girls (N=298, mean age: 14.3 years). Boys had on average a lower 2d:4d than girls (F=42.15; p

There is a large interindividual variation in serum (free) testosterone (FT) levels in men, underlain in part by genetic components.The objective of the study was to explore the hypothesis that this variability results in part from differences in androgen sensitivity and feedback loop set point and assess the role of the androgen receptor (AR) polyglutamine tract polymorphism encoded by a CAG repeat of variable length in exon 1 of the AR gene.We performed a cross-sectional analysis in two independent populations of healthy men, consisting of 2322 men aged 35-59 yr (Belstress study) and 358 men aged 25-45 yr (Siblos study), respectively.Serum hormonal levels and the AR gene CAG repeat length were determined.In the Belstress population, serum testosterone and calculated FT showed a positive linear association with LH (P0.001). In the 200 men with lowest FT, CAG repeat number was lower than in the 200 men with highest FT (P = 0.004). As studied in a larger subset of the population consisting of 857 men covering the whole FT range, FT increased progressively with CAG repeat length (P = 0.003). These findings of a positive relation of FT with both LH and CAG repeat length were confirmed in the Siblos study population (both Por = 0.001). Difference in FT between extreme quartiles of CAG repeat was 10 and 14% in the Belstress and Siblos study, respectively. In both study populations, CAG repeat length was also positively associated with serum total testosterone (Por = 0.004).The data support the view that between-subject variability in serum FT in healthy men is underlain in part by differences in androgen sensitivity and feedback set point, with a contributory role of AR polymorphism. These findings have potential implications for the interpretation of epidemiological studies, diagnosis of hypogonadism, and pharmacogenetics of androgen treatment in men.

Objective: The androgen receptor (AR) gene contains a CAG repeat polymorphism coding for a polyglutamine chain, the length of which is inversely correlated with AR transcriptional activity. We explored whether this polymorphism modulates the activities of testosterone (T) related to body composition in elderly men. Design: We performed cross-sectional analyses using data from a 4-year follow-up study in community-dwelling men aged 75–89 years (n=159). Methods: Body composition was assessed by dual-energy X-ray absorptiometry and its relation with T and the AR gene CAG repeat length was assessed by multiple linear regression analyses, adjusting for confounding and exploring effect modification. Results: AR gene CAG repeat length was not directly related to body composition, either with or without adjustment for confounding variables like age, weight, total T or sex hormone binding globulin (SHBG) levels. However, exploration of effect modification showed that CAG repeat length modulated the relation between T and body composition (standardized regression coefficients of interaction term: β=0.12, PPPP Conclusion: These findings suggest that the AR gene CAG polymorphism contributes, albeit modestly, to the between-subject variation of T action on body composition in community-dwelling elderly men.