Increased Serum Total Testosterone Research Articles

High serum Androgen and Insulin concentrations increase the tendency of Endometrial Carcinoma.

Purpose: The objective of the study was to evaluate the important role played by androgen and insulin in the development of endometrial carcinoma (EC), and their combined effect on EC risk.Methods: We enrolled 510 type I EC patients and 510 age-, time-, and nationality-matched subjects into this study. Metabolic and hormonal parameters of enrolled subjects were examined. Univariate and multivariate logistic regression analyses for EC and control subjects were performed. Type I EC risk was evaluated with respect to testosterone, androstenedione, and insulin levels based on odds ratios (ORs) using stratified data.Results: EC risk was positively associated with C-peptide, estrone, androgen (including testosterone and androstenedione) and insulin levels, BMI, WHR, family history of cancer, nulliparity, irregular menstruation, diabetes, and hypertension. In multivariate logistic regression models, high C-peptide and testosterone levels, diabetes, and hypertension were independent risk factors after adjustment for BMI, WHR, family history of cancer, high serum insulin, and estrone levels. Increased serum total testosterone and insulin levels were positively correlated with EC risk in total, premenopausal, and postmenopausal women. Androstenedione was correlated with EC in total and postmenopausal, but not in premenopausal subjects. Compared with higher testosterone and insulin, odds ratios (ORs) for higher testosterone with lower insulin and lower testosterone with higher insulin were decreased in total, premenopausal, and postmenopausal women. Similarly, compared to both higher FAI and insulin, ORs for higher FAI with lower insulin and lower FAI with higher insulin were decreased in all three groups. Coordinately, ORs for higher androstenedione with lower insulin and lower androstenedione with higher insulin were decreased in total and postmenopausal, but not premenopausal subjects.Conclusions: These findings suggested that androgen and insulin were risk factors of type I EC, and relatively high levels of both testosterone and insulin synergistically affected EC risk.

Efficacy of oral estrogen plus testosterone gel to improve sexual function in postmenopausal women

Objective: This study aimed to study the efficacy and safety of estrogen plus low-dose testosterone gel in improving sexual function in postmenopausal women.Methods: A double-blind, randomized, active-controlled trial was conducted. Seventy postmenopausal women with low sexual function were randomized into two groups. They received weekly 50 mg of transdermal testosterone plus daily oral 1 mg estradiol valerate or only estrogen for 8 weeks. The Female Sexual Function Index (FSFI) score, hematocrit, liver enzymes, lipid profiles, total testosterone, free and bioavailable testosterone, free androgen index, sex hormone binding globulin (SHBG), and endometrial thickness were assessed before and after treatment.Results: After 8 weeks, the FSFI score significantly improved in both groups. However, the change of FSFI score in the testosterone group was significantly higher than in the only estrogen group, 7.2 ± 5.5 and 4.6 ± 3.9, respectively (p = 0.02). There were significantly increased serum total testosterone levels, but not the free or bioavailable form, in the testosterone group. There was no significant difference in serum SHBG levels after treatment between both groups. There was no serious adverse effect, only acne was found.Conclusion: The addition of low-dose testosterone gel to daily estrogen may improve sexual function in postmenopausal women, but further evaluation and safety data are needed.Trial registration: Thai Clinical Trials Registry identifier: TCRT20180423001.

Vigorous Physical Activity is Associated with Regular Aerobic Exercise-Induced Increased Serum Testosterone Levels in Overweight/Obese Men

Testosterone is a male sex hormone and low circulating testosterone levels are associated with various health disorders in men. Obesity results in reduced circulating testosterone levels in men. Previously, we demonstrated that lifestyle modifications (combination of aerobic exercise and dietary modification) increase circulating testosterone levels in overweight/obese men. However, the effect of regular aerobic exercise on serum testosterone levels remains unclear. The purpose of this study was to investigate the effect of a 12-week aerobic exercise intervention on circulating testosterone levels in normal-weight and overweight/obese men. Sixteen normal-weight men and twenty-eight overweight/obese men completed a 12-week aerobic exercise intervention. Before and after the intervention, we measured serum total testosterone, free testosterone, and bioavailable testosterone levels, and categorized the physical activity levels (light, moderate, or vigorous) in all participants. At baseline, serum total testosterone, free testosterone, and bioavailable testosterone levels were significantly lower in overweight/obese men than in normal-weight men (all p<0.01). After the 12-week aerobic exercise intervention, serum total testosterone, free testosterone, and bioavailable testosterone levels significantly increased in overweight/obese men (p<0.01). In addition, stepwise multivariable linear regression analysis revealed the increase in vigorous physical activity was independently associated with increased serum total testosterone levels (β=0.47, p=0.011). We demonstrated that a 12-week aerobic exercise intervention increased serum total testosterone, free testosterone, and bioavailable testosterone levels in overweight/obese men. We suggest that an increase in vigorous physical activity increased circulating testosterone levels in overweight/obese men.

Atypical circumstances of 46,XY female diagnosis

A 35-year-old woman was referred to the endocrinologist after measurement of an increased serum total testosterone above 8-fold the upper value of the normal range [6.5 ng/mL (N: 0.2–0.8)]. She spontaneously reported recent hair loss. Anamnesis reported a primary amenorrhea and a consanguineous family. At clinical examination, she was slightly overweight (height: 167 cm; weight: 77 kg; BMI: 28) with a normal breast development and adult external genitalia but no axillary or pubic hair. There was no hirsutism nor acne nor hyperseborrhea. Biology showed normal 17-hydroxy-progesterone (1.12 ng/mL) and elevated AMH [98 ng/mL (N: 1.5–6.5)]. Pelvic ultrasonography revealed an absence of uterus, a short vagina and bilateral intra-abdominal gonads without follicles nor individualized tumor. The absence of sexual hair contrasted with the high levels of total testosterone suggesting an androgen resistance. The elevated AMH suggested a testicular origin and explained the absence of uterus. Caryotype was 46,XY confirming the suspected diagnosis of complete insensitivity to androgens syndrome (CAIS). CAIS is a rare cause of primary amenorrhea with normal breast development. The medical management consists in bilateral gonadectomy after pubertal induction in order to prevent the risk of gonadal cancerization. The particularity of the present case is the atypical circumstances of diagnosis, which demonstrate the importance of the psychological care and the need of a multidisciplinary team. Indeed, our patient has a female phenotype without ambiguity and a female sexual and social identity despite her male genotype.

Effects and mechanisms of acupuncture and moxibustion on reproductive endocrine function in male rats with partial androgen deficiency.

Partial androgen deficiency of the aging male (PADAM) is characterised by a deficiency in serum androgen levels. Both electroacupuncture (EA) and mild moxibustion (MM) can raise serum testosterone levels in PADAM. We investigated the mechanisms underlying the use of EA and MM in a rodent model of PADAM. Fifty rats received cyclophosphamide injection over 5 consecutive days to induce PADAM, which was verified by comparing total testosterone (TT) and free testosterone (FT) levels with 10 non-PADAM healthy control rats (CON). Successful modelling was confirmed in 43 of 50 rats, 40 of which were randomly divided into untreated (PADAM), EA-treated (PADAM+EA), MM-treated (PADAM+MM), and androlin (AD)-treated (PADAM+AD) groups (n=10 each). EA and MM were administered at BL23 and CV4 acupuncture points for 8 weeks, and no treatment was given to rats in the PADAM and CON groups. Serum levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH), mRNA expression of cytochrome P450c17 (P450c17) and 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), and protein levels of cytochrome P450 side chain cleavage (P450scc), 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) and steroidogenic factor 1 (SF-1) were evaluated after 8 weeks. Both EA and mild MM significantly increased serum TT and FT levels with MM displaying superiority. P450scc, 17β-HSD3 and SF-1 protein expression, and P450c17 and 3β-HSD1 mRNA expression, were significantly increased and serum LH and FSH levels were significantly decreased in PADAM+EA and PADAM+MM relative to PADAM rats. Moreover, serum LH and FSH levels were significantly lower and 17β-HSD3 protein expression significantly higher in PADAM+MM relative to PADAM+EA rats. EA and MM at the BL23 and CV4 acupuncture points appear to be effective treatments for PADAM, and MM displays superior efficacy to EA.

Recovery after Heavy Resistance Exercise and Skeletal Muscle Androgen Receptor and Insulin-Like Growth Factor-I Isoform Expression in Strength Trained Men

The effects of heavy resistance exercise on skeletal muscle androgen receptor (AR) protein concentration and mRNAs of AR, insulin-like growth factor-I (IGF)-IEa, and mechano growth factor (MGF) expression were examined from biopsies of vastus lateralis (VL) muscle before and 48 hours after heavy resistance exercise (5 × 10 repetition maximum [RM] leg press and 4 × 10RM squats) in 8 adult strength trained men. The present exercise induced an acute decrease in maximal isometric force and increased serum total testosterone (T) and free testosterone (FT) concentrations. During 2 recovery days, maximal isometric force and subjective perception of physical fitness remained significantly lowered, whereas serum creatine kinase activity, subjective muscle soreness, and muscle swelling (i.e., thickness of VL by ultrasound) were significantly increased compared to pre-exercise values. Subjective perception of physical fitness was followed up to 7 days, and by 6 days postexercise, it was elevated above the pre-exercise level. Basal T and FT concentrations remained unaltered after the exercise. No statistically significant changes were observed in AR protein or mRNA expression, but IGF-IEa (p < 0.05) and MGF (p < 0.05) mRNA expression were increased compared to pre-exercise levels. These findings indicate that IGF-IEa and MGF responses may be related to acute regenerative processes in muscle because of exercise and may contribute to muscular adaptation to resistance exercise. Subjective perception of physical fitness suggests that recovery over a pre-exercise level of the present type of heavy resistance exercise can take approximately 6 days.

Circulating Estradiol and Mortality in Men With Systolic Chronic Heart Failure

Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF. To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF). A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol (quintile 1, < 12.90 pg/mL; quintile 2, 12.90-21.79 pg/mL; quintile 3, 21.80-30.11 pg/mL; quintile 4, 30.12-37.39 pg/mL; and quintile 5, > or = 37.40 pg/mL). Quintile 3 was considered prospectively as the reference group. Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays. Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001). Among men with chronic HF and reduced LVEF, high and low concentrations of estradiol compared with the middle quintile of estradiol are related to an increased mortality.

Endocrine and hormonal regulation of myocardial oxygen demand in polycystic ovary syndrome women and healthy controls

OBJECTIVE: Hyperandrogenism, hyperinsulinemia and abnormal lipid profile are established risk factors for cardiovascular disease (CVD) development and polycystic ovary syndrome (PCOS) is a model of metabolic syndrome in young, hyperandrogenic women. This study aimed at evaluation of resting myocardial oxygen consumption (expressed as “central rate-pressure product” – CRPP) in women with PCOS and healthy body mass index (BMI)- and age-matched controls in relation to selected hormonal and metabolic indices. DESIGN: Prospective observational study. MATERIALS AND METHODS: Eleven PCOS women and 7 age-matched, healthy, regularly cycling controls (28.6±1.4 vs. 28.4±2.0 yrs of age respectively; NS; mean±SEM) were examined in 1st phase of menstrual cycle. None of the subjects had diabetes nor hypertension. Serum total testosterone (TT), glucose and insulin were measured with specific chemiluminescence assays and oral glucose tolerance tests with 75g of glucose (OGTT) were performed. Lipid profile was evaluated in all subjects. Resting CRPP was quantified as a product of resting heart rate and aortic systolic blood pressure (evaluated noninvasively by tonometry - Sphygmocor Mx). Nonparametric unpaired Mann-Whitney test and Spearman correlation were used in statistical analysis. RESULTS: BMI was comparable in PCOS and controls (30.8±2.0 vs. 30.1±1.4 kg/m2, NS). Serum TT (0.90±0.1 vs. 0.32±0.05 ng/mL; p<0.001) and LDL cholesterol (123.5±9.8 vs. 97.3±8.6 mg/dL; p<0.05) were significantly higher in PCOS subjects when compared to controls whereas HDL level was significantly lower (52.7±3.4 vs. 67.0±4.3 mg/dL; p<0.05). There were no statistically significant differences in CRPP, fasting glucose and insulin between PCOS patients and controls. However resting CRPP was significantly correlated with TT (r=0.62; p<0.01), LDL cholesterol (r=0.50; p<0.05), and glucose measured during OGTT at 30, 60 and 90 minutes (r≥0.53; p<0.05). In addition, CRPP was significantly correlated with BMI (r=0.54; p<0.05). CONCLUSIONS: We conlude that although resting CRPP is comparable in PCOS and healthy women, it is strongly related to hormonal and metabolic status. It appears that increased resting myocardial oxygen consumption is associated with increased serum TT, LDL and glucose during OGTT as well as higher BMI. Thus our preliminary findings may suggest that higher resting CRPP reflects some abnormalities in endocrine and metabolic control of myocardial oxygen demand.