Single Dose Of Testosterone Research Articles

Does Testosterone Advance the Meatus in Children with Proximal Hypospadias?

Background: Pre-operative preparation of the children with hypospadias may involve the administration of testosterone to argument penile dimensions. However, the effect of testosterone on the urethral meatus is not established. The aim of this study was to prospectively evaluate the effect of testosterone on the location of the hypospadiac meatus. Materials and Methods: This was a prospective observational study of children, aged 15 years and younger, who are being prepared for hypospadias repair at the pediatric surgery unit of a teaching hospital in Enugu, Nigeria. This study covered a 5-year period. The following data were analyzed: age of the patients at presentation, type of hypospadias, proximal and distal penile measurements at onset and at 4 weeks after testosterone injection. Results: A total of 24 cases of proximal hypospadias were recruited into the study. The ages of the patients at presentation ranged from 1 month to 18 months with a median age of 3 months. Majority of the patients had mid-penile hypospadias. Regarding response to testosterone, proximal part of the penile shaft responded more than the distal part. However, statistical analysis showed no advancement in the location of the meatus. Conclusion: This is study has shown that a single dose of testosterone has no effect on the location of meatus in children with hypospadias.

Effects of Saussurea costus on apoptosis imbalance and inflammation in benign prostatic hyperplasia

Ethnopharmacological relevanceSaussurea costus (synonym: Aucklandia lappa Decne) is a medicinal plant distributed in Yunnan, Guangxi, and Sichuan in China. In traditional Korean medicine, the plant parts (especially the root—“radix aucklandiae”) is widely used to treat vomiting, diarrhea, and inflammation. However, little has been reported on its effect on benign prostatic hyperplasia (BPH), which is common in middle-aged men. Aim of the studyBPH is caused by apoptosis imbalance and inflammation due to aging of the prostate. Therefore, the aim of this was to prove the efficacy of S. costus by analyzing its effect on the biological mechanisms leading to BPH progression. Materials and methodsWistar rats were injected subcutaneously with a single dose of testosterone (125 mg/kg) to induce BPH, and were later administered with S. costus (20, 40 mg/kg). After 12 weeks, histological changes in the prostate and hormone regulation factors were assessed in all animals. Furthermore, apoptotic protein and apoptotic body values were analyzed to confirm the improvement of apoptosis imbalance, and inflammatory cytokines were analyzed to confirm the anti-inflammatory efficacy of S. costus. ResultsIn the serum and tissue of S. costus-treated BPH rats, a significant reduction in prostate weight, prostate index, and hormone regulation factors was observed. S. costus also increased the levels of apoptosis marker proteins and reduced the levels of inflammatory cytokines. It also decreased the expression of B-cell lymphoma 2 (BCL-2) and increased the expression of BCL-2 associated X protein (BAX) in the prostate. Histological changes such as epithelial thickness significantly increased in BPH induced group but significantly decreased in the S. costus-treated groups (p < 0.001). ConclusionsS. costus may prevent and treat BPH occurrence by modulating inflammation and apoptosis imbalance.

Bioanalytical Detection of Steroid Abuse in Sports Based on the Androgenic Activity Measurement

The anabolic androgenic steroids (AAS) are the most frequently consumed performance enhancing drugs (PED) in sports. In the anti-doping field, the detection of AAS is carried out by the analysis of the athlete’s urine using methodologies based on liquid/gas chromatography-mass spectrometry. Unfortunately, the detection of unknown compounds is not possible. BDS’s AR CALUX® bio detection technology was studied as an indirect method to detect the administration of a single dose of testosterone (T). Twelve T and placebo single dose administered men volunteers underwent a triple-blind crossover clinical trial. The UGT2B17 deletion was present among the volunteers and evenly distributed in heterozygous (ins/del), wild-type homozygous (ins/ins), and mutated homozygous (del/del) groups. A significant statistical difference in terms of bioluminescence was observed after the testosterone (T) administration for the three types of polymorphic groups. The ratio of means between the pre- and post-T administration periods, depending on the type of polymorphism, was in group ins/ins 3.31 (CI. 95%: 2.07–5.29), group ins/del 4.15 (CI 95%: 3.05–5.67), and group del/del 2.89 (CI 95%: 2.42–3.46). The results of the study are very promising, as they may offer us the possibility of designing a detection approach that, based on intra-individual monitoring of androgenic values, in the UGT2B17 deletion type.

Single dose of testosterone in children with hypospadias: any effect on the diameter of the glans penis?

BackgroundThe purpose of this study was to assess the effect of a single dose of testosterone on the diameter of the glans penis.MethodsThis was a prospective evaluation of the effect of a single dose of testosterone on the diameter of the glans penis of children with hypospadias. The diameter of the glans penis was measured transversely at the level of the coronal sulcus using Vernier calipers. The patients were categorized into two groups: Group A and Group B. Group A received intramuscular testosterone at the dose of 2 mg per kilogram body weight. Group B did not receive any testosterone and served as control. The diameter of the glans penis was evaluated at the beginning of the study and at 4 weeks after the testosterone injection.ResultsOverall, 64 patients were evaluated. There were 32 patients in group A (50%) and 32 patients in group B (50%). The mean diameter in group A before and after testosterone injection was 17.6 mm ± 2.5 SD and 17.8 ± 2.3 SD, respectively. The mean diameter in group B at onset and after 4 weeks was 17.6 mm ± 2.4 SD and 17.7 ± 2.4 SD, respectively. p = 0.12 which is statistically insignificant.ConclusionSingle dose of testosterone in children with hypospadias does not produce significant increase in the diameter of the glans penis.

Single-Dose of Testosterone and the MAOA VNTR Polymorphism Influence Emotional and Behavioral Responses in Men During a Non-social Frustration Task.

Previous studies suggest that testosterone and several neurotransmitters might interactively influence human aggression. The current study aimed to test potential interactions of a genetic variation linked to the catabolism of serotonin, dopamine, and norepinephrine and exogenous testosterone on the reaction towards non-social provocation. In total, 146 male participants were genotyped for a prominent polymorphism of the monoamine oxidase A (MAOA) gene resulting in a short and long variant. Participants completed a non-social frustration task after receiving either testosterone or a placebo gel in a double-blind set-up. Participants performed a non-social frustration task, where they had to direct a virtually moving ball into a barrel by pulling a joystick (neutral block). During a frustration block, the joystick repeatedly did not respond to participants’ reactions thereby causing failed trials to which participants reacted with increased anger and stronger pulling of the joystick. We analyzed the effect of testosterone administration on emotion and behavior in individuals who either carried a low (L) or high (H) activity MAOA variant. Testosterone administration increased provocation-related self-reported anger and abolished the association between trait aggression and joystick deflection in the frustration block. In MAOA-H carriers endogenous testosterone levels at baseline were associated with increased joystick deflection in both blocks. There was, however, no interaction of testosterone administration and genotype. Although preliminary, the results rather indicate independent influences of exogenous testosterone administration and MAOA, but support an interaction of endogenous testosterone levels and MAOA genetics in a frustration task. The administration of testosterone seems to act on the subjective emotional experience in a provoking situation, while endogenous testosterone levels increased pulling impulses only in carriers of the MAOA-H variant.

No effect of testosterone on behavior in aged Wistar rats.

In men, aging is accompanied by a gradual decline in androgen secretion. Studies suggest beneficial effects of endogenous and exogenous testosterone on affective behavior and cognitive functions. The aim of this study was to describe behavioral and cognitive sex differences and to analyze the effects of long-term androgen deficiency in aged male rats. Thirty-months old rats divided into three groups (males, females and males gonadectomized as young adults) underwent a battery of behavioral tests assessing locomotor activity, anxiety, memory, anhedonia, sociability and depression-like behavior. No major effect of gonadectomy was found in any of the analyzed behavioral measures in male rats. The only consistent sex difference was confirmed in depression-like behavior with longer immobility time observed in males. In an interventional experiment, a single dose of testosterone had no effect on gonadectomized male and female rats in the forced swim test. In contrast to previous studies this comprehensive behavioral phenotyping of aged rats revealed no major role of endogenous testosterone. Based on our results long-term hypogonadism does not alter the behavior of aged male rats, neither does acute testosterone treatment. Whether these findings have any consequences on androgen replacement therapy in aged men remains to be elucidated.

Changes in spatial cognition and brain activity after a single dose of testosterone in healthy women

Studies have consistently shown that males perform better than females on several spatial tasks. Animal and human literature suggests that sex hormones have an important role in both establishing and maintaining this difference. The aim of the present study was to examine the effects of exogenous testosterone on spatial cognition and brain activity in healthy women. A cross-sectional, double-blind, randomized, placebo-controlled study was performed in 42 healthy young women who either received one dose of 0.5mg sublingual testosterone or placebo. They then learned a virtual environment and performed navigation tasks during functional magnetic resonance imaging (fMRI). Subsequently, their knowledge of the virtual environment, self-reported navigation strategy, and mental rotation abilities were measured. The testosterone group had improved representations of the directions within the environment and performed significantly better on the mental rotation task compared to the placebo group, but navigation success and navigation strategy were similar in the two groups. Nevertheless, the testosterone group had significantly increased activity within the medial temporal lobe during successful navigation compared to the placebo group, and a positive correlation between testosterone load and medial temporal lobe activity was found. Fetal testosterone levels, measured as second-to-fourth digit length ratio, interacted significantly with parahippocampal activity and tended towards giving higher mental rotation task scores. These results demonstrated that testosterone had a limited effect pertaining specifically to spatial cognition involving 3D-visualization in healthy women, while complex behaviors such as navigation, relying more on learned strategies, were not altered despite increased neuronal activity in relevant brain regions.

Long-term testosterone supplementation is useful for ED with testosterone deficiency

Long-term testosterone supplementation is useful for ED with testosterone deficiency

Factors determining the kinetics of a single dose of testosterone in rats

The results from different authors regarding testosterone and cognitive research show controversial results. One of the reasons may be the form of testosterone used in the experiment. The aim of our study was to evaluate the testosterone levels in plasma and its kinetics after the single application of either a long-acting or a short-acting form of this hormone. Twenty female and twenty male adult Wistar rats were divided into two groups that were either gonadectomized or not. The two groups were divided into 4 subgroups depending on whether the animals received testosterone propionate or testosterone isobutyrate intramuscularly. Samples for analysis were collected before and at 2, 4, 24, 48, 72, 96 and 168 h after injection. The results showed significant differences in the dynamics between rapid and depot forms of testosterone, together with the rebound effect and hormonal negative feedback. These aspects of testosterone kinetics need to be considered when planning experiments on the physiology of testosterone.

ORIGINAL RESEARCH—ANATOMY/PHYSIOLOGY: Childhood Sexual Abuse, Selective Attention for Sexual Cues and the Effects of Testosterone with or without Vardenafil on Physiological Sexual Arousal in Women with Sexual Dysfunction: A Pilot Study

Female sexual dysfunction (FSD) may be associated with reduced central sensitivity for sexual cues. A single dose of testosterone might induce an increase in sensitivity for sexual stimuli, which in turn allows a PDE5 inhibitor to be effective in boosting the physiological sexual response. Negative sexual experience-like childhood sexual abuse (CSA)-might be an important intervening factor in these drugs-induced alterations. To investigate if the combination of testosterone and vardenafil causes an increase in sensitivity for sexual cues and an increase in physiological sexual responding in women suffering from hypoactive sexual desire disorder (HSDD). Thirteen women with HSDD underwent four different drug treatments: (i) placebo; (ii) vardenafil; (iii) testosterone; and (iv) combination of testosterone and vardenafil. During each treatment, they performed an emotional Stroop task and watched neutral and erotic film clips. A masked version of the emotional Stroop task, and the vaginal pulse amplitude (VPA). We found different effects in women who had reported CSA (N = 5) compared with those who had not (N = 8). In women without CSA, testosterone induced an increase in their originally low levels of preconscious attention for sexual cues, while women with CSA showed a decrease in their originally high levels of attention. In these groups, we also found different effects of the combination of testosterone and vardenafil on the VPA: women without CSA revealed a statistically significant increase in their VPA during treatment with the combination of testosterone and vardenafil as compared with placebo. Women with CSA, however, showed no alterations in their physiological sexual responding during this combined drug treatment. In women without CSA, testosterone appears to activate central sexual mechanisms resulting in higher VPA under the combination of testosterone and vardenafil. This effect did not occur in women with CSA.

ORIGINAL RESEARCH—ENDOCRINOLOGY: Transdermal Testosterone Gel prn Application for Hypoactive Sexual Desire Disorder in Premenopausal Women: A Controlled Pilot Study of the Effects on the Arizona Sexual Experiences Scale for Females and Sexual Function Questionnaire

Several studies suggest that increased plasma testosterone can improve sexual function and desire in post-oophorectomy or postmenopausal women. However, side effects of chronic daily testosterone raise questions about the generalizability of this treatment approach. Sublingual testosterone was reported to cause testosterone levels to peak after 15 minutes and then decline to baseline levels within 90 minutes. Three to 4 hours after reaching testosterone peak, increased genital sensations and sexual lust were reported. We hypothesized that a single dose of testosterone given 4-8 hours prior to planned intercourse in women with hypoactive sexual desire disorder (HSDD) might increase desire without side effects associated with chronic use. The design was randomized double-blind crossover. Premenstrual women with HSDD received eight packets of gel or identical placebo for use before intercourse twice weekly for 1 month. For a second month, the alternate treatment was given. Ratings were performed using the patient-rated Arizona Sexual Experiences Scale for females and the clinician-rated Sexual Function Questionnaire (SFQ-V1). Ten patients completed the study. On the five-item self-report Arizona, the item "How easily are you aroused?" was significantly improved on testosterone gel vs. placebo, P = 0.03. There were similar trends on the physician-rated SFQ-V1 "arousal-sensation" cluster. These preliminary results suggest that testosterone gel given prn before intercourse has effects on sexual arousal, and further research is needed to define dosage and time schedule to optimize this effect and determine its clinical relevance.

Testosterone Reduces Unconscious Fear but Not Consciously Experienced Anxiety: Implications for the Disorders of Fear and Anxiety

The fear-reducing properties of testosterone have been firmly established in animals but not in humans. However, human data on the relation between testosterone, fear, and anxiety have predominantly involved questionnaires that index cortically executed conscious appraisal of anxious mood. Animal studies, on the other hand, indicate that the effects of testosterone on motivation and emotion are of subcortical origin and of unconscious nature. Presently, it was hypothesized that a single testosterone administration to humans would reduce unconscious fear but not consciously experienced anxiety. In a placebo-controlled, double-blind crossover design, a single dose of testosterone (.5 mg) or placebo was administered to 16 healthy female volunteers. Afterward, a masked emotional Stroop task measured unconscious emotional responses to fearful faces, while multiple self-reports of mood indexed consciously experienced anxiety. As hypothesized, the habitual vigilant emotional response to the masked fearful face observed in the placebo condition was significantly reduced after testosterone was administered, while the self-reported measures of anxiety remained unaffected. These data provide the first direct evidence for fear-reducing properties of testosterone in humans. Furthermore, by dissociating specific aspects of fear and anxiety in humans, this outcome highlights that testosterone's effects on motivation and emotion concern the subcortical affective pathways of the brain.

Pharmacokinetics and Acute Safety of Inhaled Testosterone in Postmenopausal Women

This was a preliminary feasibility study to assess the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system in postmenopausal women. Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose of testosterone (0.1, 0.2, or 0.3 mg) by inhalation. Plasma concentrations of sex steroids were measured between 1 and 360 minutes. Pulmonary and cardiovascular adverse events were monitored. Inhaled testosterone produced a dose-dependent increase in plasma total and free testosterone. At the highest dose (0.3 mg), total and free testosterone increased from baseline (mean +/- SD, 0.6 +/- 0.3 nmol/L, 2.5 +/- 1.0 pmol/L) to maximum levels of 62.6 +/- 20.4 nmol/L (total) and 168.2 +/- 50.2 pmol/L(free), occurring 1 to 2 minutes after dosing. A 2-compartment model best described the free and total testosterone pharmacokinetic profile. Dihydrotestosterone levels were higher than baseline at 60 minutes (P < .0002). Estradiol did not vary, but sex hormone binding globulin and albumin fell. There were no adverse events related to the treatment. Administration of inhaled testosterone is safe and achieves a supraphysiologic "pulse" kinetic profile of total and free testosterone with a rapid return to pretreatment levels.

Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism

It is known that steroid hormones can affect neuronal susceptibility to different types of insults, including oxidative stress. Using an in vitro/ex vivo model, we have previously shown that cerebellar granule cells prepared from neonatal rats treated with a single dose of testosterone are less vulnerable to oxidative stress-induced cell death, via a mechanism involving an upregulation of the cellular antioxidant defenses. Whether the testosterone protective action on cerebellar granule cells was direct or indirect remained to be clarified. Therefore, in this study we have investigated the effects of in vitro testosterone treatment, to see whether it also protects cerebellar granule cells from oxidative stress-induced damage. Cerebellar granule cells treated with 10 −6 M testosterone for 48 h were found less susceptible to damage induced by 50 μM hydrogen peroxide, as shown by a 30% decrease in the number of cells with apoptotic morphology. The addition of the androgen receptor antagonist flutamide abolished the protective effect of testosterone, suggesting an androgen receptor-mediated mechanism. This hypothesis was further supported by the presence of the androgen receptor in cultured cerebellar granule cells. The activity of the antioxidant enzyme catalase was also measured, and a 2-fold increase was detected in the testosterone treated cells, but not in the cells co-treated with flutamide. The present results demonstrate that cerebellar granule cells treated in vitro with testosterone are protected from oxidative stress via a mechanism mediated by the androgen receptor. Similarly to what we observed after in vivo administration of testosterone, the potentiation of the antioxidant defences seems to play a major role in the protection afforded by testosterone.

Retinol-binding protein mRNA is induced by estrogen in the kidney but not in the liver.

Vitamin A is mobilized from the liver and transported in plasma as retinol bound to retinol-binding protein (RBP). In addition to the liver, several extrahepatic tissues including the kidney have been shown to contain RBP mRNA. A study was conducted to explore the role of sex hormones in the regulation of RBP mRNA levels in the kidney compared to those in the liver. Treatment of female rats with a single dose of testosterone or chronic treatment with testosterone had only a slight effect on the steady-state level of RBP mRNA in the kidney and the liver. However, treatment of male rats with estrogen caused an increase in the steady-state level of RBP mRNA in the kidney but not in the liver. A single injection of 17 beta-estradiol, either 1.0 or 0.1 micrograms/g body weight, resulted in a rapid rise in the level of RBP mRNA in the kidney which was maximal at 3-6 h (fivefold induction) after treatment. In addition, treatment of ovariectomized female rats with estrogen also resulted in a rapid rise in the accumulated level of RBP mRNA in the kidney while having no influence in the liver. Finally, studies using the anti-estrogen drug, hydroxytamoxifen, resulted in blockage of the estrogen-related induction of RBP mRNA in the kidney, suggesting that the induction of RBP mRNA in the kidney by estrogen may be mediated by the nuclear estrogen receptor. Taken together these data suggest that the regulation of RBP mRNA, levels in the liver and kidney, at least with respect to estrogen, is different.

Androgen induction of ornithine decarboxylase mRNA in mouse kidney as studied by complementary DNA.

To investigate the mechanisms by which androgens regulate ornithine decarboxylase (OrnDCase; L-ornithine carboxy-lyase, EC 4.1.1.17) in mouse kidney, a cDNA clone encoding OrnDCase mRNA was prepared. Purification of OrnDCase mRNA from kidneys of androgen-treated mice was accomplished by immunoadsorption of renal polysomes to a protein A-Sepharose column and enrichment for poly(A)-containing RNA by oligo(dT)-cellulose. Double-stranded cDNA synthesized from this mRNA was inserted into the Pst I site of plasmid pBR322 by using oligo(dG . dC)-tailing and was propagated in Escherichia coli. Plasmids containing cDNA sequences coding for OrnDCase were identified by differential colony hybridization, by radioimmunological detection of OrnDCase-like antigens in bacterial cultures, and by cell-free translation of hybrid-selected mRNA followed by immunoprecipitation with monospecific OrnDCase antiserum. A restriction endonuclease fragment of the selected plasmid DNA (pODC54) was labeled by nick-translation and used to study changes in OrnDCase mRNA concentration. After a single dose of testosterone, renal OrnDCase mRNA concentration increased as soon as 6 hr and peaked 24 hr after steroid injection, as measured by RNA blot hybridization. Continuous androgen treatment for 4 days resulted in a 10- to 20-fold increase in OrnDCase mRNA concentration in normal animals, but no induction of this mRNA was detected in mice that have an inherent defect of the androgen receptor (testicular feminization). These results indicate that androgens regulate OrnD-Case synthesis in mouse kidney, at least in part, by increasing OrnDCase mRNA accumulation.

STIMULATION OF NUCLEIC ACID AND PROTEIN SYNTHESIS IN THE EPIDIDYMIS AND ACCESSORY ORGANS OF THE RAT BY TESTOSTERONE

The effects of a single dose to testosterone on the content of DNA, RNA and protein and the incorporation of [3H]phenylalanine into protein in the epididymis, vas deferens and ventral prostate of the rat were studied. A single dose of testosterone did not increase the weights of the accessory organs but restored the incorporation of [3H]phenylalanine into proteins in the catput, corpus and cauda epididymides, vas deferens and ventral prostate to the normal level. Within 1 h of hormone administration, significant increases in the content of DNA, RNA and protein were noticed in the cauda epididymidis and ventral prostate. The catput and corpus epididymides and was deferens whoed decreasing order to responsiveness to testosterone. These data are discussed with respect to the relative responsiveness of these organs to reinitiation to their function by administration of a single dose of testosterone. The new protein(s) synthesized in response to hormonal stimulation associated with growth and secretory activity of the cells may be different from the new protein macromolecules synthesized after hormone withdrawal or inhibition of hormone action which are involved in autolytic processes.

Postneonatal testosterone treatment fails to alter hormonal regulation of body weight and food intake of female rats

Daily injections of testosterone propionate (2 mg/da) from 30–50 days of age failed to affect any of the aspects of food intake or body weight that have previously been shown to be altered by a single dose of testosterone during the first five days of postnatal life. Specifically, postneonatal testosterone did not: (1) increase body weight; (2) reduce the sensitivity of weight control mechanisms to estradiol; or, (3) enhance the sensitivity of these mechanisms to testosterone. These results support the position that the sensitivity of these regulatory mechanisms to gonadal hormones is organized prior to puberty.

Sex differences and hormonal control of histamine methyltransferase activity

Kidneys from male rats have twice as much histamine methyltransferase ( S-adenosylmethionine:histamine N-methyltransferase, EC 2.1.1.8) activity as kidneys from female rats. Estradiol and testosterone administration to intact males and females respectively does not affect the sex difference in enzyme activity. Castration reduces male activity; the effect of castration can be reversed by a single dose of testosterone. Oophorectomy does not affect female kidney histamine methyltransferase activity. A single injection of testosterone, however, elevates enzyme activity of oophorectomized females. In contrast to rats, the kidneys of female mice contain twice the activity of male kidneys. The sex difference in histamine methyltransferase activity of rat kidneys can explain the sex differences in urinary histamine excretion in rats.

Oestrus-inducing activity of testosterone in the ewe.

ON the basis of results obtained with testosterone administered, together with pregnant mare serum gonadotrophin, to anœstrous ewes Cole1 suggested that androgen may be responsible for the induction of œstrous behaviour in the sheep. Robinson2, however, has shown that œstrogen given following a period of progesterone priming will induce both behavioural and vaginal œstrus in spayed ewes, and it is probable that normal cyclic œstrous behaviour is due to an interaction of these two hormones. In the course of work on the interaction of several steroid hormones on behavioural and vaginal œstrus in spayed ewes, a preliminary trial showed that a single dose of testosterone or of testosterone propionate resulted in mating behaviour in a number of animals. Consequently, a factorial design test, using 72 spayed ewes, was conducted to examine this phenomenon and to define the nature of the apparent œstrous response. The variables introduced (with n = 12) were priming treatment (no progesterone or 10 mgm. per day for 12 days)3, and dose of androgen (1.0, 3.2 or 10.0 mgm.). The androgen was testosterone propionate. Sexual receptivity of the ewes was determined using 8 intact rams fitted with ‘Sire-sine’ harnesses and crayons4 and the vaginal response was determined by smears taken for four days following injection of androgen5. Results are presented in Table 1.