Serum Free Testosterone Concentrations Research Articles

SHBG gene polymorphisms and their influence on serum SHBG, total and free testosterone concentrations in men.

Genetic variation in sex hormone-binding globulin (SHBG) structure may affect estimates of sex steroid exposure by altering the affinity of the protein for its ligand. Consequently, free hormone calculations assuming constant binding affinity may, for certain genetic variations, lead to incorrect diagnoses if genetic variation is not taken into consideration. To investigate the effects of genetic variation in SHBG on calculated and measured serum free testosterone (T) in men. Population-based sibling-pair study in 999 healthy men aged 25 to 45 (mean: 34.5) years. Genotyping using microarray (Illumina®) for SNPs suggested to affect binding affinity and/or concentration of SHBG or T. SHBG concentrations were measured using immunoassay and in a subset (n = 32) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total T was measured using LC-MS/MS. Free T was calculated and in a subset (n = 314) measured directly using LC-MS/MS after equilibrium dialysis. Allelic frequencies of analyzed SNPs ranged from 0.5% to 58.2%. Compared to wild-type, SHBG concentrations were lower in rs6258 heterozygotes (-24.7%; p < 0.05) and higher in rs6259 heterozygotes, rs727428 homozygotes, and carriers of rs1799941 (+10.8 to 23.1%; all p < 0.05). Total T was higher in rs727428 homozygotes and carriers of rs5934505, rs1799941and rs6259 (+3.9 to 21.4%; all p < 0.05). No clear effects on measured free T were found, except for a trend towards higher values in rs6259 homozygotes, significant for calculated free T (+18.7%; p < 0.05) in the larger global study population. In these men, analyzed SNPs were relatively prevalent and affected serum concentrations of total T and SHBG but not calculated or measured free T except for a higher trend in rs6259 homozygotes.

Dietary fat quality and serum androgen concentrations in middle-aged men

Background/ObjectivesAverage testosterone concentrations in men have declined over the last few decades. The reasons for this are not fully known, but changes in dietary fat quality have been suggested to have a role. This study aimed to investigate the associations of different dietary fatty acids with serum androgen concentrations.Subjects/MethodsA total of 2546 men with a mean age of 53 from the Kuopio Ischaemic Heart Disease Risk Factor Study were included in this cross-sectional study. Associations between dietary saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and trans (TFA) fatty acids and concentrations of serum total and free testosterone and steroid hormone binding globulin (SHBG) were analyzed with analysis of covariance and linear regression analysis. Associations of isocaloric replacement of nutrients and androgen concentrations were analyzed with multivariate nutrient-density models.ResultsAfter adjustment for age, examination year and energy intake, higher SFA intake was associated with higher serum total and free testosterone and SHBG concentrations, and higher PUFA intake with lower concentrations. However, the associations were attenuated and not statistically significant after further adjustments for potential confounders. MUFA and TFA intakes were not associated with androgen concentrations. In isocaloric substitution models, replacing dietary protein with SFA was associated with higher serum total testosterone and SHBG concentrations. After excluding men with history of CVD or diabetes (n = 1021), no statistically significant associations were found.ConclusionsDietary fat quality was not independently associated with serum androgen concentrations in middle-aged men. However, replacing protein with SFA may be associated with higher serum androgen concentrations.

Combined treatment of idiopathic male infertility using low-intensity laser therapy and complex prostate peptides: single-centre experience

Introduction. The study of effective and safe combined methods of conservative treatment of idiopathic male infertility is of great interest.Objective. To evaluate the effectiveness of the combined use of low-level laser therapy (LLLT) in the infrared (IR) spectrum and bioregulatory therapy with complex prostate peptides on the semen parameters and sperm DNA fragmentation (SDNAF) in men with idiopathic infertility.Materials &amp; methods. The study is based on the results of examination and treatment of 97 men with idiopathic infertility. Prior to the start of treatment, all patients were divided into three groups by randomization. Patients in group 1 (n = 34) underwent a course of LLLT in the IR spectrum consisting of 10 procedures q.o.d. Patients in group 2 (n = 31) were prescribed complex prostate peptides Supp. Prostatilen® AC (30 + 180 mg) PR q.h.s. FXD, with a repeat of the course of treatment after 5 days. Patients in group 3 (n = 32) underwent combined treatment: LLLT sessions in the IR spectrum (10 procedures q.o.d.) and a course of Supp. Prostatilen® AC (30 + 180 mg) PR q.h.s. FXD, with a repeat of the course of treatment with peptides according to the same scheme after 5 days. Control examination of patients in all groups was carried out two months after the end of treatment.Results. As a result of treatment of patients in groups 1, 2, and 3, a significant improvement in the main semen parameters, a decrease in the grade of pathological SDNAF, an increase in serum total and free testosterone concentration (p &lt; 0.05) were observed. A comparative statistical analysis of the results obtained in three groups of patients showed that the combined treatment of patients of group 3, who were prescribed a course of LLLT in combination with complex prostate peptides Supp. Prostatilen® AC, was significantly more effective in improving concentration (p &lt; 0.01) and progressive sperm motility (p &lt; 0.01), as well as a decrease in the grade of pathological SDNAF (p &lt; 0.05), than in groups 1 and 2.Conclusion. Combined therapy that includes complex prostate peptides and LLLT in the IR spectrum improves the main semen parameters and reduces the grade of pathological SDNAF in men with idiopathic infertility.

Training-induced impairment of endothelial function in track and field female athletes

Professional athletes are often exposed to high training loads that may lead to overfatigue, overreaching and overtraining that might have a detrimental effects on vascular health. We determined the effects of high training stress on endothelial function assessed by the flow-mediated dilation (FMD) and markers of glycocalyx shedding. Vascular examination as well as broad biochemical, hormonal and cardiometabolic evaluation of sprint and middle-distance female runners were performed after 2 months of preparatory training period and compared to age-matched control group of women. Female athletes presented with significantly reduced FMD (p < 0.01) and higher basal serum concentrations of hyaluronan (HA) and syndecan-1 (SDC-1) (p < 0.05 and p < 0.001, respectively), that was accompanied by significantly lower basal serum testosterone (T) and free testosterone (fT) concentrations (p < 0.05) and higher cortisol (C) concentration (p < 0.05). It resulted in significantly lower T/C and fT/C ratios in athletes when compared to controls (p < 0.01). Moreover, fT/C ratio were significantly positively correlated to FMD and negatively to HA concentrations in all studied women. Accordingly, the training load was significantly negatively correlated with T/C, fT/C and FMD and positively with the concentrations of HA and SDC-1. We concluded that young female track and field athletes subjected to physical training developed impairment of endothelial function that was associated with anabolic-catabolic hormone balance disturbances. Given that training-induced impairment of endothelial function may have a detrimental effects on vascular health, endothelial status should be regularly monitored in the time-course of training process to minimalize vascular health-risk in athletes.

PS-BPC07-2: EFFECTS OF MINERALOCORTICOID RECEPTOR ANTAGONISTS ON SEX HORMONES AND BODY COMPOSITION IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Mineralocorticoid receptor antagonists are frequently used for the treatment of primary aldosteronism. Steroidal mineralocorticoid receptor antagonists may have antagonistic actions on androgen receptors, agonistic actions on progesterone receptors, and antagonistic actions on mineralocorticoid receptors. Because anti-androgen effects may cause body fat accumulation and skeletal muscle atrophy, there are concerns that this drug may have adverse effects on body composition. Design and method: Therefore, in this randomized prospective study, we compared the adverse effects of spironolactone, a steroidal mineralocorticoid receptor antagonist, and esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist, on sex hormone levels and body composition in patients with primary aldosteronism without severe renal dysfunction. Results: The serum concentration of free testosterone was significantly higher in the spironolactone group than in the esaxerenone group in both males and females. However, the levels of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone did not significantly increase. Changes in body fat percentage and muscle mass rate were not significantly different between the two groups. No patient showed a serum potassium level &gt; 6.0 mEq/L; however, serum potassium levels were significantly higher in the spironolactone group than in the esaxerenone group. Conclusions: These data indicate that spironolactone may have antagonistic effects on androgen receptors. Esaxerenone did not show any apparent adverse effects, suggesting that it can be safely used in patients with primary aldosteronism.

Sympathetic Responses to Chemoreflex Stress in Lean Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive‐aged women, affecting ~10% of premenopausal women. Women with PCOS present with myriad cardiovascular risk factors including greater muscle sympathetic nerve activity (MSNA), however this has yet to be assessed during periods of reactivity. Interestingly, there is limited evidence to suggest that testosterone (i.e. free testosterone), which is elevated in ~75% of women with PCOS, may play a role in mediating greater MSNA in PCOS. Therefore, the purpose of this study was to test the hypotheses that (a) women with PCOS would exhibit greater MSNA reactivity in response to acute stress relative to control (CTRL) women, and (b) MSNA reactivity to stress would be positively correlated with elevated testosterone levels. We tested 4 lean women with PCOS and 4 CTRL women (age: 20±1 vs. 23±3 yrs, P=0.12; BMI: 25±3 vs.24±2 kg/m2, P=0.41). Heart rate (3‐lead ECG), beat‐by‐beat blood pressure (Finapres) and MSNA (microneurography at the peroneal nerve) were measured during 3‐min of quiet rest and during a maximal voluntary end‐expiratory breath hold. Analyses were performed comparing baseline to the latter half of the apnea, in which sympathetic reactivity was the greatest. Baseline mean arterial pressure (MAP) was similar between PCOS and CTRL (87±7 vs.86±5 mmHg, P=0.97), as were MSNA burst frequency (BF) and MSNA burst incidence (BI) (BF: 7±5 vs. 10±7 bursts/min, P=0.51; BI: 10±8 vs. 16±10 bursts/100hb, P=0.50). Apnea induced increases in MAP and MSNA in both groups (main effects of condition: MAP, P&lt;0.05; BF, P&lt;0.01; BI, P&lt;0.01). However, MSNA during apnea was higher in women with PCOS compared to CTRL women (BF: 55±7 vs.35±12 bursts/min, P&lt;0.05; BI: 81±18 vs.50±13 bursts/100hb, P&lt;0.05). When all participants were pooled together, a trend towards a positive modest correlation between serum free testosterone concentrations and MSNA BI during apnea was observed (R2=0.33; P=0.18). These preliminary data provide some evidence that elevated testosterone levels observed in women with PCOS may contribute to greater sympathetic reactivity, although this requires further study. Importantly, despite greater MSNA responses to apnea, women with PCOS demonstrated similar BP responses to the CTRL group. These findings suggest that these young lean women with PCOS may benefit from an offsetting of high MSNA, which may be mediated by blunted neurovascular transduction.

Effects of Upper Body Eccentric versus Concentric Strength Training and Detraining on Maximal Force, Muscle Activation, Hypertrophy and Serum Hormones in Women.

Effects of eccentric (ECC) versus concentric (CON) strength training of the upper body performed twice a week for 10 weeks followed by detraining for five weeks on maximal force, muscle activation, muscle mass and serum hormone concentrations were investigated in young women (n = 11 and n = 12). One-repetition bench press (1RM), maximal isometric force and surface electromyography (EMG) of triceps brachii (TB), anterior deltoid (AD) and pectoralis major (PM), cross-sectional area (CSA) of TB (Long (LoH) and Lateral Head (LaH)) and thickness of PM, as well as serum concentrations of free testosterone, cortisol, follicle-stimulating hormone, estradiol and sex hormone-binding globulin were measured. ECC and CON training led to increases of 17.2 ± 11.3% (p < 0.001) and 13.1 ± 5.7% (p < 0.001) in 1RM followed by decreases of -6.6 ± 3.6% (p < 0.01) and -8.0 ± 4.5% (p < 0.001) during detraining, respectively. Isometric force increased in ECC by 11.4 ± 9.6 % (p < 0.05) from week 5 to 10, while the change in CON by 3.9±6.8% was not significant and a between group difference was noted (p < 0.05). Maximal total integrated EMG of trained muscles increased only in the whole subject group (p < 0.05). CSA of TB (LoH) increased in ECC by 8.7 ± 8.0% (p < 0.001) and in CON by 3.4 ± 1.6% (p < 0.01) and differed between groups (p < 0.05), and CSA of TB (LaH) in ECC by 15.7 ± 8.0% (p < 0.001) and CON by 9.7 ± 6.6% (p < 0.001). PM thickness increased in ECC by 17.7 ± 10.9% (p < 0.001) and CON by 14.0 ± 5.9% (p < 0.001). Total muscle sum value (LoH + LaH + PM) increased in ECC by 12.4 ± 6.9% (p < 0.001) and in CON by 7.1 ± 2.9% (p < 0.001) differing between groups (p < 0.05) and decreased during detraining in ECC by -6.5 ± 4.3% (p < 0.001) and CON by -6.1 ± 2.8% (p < 0.001). The post detraining combined sum value of CSA and thickness was in ECC higher (p < 0.05) than at pre training. No changes were detected in serum hormone concentrations, but baseline free testosterone levels in the ECC and CON group combined correlated with changes in 1RM (r = 0.520, p < 0.016) during training. Large neuromuscular adaptations of the upper body occurred in women during ECC, and CON training in 10 weeks. Isometric force increased only in response to ECC, and total muscle sum value increased more during ECC than CON training. However, no changes occurred in serum hormones, but individual serum-free testosterone baseline concentrations correlated with changes in 1RM during strength training in the entire group. Both groups showed significant decreases in neuromuscular performance and muscle mass during detraining, while post detraining muscle sum value was only in ECC significantly higher than at pre training.

Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy.

Male hypogonadism is poorly characterized in young-to-middle-aged people with HIV (PWH). We used a reliable free testosterone assay to assess the prevalence and predictive factors for male hypogonadism in PWH on effective combined antiretroviral therapy (cART). A French cross-sectional study from January 2013 to June 2016. We included HIV-1-infected men aged between 18 and 50years with HIV loads of 50 RNA copies/ml or less, on effective cART for at least 6 months. Hypogonadism was defined, according to guidelines, as a mean calculated serum free testosterone concentration less than 70pg/ml (Vermeulen equation). Sociodemographic, anthropo-metric, bone-densitometry, hormonal, immunovirological, metabolic, and therapeutic parameters were collected. The IIEF-5, HAM-D, and AMS scales, respectively, assessed erectile function, depression, and quality of life. Overall, 240 patients were enrolled, 231 were analyzed. Low free testosterone concentrations (<70pg/ml) were recorded in 20 patients (8.7%), and were exclusively of secondary origin. In multivariable analysis, the risk factors predictive of male hypogonadism were age more than 43 years [adjusted odds ratio (aOR) 3.17, 95% confidence interval (95% CI) 1.02-9.86; P = 0.04], total fat percentage more than 19% (aOR3.5, 95% CI 1.18-10.37; P = 0.02), and treatment including efavirenz (aOR3.77, 95% CI 1.29-10.98; P = 0.02). A nadir CD4+ T-cell count more than 200 cells / μl (aOR 0.22, 95% CI 0.07-0.65;P < 0.01) were protective. Male hypogonadism remains common in young-to-middle-aged PWH with stably suppressed viral replication. Treatment including efavirenz, being over 43 years old, and having a total body fat percentage greater than 19% could be used as criteria for identifying PWH at risk. Early screening for male hypogonadism might improve care by identifying patients requiring testosterone replacement.

Effects of mineralocorticoid receptor antagonists on sex hormones and body composition in patients with primary aldosteronism

Mineralocorticoid receptor antagonists are frequently used for the treatment of primary aldosteronism. Steroidal mineralocorticoid receptor antagonists may have antagonistic actions on androgen receptors, agonistic actions on progesterone receptors, and antagonistic actions on mineralocorticoid receptors. Because anti-androgen effects may cause body fat accumulation and skeletal muscle atrophy, there are concerns that this drug may have adverse effects on body composition. Therefore, in this randomized prospective study, we compared the adverse effects of spironolactone, a steroidal mineralocorticoid receptor antagonist, and esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist, on sex hormone levels and body composition in patients with primary aldosteronism without severe renal dysfunction. The serum concentration of free testosterone was significantly higher in the spironolactone group than in the esaxerenone group in both males and females. However, the levels of estradiol, progesterone, luteinizing hormone, and follicle stimulating hormone did not significantly increase. Changes in body fat percentage and muscle mass rate were not significantly different between the two groups. No patient showed a serum potassium level ≥6.0 mEq/L; however, serum potassium levels were significantly higher in the spironolactone group than in the esaxerenone group. These data indicate that spironolactone may have antagonistic effects on androgen receptors. Esaxerenone did not show any apparent adverse effects, suggesting that it can be safely used in patients with primary aldosteronism.

EFFICACY OF FLAXSEED CRACKERS IN AMELIORATING CLINICAL AND BIOCHEMICAL HYPERANDROGENISM IN YOUNG ADULT SOUTH INDIAN WOMEN DIAGNOSED WITH PCOS

Young women of reproductive age are more prone to hormonal/endocrine disorders, the most common being Polycystic Ovarian Syndrome (PCOS). Research in different cultural contexts to enhance the physical, emotional, social, and reproductive health of women has been the focus of several scientific studies. High lignan foods reduce the bioavailability of free testosterone through increasing Sex hormone Binding globulin (SHBG) levels. A randomized single-blind placebo-controlled trial was carried out among women of 20 - 25 years from a single on-campus hostel facility in Chennai, India based on the Rotterdam criteria of PCOS diagnosis. The results showed a statistically significant lower serum free testosterone concentrations (1.02 ± 0.428 ng/dl) in the flax group compared to the placebo (1.64 ± 0.504 ng/dl), after the study period. Similarly, it was noted that the lowered levels of Sex hormone Binding Globulin (SHBG) were elevated to 15.22 ± 14.593 nmol/L as compared to only 9.64 ± 5.124 nmol/L in the placebo though not statistically significant, thus creating a promising platform for improving the imbalances in the hormone levels. Also, elevated serum insulin concentration was lowered in the flax group (15.67 ± 6.928 µU/mL) than the control group (19.09 ± 8.526 µU/mL). The FG score significantly reduced in the flax group thus alleviating the clinical manifestation of hirsutism. Lowering of free testosterone, serum insulin, and elevation of serum SHBG levels is attributed to the phytoestrogen (SDG) present in flaxseeds and can be an ideal alternate replacing the conventional drugs for PCOS.

Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study.

The present randomized, double-blinded, placebo-controlled study investigated the effect of a standardized fenugreek extract (FHE) on perimenopausal discomforts and its influence on hormonal balance and safety. Healthy women characterized with perimenopausal symptoms (n=48), as assessed by MRS questionnaire, were randomized either to FHE (n=24) or placebo (n=24) and supplemented with 250mg×2/day for 42days. Both inter and intra-group comparison revealed a significant improvement in somatic, psychological, and urogenital scores in FHE group, especially for hot flashes (25.9%), night sweats (26.5%), depression (31.8%), and insomnia (21.6%). Further hormone analysis revealed an enhancement in serum estradiol (18.9%), free testosterone (38.2%), and progesterone (19.9%) concentrations and a significant decrease in FSH (38.2%) and SHBG (21.1%) concentrations toward establishing a hormonal balance among FHE-group; without significant changes in other clinical safety parameters. Thus, FHE supplementation offered a significant reduction in vasomotor effects and depression in perimenopausal women, without any adverse effects PRACTICAL APPLICATIONS: Fenugreek is a popular kitchen spice and Ayurvedic medicine for a variety of health conditions including diabetes, hypercholesterolemia, hepatotoxicity, gastritis, and also for a variety of hormone-related health conditions such as sexual functions, lactation, osteoporosis, PCOS, and post/perimenopausal discomforts. Fenugreek is rich in alkaloids, steroidal saponins, flavonoids and 4-hydroxyisoleucine. The present randomized-controlled study investigated the plausible application of a standardized hydro-ethanolic extract of fenugreek seeds (FHE) having a unique 3:1 ratio for protodioscin to trigonelline in the management of perimenopausal discomforts. It was observed that FHE at a dosage of 250mg×2/day for 42days significantly reduced the discomforts, especially vasomotor symptoms and depression, and helped to attain a hormonal balance without any adverse effects or deviations in clinical safety parameters. Thus, FHE could be a potential natural agent for the management of post and perimenopausal discomforts and has to be explored in future studies.

Muscle Glycogen Content during Endurance Training under Low Energy Availability

The present study investigated the effects of three consecutive days of endurance training under conditions of low energy availability (LEA) on the muscle glycogen content, muscle damage markers, endocrine regulation, and endurance capacity in male runners. Seven male long-distance runners (19.9 ± 1.1 yr, 175.6 ± 4.7 cm, 61.4 ± 5.3 kg, maximal oxygen uptake [V˙O2max]: 67.5 ± 4.3 mL·kg·min) completed two trials consisting of three consecutive days of endurance training under LEA (18.9 ± 1.9 kcal·kg FFM·d) or normal energy availability (NEA) (52.9 ± 5.0 kcal·kg FFM·d). The order of the two trials was randomized, with a 2-wk interval between trials. The endurance training consisted of 75 min of treadmill running at 70% of V˙O2max. Muscle glycogen content, respiratory gas variables, and blood and urine variables were measured in the morning for three consecutive days of training (days 1-3) and on the following morning after training (day 4). As an indication of endurance capacity, time to exhaustion at 19.0 ± 0.8 km·h to elicit 90% of V˙O2max was evaluated on day 4. During the training period, body weight, fat-free mass, and skeletal muscle volume were significantly reduced in LEA (P = 0.02 for body weight and skeletal muscle volume, P = 0.01 for fat-free mass). Additionally, muscle glycogen content was significantly reduced in LEA (~30%, P < 0.001), with significantly lower values than those in NEA (P < 0.001). Time to exhaustion was not significantly different between the two trials (~20 min, P = 0.39). Three consecutive days of endurance training under LEA decreased muscle glycogen content with lowered body weight. However, endurance capacity was not significantly impaired.

Hypogonadism in chronic obstructive pulmonary disease (COPD): Risk factors

Bacground/Aim. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality in pulmonary pathology. However, apart from its own pulmonary manifestations, this disease is also characterized by systemic effects, including hypogonadism which is described especially in the group of men with COPD. The aim of this study was to evaluate risk factors for hypogonadism in men with COPD. Methods. The study included 96 male patients with COPD in stable phase of the disease. All patients were checked for concentration of free testosterone in serum, markers of systemic inflammation, tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and C reactive protein (CRP), pulmonary function test, gas exchange parameters, a 6-minute walk test (6MWT), nutritional status and condition of skeletal muscle (midthigh muscle cross-sectional area ? MTCSA using computed tomography). Results. Decreased value of free testosterone was found in 37.5% of the patients. In the group with hypogonadism (free testosterone &lt; 4.5 pg/mL), we found significantly increased serum concentration of TNF-? (5.88 ? 3.21 vs. 3.16 ? 2.53 pg/mL; p &lt; 0.05), significantly lower MTSCA (68.2 ? 18.72 vs. 91.1 ? 21.4 cm2; p &lt; 0.05) and the 6MWT (268.33 ? 32.35 vs. 334.25 ? 43.25 m; p &lt; 0.05). Lung function, gas exchange markers and body mass index (BMI) were similar in both groups. The multivariate regression analysis singled out serum value of TNF-? as an independent predictor of serum concentrations of free testosterone (B = -0.157; 95% confidence interval: -0.262?0.053). Conclusion. In our analysis we found that TNF-? as a marker of systemic inflammation is an independent predictor of the presence of hypogonadism in the patients with COPD. Our results indicate that hypogonadism predisposes to skeletal muscle wasting and exercise intolerance in male COPD patients.

Cross-sectional and longitudinal associations between serum testosterone concentrations and hypertension: Results from the Fangchenggang Area Male Health and Examination Survey in China

BackgroundLow testosterone concentrations have been suggested as a risk factor for hypertension, but their contribution to the development of hypertension is not well studied. We carried out a cohort study based on the results of an earlier cross-sectional investigation. We established the association between testosterone concentrations and hypertension. MethodData on 2427 healthy male subjects, aged from 17 to 88 y, were collected for the cross-sectional study. A representative sample of 853 individuals who did not suffer from hypertension at baseline was followed up for 4 y. Differences between the tertiles groups of sex hormones were analyzed, relative risks (RR) were estimated using binary logistic regression model. ResultsIn the cross-sectional analysis, the serum total testosterone (TT), free testosterone (FT), and bioavailable testosterone (BT) concentrations of the hypertensive population were lower than those of the non-hypertensive population. Binary logistic regression analysis showed that TT, BT, and FT were inversely associated with hypertension. Moreover, decreasing odds ratio (OR) was observed from the lowest tertile group to the highest tertile group. After multivariate adjustment, the correlation between FT, BT, and hypertension was attenuated. Statistically significant differences remained only in the middle tertile group of TT and in the highest tertile group of TT, FT, and BT. In the longitudinal analysis, the 4-y incidence of hypertension was higher in participants with lower TT than in those with higher TT. Subjects in the middle and highest tertile groups of TT had an RR of 0.35 (0.22–0.57) and 0.30 (0.18–0.50), respectively (P for trend <0.001). After further adjustments, these associations still remained statistically significant. ConclusionsSerum TT, FT, and BT concentrations were inversely associated with blood pressure in man, and TT independent of age and body mass index (BMI) influences the development of hypertension. Furthermore, TT can be employed as a risk marker for hypertension in the identification of high-risk individuals.

Transfer of Topical Testosterone to Subcutaneous Microdialysate, Blood and Saliva in Healthy Young Men.

We evaluated percutaneous penetration of topical testosterone and subsequent transfer to subcutaneous tissue, blood and saliva. This microdialysis trial involved eight healthy male volunteers. Five participants received a single dose of 50 mg testosterone gel on the abdominal skin and three untreated participants served as controls. Two microdialysis probes were inserted percutaneously into the abdominal subcutaneous adipose tissue. On the skin above one probe, testosterone gel was applied (ipsilateral side). A second control probe was inserted on the contralateral side. For the determination of total and free testosterone, samples of subcutaneous microdialysate, serum, and saliva were collected over six hours, frozen, and analysed using ELISA procedures. Testosterone values in the ipsilateral microdialysate of treated subjects increased significantly within 6 h after gel application compared to controls. Salivary testosterone levels showed a rapid increase within 20 min after transdermal application followed by a plateau phase with tenfold increased testosterone levels. Microdialysate testosterone of the contralateral site started to rise moderately within the normal range 1 h after administration of testosterone gel whereas total and free testosterone serum concentrations increased within 2 h in each case followed by a plateau phase. Single topical administration of testosterone gel leads to a continuous increase of testosterone in the subcutaneous ipsilateral microdialysate. Rapid salivary testosterone increase happens after gel administration followed by tenfold increased testosterone plateau values. Despite continuous influx, testosterone concentrations in serum, saliva, and contralateral microdialysate show a plateau formation thus avoiding testosterone excess.

Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels.

Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.

Relationships of sex hormone levels with leukocyte telomere length in Black, Hispanic, and Asian/Pacific Islander postmenopausal women.

Sex hormones may play important roles in sex-specific biological aging. In the study, we specifically examined associations between circulating sex hormone concentrations and leukocyte telomere length (TL). A cross-sectional study was conducted among 1124 Black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Estradiol and testosterone concentrations were measured using electrochemiluminescence immunoassays; TL was measured using quantitative polymerase chain reaction. Women in the study were aged 50-79 years. Estradiol concentrations were not significantly associated with TL in this sample. The associations between total and free testosterone and TL differed by race/ethnicity (Pinteraction = 0.03 and 0.05 for total and free testosterone, respectively). Total and free testosterone concentrations were not associated with TL in Black and Hispanic women, whereas in Asian/Pacific Islander women their concentrations were inversely associated with TL (Ptrend = 0.003 for both). These associations appeared robust in multiple subgroup analyses and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islander women, a doubling of serum free and total testosterone concentrations was associated with a 202-bp shorter TL (95% confidence interval [CI] 51-353 bp) and 203-bp shorter TL (95% CI 50-355 bp), respectively. Serum estradiol concentrations were not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone concentrations were inversely associated with TL in Asian/Pacific Islander women, but not in Black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relationships.

Serum Testosterone Concentrations Remain Stable Between Injections in Patients Receiving Subcutaneous Testosterone.

Purpose:Intramuscular (IM) testosterone is the most common modality for testosterone therapy of both male hypogonadism and female-to-male (FTM) gender transition. However, IM injections can be painful and often are not self-administered by the patient. The objective of this study was to further characterize subcutaneous (SC) administration of testosterone as an effective and safe alternative to IM injections by evaluating the pharmacodynamics of serum total and free testosterone concentrations between weekly testosterone injections.Methods:Eleven FTM transgender patients already receiving weekly SC testosterone cypionate with documented therapeutic levels prior to enrollment had free and total serum testosterone levels measured at eight different time points during a 1-week dosing interval.Results:Mean levels of total and free testosterone were stable and remained well within the normal range between injections. Overall mean ± standard deviation levels for the seven samples taken between injections were 627 ± 206 ng/dL (range, 205 to 1410) for total testosterone and 146 ± 51 pg/mL (range, 38 to 348) for free testosterone. No adverse effects were encountered.Conclusions:The results of this study support use of SC testosterone to achieve therapeutic and stable serum testosterone levels for the purpose of gender transition. It is anticipated that these results can be extended to hypogonadal men. This route may be preferred over IM testosterone because it is relatively painless and easy to self-inject thus allowing for the convenience and economy of patient self-administration.

Metabolism of sex steroids is influenced by acquired adiposity—A study of young adult male monozygotic twin pairs

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22–36kg/m2] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m2]. Sex steroid concentrations were determined by liquid chromatography–tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI=5.9kg/m2), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs. 2.4 (1.0) nmol/l, P=0.040] and mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) higher in the heavier compared to the leaner co-twins. Serum free 17β-estradiol (E2) was higher [2.3 (0.5) vs. 1.9 (0.5) pmol/l, P=0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs. 90 (22) pmol/l, P=0.006; and 123 (43) vs. 105 (27) pmol/l, P=0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations (P<0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG (P<0.05), and 3) liver fat with SHBG (P=0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2, HSD11B1, and aromatase in adipose tissue (P<0.05). In conclusion, acquired adiposity was associated with decreased serum DHT and increased estrogen concentrations, independent of genetic factors and age. The reduction of DHT could be linked to its increased degradation (by AKR1C2 and HSD11B1) and increased estrogen levels to increased adiposity-related expression of aromatase in adipose tissue.

Free testosterone concentration is inversely associated with markers of liver fibrosis in men with type 2 diabetes mellitus.

The association between serum testosterone level and liver fibrosis in patients with non-alcoholic fatty liver disease is unclear. To clarify this association, we investigated the relationship between serum free testosterone concentration and markers of liver fibrosis in men with type 2 diabetes mellitus but no obvious features of alcohol consumption. This retrospective observational cross-sectional study enrolled 248 men with type 2 diabetes mellitus. The FIB-4 index was measured as a marker of liver fibrosis, and multiple linear regression analysis was performed to examine its association with serum free testosterone concentration. In addition, the 7S domain of type IV collagen (IV-7S) was examined in 140 of the 248 patients. The mean free testosterone concentration was 10.6 ± 6.8 pg/mL and the means of the FIB-4 index and IV-7S were 1.64 ± 1.19 and 4.02 ± 1.11 ng/mL, respectively. After adjusting for all relevant variables, serum free testosterone concentrations were inversely associated with both the FIB-4 index and IV-7S (β; -0.28, P < 0.0001, and β; -0.28, P = 0.002, respectively). Measuring serum free testosterone concentrations in men with type 2 diabetes mellitus may help to predict progression to advanced liver disease. Identifying patients at risk may help to prevent the development of cirrhosis and hepatocellular carcinoma.