Low Serum Testosterone Levels Research Articles

Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness.

Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required.

Cross-sectional association between physical activity and serum testosterone levels in US men: results from NHANES 1999-2004.

Testosterone levels and physical activity each play important roles in men's health, but the relationship between the two remains unclear. We evaluated the cross-sectional association between self-reported total physical activity and serum testosterone levels in 738 men (mean age 42.4years, range 20-≥85years) who participated in National Health and Nutrition Examination Survey 1999-2004. We compared geometric mean testosterone concentrations measured by radioimmunoassay (RIA) and calculated the odds ratio (OR) of having low or low normal testosterone (≤3.46ng/mL) across tertiles of total physical activity in all men, and men stratified by age (20-49, ≥50years), and obesity status (BMI<30, ≥30kg/m(2) ). The geometric mean testosterone concentration was 5.31ng/mL; 18.6% of the men had low or low normal serum testosterone levels. Physical activity tertiles were not associated with testosterone levels overall, or when stratified by age or obesity status. Similarly, there was no association between physical activity tertiles and the odds of low or low normal testosterone, overall or by age. However, among non-obese men, those in the highest physical activity tertile were significantly less likely to have low or low normal testosterone than those in the lowest tertile (OR 0.50; 95% CI=0.26-0.95); there was no association among obese men. Greater physical activity was not associated with testosterone levels, but may be associated with a reduced odds of low or low normal testosterone in non-obese men, but not in obese men.

Determinación de la testosterona sérica durante la supresión androgénica en pacientes con cáncer de próstata: una revisión sistemática

IntroductionClinical practice guidelines recommend measuring serum testosterone (ST) during androgenic suppression (AS) to assess its efficacy and define castration resistance (CR). The objectives of this systematic review were to assess the level of scientific evidence that justify checking ST levels during AS, when to perform it and for what purpose. Material and methodsWe performed a search in PubMed with the following mesh terms: androgen suppression, testosterone, and prostate cancer. The search was narrowed to original articles published in English. ResultsWe found 8 publications that analysed the clinical impact of ST concentrations during AS. In all of the series, ST was measured using chemiluminescent assays. However, only indirect methods based on liquid or gas chromatography for its extraction and subsequent quantification using mass spectrometry are recommended, especially for measuring low levels. The endpoints were specific survival and CR-free survival. Six studies were retrospective. The series were not uniform in terms of clinical stage, types of AS and ST assessment methods. In general, low ST levels (<20ng/dL or <32ng/dL) were related to longer CR-free survival. The measurements were performed every 3 or 6 months. Four studies confirmed the beneficial effect of adding bicalutamide when detecting microelevations above 50ng/dL. ConclusionsThe level of scientific evidence justifying the measurement of ST during AS is low, and the methods employed for quantifying ST levels are inadequate. However, we consider it useful to check ST levels during AS, and there appears to be an association between low ST levels and better disease outcomes. In the event of microelevations above 50ng/dL, we recommend the administration of bicalutamide.

The prognostic impact of serum testosterone during androgen-deprivation therapy in patients with metastatic prostate cancer and the SRD5A2 polymorphism.

Although testosterone suppression during androgen-deprivation therapy (ADT) and obesity have been reported to affect ADT efficacy, there are few comprehensive analyses on the impact on ADT outcome. Recently, we demonstrated that the SRD5A2 polymorphism was associated with metastatic prostate cancer prognosis. Therefore, in this study, we investigated the relationship between ADT serum testosterone levels or body mass index (BMI) and the prognosis among men treated with primary ADT for metastatic prostate cancer. In addition, we examined the association of serum testosterone levels during ADT with the SRD5A2 polymorphism. This study included 96 Japanese patients with metastatic prostate cancer. The relationship between clinicopathological parameters, including serum testosterone levels during ADT and BMI, and progression-free survival, overall survival and survival from progression following primary ADT treatment for metastatic prostate cancer was examined. Additionally, the association between the SRD5A2 gene polymorphism (rs523349) and serum testosterone levels during ADT was examined in 86 cases. Among clinicopathological parameters, the lowest quartile of serum testosterone levels during ADT was a significant predictor of better overall survival as well as survival from castration resistance. However, BMI was not associated with prognosis. The CC allele in the SRD5A2 gene (rs523349), encoding the less active 5α-reductase, was associated with lower serum testosterone levels during ADT. Taken together, these findings revealed a dramatic suppression of serum testosterone by ADT was associated with better survival among men with metastatic prostate cancer that have undergone primary ADT, which may be affected by the SRD5A2 gene polymorphism.

Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of literature and clinical perspectives.

Klinefelter syndrome (KS) is the most frequently occurring sex chromosomal aberration in males, with an incidence of about 1 in 500-700 newborns. Data acquired from large registry-based studies revealed an increase in mortality rates among KS patients when compared with mortality rates among the general population. Among all causes of death, metabolic, cardiovascular, and hemostatic complication seem to play a pivotal role. KS is associated, as are other chromosomal pathologies and genetic diseases, with cardiac congenital anomalies that contribute to the increase in mortality. The aim of the current study was to systematically review the relationships between KS and the cardiovascular system and hemostatic balance. In summary, patients with KS display an increased cardiovascular risk profile, characterized by increased prevalence of metabolic abnormalities including Diabetes mellitus (DM), dyslipidemia, and alterations in biomarkers of cardiovascular disease. KS does not, however, appear to be associated with arterial hypertension. Moreover, KS patients are characterized by subclinical abnormalities in left ventricular (LV) systolic and diastolic function and endothelial function, which, when associated with chronotropic incompetence may led to reduced cardiopulmonary performance. KS patients appear to be at a higher risk for cardiovascular disease, attributing to an increased risk of thromboembolic events with a high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism with higher risk of deep venous thrombosis or pulmonary embolism. It appears that cardiovascular involvement in KS is mainly due to chromosomal abnormalities rather than solely on low serum testosterone levels. On the basis of evidence acquisition and authors' own experience, a flowchart addressing the management of cardiovascular function and prognosis of KS patients has been developed for clinical use.

The Role of Estrogen Modulators in Male Hypogonadism and Infertility.

Estradiol, normally considered a female hormone, appears to play a significant role in men in a variety of physiologic functions, such as bone metabolism, cardiovascular health, and testicular function. As such, estradiol has been targeted by male reproductive and sexual medicine specialists to help treat conditions such as infertility and hypogonadism. The compounds that modulate estradiol levels in these clinical conditions are referred to as selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). In a certain subset of infertile men, particularly those with hypogonadism, or those who have a low serum testosterone to estradiol ratio, there is some evidence suggesting that SERMs and AIs can reverse the low serum testosterone levels or the testosterone to estradiol imbalance and occasionally improve any associated infertile or subfertile state. This review focuses on the role these SERMs and AIs play in the aforementioned reproductive conditions.

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes.

Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes.

Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease.

Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl−1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml−1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.

Comparison of the post-operative infection by using different type of prophylactic antibiotics and placebo in healthy adult patients who underwent ureterorenoscopic surgery

Comparison of the post-operative infection by using different type of prophylactic antibiotics and placebo in healthy adult patients who underwent ureterorenoscopic surgery

Urolithiasis is associated with higher prevalence of low serum testosterone level in patients with erectile dysfunction

Urolithiasis is associated with higher prevalence of low serum testosterone level in patients with erectile dysfunction

Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice.

Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg−1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo.

Abstract 16401: Cardiovascular Clinical Effects of Testosterone Supplementation Among Healthy Hypo-androgenic Men: Information From the Intermountain Healthcare Health Plans Database

Introduction: Epidemiologic studies have identified low serum testosterone (T) levels as an independent risk factor for cardiovascular (CV) and total mortality. However, the cardiovascular safety of T therapy among healthy men with low T levels is unknown. Hypothesis: We hypothesized that T supplementation among healthy men over the age of 50 yrs with low T levels is not associated with an increased risk of major adverse cardiovascular events (MACE). Methods: All men in the Intermountain Healthcare Health Plans Database &gt;50 years of age, with no prior history of CV disease, a documented low (&lt;212 ng/dL) baseline T level, at least 1 follow-up (f/u) T level and 3 years of clinical f/u were stratified by whether or not they received at least 90 days of T supplementation (topical gel or injection) or not. Cox hazard regression analysis, adjusting for 17 baseline variables, was performed to determine any association between T supplementation and 3 year MACE (death [D], non-fatal MI, and stroke). Results: A total of 1,472 men (age 57.0 ± 5.5 y, diabetes: 20%, hypertension: 41%, hyperlipidemia: 43%, smokers: 13%) were studied. Event rates at 1 and 3-y by supplementation status, and adjusted HRs, are shown in the Table. Overall 3-y rates of MACE, D, MI and stroke were low consistent with the baseline age and health of the population. After adjustment, subjects supplemented with T had statistically reduced 1 and 3 year rates of D and total MACE, including numerically reduced rates of MI and stroke compared to those receiving no supplementation. Conclusions: Among a generally healthy and relatively young population of hypo-androgenic men, T therapy was associated with reduced MACE and D over 3-y compared to no T supplementation. These findings provide further observational evidence of the CV safety associated with T supplementation in this population.

Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease

Coronary artery calcification (CAC) is a pandemic condition in elderly patients with coronary artery disease (CAD) and associated with a worse prognosis. Although available data have shown an association between testosterone levels in men and CAD, the association between testosterone and CAC in elderly male patients with CAD remains unknown. A total of 211 consecutive male patients (age ≥ 65 years) who underwent first multidetector computed tomography and following angiography were enrolled from our institution between March 2009 and September 2014. CAD was angiographically documented as significant stenoses (reduction ≥ 50% of the lumen diameter) on any major coronary vessel. The standard Agatston calcium score was calculated. The relationship of serum testosterone level with the CAC score measured by multidetector computed tomography in elderly male patients with stable CAD was evaluated. For data analyses, the CAC score was divided into four categories: ≤ 10, 11-99, 100-399, and ≥ 400, corresponding to minimal, moderate, increased, and extensive calcification. Patients with higher CAC scores had significantly lower testosterone levels than patients with lower CAC scores (P = 0.048). In logistic regression analysis, testosterone level remained an independent predictor of extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P = 0.043). Our findings indicate an inverse association between testosterone level and the susceptibility to extensive CAC in elderly men with stable CAD.

Inhibition of adipogenic differentiation of human SGBS preadipocytes by androgen-regulated microRNA miR-375

Late-onset hypogonadism (LOH), defined as a combination of low serum testosterone (T) levels in combination with clinical signs and symptoms of androgen deficiency in ageing men, is nowadays a well-characterized disease. Testosterone therapy in males affected by hypogonadism leads to a significant decrease of fat mass. In humans, the exact molecular mechanism of T effects on inhibition of adipogenesis is still unknown. We hypothesized that specific microRNAs could be regulated by androgens which might cause an inhibition of adipogenic differentiation. To confirm this hypothesis, human mesenchymal stem cells and a preadipocyte cell line were differentiated into mature adipocytes and in parallel treated with testosterone and dihydrotestosterone. The expression level of miR-375 was upregulated during adipogenic differentiation and downregulated after androgen treatment. Furthermore, we could show that after androgen treatment the decreased expression of miR-375 led to increased expression levels of adiponectin receptor 2 (ADIPOR2) compared to untreated adipocytes. Moreover, inhibition of miR-375 also mediated a decreased adipogenic differentiation and increased ADIPOR2 expression levels. In summary, we identified miR-375 as an androgen regulated microRNA, which could play an important role for understanding the mechanism of the increase in visceral fat mass and the associated insulin resistance caused by testosterone deficiency.

Testosterone in the management of metastatic prostate cancer

Background Among all cancer types, prostate cancer (PCa) is the most prevalent cancer and is the third-leading cause of cancer-related death in men. The biologic function of the prostate is decisively influenced by testosterone and its metabolic product dihydrotestosterone. However, there is general uncertainty about the role of testosterone in metastatic castration-resistant prostate cancer (mCRPC). For many years, the androgen hypothesis had been accepted to explain the correlation between testosterone levels and the development or progression of PCa. However, extensive study analyses revealed contradictory results, leading to a reconsideration of the androgen hypothesis. High serum testosterone levels do not predispose to PCa development and low serum testosterone levels are not protective. The importance of testosterone levels in patients with mCRPC has been shown in several registration studies with new drugs, such as abiraterone acetate and enzalutamide. There is growing evidence suggesting a prognostic role of testosterone levels in mCRPC.

Use of statins is associated with lower serum total and non-sex hormone-binding globulin-bound testosterone levels in male participants of the Rotterdam Study

Statins, or HMG-CoA reductase inhibitors, decrease cholesterol production. Because cholesterol is a precursor of the testosterone biosynthesis pathway, there is some concern that statins might lower serum testosterone levels. The objective of the present study was to investigate the association between the use of statins and serum testosterone levels in men. Cross-sectional study within the prospective population-based Rotterdam Study. We included 4166 men with available data on total testosterone, non-sex hormone-binding globulin (SHBG)-bound testosterone, and medication use. Multivariable linear regression analysis was used to compare the differences in serum testosterone levels (nmol/l) between current, past, and never statin users. We considered dose and duration of use. Analyses were adjusted for age, BMI, cardiovascular disease, diabetes mellitus, hypertension, and estradiol levels. We identified 577 current (mean age 64.1 years), 148 past (mean age 64.6 years), and 3441 never (mean age 64.6 years) statin users. Adjusted for all covariables, current statin use of 1-≤ 6 months or >6 months was significantly associated with lower total testosterone levels as compared to non-users (β -1.24, 95% CI -2.17, -0.31, and β -1.14, 95% CI -2.07, -0.20 respectively). Current use of 1-≤ 6 months was also associated with significantly lower non-SHBG-bound testosterone levels (β -0.42, 95% CI -0.82, -0.02). There was a trend toward lower testosterone levels at higher statin doses both for total (P(trend) 2.9 × 10(-5)) and non-SHBG-bound (P(trend) 2.0 × 10(-4)) testosterone. No association between past statin use and testosterone levels was found. We showed that current use of statins was associated with significantly lower serum total and non-SHBG-bound testosterone levels. The clinical relevance of this association should be further investigated.

Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid, and Strontium Levels in Adult Men According to the US 2011-2012 National Health and Nutrition Examination Survey.

BackgroundLittle is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011–2012).MethodsUrinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio.ResultsAdjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone.ConclusionsThe National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men.

Low testosterone in men predicts impaired arterial elasticity and microvascular function

BackgroundA low testosterone level in men is associated with increased adiposity, insulin resistance, and dyslipidemia. Whether low testosterone level is associated with arterial stiffness and endothelial and microvascular dysfunction remains unknown and was investigated in this study. MethodsSerum testosterone was measured in 237 healthy men aged 50years (SD 12). Endothelial and microvascular function were assessed as brachial artery flow-mediated dilation (FMD) and digital reactive hyperemia index (RHI), respectively. Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and central augmentation index (AIX). ResultsMean total testosterone level was 16.3nmol/L (SD 6.11) and 25% of subjects had low levels (<12.0nmol/L). Testosterone level correlated positively with RHI (r=0.24, p<0.001) and inversely with AIX (r=−0.14, p=0.033) but not with FMD or PWV, indicating impaired microvascular hyperemia and arterial elasticity with lower testosterone levels. After multivariate adjustment for the Framingham Risk Score and weight, testosterone level remained an independent predictor of RHI and AIX (β=0.23, −0.13; p=0.001, 0.04, respectively). ConclusionIn men with few co-morbidities, lower serum testosterone level is associated with microvascular dysfunction and increased pulse wave reflections, mechanisms by which lower testosterone levels may confer increased cardiovascular risk. Whether normalization of low testosterone level improves vascular function needs further investigation.

The prevalence and association of low testosterone levels in a South African male, diabetic, urban population

Background: According to the literature, low serum testosterone levels are associated with diabetes mellitus. No or minimal data exist for its prevalence or predictors in South Africa.Design: This was a cross-sectional study.Setting: The setting was an academic centre, i.e. the University of Pretoria and Steve Biko Academic Hospital Diabetes Clinic.Subjects: A total of 150 consecutive male patients aged 50 years and older with diabetes mellitus were selected using convenience sampling.Outcome measures: The patients were evaluated for diabetes control and complications, and for hypogonadism symptoms. Early-morning serum testosterone levels were determined.Results: The prevalence of androgen deficiency symptoms was 94.7%. Some 50% of the men had low total testosterone levels. Using multivariate logistic regression, the significant factors associated with low total testosterone were waist circumference and known cardiovascular disease. The prevalence of symptoms of androgen deficiency was very high; 94.7% of...

Characteristics of Men Undergoing Testosterone Replacement Therapy and Adherence to Follow-up Recommendations in Metropolitan Multicenter Health Care System

To identify the frequencies of treatment and recommended laboratory follow-up for men with low serum testosterone levels. The Electronic Data Warehouse was queried to identify men of ages 18-85 years, who obtained a testing for serum total testosterone level from 2009 to 2012. The frequency of testosterone replacement therapy (TRT), patient demographics, and clinical characteristics were collected. The frequency of follow-up with serum total testosterone and complete blood count levels was documented. Among 9176 men who underwent testing for low testosterone levels, 3320 (36%) of them were hypogonadal with a mean serum total testosterone level of 194.3 ± 64.9 ng/dL. Of them, 17.7% men were treated with TRTs. The treatment frequency significantly increased from 8.3% in 2009 to 24% in 2012. A total of 4.8% of men of reproductive ages (age, 18-35 years) were placed on TRTs. Within 180 days of initial testing, only 40% of treated men received follow-up with liver function tests and/or complete blood count, and only 49% had a follow-up serum testosterone level. Although the frequency of TRT is increasing, only a small percentage of hypogonadal men are actively undergoing treatment. A significant proportion of men of reproductive age are being treated with significant impacts on potential fertility. Less than half of the patients treated are being monitored appropriately after testosterone replacement. This highlights the importance of further education for providers prescribing testosterone replacement.