Mean Free Testosterone Levels Research Articles

P-696 Serum androgen levels and risk of endometrial hyperplasia and malignancy in patients with polycystic ovarian syndrome: a cross-sectional analysis

Abstract Study question In patients with polycystic ovarian syndrome (PCOS), are serum androgen levels (total and free testosterone) associated with the risk of endometrial hyperplasia or cancer? Summary answer Patients with PCOS diagnosed with endometrial hyperplasia or cancer had statistically significantly lower serum levels of androgens compared to PCOS patients with a normal endometrium. What is known already PCOS affects as many as 12% of women of reproductive age. Women with PCOS are almost three times as likely to develop endometrial cancer as women without PCOS, and endometrial hyperplasia precedes cancer in 36% of cases. Known risk factors of endometrial hyperplasia include anovulation, obesity, and resultant unopposed estrogen stimulation of the endometrium. A hallmark of PCOS is hyperandrogenism, however the effect of androgens on the endometrium is unclear. Study design, size, duration This was a cross-sectional, retrospective study of patients aged 18-40, being evaluated for oligomenorrhea and/or PCOS in the Reproductive Endocrinology Clinic at Los Angeles County Hospital, California, USA. All patients underwent an endometrial biopsy and serum measurement of free and total testosterone, estradiol, and hemoglobin A1c. Patients diagnosed with PCOS and with an endometrial biopsy diagnosis were included in the study. Patients on any hormonal therapy were excluded. Participants/materials, setting, methods In all patients included in the study, serum androgen levels (free and total testosterone) were measured by mass spectrometry. All endometrial biopsies were analyzed by an experienced histopathology, and all diagnoses of endometrial hyperplasia or cancer were confirmed by histologic studies. Main results and the role of chance Using the Rotterdam criteria, a total of 232 patients were diagnosed with PCOS during the study period. Of these patients, 161 patients (70%) had a normal endometrium, 19 (8%) were diagnosed with endometrial hyperplasia (EH) without atypia, 38 (16%) were diagnosed with EH with atypia, and 14 (6%) were diagnosed with endometrial cancer. Patients with a normal endometrium had a mean total testosterone of 60.9 ng/dL and mean free testosterone of 9.3 ng/dL. Relatively, patients with EH without atypia, EH with atypia, and endometrial cancer had lower mean total testosterone levels of 50.1 ng/dL, 45.5 ng/dL, and 30.1 ng/dL, respectively (p-values 0.04, 0.02, 0.001, respectively), as well as lower mean free testosterone levels of 8.2 pg/mL, 6.7 pg/mL, and 5.5 pg/mL, respectively (p-values 0.04, 0.03, and 0.01, respectively). There was no significant difference in age, parity, BMI, estradiol levels, or hemoglobin A1c between the four groups. Limitations, reasons for caution Limitations of our study include its retrospective nature. Furthermore, hormone levels were only measured in the serum, and not in the endometrial tissue directly, which would give the most insight into their actions on the endometrium. Wider implications of the findings Our findings suggest that androgens have a protective effect on the endometrium against endometrial hyperplasia and cancer. Further studies are needed to evaluate the therapeutic potential role of androgens in the prevention or treatment of these conditions. Trial registration number not applicable

Characterization of perioperative androgen profiles in men with bladder cancer undergoing radical cystectomy

BackgroundPrior studies have demonstrated declines in androgen levels in men with cancer and patients undergoing anesthesia and surgery. In this study, we hypothesized that decreased serum androgen levels are prevalent in male patients undergoing radical cystectomy (RC) for bladder cancer and that it persists in the postoperative period. We characterized perioperative androgen hormonal profiles and examined for associated changes indicative of sarcopenia on computed tomography scans in men undergoing RC. MethodsWe implemented a prospective observational trial in men with newly diagnosed non-metastatic bladder cancer undergoing RC. Baseline pre-operative total testosterone (TT), free testosterone (FT), and luteinizing hormone (LH) were obtained on morning lab draws with 30 days of surgery. TT and FT were then repeated on postoperative days (POD) 2, 3, 30, and 90. The threshold for normal TT was defined as >300 ng/dl, consistent with the AUA Guidelines for Evaluation and Management of Testosterone Deficiency. We evaluated postoperative changes in weight and psoas muscle cross-sectional area using computed tomography scans to assess for sarcopenic changes. ResultsUnivariable statistical analysis was performed. 25 patients were enrolled. The mean patient age was 68.9 years. The mean pre-operative TT was 308 ng/dl, and 12/23 (52.5%) patients had low testosterone. Mean TT onPOD 2 and 3 were 166 ng/dl and 161 ng/dl, respectively (range 24–345). 19/20 (95%) of men who had morning lab draws had decreased TT. The mean TT at 30 days was 253 ng/dl with 37.5% of men having low TT. Mean TT at 90 days was 306 ng/dl. The mean FT levels were 43 ng/dl, 29.25 ng/dl, 28.2 ng/dl, 40.89 ng/dl, and 42.62 ng/dl at baseline, POD 2, POD 3, POD 30, and POD 90, respectively. Mean LH at baseline was 9.9 IU/L. Average weight loss at 30- and 90- days postop was -4.29 and -4.38 kilograms, respectively. Weight loss was persistent with only 3/23 (13%) returning to their presurgery weight by 90 days. Despite significant declines in weight and perioperative TT, no significant differences in psoas muscle cross-sectional area were observed (net change -92 mm2, P= 0.13) ConclusionsPerioperative disruption of androgen levels is prevalent in men undergoing RC. Our trial demonstrates a pre-op, immediate postop, 30- and 90-day postoperative prevalence of low TT of 52%, 95%, 63%, and 37.5%, respectively. Significant changes in baseline weight were noted, although no significant changes in psoas muscle cross-sectional area were observed, limiting conclusions regarding a link between changes in androgens and sarcopenia in this setting.

Effects of Tadalafil 5 mg Once-Daily on Serum Testosterone Level, Erectile Function, and Highly Sensitive C-Reactive Protein Value in Hypogonadal Patients with Lower Urinary Tract Symptoms

Five mg tadalafil was administered once-daily to 48 patients for 6 months. Their International Prostatic Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS), Sexual Health Inventory for Men (SHIM), post-voided residual (PVR) volume, free testosterone (FT) level, prostate-specific antigen level, and highly sensitive C-reactive protein (hsCRP) value obtained before and 6 months after the treatment were analyzed. The treatment significantly improved the IPSS, OABSS, SHIM score, and PVR volume (P<0.05), and significantly increased the mean FT level from 6.68 to 7.10 pg/ml ; P<0.05. We observed no significant changes in the hsCRP value and PSA level. However, elevated FT values were noted in 25 (52.1%) patients 6 months after the treatment (FT-increased group). Compared with the non-FT-increased group, the FT-increased group had markedly lower baseline FT value and higher prostatic volume. In both groups, IPSS and OABSS improved considerably. Moreover, the PVR volume, SHIM score, and hsCRP value markedly improved in the FT-increased group (P<0.05). Thus, 5 mg tadalafil administered oncedaily improved IPSS, OABSS, and erectile function, and increased the FT value, in hypogonadal patients with lower urinary tract symptoms. Furthermore, the hsCRP value declined considerably in patients with posttreatment elevated FT level.

Lean Tissue Index and Body Cell Mass Can Be Predictors of Low Free Testosterone Levels in Men on Hemodialysis

Testosterone deficiency is a common disorder among men treated with hemodialysis. The aim of our study was to evaluate the relationship between free testosterone levels and body composition, biochemical markers of nutritional status, and inflammation in men on hemodialysis. Prospective analysis of men treated with hemodialysis for more than 3months in one hemodialysis center. A total of 56 men-41 men undergoing hemodialysis treatment thrice-weekly over a period of at least 3months (HD group) and 15 men without kidney disease, with estimated glomerular filtration rate >60mL/min/1.73m2 (C group)-were included. Serum levels of free testosterone, creatinine, protein, albumin, prealbumin, high-sensitivity C-reactive protein, and interleukin 6 and body composition by bioimpedance spectroscopy, waist-to-hip ratio, and waist-to-height ratio were measured. None, observational study. Free testosterone level. The mean free testosterone level was significantly lower in the HD group than that in the C group and positively correlated with lean tissue index (LTI, r=0.51, P=.001) and body cell mass (BCM, r=0.57, P<.001). Significant, negative correlations were observed between free testosterone level and age (r = -0.4, P=.004) as well as fat tissue index (r = -0.36, P=.018). In a subgroup of men on hemodialysis who have low testosterone levels (<9.4 pg/mL), we observed a lower LTI and BCM and higher age, fat tissue index, and loginterleukin-6. In our receiver operating characteristic curve analysis, LTI and BCM were shown to be good predictors of a low testosterone level with cutoff points of 13.3kg/m2 and 22.3kg, respectively, meaning that men on hemodialysis with LTI <13.3kg/m2 were 26 times more likely to have free testosterone levels below 9.4 pg/mL (odds ratio, 26.7; 95% confidence interval: 3.0-236.6). Low lean tissue mass and BCM can be predictors of low testosterone level.

The relationship between the level of serum-free testosterone and depression in obese adolescent men in Sharkia Governorate

BackgroundObesity among children and adolescents is considered as one of the most serious public health concerns; low levels of testosterone have been associated with higher levels of morbidity and may have been associated with depression.ObjectiveTo assess the relationship between the level of serum-free testosterone and depression in obese adolescent men in Sharkia Governorate.Patients and methodsThe present study was conducted on 240 age-matched healthy Egyptian adolescent men, collected from the obesity clinic, Internal Medicine Department, Zagazig University Hospital and five high schools in Sharkia Governorate; all the included participants were subjected to: (a) history taking; (b) physical examination (weight, height, BMI, waist circumference, waist to hip ratio, and Tanner stage using Prader orchidometer); (c) hormonal investigations (free testosterone, estradiol, follicular-stimulating hormone, and luteinizing hormone); (d) psychological assessment for depression using: Mini International Neuropsychiatric Interview for Children and Adolescents and children’s depression inventory.ResultsThere was a significant inverse correlation between free testosterone levels and waist circumference among both control and obese cases (r= –0.31, P=0.031 and r= –0.30, P=0.01, respectively). The free testosterone level was significantly lower in obese cases with depression (2.81±2.32 pg/ml) in comparison with obese cases without depression (3.63±2.65 pg/ml) (P=0.04) and testosterone levels was significantly lower in obese cases having some depressive symptoms (feeling depressed, feeling restless, feeling guilty, eating disorders, sleeping disorders, feeling restless, and suicidality). There were significant inverse correlations (P<0.05) between mean free testosterone level and both mild and moderate depression (r= –0.45, P=0.02 and r= –0.58, P=0.012, respectively), and with the following depressive symptoms; feeling depressed, feeling restless, feeling guilty, eating disorder, sleeping disorders, poor concentration, and suicidality.ConclusionObese adolescent men in Sharkia Governorate are significantly associated with lower free testosterone levels. Most of the depression symptoms and their degree are inversely correlated with the levels of free testosterone, otherwise the levels of luteinizing hormone, follicular-stimulating hormone, and estradiol showed no correlation with the depression symptoms or their degree. We recommend further larger studies to prove the relationship between the level of serum-free testosterone and depression in obese adolescent men and try to put a management protocol.

Prevalence of low androgen levels among middle and old age men attending Outpatient Clinics

Introduction: Tiredness is a common symptom of hypogonadism, which can be profound, but there are many medical practitioners who do not include the assessment of testosterone levels in the clinical workup of this symptom. Although male hypogonadism is an established clinical condition, which can be treated, many men experiencing it are undiagnosed.Aim:The aim was to assess the prevalence of low androgen level among middle and old age men in a cohort of patients attending Kasr Elaini hospital outpatient clinics.Patients and Methods: A total of 265 male patients older than 40 years attending the outpatient clinics in different specialty were included. All included men were subjected to full history taking and complete general and local examinations. All participants were interviewed personally face to face using Arabic generic version of full aging male scale (AMS) questionnaire. Venous blood samples were withdrawn between 8 and 10 a.m. after a 12-h overnight fast for measurements of total and free testosterone levels.Results: The mean total testosterone level was 4.0 ± 2.6 ng/ml, ranging from 0.4 to 16.4 ng/ml. The mean free testosterone level was 6.9 ± 2.4 pg/ml, with range between 1.4 and 18.5 pg/ml. Low androgen level was founded in 19.2% of the participants based on total testosterone and in 36.2% when adding the participants with low free testosterone levels. AMS score showed statistically significant difference between age groups (P<0.001). Age is negatively correlated with total and free testosterone levels (r=-0.226 and -0.242, respectively), but the correlation is weak. Total testosterone level shows strong positive correlation with free testosterone level and weak negative correlation with AMS score (r=0.732 and -0.240, respectively).Conclusion: The prevalence of hypogonadism among middle and old age males seeking medical consultation in different specialties may be high.

Gestational Diabetes Mellitus and Metabolic Disorder Among the Different Phenotypes of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder related to several metabolic consequences. However, there remains uncertainty regarding the metabolic features of various phenotypes. The aim of this study was to explore the relationship between the prevalence of gestational diabetes mellitus (GDM) and metabolic disorders among the four different phenotypes of PCOS. A cross-sectional study was performed in Royan Institute including 208 pregnant women with a history of infertility and PCOS. Using the diagnostic criteria of the American Diabetes Association (ADA), pregnant women with a documented diagnoses of PCOS were further categorized into four different phenotypes (A, B, C, and D) as defined by the Rotterdam criteria. The prevalence of GDM failed to demonstrate a significant relationship among the four phenotypes of PCOS. The mean levels of fasting blood sugar, plasma glucose concentrations at three hours (following the 100 g oral glucose tolerance test) and triglyceride levels were significantly higher in phenotype B compared to the remaining phenotypes (p < 0.050). There was a statistically significant difference between the mean free testosterone level and phenotypes A and C groups (1.8±1.6 vs. 1.1±1.0, p = 0.003). Women with a known diagnosis of PCOS who exhibited oligo/anovulation and hyperandrogenism demonstrated an increase of metabolic disorders. These results suggest that metabolic screening, before conception or in the early stages of pregnancy, can be beneficial particularly in women with PCOS phenotypes A and B. Early screening and identification may justify enhanced maternal fetal surveillance to improve maternal and fetal morbidity among women affected with PCOS.

Effect of green tea on metabolic and hormonal aspect of polycystic ovarian syndrome in overweight and obese women suffering from polycystic ovarian syndrome: A clinical trial.

BACKGROUND AND OBJECTIVE:Polycystic ovarian syndrome (PCOS) is the common cause of Oligo-ovulation. This syndrome causes long-term metabolic issues as well as increase the risk of diabetes type 2, hypertension, dyslipidemia, and cardiovascular disease. The current research aimed to study the effect of green tea on weight and hormonal changes of women suffering from PCOS.METHODS:This two group, double-blind, randomized clinical trial was conducted in Isfahan city. Overweight women suffering from PCOS (n = 60) were randomly divided into two groups. Green tea was prescribed to the experimental group, and placebo was prescribed to the control group. Free testosterone hormones and fasting insulin were compared in both groups at the beginning and 12 weeks after the study commencement. The weight of participants of both groups was also measured before and after the study. The statistical data were analyzed by SPSS software and paired t-test.RESULTS:The paired t-test showed that there was no significant difference in the mean weight of both groups before the intervention (P = 0.812), but the difference was significant after the intervention (P = 0.031). There was no significant difference in the mean fasting insulin of both groups before the intervention (P = 0.352), but the difference was significant after the intervention (P < 0.0001). Moreover, there was no significant difference in the mean free testosterone level of both groups before the intervention (P = 0.638), but the difference was significant after the intervention (P < 0.0001).CONCLUSION:The consumption of green tea by overweight and obese women suffering from PCOS leads to weight loss, a decrease in fasting insulin, and a decrease in the level of free testosterone.

The Association of Free Testosterone Levels in Men and Lifestyle Factors and Chronic Disease Status

Hypogonadism is highly prevalent in men older than 45 years and is associated with an increased risk of chronic diseases, including obesity, metabolic syndrome, diabetes, and cardiovascular disease. The objective of this study was to determine whether lifestyle factors such as smoking, diet, and exercise are associated with reduced testosterone levels. In this cross-sectional study, 147 men older than 44 years were recruited from a collaborative network of primary care clinics in the Dallas/Fort Worth, Texas, metropolitan area. Free testosterone levels were measured in plasma samples via an enzyme-linked immunosorbent assay-based method, and analyzed by simple and multiple linear regression in relationship to age, race/ethnicity, smoking, diet, exercise, obesity, diabetes, hypertension, and dyslipidemia. The participants had a mean free testosterone level of 3.1 ng/mL (standard deviation [SD] = 1.5) and mean age of 56.8 years (SD = 7.9). In simple regression analysis, free testosterone levels were associated with increased age (β = -0.04; P = .02), diet (β = -0.49; P = .05), diabetes (β = -0.9; P = .003), and hypertension (β = -0.55; P = .03) but not with race/ethnicity, smoking, exercise, obesity, or dyslipidemia. In multiple regression analysis, free testosterone values were significantly associated only with age (β = -0.05; P = .01) and diet (β = -0.72; P = .01). This study implicates diet, in addition to advanced age as a possible risk factor in the development of reduced testosterone levels.

Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients

Crizotinib is a tyrosine kinase inhibitor active against ALK, MET, and ROS1. We previously reported that crizotinib decreases testosterone in male patients. The detailed etiology of the effect, its symptomatic significance, and the effectiveness of subsequent testosterone replacement have not been previously reported. Male cancer patients treated with crizotinib had total testosterone levels measured and results compared with non-crizotinib-treated patients. Albumin, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and/or luteinizing hormone (LH) were tracked longitudinally. A subset of patients had free testosterone levels measured and a hypogonadal screening questionnaire administered. Patients receiving subsequent testosterone supplementation were assessed for symptomatic improvement. Mean total testosterone levels were -25% below the lower limit of normal (LLN) in 32 crizotinib-treated patients (27 of 32 patients below LLN, 84%) compared with +29% above LLN in 19 non-crizotinib-treated patients (6 of 19 below LLN, 32%), P = .0012. Levels of albumin and SHBG (which both bind testosterone) declined rapidly with crizotinib, but so did FSH, LH, and free testosterone, suggesting a centrally mediated, true hypogonadal effect. Mean free testosterone levels were -17% below LLN (19 of 25 patients below LLN, 76%). Eighty-four percent (16 of 19) with low free levels, and 79% (19/24) with low total levels had symptoms of androgen deficiency. Five of 9 patients (55%) with low testosterone given testosterone supplementation had improvement in symptoms, coincident with increases in testosterone above LLN. Symptoms of androgen deficiency and free or total/free testosterone levels should be tracked in male patients on crizotinib with consideration of testosterone replacement as appropriate.

The relation of testosterone levels with fatigue and apathy in Parkinson's disease

Objective Fatigue and apathy are frequent in patients with Parkinson's disease (PD). Testosterone deficiency in male patients may contribute in development of fatigue and apathy as well. We investigated whether a possible relation exists between serum testosterone levels, fatigue and apathy in male PD patients. Materials and methods We included 29 non-demented and non-depressed PD patients and 30 age- and sex-matched healthy subjects. Fatigue Severity Scale (FSS) and Apathy Evaluation Scale (AES-C) were used for the evaluations. In PD patients and healthy subjects, a relationship between FSS, AES-C scores and plasma testosterone levels were assessed. In addition, a correlation between FSS, AES-C and Unified Parkinson's Disease Rating Scale was investigated in PD group. Results The mean scores of FSS and AES-C were significantly higher in PD patients than those of the control group. The Unified Parkinson's Disease Rating Scale (UPDRS) scores were significantly correlated with FSS and AES-C scores. Mean free testosterone level was significantly lower in PD patients than controls ( p = 0.008). f-Testosterone levels of PD patients were not correlated with FSS or AES-C scores. Conclusion Apathy and fatigue are frequent in PD and show significant correlation with the severity of the disease. f-Testosterone levels are not related with apathy or fatigue in male PD patients and the role of testosterone in the pathophysiology of these non-motor symptoms is still controversial.

A Pilot Study of an Investigational Testosterone Transdermal Patch System in Young Women with Spontaneous Premature Ovarian Failure

Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women. The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone. This was an open-label study (2-month baseline period followed by 2-month treatment period). Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded. Four consecutive 28-d cycles of transdermal estradiol (E2; 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 microg/d) was applied twice weekly to the abdomen. Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied. The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9-9.9) pg/ml; 26.0 (17.2-34.6) pmol/liter (with E2), and 6.9 (4.9-8.8) pg/ml; 23.9 (17.2-30.5) pmol/liter (with E2 and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 pg/ml (23.5 pmol/liter), although the mean values are slightly above this. The addition of TTP to cyclic E2/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress.

Human immunodeficiency virus infection in women without wasting is associated with menstrual cycle decreases in free testosterone levels.

Human immunodeficiency virus infection in women without wasting is associated with menstrual cycle decreases in free testosterone levels.

AN ASSESSMENT OF THE CLINICAL RELEVANCE OF SERUM TESTOSTERONE LEVEL DETERMINATION IN THE EVALUATION OF MEN WITH LOW SEXUAL DRIVE

Purpose We evaluated the relationship between sexual drive and serum testosterone level among men with erectile dysfunction. Materials and Methods A retrospective medical record review of 180 men who attended a hospital based erectile dysfunction clinic between April 1997 and January 1998 was performed. Sexual drive was assessed using the Brief Sexual Function Inventory questionnaire, and serum total and free testosterone levels were measured. Results A total of 108 complete records were included in this report. Mean patient age plus or minus standard deviation was 59.5 +/− 10.2 years (range 33 to 79). Of the men 55 (50.9%) had low, 38 (35.2%) moderate and 15 (13.9%) high sexual drive. Mean sexual drive, bothersomeness and total sexual function scores among the groups were significantly different (p <0.001). Mean serum total testosterone levels among men with low, moderate and high sexual drive were 2.8, 3.2 and 3.4 mg./ml. (normal 2.8 to 8.8), respectively, and mean free testosterone levels were 9.1, 9.5 and 11.4 pg./ml. (normal 8.7 to 54.7), respectively. Differences among means were not statistically significant. As a screening test for low sexual drive, low total testosterone had a positive predictive value, negative predictive value and yield of 59.2, 55.9 and 26.9%, respectively. Conclusions Serum total or free testosterone level is an inadequate measure of sexual drive in men. More research is needed to define the appropriate indications and value of routine testosterone level determination among men with erectile dysfunction and/or low sexual drive.