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Effect of testosterone administration on rates of ethanol elimination in hypogonadal patients.

Rates of ethanol elimination were determined in four hypogonadal subjects at one week and again at eight weeks after the administration of one dose of 200 mg of testosterone cypionate (Depo-testosterone). Ethanol elimination was unchanged in two patients, slightly decreased in one, and markedly increased in one patient at eight weeks as compared to one week after testosterone administration. In the three patients with little or no change in ethanol elimination, initial high levels of plasma-free testosterone, ranging from 445.0 to 3.8 ng/dl did not decrease to abnormally low levels, but ranged between 1.6 and 7.7 ng/dl (normal, 1.20-2.10 ng/dl). In the fourth patient, an increase in ethanol elimination from 86.6 to 107.4 mg/kg body weight/hr was associated with a decrease in plasma-free testosterone from a high level of 4.7 to 0.8 ng/dl. These results indicate that pharmacological plasma concentration of testosterone do not affect the rate of ethanol elimination. A suppressing effect of testosterone on rate of ethanol elimination may occur at levels of plasma-free testosterone which extend from abnormally low up into the normal physiologic range.

Adult↗

PubMed1991

An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis.

The study of testosterone is likely to be prominent in future epidemiological work on endocrine function and the clinical treatment of age-related diseases. Thus, understanding the hormonal changes involved in the normal male aging process will be critical. Using techniques of meta-analysis, the authors examined 88 published studies of the age-testosterone relation in men. These studies reported conflicting results: age-testosterone correlations ranged from -0.68 to +0.68. In cross-study comparisons, certain research design characteristics (e.g. time of day of blood sampling) and various sample characteristics (e.g. volunteers vs patients as subjects) were related to both mean testosterone level and the slope of the age-testosterone relation. For example, for subgroups of subjects that did not exclude ill men, the mean testosterone levels were low, and did not decline with age. Subgroups that included only healthy subjects, in contrast, had higher overall testosterone levels and showed a decline of testosterone with age. Implications of these results for design, analysis and reporting of future epidemiologic studies will be discussed. These results also illustrate the utility of meta-analysis for research with the aged.

Adult↗

PubMed1994

Comparison of testosterone metabolism in benign prostatic hyperplasia and human prostate cancer cell lines in vitro.

Pathways of testosterone metabolism in tissue slices and cell suspensions of human benign hyperplastic prostate (BPH) tissue and human prostate cancer cell lines (DU145, HPC-36M, PC-3/MA2 and LNCaP) were investigated. Thin layer chromatography analysis was used to identify the following tritiated metabolites: testosterone, 5 alpha-dihydrostestosterone (DHT), 5 alpha-androstane-3 alpha/3 beta-17 beta-diol (androstanediols), 4-androstene-3,17-dione (androstenedione) and 5 alpha-androstanedione. The predominant pathway for testosterone metabolism in BPH was via 5 alpha-reductase producing 5 alpha-dihydrotestosterone (71% and 75% total metabolites in slices and suspensions incubated for 24 h, respectively). The cancer cell lines DU145 and HPC-36M resembled BPH by metabolizing testosterone predominantly to DHT (68% and 82% total metabolites, respectively), although the rate of metabolism was much lower in the cell lines (0.099 and 0.05 pmol testosterone/mg protein/h in DU145 and HPC-36M) compared to the BPH cell suspensions (6.4 pmol testosterone/mg protein/h). In contrast, PC-3/MA2 contained high 17 beta-HSD activity forming large amounts of 4-androstene-3,17-dione (84% total metabolites), converting testosterone at a rate faster (12.8 pmol testosterone/mg protein/h) than the BPH cell suspensions. LNCaP rapidly converted testosterone exclusively to a glucuronide conjugate (7.4 pmol testosterone/mg protein/h), although after incubation with [3H]-4-androstene-3,17-dione, 5 alpha-reductase activity was demonstrated. LNCaP was the only cell line whose growth and colony-forming ability was stimulated by testosterone and DHT. BPH and all the cell lines tested had 5 alpha-reductase activity, but only the prostate tissue and the cell lines DU145 and HPC-36M converted testosterone predominantly to DHT.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1995

Arginine and ornithine metabolizing enzymes in testosterone-induced hypertrophic mouse kidney.

Administration of testosterone to female mice causes hypertrophy of their kidneys with spectacular induction of ornithine decarboxylase and significant increase in the level of putrescine. We tried to find out whether testosterone treatment affects also the renal activities of enzymes participating in the formation and utilization of ornithine, specifically arginase and ornithine aminotransferase, and whether they are dependent on putrescine level. Swiss, CFW, DBA2 or F1 (CFW x DBA2) female and male mice were injected with testosterone (125 mg/kg) or CB 3717 (100 mg/kg). DFMO was applied in the drinking water. The activities of the enzymes were determined 24 hr or 5 days after administration of CB 3717 or testosterone, respectively. Renal activities of ornithine decarboxylase (ODC), arginase and ornithine aminotransferase (OAT) were found to be sex-differentiated. The highest activity of ODC was characteristic for the kidneys of males, whereas those of arginase and OAT for the kidneys of females. In the kidneys of testosterone-treated female mice a decrease (50%) of OAT, and a significant increase of arginase activities (up to 200%), were observed. In the males these changes were less pronounced. DFMO, which completely inhibited the activity of renal ODC, did not influence significantly the testosterone-induced arginase and the testosterone-decreased OAT. Arginase and OAT, in contrast to ODC, were not changed in CB 3717-induced hyperplastic kidney. The study showed testosterone-induced differential changes in the activity of two enzymes involved in ornithine biosynthesis and catabolism which accompanied ODC induction in female mouse kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Assessment of urine and fecal testosterone metabolite excretion in Chinchilla lanigera males.

Endemic chinchilla (Chinchilla spp.) populations are nearly extinct in the wild (South America). In captive animals (Chinchilla lanigera and C. brevicaudata), reproduction is characterized by poor fertility and limited by seasonal breeding patterns. Techniques applied for studying male reproductive physiology in these species are often invasive and stressful (i.e. repeated blood sampling for sexual steroids analysis). To evaluate endocrine testicular function, the present experiments were designed to (a) determine the main route of testosterone excretion (14C-testosterone infusion in four males); (b) validate urine and fecal testosterone metabolite measurements (HPLC was used to separate metabolites and immunoreactivity was assessed in all metabolites using a commercial testosterone radioimmunoassay, and parallelism, accuracy and precision tests were conducted to validate the immunoassay); and (c) investigate the biological relevance of the techniques applied (quantification of testosterone metabolite excretion into urine and feces from five males injected with hCG and comparison between 10 males and 10 females). Radiolabelled metabolites of 14C-testosterone were excreted, 84.7+/-4.2 % in urine and 15.2+/-3.9 % in feces. A total of 82.7+/-4.2% of urinary and 45.7+/-13.6% of fecal radioactivity was excreted over the first 24 h period post-infusion (metabolite concentration peaked at 8.2+/-2.5 h and 22.0+/-7.0 h, respectively). Several urinary and fecal androgen metabolites were separated by HPLC but only fecal metabolites were associated with native testosterone; however, there was immunoreactivity in more than one metabolite derived from 14C-testosterone. After hCG administration, an increase in androgen metabolite excretion was observed (p<0.05). Males excreted greater amounts daily of urinary androgen metabolites as compared with females (p<0.05); this difference was not evident in feces. Results of the present study indicate that the procedure used is a reliable and non-invasive method to repeatedly monitor variations in testicular endocrine activity in this species. It can be a useful tool that would help ensure the survival of the wild populations as well as to provide the basis for a more efficient use by the fur industry.

Androgens↗

PubMed2005

Testosterone conjugating activities in invertebrates: are they targets for endocrine disruptors?

Testosterone conjugation activities, microsomal acyltransferases and cytosolic sulfotransferases, were investigated in three invertebrate species, the gastropod Marisa cornuarietis, the amphipod Hyalella azteca, and the echinoderm Paracentrotus lividus. The goals of the study were to characterize steroid conjugation pathways in different invertebrate phyla and to assess the susceptibility of those processes to disruption by environmental chemicals. All three species exhibited palmitoyl-CoA: testosterone acyltransferase activity (ATAT) in the range of 100-510 pmol/min/mg protein. Despite similarities in specific activities, kinetic studies indicated that ATAT had a higher affinity for testosterone but a lower V(max) in M. cornuarietis than in P. lividus, and intermediate values were found for H. azteca. In contrast, the activity of testosterone sulfotransferase (SULT) was rather low (0.05-0.18 pmol/min/mg protein) in M. cornuarietis and H. azteca. The low activity precluded kinetic analyses and inhibition studies with these species. P. lividus digestive tube displayed high SULT activity (50-170 pmol/min/mg protein) at moderate testosterone concentrations, but was inhibited at high testosterone concentrations. The interference of model pollutants (triphenyltin (TPT), tributyltin (TBT), and fenarimol) with these conjugation pathways was investigated in vitro. Both TPT and TBT (100 microM) inhibited ATAT in P. lividus (68 and 42% inhibition, respectively), and appeared to act as non-competitive inhibitors. ATAT activity in M. cornuarietis was less affected by organotins, and a significant inhibition (20% inhibition) was detected only with TBT. Fenarimol (100 microM) did not affect ATAT in any of the species tested. Sulfation of testosterone was suppressed by the organotins as well as fenarimol when using cytosolic preparations from P. lividus. These results demonstrated the existence of interphyla differences in testosterone conjugation, and revealed that these processes can serve as targets for endocrine disrupting chemicals.

Acyltransferases↗

PubMed2004

Combined effect of testosterone and apocynin on nitric oxide and superoxide production in PMA-differentiated THP-1 cells.

Human inducible nitric oxide synthase (iNOS) is most readily observed in macrophages from patients with inflammatory diseases like atherosclerosis. The aim of the present study was to find out the combined effect of male sex hormone; testosterone and apocynin (NADPH oxidase inhibitor) on cytokine-induced iNOS production. THP-1 cells were differentiated into macrophages by phorbol myristate acetate (PMA). Expression of iNOS was induced by the addition of cytokine mixture? Testosterone was added at different concentrations (10(-6)-10(-12) M) with apocynin (1 mM). Testosterone (10(-8), 10(-10) M) inhibited NOx production in cytokine-added THP-1 cells which was further confirmed by quantikine assay of iNOS protein and RT-PCR analysis. Testosterone treatment decreased 40% of superoxide anion production. Testosterone showed inhibition of NADPH oxidase, especially expression of p67phox and p47phox (cytosol subunits). Addition of testosterone with apocynin further decreased the expression of p67phox and p47phox subunits of NADPH oxidase. The findings of the present study suggest that, testosterone; the male androgen plays an important role in the prevention of atherogenesis. Even though apocynin does not have any role on NO production, addition of apocynin together with testosterone is effective in suppressing iNOS activity.

Acetophenones↗

PubMed2005

Testosterone reduces unconscious fear but not consciously experienced anxiety: implications for the disorders of fear and anxiety.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed2006

Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents.

BACKGROUND: In animals, strong evidence exists for an association between testosterone and aggression. In humans, and particularly in children and adolescents, findings have been less consistent. Previous research has suggested that this may partly be due to moderating effects of other factors, e.g., hormones. This study aims to investigate the moderating effect of cortisol on the relationship between testosterone and subtypes of aggression in delinquent male adolescents. METHODS: Participants were 103 boys (mean age 13.7) referred to a delinquency diversion program. Testosterone and cortisol levels were determined from saliva samples collected during resting conditions and related to self-report scores on overt and covert aggression. RESULTS: Linear regression analyses revealed a significant interaction between cortisol and testosterone in relation to overt aggression, with a significant positive relationship between testosterone and overt aggression in subjects with low cortisol levels but not in subjects with high cortisol levels. Using the same model for covert aggression, no significant effects of testosterone, cortisol, or testosterone x cortisol interaction were found. CONCLUSIONS: These results indicate a moderating effect of cortisol on the relationship between testosterone and overt aggression in delinquent male adolescents. Implications and directions for future research are discussed.

Adolescent↗

PubMed2005

Exogenous testosterone modulates tumor necrosis factor-alpha and acute phase protein responses to repeated endotoxin challenge in steers.

Clinical responses to some disease agents differ between sexes and this dimorphism has been attributed to the immunomodulating effects of steroid hormones. Our objective was to determine in steers the effect of testosterone on circulating concentrations of immune response mediators (tumor necrosis factor-alpha, TNF-alpha; serum amyloid-A, SAA; haptoglobin, HG; xanthine oxidase, XO; nitric oxide, NO) after two consecutive endotoxin challenges (LPS1 and LPS2, 5 days apart; 0.25 microg/kg BW). Sixteen crossbred steers (328+/-6 kg) were assigned to control (CON, n=8) or testosterone cypionate treatment (TES, n=8; 100 mg/m2 body surface; i.m. injection 12 and 2 days before LPS1). The response to LPS was calculated as area under the timexconcentration curve (AUC) for the parameter measured. After LPS1, TNF-alpha AUC was greater in TES than CON (P<0.05). Plasma HG and SAA concentrations increased (P<0.01) after LPS1 and LPS2. In all steers SAA AUC was greater after LPS1 than LPS2 (P<0.01) but the response was augmented over CON with testosterone treatment (P<0.05). HG response to LPS1 within 24 h was not affected by testosterone. However, 5 days after LPS1 mean plasma HG concentration remained higher in TES than CON (P<0.01). HG response to LPS2 was greater in TES than CON (P<0.01). Plasma nitrate+nitrite concentration (NO production marker) and XO activity increased after each LPS challenge but responses were not affected by testosterone treatment. Results indicate that the presence of circulating testosterone increases the magnitude of the TNF-alpha response to LPS challenge as well as the subsequent increases in acute phase proteins (APP). Effects of testosterone on increases in TNF-alpha and APP may underlie a differential presentation of disease symptoms between sexes or between steers and bulls. The data also suggest a role for testosterone in the development of tolerance to repeated immune challenge through its effect on the increased magnitude and duration of HG response.

Acute-Phase Proteins↗

PubMed2006

The effect of testosterone on insulin sensitivity in men with heart failure.

Resistance to insulin occurs in chronic heart failure (CHF) and is related to prognosis. Studies of testosterone in non-(CHF) males suggest that physiological testosterone therapy improves insulin sensitivity. This was a single-blind placebo controlled crossover trial to determine the effect of testosterone replacement on insulin sensitivity in 13 men with moderate to severe CHF (ejection fraction 30.5+/-1.3). The primary outcome was the homeostatic model index (HOMA-IR) of fasting insulin sensitivity and secondary outcomes were body composition as measured by bioelectrical impedance and glucose tolerance to a standard 75 g oral glucose load. Analysis was performed on the delta values with the treatment effect of placebo compared with that of testosterone. At baseline HOMA-IR correlated with measures of body fat [% fat mass (rP=0.84, p=0.0001) and body mass index (rP=0.79, p=0.01)] but not with CHF severity. Testosterone reduced HOMA-IR (-1.9+/-0.8, p=0.03) indicating improved fasting insulin sensitivity. Testosterone also increased total mass (+1.5+/-0.5 kg, p=0.008) and decreased body fat (-0.8+/-0.3%, p=0.02). Testosterone improves fasting insulin sensitivity in men with CHF and may also increase lean body mass, these data suggest a favourable effect of testosterone on an important metabolic component of CHF.

Aged↗

PubMed2006

Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences.

INTRODUCTION: Erectile dysfunction (ED) and decline of testosterone levels are frequently observed with age and also in illnesses with a common basis of endothelial damage. OBJECTIVES: To review molecular mechanisms underlying androgen action upon its receptor and phosphodiesterase type 5 (PDE5) expression and regulation by testosterone in cavernous tissue and their clinical implication in the treatment of ED refractory to PDE5 inhibitors (PDE5-Is). METHODS: From January 2003 to May 2006 [corrected] we performed an extensive, unsystematic MEDLINE literature search reviewing relevant data on basic and clinical studies regarding the efficacy of combination therapies. RESULTS: Most trials using testosterone alone for treatment of ED in hypogonadal men suffer from methodologic problems and report inconsistent results, but overall the trials suggest that testosterone is superior to placebo. Orally effective PDE5-Is, such as sildenafil, tadalafil, or vardenafil, may be ineffective depending on the demonstration of testosterone regulation of PDE5 expression in human corpus cavernous, and their efficacy may be enhanced by testosterone adjunction whenever necessary. CONCLUSIONS: Screening for hypogonadism in all men with ED is necessary to identify men with severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment. Identification of threshold values for testosterone supplementation to appropriately benefit from PDE5-Is failure may improve clinical management of unresponsive patients with minimization of unwanted effects.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2006

Effects of treatment with testosterone alone or in combination with estrogen on insulin sensitivity in postmenopausal women.

OBJECTIVE: Little is known about metabolic effects of testosterone treatment in postmenopausal women. The aim of the study was to compare the treatment effects of testosterone, estrogen, and testosterone plus estrogen on insulin sensitivities, body compositions, and lipid profiles in healthy postmenopausal women. DESIGN: An open, randomized clinical study with parallel group comparison. SETTING: Women's health clinical research unit at a university hospital. PATIENT(S): Sixty-three naturally postmenopausal women participated in the study. INTERVENTION(S): The participants were randomly assigned to 3 months of treatment with testosterone undecanoate (40 mg every second day), estradiol valerate (2 mg daily), or the combination of both. MAIN OUTCOME MEASURE(S): Insulin sensitivity assessed by euglycemic hyperinsulinemic clamp, body composition, and serum lipids. RESULT(S): Insulin-induced glucose disposal was reduced by approximately 20% after treatment with testosterone alone, and after the combined treatment, but not by estrogen alone. Body weight, but not total body fat, increased significantly by about 1 kg in all groups. Lean body mass was significantly increased in the group of combined treatment and tended to be increased by testosterone alone. High-density lipoprotein (HDL)-cholesterol decreased significantly by testosterone treatment. In contrast, HDL-cholesterol increased, whereas low-density lipoprotein (LDL)-cholesterol and lipoprotein-(a) [Lp(a)] decreased with estradiol treatment. CONCLUSION(S): We conclude that 3 months of treatment with testosterone undecanoate in postmenopausal women induces insulin resistance and an adverse serum lipid profile but may increase lean body mass.

Adult↗

PubMed2005

The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting.

OBJECTIVE: Inflammation markers can predict restenosis after successful intracoronary stenting. There is evidence that testosterone suppresses the expression of the inflammatory cytokines. We hypothesized that testosterone therapy after coronary stenting can reduce the inflammation markers. METHODS: We selected 41 men with coronary artery disease who underwent successful stent implantation for a >70% diameter stenosis of a major coronary artery. Patients, who had stable angina and positive exercise test results, were recruited after diagnostic coronary angiography. Twenty-five men were treated with 3 doses of i.m. testosterone administration once a week for 3 weeks following diagnostic angiography. Sixteen patients were recruited as a control group and they received standard therapy. First venous blood samples were obtained after angiography. Stents were implanted 3 weeks after diagnostic angiography. Second venous blood samples were taken 24 h after the coronary stenting. RESULTS: Baseline biochemical or hematological parameters were similar between the control and treatment groups. After coronary stenting, free testosterone, total testosterone, and sex hormone binding globulin were significantly elevated in the testosterone group (P<0.0001, P<0.0001 and P=0.02; respectively). After coronary stent implantation, there was a significant increase in IL-6 and CRP levels in the control group only (P=0.02 and P=0.038), while TNF-alpha levels were increased significantly in both groups (P=0.016 and P=0.014; respectively). Statistical analysis revealed that testosterone treatment prior to stent implantation attenuated IL-6 and hs-CRP levels significantly (P=0.042 and P=0.043; respectively). CONCLUSIONS: The present study shows that 3 weeks testosterone treatment prior to intracoronary stenting results in a significant suppression in hs-CRP and IL-6 levels after the stent implantation.

Adult↗

PubMed2006

Testosterone improves motor function in Parkinson's disease.

In Parkinson's disease (PD) there is increasing evidence that sex steroids such as estradiol and testosterone modulate, either as a positive or negative effect, the clinical expression of a variety of movement disorders involving the nigrostriatum. Testosterone deficiency is common in the older male population and has an increased prevalence in parkinsonian patients. Testosterone therapy has been shown to improve the non-motor symptoms of PD but evidence for a direct effect of testosterone on motor symptoms is lacking. This case report demonstrates a significant improvement in the resting tremor and fine motor control after testosterone administration in a parkinsonian patient with testosterone deficiency (1 nmol/L). Motor symptom change was shown by serial assessment of the patient's handwriting, self-reporting using the Unified Parkinson's Disease Rating Scale and measurement of resting tremor amplitude by an accelerometer. The improvement in motor symptoms correlated with serum testosterone levels. The use of testosterone replacement in those men with decreased levels may improve the motor symptoms as well as increase general wellbeing.

Aged, 80 and over↗

PubMed2006

Effects of testosterone on hormonal content and calcium-dependent basal secretion in female rat pituitary cells.

In vivo and in vitro effects of elevated androgens on agonist-induced gonadotropin secretion have been addressed previously. Here we investigated the effects of testosterone on hormonal content and basal (in the absence of agonists) hormone release in pituitary lactotrophs, somatotrophs and gonadotrophs from female rats. Furthermore we tested the hypothesis that testosterone action is dependent on the pattern of spontaneous and Bay K 8644 (a L-type calcium channel agonist) -induced calcium signalling. Mixed anterior pituitary cells were cultured in steroid containing or depleted media, and testosterone (1pM to 10nM) was added for 48h. Cells were studied for their spontaneous and Bay K 8644-induced calcium signalling pattern and total hormone levels (release and hormonal content). In lactotrophs, somatotrophs and gonadotrophs testosterone did not affect the pattern of spontaneous calcium signalling. Bay K 8644-induced calcium signalling and hormone release were not affected by testosterone. In both steroid-depleted and -containing medium, testosterone inhibited prolactin (PRL), luteinizing hormone (LH) and growth hormone (GH) cellular content and release in a dose-dependent manner, with IC(50)s in a sub-nanomolar concentration range. These results indicate that testosterone inhibits basal hormone release from lactotrophs, somatotrophs and gonadotrophs without affecting intracellular calcium signalling. This action of testosterone is not dependent on the presence of other steroid hormones.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2005

Effects of testosterone on muscarinic acetylcholine receptors in the rat epididymis.

The effect of testosterone on the expression of muscarinic acetylcholine receptor (mAChR) subtypes was studied in the rat epididymis, at mRNA and protein level. The rat androgen status was monitored by measuring plasma testosterone level and caput and cauda epididymis wet weight. Ribonuclease protection assay (RPA) and [3H]quinuclidinyl benzilate ([3H]QNB) binding assay were performed in the caput and cauda epididymis from control (50-day old), castrated, castrated and treated with testosterone and sexually immature (30-day old) rats. The expression of each mAChR transcript subtype differed depending on the epididymal region analyzed and rat testosterone and/or testicular factors status. In control rats, RPA showed the presence of mRNA for M1, M2 and M3 mAChR in the caput and cauda epididymis. The abundance of m2 and m3 transcripts in the cauda was higher than that in the caput epididymis. Low amount of m1 transcript was observed in both regions. Orchidectomy increased m1 mRNA amount in the caput and cauda epididymis when compared to control rats, an effect slightly modified by testosterone replacement. Although orchidectomy down-regulated the level of m2 transcript in both epididymal regions, castration significantly increased m3 mRNA amount in the caput region. These effects on m2 and m3 transcripts were prevented by testosterone replacement to castrated rats. Similar abundance of m3 transcript, however, was detected in the cauda epididymis of all experimental group tested. [3H]QNB binding studies revealed that orchidectomy down-regulated the number of mAChR detected in both epididymal regions, an effect also prevented by testosterone replacement. Thus, testosterone and/or testicular factors may play a role in the regulation of mAChR expression in the rat epididymis.

Animals↗

PubMed2004

Effect of testosterone supplementation on sexual function in hypogonadal men with erectile dysfunction.

OBJECTIVES: To evaluate the impact of normalization of testosterone levels in men with documented hypogonadism and erectile dysfunction on erectile function and sexual satisfaction. Although the data support the role of testosterone in the preservation of libido and nocturnal erectile function, the evidence supporting the use of testosterone supplementation in hypogonadal men with erectile dysfunction is weak. METHODS: This analysis used two validated questionnaires, the International Index of Erectile Function and the Erectile Dysfunction Inventory of Treatment Satisfaction, in a serial fashion at baseline (before treatment) and 1, 3, and 6 months after the achievement of a therapeutic testosterone level. RESULTS: A total of 32 men met all inclusion criteria; 69% of men achieved therapeutic testosterone levels using transdermal testosterone gel, 19% required a transdermal patch, and 12% required intramuscular delivery. Statistical significance was reached for the difference between the baseline and 1-month International Index of Erectile Function erectile function domain score and all post-treatment International Index of Erectile Function libido scores. A steady decrease occurred in the Erectile Dysfunction Inventory of Treatment Satisfaction scores from the 1 to 6-month values that reached statistical significance. CONCLUSIONS: In men with documented hypogonadism and erectile dysfunction, normalization of serum testosterone levels was associated with only short-term improvement in erectile function and sexual satisfaction. The use of testosterone supplementation in this population for the treatment of erectile dysfunction is questionable.

Administration, Cutaneous↗