Higher Serum Testosterone Levels Research Articles

Habitual physical activity seems to be related with higher serum testosterone levels and improved insulin resistance in elderly diabetic individuals: IKARIA study

Habitual physical activity seems to be related with higher serum testosterone levels and improved insulin resistance in elderly diabetic individuals: IKARIA study

Serum Testosterone Levels and Clinical Outcomes in Male Hemodialysis Patients

Studies linking low serum testosterone concentration to adverse clinical outcomes in hemodialysis patients have been relatively small. We investigated the role of testosterone in adverse outcomes and quality of life in an incident cohort of male Canadian hemodialysis patients. A prospectively designed multicenter observational study using data from the Canadian Kidney Disease Cohort Study (CKDCS). Male patients initiating hemodialysis therapy since February 14, 2005, in 3 Canadian centers serving ethnically diverse populations were studied (N = 623). Serum testosterone levels using the International Society of Andrology, International Society for the Study of the Aging Male, and European Association of Urology cutoffs (low, <231 ng/dL; borderline, 231-346 ng/dL; normal, >346 ng/dL). All-cause mortality, fatal and nonfatal cardiovascular (CV) events, and Health Utility Index (HUI)-assessed health-related quality of life. Participants completed a structured interview on demographics and medical history and an HUI questionnaire (version 3). Routine laboratory test results captured into the study database, and serum testosterone measured within 3 months after initiation of the baseline hemodialysis session. During a median follow-up of 20 (range, 1-81) months, 166 (27%) died and 98 (20%) had a CV event. Mean serum testosterone level was 234.1 ± 146.1 (SD) ng/dL. Higher serum testosterone levels were associated with significantly decreased unadjusted risk of death (HR per 10-ng/dL increase, 0.58; 95% CI, 0.37-0.90). There was a statistically significant trend for higher all-cause mortality with low serum testosterone levels in adjusted analyses (P < 0.001). Higher levels of log-transformed testosterone were associated with significantly higher HUI scores (P for trend<0.001), and low levels of serum testosterone were associated significantly with lower HUI scores (P for trend<0.001). Although there was a significant trend in the unadjusted risk of CV events among participants with low serum testosterone levels (P < 0.001), the risk was no longer significant after adjustment for age. There was no significant interaction with age and serum testosterone level tested as continuous variables (P = 0.07). A short follow-up period and serum testosterone measured on a single occasion. Low serum testosterone concentration may be a modifiable risk factor for adverse outcomes and poor quality of life in male hemodialysis patients. This hypothesis should be tested in randomized controlled trials.

Elevated Testosterone Levels in HIV-Infected Men

Little is known about HIV-infected patients with serum testosterone levels in high normal to elevated ranges. An HIV-infected patient with hepatitis C and unexplained high serum testosterone levels prompted a retrospective chart review into the association of hepatitis C and serum testosterone levels greater than 1000 ng/mL in our clinic. The charts of 1419 male HIV patients were reviewed. Out of 1419 patients, 159 (11%) met the criteria for data analysis. A total of 8 patients had serum testosterone levels greater than 1000 ng/mL. There was no significant correlation between hepatitis C antibody positivity or presence of hepatitis C viremia as measured by viral load, nor was there any significant correlation with CD4+ cell counts. We found a weak positive association between years since reported diagnosis of HIV and high testosterone levels.

Effect of different cryoprotectant agents on spermatogenesis efficiency in cryopreserved and grafted neonatal mouse testicular tissue

Restoration of male fertility associated with use of the cryopreserved testicular tissue would be a significant advance in human and animal assisted reproductive technology. The purpose of this study was to test the effects of four different cryoprotectant agents (CPA) on spermatogenesis and steroidogenesis in cryopreserved and allotransplanted neonatal mouse testicular tissue. Hank’s balanced salt solution (HBSS) with 5% fetal bovine serum including either 0.7M dimethyl sulfoxide (DMSO), 0.7M propylene glycol (PrOH), 0.7M ethylene glycol (EG), or glycerol was used as the cryoprotectant solution. Donor testes were collected and dissected from neonatal pups of CD-1 mice (one day old). Freezing and seeding of the testicular whole tissues was performed using an automated controlled-rate freezer. Four fresh (non-frozen) or frozen–thawed pieces of testes were subcutaneously grafted onto the hind flank of each castrated male NCr nude recipient mouse and harvested after 3months. Fresh neonatal testes grafts recovered from transplant sites had the most advanced rate of spermatogenesis with elongated spermatid and spermatozoa in 46.6% of seminiferous tubules and had higher levels of serum testosterone compared to all other frozen–thawed-graft groups (p<0.05). Fresh grafts and frozen–thawed grafts in the DMSO group had the highest rate of tissue survival compared to PrOH, EG, and glycerol after harvesting (p>0.05). The most effective CPA for the freezing and thawing of neonatal mouse testes was DMSO in comparison with EG (p<0.05) in both pre-grafted and post-grafted tissues based on histopathological evaluation. Likewise, the highest level of serum testosterone was obtained from the DMSO CPA group compared to all other cryoprotectants evaluated (p<0.05). The typical damage observed in the frozen–thawed grafts included disruption of the interstitial stroma, intercellular connection ruptures, and detachment of spermatogonia from the basement membrane. These findings indicate that neonatal mouse testes were most effectively preserved when frozen with HBSS medium with DMSO and that the type of CPA is a significant factor to obtain the most advanced stages of spermatogenesis and steroidogenesis after cryopreservation, thawing, and transplantation of neonatal mouse testes.

The clinical significance and primary determinants of hirsutism in patients with polycystic ovary syndrome

Hirsutism is frequently present in patients with polycystic ovary syndrome (PCOS) and is a major sign of hyperandrogenism. However, other disorders frequently present in PCOS, particularly abdominal obesity and insulin resistance (IR), have also been implicated in the development of hirsutism in this population but relevant data are limited. We aimed to define the determinants of the presence of hirsutism in PCOS. Observational study. We studied 1297 patients with PCOS (age 24.3±5.8 years, BMI 26.8±6.9 kg/m(2)). Hirsutism was defined as a modified Ferriman-Gallwey score ≥8. Women with hirsutism were younger, had greater BMI, and had higher levels of circulating androgens than women without hirsutism; markers of IR did not differ between the two groups after adjustment for age and BMI. The prevalence of hirsutism progressively declined with age, was lower in normal-weight women than in overweight and obese women, and was comparably prevalent in the hyperandrogenemic phenotypes of PCOS. In binary logistic regression analysis, independent predictors of the presence of hirsutism were younger age, larger waist circumference (W), and higher serum testosterone levels. In stepwise linear regression analysis, the Ferriman-Gallwey score independently correlated with age, W, free androgen index, and serum Δ4-androstenedione and DHEAS levels. Besides hyperandrogenemia, abdominal obesity, and young age are independently associated with the presence of hirsutism. In contrast, the relationship between IR and hirsutism appears to be mediated by the more severe obesity of insulin-resistant patients with PCOS.

Endocrine reproductive dysfunctions in women with epilepsy on antiepileptic therapy

Rationale. The aim of this study is to evaluate sex hormones abnormalities and incidence of polycystic ovary syndrome among young women with epilepsy, analyzing the possible impact of antiepileptic therapy. Material and methods. In this study we included 41 women with epilepsy, aged between 18 to 40 years, not receiving hormones, with disease duration for 1 to 15 years. The assessment included clinical examination, transvaginal ultrasonography and measurement of sex hormones serum concentration (total testosterone, estradiol, SHBG, LH and FSH) from days 1 to 10 of one menstrual cycle. The patients were compared with a healthy control group. Hormonal data were correlated with the concomitant antiepileptic therapy. Results. PCO (polycystic ovaries) were found in 19 patients (46%) associated frequently with valproate treatment started before the age of 20 years. PCOS (polycystic ovary syndrome) was found in 20% of the patients, also under valproate therapy. In 22 patients (53%), a high serum testosterone level (19 patients under valproate mono- or add-on therapy). LH/FSH ratio appears bigger than 1 in 21 patients (51%) (17 patients treated with valproate mono- or add-on therapy). Conclusions. The endocrine - reproductive dysfunctions occurred more frequently in epileptic women treated with valproate; these endocrine abnormalities may have a negative impact on fertility in women with epilepsy and therefore young patients should be screened and carefully evaluated in an endocrinology service prior to start the antiepileptic treatment.

Sex-specific offspring growth according to maternal testosterone, corticosterone, and glucose levels

Sex allocation theory in vertebrates has greatly benefited from the recent advances in studies on the physiological mechanisms of birth sex ratio variation (e.g., maternal glucose, stress, and testosterone levels). The same physiological mechanisms may, however, also mediate permanent sex-specific effects on individuals after birth. Together with biased maternal postpartum investment on sex allocation, they can have long-term fitness consequences for the offspring. We studied whether maternal preconception levels of serum glucose and testosterone, and fecal corticosterone metabolites differently influenced male and female pup weight until weaning in field voles (Microtus agrestis). In this species, high maternal preconception serum glucose and testosterone levels have previously been associated with the excess of male pups at birth. Our results suggest that male, but not female, pup weight increases with higher maternal preconception testosterone level whereas high maternal serum glucose level promoted female pup weight only. The level of maternal fecal corticosterone metabolites was not related to pup weight in either sex. These findings suggest that in field voles the same physiological mechanisms influencing sex ratio at birth may also influence offspring postnatal weight; however, such influences can act in conflict, as seen in the case of maternal glucose level.

Senescence and steroid hormone receptor reactivities in accessory sex glands of elderly rats (Sprague-Dawley) following exogenous hormonal therapy

The aim of this study was to characterize the stromal and epithelial distribution of AR, ERα and ERβ reactivities in the different accessory sex glands of elderly rats and during strong hormonal changes. Ten month old male rats were divided into six senile groups and submitted to treatment: Senile/Control group (SC); Senile/Testosterone group (ST): Senile/Estrogen group (SE); Castrated group (CA); Castrated/Testosterone group (CT); Castrated/Estrogen group (CE). After a 30-day treatment, the prostatic ventral lobe (VL), dorsal lobe (DL) and coagulating gland (CG) samples were processed for immunohistochemistry and Western Blotting. The results showed that AR immunoreactivity was characterized in the epithelium of VL and DL in senile/control rats and senile rats submitted to exogenous hormonal therapy. AR reactivity in the coagulating gland was verified predominantly in the stromal cells in the different experimental groups. ERα reactivity occurred predominantly in the stromal compartment in all accessory sex glands. In the DL and CG, ERα immunoreactivities were intense in the groups which received testosterone (ST) and estrogen (SE). ERβ immunoreactivity in the CG was verified in the stromal compartment in the different experimental groups, showing a positive response to both increased testosterone and estrogen levels. ERβ reactivity, in the DL, was intensified in the stroma of senile rats with higher serum testosterone levels, and in senile rats with increased serum estrogen levels, especially in the glandular epithelium. Thus, the results revealed different distribution pattern of steroid hormone receptors in each one of the prostatic lobes in senescence, especially in the prostate dorsal lobe and coagulating gland, which is a fundamental factor due to the fact that major prostatic diseases occur in a later period of life.

Aromatase Activity After a Short-course of Letrozole Administration in Adult Men at Sea Level and at High Altitude (with or without Excessive Erythrocytosis)

Men living at high altitudes in Peru compared to sea level counterparts have erythrocytosis (hemoglobin 16-21 g/dl) or excessive erythrocytosis (hemoglobin>21 g/dl). High testosterone (T) levels in men at high altitude (HA) were associated with excessive erythrocytosis. High androgen levels could be due to a low aromatase activity or to an elevated rate of conversion from precursors to testosterone. The aim of this study was to evaluate aromatase activity and rate of conversion from precursors to testosterone before and after administration of the aromatase enzyme inhibitor letrozole (5 mg/day) for a 5-day period to men at HA and at sea level (SL). The response to short term aromatase inhibition was assessed in 30 adult men living at sea level, 31 native men at HA with erythrocytosis (Hb 16-21 g/dl), and 35 men at HA with excessive erythrocytosis (Hb>21 g/dl). Serum hormone levels, estradiol/testosterone, testosterone/androstenedione, and testosterone/dehydroepiandrosterone sulfate (DHEAS) ratios were measured. Men with erythrocytosis had lower basal serum T/androstenedione ratios than men with excessive erythrocytosis at HA and men at sea level. Men at HA with excessive erythrocytosis had higher T/DHEAS ratios than men with erythrocytosis and than those at sea level before and after letrozole administration. After letrozole administration, both groups of men at high altitude (with erythrocytosis or with excessive erythrocytosis) showed lower aromatase activities than those at sea level. In conclusion, higher serum testosterone levels in men with excessive erythrocytosis were associated with an increased rate of conversion from DHEAS to testosterone rather than to a lower aromatase activity.

Registry study shows link between high testosterone and reduced CV risk

A prospective registry study involving 2,416 elderly (69–81 year-old) men has shown that high serum testosterone levels are linked with reduced risk of nonfatal and fatal cardiovascular (CV) events.

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

Chronic mountain sickness (CMS), a lack of adaptation to altitude characterized by excessive erythrocytosis (EE), is a health problem associated with life at high altitude. The erythropoietic process is regulated by both erythropoietin and testosterone. Zinc (Zn) is known to be related with testosterone and hemoglobin levels; meanwhile, nitric oxide was also associated with adaptation to high altitude. The aim of this study was to determine the relationship of hemoglobin and CMS score with serum levels of zinc, total testosterone (TT), calculated free testosterone (cFT), bioavailable testosterone (BAT), hemoglobin, and nitric oxide in men at high altitude with or without EE. Men residing in Lima (150m) and Cerro de Pasco (4,340m), Peru, were divided into three groups: (1) low altitude, (2) high altitude without EE (hemoglobin<21g/dl), and (3) high altitude with EE (hemoglobin≥21g/dl). Adjusted multivariable regression models showed that serum testosterone (total or free) and Zn levels were independently correlated with increased hemoglobin levels. Similarly, hemoglobin was positively related with signs/symptoms of CMS; however, both increased the serum Zn and the nitric oxide levels correlated with reduced risk for signs/symptoms of CMS. In conclusion, higher serum testosterone levels and Zn levels were associated with EE, and low scores of signs/symptoms of CMS were associated with higher Zn and nitric oxide levels.

Hemoglobina y testosterona: importancia en la aclimatación y adaptación a la altura

The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

The relationship between serum testosterone levels and bladder storage symptoms in a female population with polycystic ovary syndrome

To examine the relationship between bladder symptoms and serum testosterone levels in women with polycystic ovary syndrome (PCOS). A total of 140 patients diagnosed with PCOS according to ESHRE/ASRM criteria in two clinics were evaluated for the effects of testosterone on bladder symptoms. The effect of testosterone on bladder symptoms was quantified by self-administered pelvic pain and urgency/frequency questionnaire (PUFq) and an extra special question performed for urge incontinence. Ultrasonographic bladder capacity and postvoid residual volume were also recorded in all patients. Correlation between serum testosterone level and total, symptom and bother scores of PUFq, score of each question of PUFq separately, and ultrasonographic findings were analyzed. The median (range) age, testosterone, DHEAS, estradiol, glucose, urine pH, urine density, ultrasonographic bladder capacity, and PUFq score were 25 years (17-40), 53 ng/dl (25-229), 258 µg/dl (92-645), 74 pg/ml (20-184), 81 mg/dl (62-128), 5.5 (4.8-7.0), 1.015 (1.001-1.028), 400 ml (100-650), and 2.5 (0-23), respectively. Significant positive correlation was found between serum testosterone level and total, symptom and bother scores of PUFq, symptom of dyspareunia, urgency, nocturia, and bladder/pelvic pain. There was no correlation between serum testosterone level and ultrasonographic findings such as bladder capacity, postvoid residual volume and symptom of frequency. This study indicates that women who have higher serum testosterone level are more likely to report bladder symptoms.

Prospective association of low serum total testosterone levels with health care utilization and costs in a population‐based cohort of men

Despite the burgeoning interest in the field of andrology, no studies have specifically addressed the impact of serum testosterone levels on healthcare utilization and costs. We analysed data from the population-based cohort Study of Health in Pomerania (SHIP), Germany, to assess the association of serum testosterone levels with self-reported health care utilization and costs at baseline and at 5 years follow up. Study sample comprised 2023 men at baseline, of whom 1530 men were repeatedly examined. Low and high serum testosterone levels, defined according to the age-specific 10th and 90th percentile, were compared with reference subjects with serum testosterone levels ≥10th -≤90th percentile. Two-part econometric models were applied adjusting for socio-economic and medical confounders. Cross-sectional models revealed higher numbers of outpatient visits and higher costs for both, men with low (+19.1 and +19.9%, respectively) and high serum testosterone levels (+25.3 and +30.2%, respectively), whereas number of inpatient days and costs were not associated with serum testosterone levels. Adjustment for age, educational level, income, waist circumference, smoking status, physical activity and alcohol consumption did not considerably alter the results. Longitudinal models revealed a significant association of low serum testosterone levels with increased number of follow-up outpatient visits (age-adjusted: +28.6%) and costs (+38.0%) only. Low and high serum testosterone levels were associated with increased short-term outpatient health care costs, whereas low serum testosterone levels appear to be predictive of long-term outpatient health care costs. Cost-effectiveness studies of available treatments are necessary to identify benefits for physicians, patients and health care system as a whole.

A comparative study of cutaneous manifestations of hyperandrogenism in obese and non-obese Taiwanese women

The aim of the study was to investigate the impact of obesity on cutaneous manifestations of clinical hyperandrogenism. A total of 627 Taiwanese women of reproductive age were included. Women with acne had a greater incidence of PCOS, hyperandrogenemia and hirsutism, and had higher serum total testosterone than women without acne. Obese women, even with significantly higher serum total testosterone levels, had lower incidence of acne than non-obese women, and this was found uniformly across the hyperandrogenemia and the non-hyperandrogenemia groups. Although BMI had a significantly positive correlation with serum total testosterone in the studied women, obese women presented less acne than the non-obese subjects. Obese women, regardless of having higher serum testosterone levels, had a lower incidence of acne than non-obese women; however, the factuality was not found in hirsutism.

Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79

Although the association of low serum testosterone levels with mortality has gained strength in recent research, there are few population-based studies on this issue. This study examined whether low serum testosterone levels are a risk factor for all-cause or cause-specific mortality in a population-based sample of men aged 20-79. We used data from 1954 men recruited for the prospective population-based Study of Health in Pomerania, with measured serum testosterone levels at baseline and 195 deaths during an average 7.2-year follow-up. A total serum testosterone level of less than 8.7 nmol/L (250 ng/dL) was classified as low. The relationships of low serum testosterone levels with all-cause and cause-specific mortality were analysed by Cox proportional hazards regression models. Men with low serum testosterone levels had a significantly higher mortality from all causes than men with higher serum testosterone levels (HR 2.24; 95% CI 1.41-3.57). After adjusting for waist circumference, smoking habits, high-risk alcohol use, physical activity, renal insufficiency, and levels of dehydroepiandrosterone sulfate, low serum testosterone levels continued to be associated with increased mortality (HR 2.32; 95% CI 1.38-3.89). In cause-specific analyses, low serum testosterone levels predicted increased risk of death from cardiovascular disease (CVD) (HR 2.56; 95% CI 1.15-6.52) and cancer (HR 3.46; 95% CI 1.68-6.68), but not from respiratory diseases or other causes. Low serum testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. As serum testosterone levels are inversely related to mortality due to CVD and cancer, it may be used as a predictive marker.

A rare case of hyperandrogenism: bilateral Leydig cell tumor of the ovary

The androgen-secreting tumors constitute fewer than 1% of ovarian tumors. Leydig cell tumor is one of the most common of this type of lesion and it is usually benign, small and unilateral. A 67 year old woman was referred to the Endocrine clinic due to hirsutism (score 22 Ferriman-Gallwey) and male type alopecia with 3 years of evolution and progressive worsening. Biochemically she had high levels of serum testosterone - 662 ng/dl (N < 62 ng/dl). Transvaginal ultrasonography and abdomen-pelvic CT scan didn't show any signs of adrenal or ovarian tumors. Bilateral oophorectomy was performed and histopathologic exam revealed bilateral Leydig cell tumors, measuring 1cm each. Four months after surgery, the patient had a marked improvement of the signs (score 3 Ferriman-Gallwey) and normalized testosterone levels (35.9 ng/dl). Androgen-secreting tumors are rare, but they should be excluded in cases of rapid onset of virilization and elevated androgen levels. Tumors are frequently undetectable by imaging techniques because of their small dimensions, exploratory surgery by a skilled team is frequently necessary and is often the best treatment for the majority of these cases. In this case report we present a rare case of bilateral Leydig cell tumor. Only five cases have been reported in the literature.The clinical history and the elevated levels of testosterone had suggested the presence of an androgen-producing tumor, despite the difficulty of the diagnosis on imaging techniques. Due to the fact that our patient was in a post-menopausal stage, we decided that the appropriate treatment would be bilateral oophorectomy. The histopathologic disclosed the diagnosis and allowed the patient's cure.

Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men

Obesity and metabolic syndrome are associated with low serum testosterone levels. Hepatic steatosis contributes to the metabolic syndrome and might be regarded as its hepatic manifestation. In this study, we sought to investigate the relationship between hepatic steatosis, serum testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in men. This is a cross-sectional population-based study. We used data of 1912 men recruited for the population-based Study of Health in Pomerania, which was conducted in a region with high prevalence of metabolic syndrome and related diseases. Hepatic steatosis was defined according to sonographic criteria. The relationship of hepatic steatosis with serum testosterone and DHEAS levels was analysed by multivariable logistic regression. Men with low serum testosterone levels had a higher risk of hepatic steatosis than men with high serum testosterone levels. Adjustment for age and further confounders attenuated this association, but did not affect statistical significance (odds ratio 2.36; 95% confidence interval 1.66-3.37; p < 0.05). In the full model, the highest risk of hepatic steatosis was found in subjects with the highest serum DHEAS levels (odds ratio 1.59; 95% confidence interval 1.04-2.43; p < 0.05). Exclusion of men with high alcohol consumption did not affect these results substantially. Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels. These associations are independent of alcohol consumption.

The association of serum testosterone levels and ventricular repolarization

It is assumed that testosterone is an important regulator of gender-related differences in ventricular repolarization. Therefore, our aim was to study whether serum levels of testosterone are associated with QTc, QT and RR interval variation. Setting: two independent population-based cohort studies. Participants: 445 male participants (≥55 years) from the Rotterdam study cohort and 1,428 male participants from the study of health in Pomerania (SHIP) with an electrocardiogram who were randomly sampled for assessment of serum testosterone at baseline, after exclusion of participants with testosterone altering drugs, QTc prolonging drugs or dig(it)oxin, left ventricular hypertrophy and left and right bundle branch block. Endpoints: length of the QTc, QT and RR intervals. Analysis: linear regression model, adjusted for the two individual studies and a pooled analysis of both studies. The pooled analysis of the Rotterdam study and SHIP showed that the QTc interval gradually decreased among the tertiles (P value for trend 0.024). The third tertile of serum testosterone was associated with a lower QTc interval compared to the first tertile [−3.4 ms (−6.5; −0.3)]. However, the third tertile of serum testosterone was not associated with a lower QT interval compared to the first tertile [−0.7 ms (−3.1; 1.8)]. The RR interval gradually increased among the tertiles (P value for trend 0.002) and the third tertile of serum testosterone showed an increased RR interval compared to the first tertile [33.5 ms (12.2; 54.8)]. In the pooled analysis of two population-based studies, serum testosterone levels were not associated with the QT interval, which could be due to a lack of power. Lower QTc intervals in men with higher serum testosterone levels could be due to the association of serum testosterone with prolongation of the RR interval.

Testosterone differentially alters cocaine-induced ambulatory and rearing behavioral responses in adult and adolescent rats

Little is known about the physiological and behavioral effects of testosterone when co-administered with cocaine during adolescence. The present study aimed to determine whether exogenous testosterone administration differentially alters psychomotor responses to cocaine in adolescent and adult male rats. To this end, intact adolescent (30-days-old) and adult (60-day-old) male Fisher rats were pretreated with vehicle (sesame oil) or testosterone (5 or 10 mg/kg) 45 min prior to saline or cocaine (20 mg/kg) administration. Behavioral responses were monitored 1 h after drug treatment, and serum testosterone levels were determined. Serum testosterone levels were affected by age: saline- and cocaine-treated adults in the vehicle groups had higher serum testosterone levels than adolescent rats, but after co-administration of testosterone the adolescent rats had higher serum testosterone levels than the adults. Pretreatment with testosterone affected baseline activity in adolescent rats: 5 mg/kg of testosterone increased both rearing and ambulatory behaviors in saline-treated adolescent rats. After normalizing data to % saline, an interaction between hormone administration and cocaine-induced behavioral responses was observed; 5 mg/kg of testosterone decreased both ambulatory and rearing behaviors among adolescents whereas 10 mg/kg of testosterone decreased only rearing behaviors. Testosterone pretreatment did not alter cocaine-induced behavioral responses in adult rats. These findings suggest that adolescents are more sensitive than adults to an interaction between testosterone and cocaine, and, indirectly, suggest that androgen abuse may lessen cocaine-induced behavioral responses in younger cocaine users.