Changes In Total Testosterone Research Articles

Modulation of circulating free testosterone fraction by testosterone, dihydrotestosterone, and estradiol during testosterone replacement therapy.

Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction. To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism. Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and dihydrotestosterone concentrations over 12 months of testosterone replacement therapy with changes in free testosterone fraction, measured using equilibrium dialysis. We used random forests to evaluate the associations of predicted mean changes in free testosterone fraction with changes in circulating concentrations of each hormone at low, mean, or high change in the other two hormones. Testosterone replacement therapy not only increased total testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations, but also the percent free testosterone, even though sex hormone binding globulin levels did not change. The predicted changes in free testosterone fraction during testosterone replacement therapy exhibited a non-linear relationship with changes in each of total testosterone, dihydrotestosterone, and estradiol concentrations. Greater increases in testosterone, dihydrotestosterone, and estradiol levels during testosterone replacement therapy were each associated with higher model-predicted percent free testosterone. Substantially smaller changes in molar concentrations of estradiol and dihydrotestosterone had a greater effect on percent free testosterone than those in testosterone. During testosterone replacement therapy of men with hypogonadism, changes in testosterone, dihydrotestosterone, and estradiol concentrations each altered percent free testosterone non-linearly. Small changes in estradiol concentrations exerted much larger effect on the free testosterone fraction than testosterone and dihydrotestosterone, suggesting complex interactions of the three hormones with the binding proteins. Assessment of changes in free testosterone during testosterone replacement therapy should include consideration of changes in all three hormones.

Association Between Vitamin D Deficiency and Testosterone Levels in Adult Males: A Systematic Review.

Vitamin D deficiency and its potential impact on testosterone levels have been subjects of scientific interest. This systematic review aims to evaluate the association between vitamin D deficiency and testosterone levels in adult males and examine the effects of vitamin D supplementation on testosterone. A comprehensive literature search was conducted in accordance with the PRISMA guidelines across PubMed, Google Scholar, and ScienceDirect. The inclusion criteria involved studies published in English between 2013 and 2023, which investigated the correlation between vitamin D and testosterone levels in adult males. The process of data extraction and synthesis encompassed various aspects, including study characteristics, participant demographics, measurement methods, and outcomes pertaining to the association. The initial search resulted in a pool of 354,235 articles. Through the application of relevant filters and the review of titles and abstracts, 48 articles were chosen for further assessment. Out of these, eight studies fulfilled the inclusion criteria and were ultimately incorporated into the final review. The included studies consisted of four cross-sectional studies, three randomized controlled trials (RCTs), and one analysis utilizing Mendelian randomization. The results showed heterogeneity among the studies, as some reported a positive correlation between vitamin D levels and testosterone, while others did not find a significant association. The effects of vitamin D supplementation on testosterone levels were inconclusive, with limited evidence of significant changes in total testosterone. However, potential influences on sex hormone-binding globulin and free testosterone levels were observed. To establish more definitive evidence regarding the impact of vitamin D on testosterone levels, there is a need for further well-designed, long-term RCTs that encompass diverse populations.

(063) Association between Comorbidities and Longitudinal Changes in Total Testosterone among men from the Baltimore Longitudinal Study of Aging

Abstract Introduction Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men. However, the longitudinal impact of acquired comorbidities in aging males on the relationship between age and testosterone has not been thoroughly investigated. Objective In this longitudinal study, we aimed to evaluate the longitudinal association between age and testosterone levels and to investigate the impact of additive comorbidity burden on this relationship. We hypothesized that when controlling for the presence of comorbidities commonly acquired with age, there would be no association between age and serum total testosterone level. Methods Participants were selected from the Baltimore Longitudinal Study of Aging. Data was obtained on presence of several comorbidities and total testosterone level during each follow-up visit. All men with diagnosis of prostate cancer or documented use of testosterone replacement therapy during their follow-up period were excluded from analysis. A stepwise regression analysis was performed, including a final multivariate panel regression model in order to determine the impact of age on testosterone level while controlling for individual comorbidities. Results A total of 1,784 men were included in this study, with a mean age of 71 years and overall mean testosterone level of 463.2 ng/dL. Participants had an average of 3.23 comorbidities. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. Conclusions In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level with age. With the overall increase in life expectancy, and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities. Disclosure No

Association between comorbidities and longitudinal changes in total testosterone among men from the Baltimore Longitudinal Study of Aging.

Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men, without consideration of acquired comorbidities in aging males. We evaluated the longitudinal association between age and testosterone levels as well as the impact of several comorbidities on this relationship using multivariate panel regression analysis. Participants were selected from the Baltimore Longitudinal Study of Aging. Data were obtained on the presence of several comorbidities and total testosterone level during each follow-up visit. A multivariate panel regression analysis was performed to determine the impact of age on testosterone level while controlling for individual comorbidities. The primary outcomes were strength of association between age and various comorbidities, and testosterone level. A total of 625 men were included in this study, with a mean age of 65years and a mean testosterone level of 463ng/dL. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. This study indicates that a decline in testosterone levels over time may be due to the presence of various comorbidities, which affects the medical management of hypogonadism in aging men. The strengths of this study include the standardized acquisition of testosterone tests and uniform collection of variables, while limitations include the lack of follow-up data from 205 patients and the limited racial/ethnic diversity in the cohort. In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level. With the overall increase in life expectancy and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities.

The Efficacy of Metformin Treatment on Insulin Resistance and Hyperandrogenism in Lean Women with Polycystic Ovary Syndrome: A Literature Review

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women, characterized by insulin resistance and hyperandrogenism. Previous studies have investigated the use of metformin, a well-known insulin sensitizer, on lean PCOS patients, but it remains unclear as to how effective the treatment is. This literature review was carried out to better assess the effects of metformin on lean PCOS patients. Methods: Related literature was fully searched using MEDLINE, EMBASE, Web of Science, and COCHRANE for metformin therapy on lean women with PCOS (last updated May 2022). A review was performed to evaluate the effects of continued metformin treatment on relevant hormonal and metabolic indicators in these women. Results: A total of fourteen studies among 300 related articles were included in the review. Significant changes in total testosterone, sex hormone binding globulin (SHBG), blood insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were reported in majority of the studies. Several studies observed significant changes in Body Mass Index (BMI), luteinizing hormone (LH), and blood glucose. Nearly none of the studies assessed reported significant changes in follicle-stimulating hormone (FSH) and androstenedione. Discussion: Current literature around the efficacy of metformin treatment on lean PCOS patients remains unclear and uncertain. The majority of studies reviewed indicate that metformin treatment significantly ameliorated total testosterone, SHBG levels, and insulin resistance in lean patients with PCOS. However, the mechanisms and effects of metformin on other treatment outcomes in lean PCOS women is unclear. Conclusion: Metformin may be a putative treatment for lean PCOS women with significant insulin resistance and/or hyperandrogenism. More research involving larger sample sizes and a greater number of clinical outcomes is required.

Relation of Testosterone, Dihydrotestosterone, and Estradiol With Changes in Outcomes Measures in the Testosterone Trials.

Many effects of testosterone are mediated through dihydrotestosterone (DHT) and estradiol. To determine the relative contributions of each hormone to the observed effects of testosterone treatment in older men with hypogonadism. Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and DHT levels over 12 months of testosterone treatment with hemoglobin, high-density lipoprotein (HDL) cholesterol, volumetric bone mineral density (vBMD) of lumbar spine, sexual desire, and prostate-specific antigen (PSA). We used random forests to model the associations of predicted mean changes in outcomes with change in each hormone at low, mean, or high change in the other 2 hormones. Stepwise regression models were run to confirm the findings of random forests. Predicted increases in hemoglobin and sexual desire were greater with larger increases in estradiol and were larger with high change in DHT compared with low change in DHT. Greater increases in estradiol were associated with larger decreases in HDL cholesterol; this association did not vary according to changes in DHT or testosterone. Change in vBMD was most robustly associated with change in estradiol and was greater with high change in testosterone and DHT. There was no consistent relation between change in PSA and change in any hormone. Change in estradiol level was the best predictor not only of the change in vBMD and sexual desire but also of the changes in hemoglobin and HDL cholesterol. Consideration of testosterone, estradiol, and DHT together offers a superior prediction of treatment response in older hypogonadal men than testosterone alone.

Role of Aromatase Inhibitors in Managing Hypogonadism in Adult Males Related to Obesity and Aging: A Systematic Review and Meta-Analysis.

No meta-analysis is available which has analysed the role of aromatase inhibitors (AIs) in hypogonadism in adult males related to obesity and aging. This meta-analysis intended to address this knowledge gap. Electronic databases were searched for studies involving adult males with hypogonadism. The primary outcomes were changes in total testosterone (TT). Secondary outcomes were alterations in oestradiol, luteinizing hormone (LH), and side-effect profile. From initially screened 177 articles, data from three randomised controlled trials(RCTs) (118 patients) and three uncontrolled studies(52 patients) were analysed. AIs were associated with significantly greater improvement in TT after three months [mean difference (MD) 7.08 nmol/L (95% Confidence Interval (CI): 5.92-8.24); P < 0.01; I2 = 0%], six months [MD 6.61 nmol/L (95% CI: 5.30-7.93); P < 0.01] and 12 months [MD 5.20 nmol/L (95% CI: 3.78-6.62); P < 0.01] therapy. AIs were associated with greater reduction in oestradiol after three months [MD -3.07 pmol/L (95% CI: -5.27- -0.87); P < 0.01; I2 = 40%], six months [MD -5.39 pmol/L (95% CI: -7.18- -3.60); P < 0.01] and 12 months [MD -8.3 pmol/L (95% CI: -15.97- -0.63); P = 0.03] therapy. AIs were associated with greater increase in LH after three months [MD 1.79 IU/L (95% CI: 0.77-2.81); P < 0.01; I2 = 0%], six months [MD 2.20 IU/L (95% CI: 0.29 - 4.11); P = 0.02] and 12 months [MD 1.70 IU/L (95% CI: 0.28-3.12); P = 0.02] therapy. Occurrence of treatment-emergent adverse events[Risk ratio (RR) 1.48 (95% CI: 0.47-4.66); P = 0.45; I2 = 0%] and severe adverse events[RR 2.48 (95% CI: 0.42-14.66); P = 0.32; I2 = 0%] were similar among AIs and controls. Following six-month treatment, AIs were associated with significantly lower bone mineral density (BMD) at lumbar-spine [MD -0.04 gm/cm2 (95% CI: -0.08- -0.01); P = 0.03], but not total hip [MD 0.01 gm/cm2 (95% CI: -0.02-0.04); P = 0.55] and femoral neck [MD 0.02 gm/cm2 (95% CI: -0.01-0.05); P = 0.12] compared to controls. This meta-analysis highlights the good efficacy of AIs in improving TT over 3-12 months of use. Adverse impact on spine bone density remains a concern in obese ageing males and warrants further evaluation.

Body Mass Index Changes in Relation to Male Reproductive Hormones: Longitudinal Results From a Community-Based Cohort Study.

The objective of the current study was to explore the relationship between longitudinal change in body mass index (BMI) and reproductive hormones in middle-aged and elderly Chinese men. A cohort study was conducted in a rural area of China. Local male residents aged 40–80 years were recruited at baseline in 2012 and were followed up in 2016. Information about weight, height, waist circumference, sex hormones, smoking status, and medical history were obtained. The change in BMI reported no significant relationship with the change in total testosterone (TT), calculated free testosterone (cFT), and bioavailable testosterone (BioT) in Pearson correlation analyses. When the change in BMI was divided into three groups—“great loss,” “normal fluctuation,” and “great gain”—TT, cFT and BioT had the highest increase (or the lowest decrease) in men with “normal fluctuation” in BMI compared with the other two groups. The advantage of maintaining a stable BMI was more evident for those who were overweight, non-smoking, and disease-free. There was a tendency of a continuous increase in cFT and BioT with BMI increase in smoking and diseased populations. Maintaining a stable BMI is associated with maintaining normal levels of reproductive hormones, especially in overweight, non-smoking, and healthy men aged over 40 years.

Comparative assessment of outcomes and adverse effects using two different intramuscular testosterone therapy regimens: 100 mg IM weekly or 200 mg IM biweekly.

This study aimed to compare the change in levels of several laboratory values and the development of adverse events using two commonly used intramuscular testosterone therapy regimens. Men were included if they were 18 years or older and received one of the following testosterone therapy regimens: 100 mg intramuscular once weekly or 200 mg intramuscular once every other week. Primary outcomes were relative changes in total testosterone, free testosterone, estradiol, prostate-specific antigen, and hematocrit at 6 months after initiation of testosterone therapy. Secondary outcomes were any significant rises in estradiol, hematocrit, prostate-specific antigen, and any other treatment-related adverse events requiring cessation of testosterone therapy. A total of 263 men were enrolled. In a subanalysis of men who had a baseline hematocrit below 54% before intramuscular testosterone therapy initiation, we found the following: men who received 100 mg weekly injections were significantly less likely to have hematocrit levels rising above 54% (1/102 (1%) vs. 4/51 (8%); p = 0.023). No significant differences were recorded in the increase in total testosterone, free testosterone, prostate-specific antigen, and estradiol levels between both groups. A higher average serum testosterone over the dosing interval seen with the 200 mg regimen appears to be associated with a higher risk of erythrocytosis.

Randomized Controlled Trial of Neurokinin 3 Receptor Antagonist Fezolinetant for Treatment of Polycystic Ovary Syndrome.

ContextPolycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility.ObjectiveThis proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS.MethodsThis was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). The study was conducted at 5 European clinical centers. Women with PCOS participated in the study. Interventions included fezolinetant 60 or 180 mg/day or placebo for 12 weeks. The primary efficacy end point was change in total testosterone. Gonadotropins, ovarian hormones, safety and tolerability were also assessed.ResultsSeventy-three women were randomly assigned, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/day were −0.80 (0.13) and −0.39 (0.12) nmol/L vs −0.05 (0.10) nmol/L with placebo (P < .001 and P < .05, respectively). Adjusted mean (SE) changes from baseline in luteinizing hormone (LH) for fezolinetant 180 and 60 mg/d were −10.17 (1.28) and −8.21 (1.18) vs −3.16 (1.04) IU/L with placebo (P < .001 and P = .002); corresponding changes in follicle-stimulating hormone (FSH) were −1.46 (0.32) and −0.92 (0.30) vs −0.57 (0.26) IU/L (P = .03 and P = .38), underpinning a dose-dependent decrease in the LH-to-FSH ratio vs placebo (P < .001). Circulating levels of progesterone and estradiol did not change significantly vs placebo (P > .10). Fezolinetant was well tolerated.ConclusionFezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ratio in women with PCOS.

English

BACKGROUND Obesity is a global pandemic in adolescent and adult population. Although changes in hypothalamic-pituitary-gonadal (HPG) axis with obesity is well known, there is dearth of literature from Eastern India especially with its relationship to obesity parameters, insulin resistance (IR) &amp; inflammatory markers. We wanted to study the changes in total testosterone (TT), sex hormone binding globulin (SHBG) and calculated free testosterone (cFT) with parameters of obesity [body mass index (BMI), waist, hip, neck, wrist circumference and waist-hip ratio], insulin resistance [homeostatic model assessment (HOMA) – insulin resistance (HOMA-IR) and (HOMA2-IR) and inflammation (adiponectin and high sensitivity C-reactive protein, hs-CRP)] in overweight and obese (OWOB) adolescent and adult males. METHODS An institution based cross-sectional study was done from January 2018 to January 2020 consisting of 323 male participants including adolescent and adults presenting to or being referred for overweight or obesity to the Department of Endocrinology and non-obese volunteers. RESULTS TT was lower in OWOB groups (adolescents - 216.6 ± 82.2 vs. 259.0 ± 111.1 ng / dl; P = &lt; 0.0001, adults - 392.3 ± 131.4 vs. 500.24 ± 137.8 ng / dl; P = &lt; 0.0001) compared to nonobese. Luteinizing hormone (LH), SHBG and cFT was also significantly lower in OWOB groups. Obesity parameters (except waist-hip ratio), HOMA-IR, HOMA2-IR and adiponectin correlated with TT, SHBG and cFT in OWOB adults and only TT in OWOB adolescents. Hs-CRP correlated with TT, SHBG and cFT in OWOB adults. CONCLUSIONS Testosterone was found to have a significant correlation with parameters of obesity, insulin resistance, and inflammation in overweight and obese adolescent and adult males. KEYWORDS Overweight, Obesity, Insulin Resistance, Testosterone, Hypogonadism

Neutral effect of exenatide on serum testosterone in men with type 2 diabetes mellitus: A prospective cohort.

Endogenous testosterone increases with weight loss from diet, exercise, and bariatric surgery. However, little is known about testosterone levels after weight loss from medication. Uncover the effects of Glucagon-Like Peptide-1 receptor agonist (GLP-1 RA) therapy on serum testosterone. Prospective cohort study of men starting GLP-1 RA therapy for type 2 diabetes mellitus. 51 men lost 2.27kg (p=0.00162) and their HbA1c values improved by 0.7% (p=0.000503) after 6months of GLP-1 RA therapy. There was no significant change in testosterone for the group as a whole. However, in subgroup analyses, there was a significant difference in total testosterone change between men starting with baseline total testosterone <320ng/dL (238.5±56.5ng/dL to 272.2±82.3ng/dL) compared to higher values (438±98.2ng/dL to 412±141.2ng/dL) (p=0.0172);free testosterone increased if the baseline total testosterone was <320ng/dL (55.2±12.8pg/mL to 57.2±17.6pg/mL) and decreased if >320ng/dL (74.7±16.3pg/mL to 64.2±17.7pg/mL) (p=0.00807). Additionally, there were significant differences in testosterone change between men with HbA1c improvements ≥1% (351.6±123.9ng/dL to 394.4±136.5ng/dL) compared to men with HbA1c changes <1% (331.8±128.6ng/dL to 316.1±126.2ng/dL) (p=0.0413). GLP-1 RA therapy improves weight and HbA1c without adverse effects on testosterone. Those starting with lower testosterone values or attaining greater improvement in HbA1c may see additional benefits.

MP45-06 SHOULD WE TREAT TESTOSTERONE DEFICIENCY IN PATIENTS WHO DO NOT HAVE SYMPTOMS?

INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) is effective for treating the symptoms and ameliorating the metabolic consequences of hypogonadism. TRT improves muscle mass, bone mineral density, mood, and sexual performance. However, a significant number of patients have low serum levels of testosterone without any subjective symptoms or complaints. We evaluated the suitability of TRT for patients with non-symptomatic late-onset hypogonadism. METHODS: Seventy patients whose initial serum levels of testosterone were < 300 ng/dL without any symptoms or complaints were consecutively enrolled and followed for 30 weeks. All patients received 1,000 mg parenteral testosterone undecanoate on day 1, followed by additional injections on weeks 6, 18, and 30. Serological tests (for total testosterone, lipid profile, glucose, and prostate-specific antigen [PSA]) were performed and Body Mass Index (BMI), International Index of Erectile Function (IIEF) score, International Prostate Symptom Score (IPSS), the Aging Males’ Symptoms (AMS) questionnaire, and the Global Assessment Questionnaire (GAQ) were performed at baseline and at the end of the study. RESULTS: Mean patient age was 56.2 ± 10.5 years. The total IIEF score increased from 44.9 ± 12.9 at baseline to 54.8 ± 13.0 on week 30 (p < 0.001). The AMS score improved from 37.9 ± 11.5 at baseline to 24.6 ± 13.2 on week 30 (p < 0.001). Baseline and 30-week total testosterone levels were 272.2 ± 48.2 and 598.2 ± 52.5 ng/dL, respectively (p < 0.0001). No significant changes were detected in the IPSS, lipid profiles, glucose, BMI, or PSA level. The percentage of patients reporting improvement in the GAQ was 58.6%. Improvements in the sexual desire domain of the IIEF, sexual subscale of the AMS, and change in total testosterone (>300 ng/dL) were significantly correlated with a positive GAQ response. The majority of adverse events were mild, reversible, and of short duration. CONCLUSIONS: Although a patient may not complain of any subjective symptoms at the initial visit, TRT can be considered in patients with low testosterone levels and decreased sexual desire and function. It is postulated that patients with low testosterone levels may not recognize their symptoms. Thus, more specific screening is needed for such patients. Source of Funding: None

Long-term testosterone undecanoate replacement therapy: Impact of ethnicity.

Testosterone replacement therapy (TRT) is indicated for symptomatic male hypogonadism. However, the safety and efficacy profiles across different ethnicities for long-term TRT remain unclear. To measure the impact of ethnicity on various biochemical parameters following testosterone undecanoate (TU) replacement. A retrospective analysis of 50 male patients treated with TU from 2006 to 2017 in a large secondary care centre was performed. Changes in total testosterone, PSA, haematocrit, haemoglobin, total cholesterol and low-density lipoprotein (LDL) over eight years of treatment were analysed. Wilcoxon rank sum test was used to assess differences in these parameters between Caucasians and South Asians. Thirty-one Caucasians (age: median (IQR) 55.0years (49.0-68.0); total duration of follow-up 6.1years (2.9-9.3)) and 19 South Asians (age: median (IQR) 52.0years (38.0-69.0); duration of follow-up 6.5years (1.3-8.4)) were treated with TU during the study period. There was no significant difference in total testosterone levels between the two ethnicities. We noted a higher free and bioavailable testosterone in South Asians than Caucasians, albeit within their reference range. PSA was higher in Caucasians than South Asians at two and eight years of TU therapy. After one year of TRT, haematocrit was higher in South Asians than Caucasians at one year, whereas LDL and total cholesterol were significantly higher in Caucasians than South Asians. Caucasians have a tendency towards increased PSA, total cholesterol and LDL compared with South Asians with TU replacement therapy. There is a higher increment of haematocrit in South Asians following one year of TU replacement therapy. All biochemical changes following TRT were within the respective reference ranges suggesting no apparent risk of prostate cancer and venous thromboembolism.

188 Comparative Assessment of Outcomes Using Two Different Intramuscular Testosterone Replacement Therapy Regimens

Hypogonadism is defined as serum total testosterone level < 300 ng/dL in combination with clinical signs or symptoms. Testosterone replacement therapy (TRT) aims to restore testosterone levels and reverse the signs and symptoms of hypogonadism. Several testosterone delivery systems, including intramuscular (IM) injections, are currently available. Nevertheless, side effect profile for the different dosing regimens of IM testosterone injections has not been investigated. We sought to compare outcomes using two different commonly used IM TRT regimens. We conducted a multi-institutional retrospective review of charts of men who presented to 4 different clinics between 2015 and 2019. Patients were included if they were 18 years or older and received one of the following TRT regimens: 100mg IM once weekly or 200mg IM once every other week. Patients were excluded if they received any additional non-TRT hormone replacement therapies in the last 6 months or had a diagnosis of prostate cancer. Primary outcomes were absolute and relative changes in Total Testosterone (TT), Free Testosterone (FT), Estradiol (E), Prostate Specific Antigen (PSA) and Hematocrit (Hct) at 3, 6 and 12 months after initiation of TRT. Secondary outcomes were any significant rises in E, Hct, PSA, and any other treatment related adverse events requiring cessation of TRT.

Effects of testosterone supplementation on body composition and lower-body muscle function during severe exercise- and diet-induced energy deficit: A proof-of-concept, single centre, randomised, double-blind, controlled trial

BackgroundSevere energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. MethodsWe conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers. FindingsFollowing energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (−0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers. InterpretationFindings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline. FundingCollaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.

Water-pipe smoking and serum testosterone levels in adult males in Qatar.

INTRODUCTIONWater-pipe (WP) smoking is the most common method of tobacco consumption in the Middle-East and is rapidly spreading on a global scale. Although, water-pipe smoking is linked to various diseases, such as emphysema and various types of cancers, its effect on testosterone levels has yet to be investigated. This study explores the effect of water-pipe smoking on serum testosterone levels in males in Qatar.METHODSIn this cross-sectional sample within a cohort study, we retrieved data for a total of 1000 male volunteers from the Qatar BioBank (QBB) project. A self-reported questionnaire was used to determine the water-pipe smoking status of participants. Moreover, participants were stratified based on the frequency of smoking. Total testosterone and sex hormone binding globulin (SHBG) were measured clinically, whereas free testosterone and bioavailable testosterone were calculated using Vermeulen’s equation. Hormone values of 541 males (277 water-pipe smokers and 264 non-smokers) were compared using multiple regression analysis based on water-pipe smoking status after adjusting for confounding factors.RESULTSNo statistically significant difference was observed between WP smokers and non-water-pipe smokers in the likelihood of having lower or higher total testosterone, after adjustment for confounding factors. Similar results were found in free testosterone, bioavailable testosterone, and sex hormone binding globulin (all p>0.05). When compared with the reference group, both light and heavy water-pipe smokers had a similar likelihood of circulating low total testosterone levels (OR=0.83, 95% CI: 0.46–1.49; and OR=0.80, 95% CI: 0.43–1.49; respectively).CONCLUSIONSOur results reveal, for the first time, that there is no significant change in total testosterone, free testosterone, bioavailable testosterone and sex hormone binding globulin in waterpipe smokers compared to non-water-pipe smokers. Therefore, we believe that further studies are needed to confirm the effect of water-pipe smoking on testosterone in different populations.

Gender difference in the relationship between serum uric acid reduction and improvement in body fat distribution after laparoscopic sleeve gastrectomy in Chinese obese patients: a 6-month follow-up

BackgroundHyperuricemia is related to obesity and fat accumulation. This study aimed to observe the effects of laparoscopic sleeve gastrectomy (LSG) on serum uric acid (sUA) level and body fat distribution in obese patients. The relationships between post-LSG improvement in sUA levels and body fat distribution changes, as well as their sex-related differences, were also explored.MethodsIn total, 128 obese patients (48 men; 80 women) who underwent LSG were enrolled. Anthropometric indicators, glucose and lipid metabolic indicators, and sUA levels were measured pre-LSG and 6 months post-LSG. The body compositions were measured via dual-energy X-ray absorptiometry. The patients were divided into normal-sUA (NUA) and high-sUA (HUA) groups based on preoperative sUA levels.ResultsCompared with the NUA group, the reduction of sUA levels 6 months post-LSG was more significant in the HUA group. In addition, sUA reduction in the female HUA group was more significant than that of the male HUA group (P < 0.01). Changes in serum uric acid levels (ΔsUA) in the male HUA group was positively correlated with changes in body weight, body mass index, neck circumference, and hip circumference (r = 0.618, 0.653, 0.716, and 0.501, respectively; P < 0.05 in all cases). It was also positively correlated with changes in fat mass in the gynoid region, android region, and legs, (r = 0.675, 0.551, and 0.712, respectively; P < 0.05 in all cases), and negatively correlated with changes in total testosterone (ΔTT) (r = − 0.517; P = 0.040). Furthermore, ΔTT in this group was closely associated with the improved sex-related fat distribution. The ΔsUA in the female HUA group was positively correlated with changes in fasting serum C peptide and ΔLNIR (r = 0.449 and 0.449, respectively; P < 0.05 in both cases). In addition, it was also positively correlated with changes in visceral adipose tissue (VAT) fat mass, VAT fat volume, and VAT fat area (r = 0.749, 0.749, and 0.747, respectively; P < 0.01 in all cases).ConclusionssUA levels of obese patients with hyperuricemia improved 6 months after LSG. Reduction of sUA after LSG was correlated with improved body fat distribution, and the relationships also displayed sex-based differences. Uric acid might be an important metabolic regulator associated with fat distribution and sex hormones.

Impact of ethnicity on the change in total testosterone, haematocrit and prostate-specific antigen with Testosterone undecanoate treatment

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The levels of adipokines in relation to hormonal changes during the menstrual cycle in young, normal-weight women.

ContextThe aim of this study was to assess the plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 levels in relation to hormonal changes during the menstrual cycle in young, healthy, normal-weight women.MethodsThe study involved 52 young, healthy, normal-weight women. Anthropometric parameters, body composition and levels of plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 in addition to serum FSH, LH, estradiol, progesterone, 17-OH progesterone, androgens, SHBG and insulin concentrations were measured during a morning in fasting state three times: between days 2–4, days 12–14 and days 24–26 of the menstrual cycle.ResultsPlasma adiponectin, omentin-1, resistin and visfatin/NAMPT, apelin, TNF-α, IL-6 and RBP4 concentrations were stable during the menstrual cycle, while leptin and vaspin levels were significantly higher in both the midcycle and the luteal phases than those in the follicular phase. Multivariate regression analyses revealed that changes in leptin and vaspin levels between the follicular and the luteal phase are strongly related to changes in total testosterone levels.ConclusionsOur results revealed stable levels of adipokines during the phases of the physiological menstrual cycle, except for leptin and vaspin, which showed increased levels in both the midcycle and the luteal phases. This effect was significantly associated with changes in the secretion of testosterone, 17-OH progesterone and insulin in the luteal phase.