Administration Of Testosterone Enanthate Research Articles

Allometric Scaling of Testosterone Enanthate Pharmacokinetics to Adolescent Hypogonadal Males (IM and SC Administration).

Intramuscular (IM) testosterone enanthate (TE) and testosterone pellets were US Food and Drug Administration approved before 1962 for pediatric use but not studied in controlled trials in adolescents. An analysis using nonlinear mixed effect (NLME) modeling was designed to evaluate the adult pharmacokinetics (PK) of subcutaneous (SC) and IM TE. This model was used to simulate SC and IM TE administration in adolescents of different weight groups. Data from adult male patients in a phase 2 trial were used to characterize the PK of TE using population PK modeling for SC and IM administration: Allometry was used to scale PK parameters from the adult model to simulate adolescent (aged 12 to < 18 years) serum testosterone levels at body weights of 30, 40, 50, and 60 kg after weekly, every-other-week (EOW), and monthly SC and IM administration of 12.5, 25, 50, 75, and 100 mg TE regimens. The final data set included 714 samples from 15 patients receiving 100 mg SC TE and 123 samples from 10 patients receiving 200 mg IM TE. In simulated populations, average serum concentration SC:IM ratios were 0.783, 0.776, and 0.757 at steady state for weekly, EOW, and monthly dosing groups, respectively. Simulated regimens of 12.5 mg SC TE monthly produced serum testosterone levels representative of early puberty and simulated pubertal stage progression following multiple subsequent testosterone dose increases. SC TE administration achieved a testosterone exposure-response relationship similar to IM TE in simulated adolescent hypogonadal males, which may reduce size of fluctuations in serum T and related symptoms.

Metabolomics of testosterone enanthate administration during severe-energy deficit

IntroductionTestosterone administration attenuates reductions in total body mass and lean mass during severe energy deficit (SED).ObjectivesThis study examined the effects of testosterone administration on the serum metabolome during SED.MethodsIn a double-blind, placebo-controlled clinical trial, non-obese men were randomized to receive 200-mg testosterone enanthate/wk (TEST) (n = 24) or placebo (PLA) (n = 26) during a 28-d inpatient, severe exercise- and diet-induced energy deficit. This study consisted of three consecutive phases. Participants were free-living and provided a eucaloric diet for 14-d during Phase 1. During Phase 2, participants were admitted to an inpatient unit, randomized to receive testosterone or placebo, and underwent SED for 28-d. During Phase 3, participants returned to their pre-study diet and physical activity habits. Untargeted metabolite profiling was conducted on serum samples collected during each phase. Body composition was measured using dual-energy X-ray absorptiometry after 11-d of Phase 1 and after 25-d of Phase 2 to determine changes in fat and lean mass.ResultsTEST had higher (Benjamini–Hochberg adjusted, q < 0.05) androgenic steroid and acylcarnitine, and lower (q < 0.05) amino acid metabolites after SED compared to PLA. Metabolomic differences were reversed by Phase 3. Changes in lean mass were associated (Bonferroni-adjusted, p < 0.05) with changes in androgenic steroid metabolites (r = 0.42–0.70), acylcarnitines (r = 0.37–0.44), and amino acid metabolites (r = − 0.36–− 0.37). Changes in fat mass were associated (p < 0.05) with changes in acylcarnitines (r = − 0.46–− 0.49) and changes in urea cycle metabolites (r = 0.60–0.62).ConclusionTestosterone administration altered androgenic steroid, acylcarnitine, and amino acid metabolites, which were associated with changes in body composition during SED.

Evaluation of the effect of nicotine and O-acetyl-L-carnitine on testosterone-induced spatial learning impairment in Morris water maze and assessment of protein markers

The hippocampus has an essential role in learning and memory and is a target for androgen actions. Thus, the effect of testosterone and its metabolites on learning and memory has attracted researchers' attention.The present study aimed to identify the effects of four-day bilateral intra-hippocampal infusion of nicotine and o-Acetyl L-carnitine alone and in combination on testosterone enanthate (TE)-induced spatial learning deficits using Morris water maze (MWM). The expression of CREB, pCREB and BDNF proteins was quantified using western blots.We observed that bilateral intra-hippocampal infusion of TE significantly impaired spatial learning and a significant decrease in CREB, pCREB and BDNF protein markers compared to a control group that did not receive TE. In addition, administration of O-acetyl L-carnitine and/or nicotine reversed TE-induced spatial learning impairment in behavioural and molecular assessments.Thus, our findings suggest that administration of TE in the hippocampus of adult male rats impairs memory function, possibly via down-regulation of cAMP/PKA-CREB-BDNF signaling pathway.

MP35-20 ANDROGEN REPLACEMENT THERAPY FOR CANCER-RELATED SYMPTOMS IN MALE ADVANCED CANCER PATIENTS

You have accessJournal of UrologyCME1 May 2022MP35-20 ANDROGEN REPLACEMENT THERAPY FOR CANCER-RELATED SYMPTOMS IN MALE ADVANCED CANCER PATIENTS Kouji Izumi, and Atshushi Mizokami Kouji IzumiKouji Izumi More articles by this author , and Atshushi MizokamiAtshushi Mizokami More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002589.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cachexia associated with advanced cancer displays a variety of physical and psychological symptoms. Hypogonadism associated with cancer is reported to cause cachexia and these symptoms. The purpose of this study was to evaluate whether androgen replacement therapy can improve cancer-related symptoms in male advanced cancer patients. METHODS: An investigator-initiated, prospective, randomized controlled study was conducted in male advanced cancer patients. Patients with low serum testosterone levels were randomly assigned to the control group or the testosterone enanthate administration group (testosterone group). Differences in quality of life questionnaires and cachexia-related serum protein levels between groups were assessed to clarify whether testosterone enanthate can improve cachexia. RESULTS: In this study, 41 and 40 patients were randomized in the control and testosterone groups, respectively. Although no significant differences in the change of subscales and total scores in Functional Assessment of Anorexia/Cachexia Treatment were noted from the baseline between the two groups, the testosterone group showed a significantly better change in the “unhappiness” item of the Edmonton Symptom Assessment System at week 12 compared to baseline versus the control group (−1.4 and 0.0 points, respectively; mean, p=0.007). The testosterone group significantly inhibited the change in serum tumor necrotic factor-α level at week 12 from the baseline compared with the control group (+0.4 and +0.1 pg/mL, respectively; mean, p=0.005). CONCLUSIONS: Testosterone enanthate did not improve most of the items in health-related quality of life questionnaires but significantly induced a better change in the “unhappiness” item of the health-related quality of life at week 12 compared with the control, associated with the inhibition of the deterioration of serum TNF-α levels in male advanced cancer patients. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e595 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kouji Izumi More articles by this author Atshushi Mizokami More articles by this author Expand All Advertisement PDF DownloadLoading ...

EP089: 47, XXY: Mathematic capabilities and the impact of Hormonal Replacement Treatment (HRT)

47,XXY, also known as Klinefelter syndrome, is the most frequently occurring sex chromosome aneuploidy with an incidence of approximately 1:600 live male births. It is medically characterized by hypogonadism, azoospermia, micropenis, and tall stature. The neurodevelopmental phenotype includes speech and motor delay, language-based learning disabilities, executive dysfunction, reduced expressive language, and increased risk for anxiety. Academic achievement for reading and writing has been shown to be largely impacted in school-aged males with 47,XXY. For example, an early study reported an increased risk for dyslexia due to challenges in processing speed, language, and memory despite intact intelligence quotients (IQ). Further, a more recent study revealed mastering school curricula often requires special education intervention. Math-related achievement, however, is a component of the 47,XXY neurodevelopmental profile that has been largely overlooked. There are a few studies that have indirectly demonstrated reduced arithmetic capabilities in 47,XXY compared to neurotypical controls, but none have delineated the specific mathematical skillsets that are impacted by a supernumerary X. Thus, we aimed to expand on this paucity of literature by comprehensively examining mathematical skills in school-aged males with 47,XXY. Further, though consistent in symptomatology, the phenotype is widely variable in severity depending on factors such as timing of diagnosis, family learning disability (FLD), and access to treatment. The potential profound benefits of Hormonal Replacement Therapy (HRT), or the administration of testosterone enanthate, on neurodevelopmental challenges in males with 47,XXY have been well-documented. In school-aged males specifically, HRT has been associated with increased expressive ability, working memory, and executive function. Therefore, we also explored the potential effect of HRT on mathematical achievement in our cohort. Our cohort consisted of 111 prenatally diagnosed school-aged males with 47,XXY (CA: 133 months). Those who were postnatally diagnosed, presented with mosaicism or other copy number variants (CNVs), or had a positive family history of learning disabilities were excluded from this study. An in-depth history was recorded in which HRT statuses were obtained. All participants were assessed by their respective pediatric endocrinologists who determined HRT administration. Study participants completed the KeyMath-3 and Wechsler Intelligence Scale for Children, 4th or 5th Edition (WISC-IV/V). For the purpose of this study, only the Arithmetic subtest was used. To investigate the potential effect of HRT on mathematical skills, participants were bifurcated into untreated (No-T, N=22) and treated (T, N=89) groups. A two-tailed t-test determined statistically significant group differences on each assessment, if any. Participants showed no significant differences on any demographic scales including maternal and paternal age (p=0.97 and p=0.19, respectively), birthweight (p=0.90), delivery method (p=0.79), race (p=0.55), or socioeconomic status (p=0.88). Significant effect of treatment was observed on several mathematical subtests of the KeyMath-3 including Numeration (p=0.005), Algebra (p=0.03), Geometry (p=0.03), Mental Computation and Estimation (p=0.005), Multiplication and Division (p=0.03), and Foundations of Problem Solving (p=0.05). The T group also demonstrated significantly increased scores on the Operations (M=115.28, p=0.004) and Total Test (M=116.38, p=0.01) areas compared to the No-T group (M=103.65 and M=106.62, respectively). Additionally, while not statistically significant, the T group exhibited higher average scores on the rest of the subtests and areas including Measurement (M=12.88), Data Analysis (M=12.40), Basic Concepts (M=117.03), Addition and Subtraction (M=12.55), Applied Problem Solving (M=12.21), and Applications (M=112.61) compared to the No-T group (M=11.95, M=11.55, M=110.90, M=11.11, M=11.18, and M=106.29, respectively). On the WISC-IV/V Arithmetic subtest, the T group (M=115.28, SD=2.72) did demonstrate a higher mean with less variability than the No-T group (M=115.28, SD=3.67), though not quite statistically significant (p=0.06). Our findings are the first to shed light on the mathematical profile of treated and untreated school-aged males with 47,XXY. Our observations of reduced scores in the untreated group corroborates a past study describing a proposed susceptibility to mathematics disability in this population. Other previous studies have documented the similar cognitive mechanisms shared between math disability and reading disability, as well as the increased risk of comorbidity. However, the neurodevelopmental profile for males with 47,XXY is usually restricted to only include language-based learning disability. Our findings suggest the phenotype may be expanded to include all learning disabilities, including those math-related.

Androgen replacement therapy for cancer-related symptoms in male: result of prospective randomized trial (ARTFORM study).

BackgroundHypogonadism associated with cancer is reported to cause cachexia and a variety of physical and psychological symptoms. This study aims to evaluate whether androgen replacement therapy can improve cancer‐related symptoms in male advanced cancer patients.MethodsAn investigator‐initiated, prospective, and randomized controlled study was conducted. Patients with low serum testosterone levels (total or free testosterone levels were <2.31 ng/mL or <11.8 pg/mL, respectively) were randomly assigned to the control or testosterone enanthate administration (testosterone group) groups. Testosterone enanthate was injected into the muscle tissue at a dose of 250 mg every 4 weeks (baseline, week 4, and week 8). Differences in quality of life questionnaires and cachexia‐related serum protein levels between groups were assessed.ResultsThis study enrolled and randomized 106 and 81 patients, respectively. Moreover, 41 and 40 patients were in the control and testosterone groups, respectively. Although no significant differences in the change of subscales and total scores in Functional Assessment of Anorexia/Cachexia Treatment were noted from the baseline between the two groups, the testosterone group showed a significantly better change in the ‘unhappiness’ item of the Edmonton Symptom Assessment System at week 12 compared with baseline versus the control group (−1.4 and 0.0 points, respectively; mean, P = 0.007). No significant differences exist in the change of serum interleukin‐6 and insulin‐like growth factor‐1 levels at week 12 from the baseline between the control and testosterone groups. Consequently, the testosterone group significantly inhibited the change in serum tumour necrotic factor‐α level at week 12 from the baseline compared with the control group (+0.4 and +0.1 pg/mL, respectively; mean, P = 0.005).ConclusionsAlthough testosterone enanthate did not improve most of the items in health‐related quality of life questionnaires, testosterone enanthate induced a significantly better change in the ‘unhappiness’ item at week 12 compared with the control. Testosterone enanthate may be a potential treatment option for male advanced cancer patients.

Cardiovascular Properties of the Androgen-Induced PCOS Model in Rats: The Role of Oxidative Stress.

Polycystic ovary syndrome (PCOS) is a multifaced reproductive endocrinopathy affecting 6-20% of women of childbearing age. It was previously shown that women with PCOS have an increased risk of cardiovascular (CV) diseases. The aim of this study was to evaluate the cardiodynamic parameters of isolated rats' hearts, blood pressure levels, and histomorphological changes in the heart tissue following the androgen-induced PCOS model in rats and the role of oxidative stress in the development of these CV properties of PCOS. 21-day-old female rats (n = 12) were divided into control and PCOS groups. PCOS was induced by administration of testosterone enanthate (1 mg/kg BW, daily) during 35 days. During the autoregulation protocol (40-120 mmHg) on the Langendorff apparatus, ex vivo cardiodynamic parameters of retrogradely perfused hearts showed enhanced contractile function and increased lusitropic effects in the left ventricle (LV) in PCOS rats. Systolic and diastolic pressures in LV were elevated at all perfusion pressure values. Systemic arterial systolic blood pressure showed borderline elevation, while mean arterial blood pressure was significantly higher in PCOS rats. Histological evaluation of heart tissue depicted hypertrophic (8.3%) alterations in LV cardiomyocytes and increase (7.3%) in LV wall thickness. Oxidative stress parameters were altered in systemic circulation, coronary venous effluent (CVE), and heart tissue. Levels of superoxide dismutase and reduced glutathione were decreased in blood and heart tissue, while catalase activity was not altered. Degree of lipid peroxidation was increased in circulation as well as heart tissue. Increased levels of O2− in CVE indicated the cardiotoxic effects in the rat PCOS model. The mentioned alterations of oxidative stress parameters in the blood, CVE, and heart could be recommended as potential contributors underlying the development of CV risk in PCOS women.

Androgen Treatment in Adolescent Males With Hypogonadism.

During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic–pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.

Effect of testosterone on penile and urethral development in Black Bengal goat

Background: Testosterone is important for proper development, growth and functional maintenance of urogenital organs in animals.The objective of this study was to determine the effect of testosterone on penile and urethral development in Black Bengal goats. Methods: Nine male Black Bengal goats (4 months old) were divided into three groups (n=3); Group-A: goats with testosterone deficient (castrated at 4 months of age), Group-B: control and Group-C: goats with excess testosterone (exogenous IM administration of testosterone enanthate; @ 125 mg/goat weekly for a period of 2 months). After getting puberty (8 months of age), goats were slaughtered and penises collected with maximum precaution and hygienic practices, and morphometric examinations performed extensively. Results: The penis of testosterone deficient (castrated) goats was significantlyshorter and narrower in diameter/circumference compared to that ofcontrol goats (with adequate testosterone). Moreover, exogenous testosterone treated non-castrated goats resulted comparatively lager penis that the control goats.The urethral lumen was significantly larger in diameter in goats with adequate testosterone (control and exogenous testosterone-treated) than testosterone deficient goats. Conclusion:The results of this study indicate that the level of testosterone positively affects thenormal development of the penis and urethra in Black Bengal goats.

The usefulness of testosterone administration in identifying false-positive elevation of serum human chorionic gonadotropin in patients with germ cell tumor.

The pituitary production of human chorionic gonadotropin (hCG) can cause false-positive results during or after germ cell tumor (GCT) treatment. Because hypogonadism leads to pituitary hCG production, testosterone administration test (TAT) has been recommended for pituitary hCG diagnosis. However, little is known about its efficacy for the discrimination of pituitary hCG as detected by currently used hCG assays in treatment of GCT. We conducted a retrospective multicenter study to determine the usefulness of TAT. The study included 60 patients who underwent TAT for the discrimination of pituitary hCG. In principle, serum hCG levels were measured 1week after testosterone enanthate administration (250mg). When the serum hCG levels decreased below the normal upper range, the results of TAT were determined positive. In this case, the elevated hCG was considered to be derived from pituitary and not from GCT. Serum hCG levels were normalized after TAT in 36 of 60 patients (60%). Before TAT, the hCG levels were below 1.0IU/L in 13 patients (36%), 1.0-1.9IU/L in 11 (31%), 2.0-2.9IU/L in 7 (19%), and >3.0IU/L in 5 (14%) of TAT-positive patients. Of them, 28 (78%) patients were successfully managed without further treatment with chemotherapy after TAT. Pituitary hCG was associated with higher levels of LH and not necessarily associated with low levels of testosterone. Determining the TAT status of patients was effective in discriminating pituitary hCG production.

Effects of testosterone enanthate treatment in conjunction with resistance training on thyroid hormones and lipid profile in male Wistar rats.

This study was conducted to determine the effects of 8-week administration of testosterone enanthate (TE) in conjunction with resistance training on thyroid hormones and lipid profiles. Sixty male adult Wistar rats were randomly divided into six groups: C: olive oil, RT: resistance training + olive oil, LD: TE (20mg/kg), HD: TE (50mg/kg), RT+LD: RT+TE (20mg/kg), RT+HD: RT+TE (50mg/kg). The RT consisted of climbing (5 reps/3 sets) a ladder carrying a load suspended from the tail. At the end, blood specimens were obtained from the orbital sinus and serum concentration of T4, T3, TSH and lipid profiles was determined. The serum concentration of TSH significantly increased in RT+HD group compared to C, and the serum concentration of T4 significantly decreased in LD, HD, RT+LD and RT+HD groups compared to the C and RT groups (p<.05). The concentration of HDL and cholesterol significantly decreased in HD and RT+HD groups compared with C group (p<.05). Both decreased T4 and increased TSH in the RT+HD group likely suggested a primary hypothyroidism as a complication of high-dose administration of testosterone enanthate along with resistance training. Alteration in lipid profile was another complication observed in rats received high doses of testosterone enanthate.

Testosterone Plus Finasteride Prevents Bone Loss without Prostate Growth in a Rodent Spinal Cord Injury Model

We have reported that testosterone-enanthate (TE) prevents the musculoskeletal decline occurring acutely after spinal cord injury (SCI), but results in a near doubling of prostate mass. Our purpose was to test the hypothesis that administration of TE plus finasteride (FIN; type II 5α-reductase inhibitor) would prevent the chronic musculoskeletal deficits in our rodent severe contusion SCI model, without inducing prostate enlargement. Forty-three 16-week-old male Sprague-Dawley rats received: 1) SHAM surgery (T9 laminectomy); 2) severe (250 kdyne) contusion SCI; 3) SCI+TE (7.0 mg/week, intramuscular); or 4) SCI+TE+FIN (5 mg/kg/day, subcutaneous). At 8 weeks post-surgery, SCI animals exhibited reduced serum testosterone and levator ani/bulbocavernosus (LABC) muscle mass, effects that were prevented by TE. Cancellous and cortical (periosteal) bone turnover (assessed by histomorphometry) were elevated post-SCI, resulting in reduced distal femur cancellous and cortical bone mass (assessed by microcomputed tomography). TE treatment normalized cancellous and cortical bone turnover and maintained cancellous bone mass at the level of SHAM animals, but produced prostate enlargement. FIN coadministration did not inhibit the TE-induced musculoskeletal effects, but prevented prostate growth. Neither drug regimen prevented SCI-induced cortical bone loss, although no differences in whole bone strength were present among groups. Our findings indicate that TE+FIN prevented the chronic cancellous bone deficits and LABC muscle loss in SCI animals without inducing prostate enlargement, which provides a rationale for the inclusion of TE+FIN in multimodal therapeutic interventions intended to alleviate the musculoskeletal decline post-SCI.

Alterations of the oxidative status in rat hippocampus and prodepressant effect of chronic testosterone enanthate administration.

In a last few decades, anabolic-androgenic steroids (AASs) abuse has become serious health concern especially among adolescents. AASs abuse has been reported to be involved in pathogenesis of various mood disorders, including depression. In order to evaluate the effects of chronic (6weeks) testosterone enanthate (TE) treatment in supraphysiological dose and exercise on depression-like behavior in rats, 32 male rats were divided into four groups: control (C), testosterone enanthate (T, 20mg/kg/w, s.c.), exercise (E, swimming for 1h/day), and combined group-testosterone enanthate plus exercise (T + E). TE produced prodepressant effect in tail suspension test (TST) parameters compared to the control and exercise groups, while exercise induced the opposite effect. Simultaneous TE administration along with exercise attenuated the antidepressant effect of exercise reversing the parameters of TST to the control values. Oxidative stress markers in rat hippocampus were significantly altered following applied protocols. TE administration increased index of lipid peroxidation (TBARS) and decreased superoxide dismutase activity (SOD), while exercise induced the opposite effect, with no change in glutathione (GSH) levels. Our results indicate that TE chronic treatment resulted in clear depressive-like behavior, even abolishing beneficial antidepressant effects of exercise in TST that was accompanied with increased oxidative damage in rat hippocampus. The antidepressant effect of exercise correlated with the improvement of redox status in hippocampal tissue. Behavioral parameters obtained in TST significantly correlated with the levels of oxidative stress markers.

Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia

Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca.

Bioavailability of testosterone enanthate dependent on genetic variation in the phosphodiesterase 7B but not on the uridine 5′-diphospho-glucuronosyltransferase (UGT2B17) gene.

To study the disposition of serum testosterone and seven of its metabolites before and after 2 days of an intramuscular dose (500 mg) of testosterone enanthate in relation to the phosphodiesterase (PDE7B) and the uridine 5'-diphospho-glucuronosyltransferase (UGT2B17) genotypes. Patients were genotyped for UGT2B17 deletion polymorphism and single nucleotide polymorphisms in the PDE7B gene. The involvement of PDE7B in hydrolysis of enanthate was assessed in human liver homogenates. Genetic variation in the PDE7B gene was found to be associated with the serum level of testosterone. Individuals homozygous for PDE7B rs7774640 G allele had a smaller increase (2.5-fold) in the serum testosterone levels compared with carriers of the A allele (3.9-fold, P=0.0006). In addition, genetic variation in the PDE7B gene significantly influences the testosterone/epitestosterone ratio, a biomarker of testosterone doping. Our in-vitro incubation studies confirmed that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate. The UGT2B17 deletion polymorphism did not show any significant association with serum testosterone levels or the other androgen metabolites investigated. We have shown that PDE7B is involved in the hydrolysis of testosterone enanthate and that genetic variation in the PDE7B gene is a determinant of the systemic levels of testosterone after administration of testosterone enanthate. It is reasonable to believe that the genetic variation in testosterone bioavailability may be correlated to varying effects of this androgen, whether it is used for replacement therapy or abused in doping. Thus our results may be important to consider in doping test programmes and in therapeutics with androgens and other esterified drugs.

Myelodysplastic syndrome treated effectively with testosterone enanthate

We report a case of myelodysplastic syndrome (MDS) treated effectively with testosterone enanthate. A 70-year-old man was diagnosed with low-risk MDS in 1998, and he was first given methenolone acetate orally because of gradual progression of anemia and thrombocytopenia. However, this treatment was not effective, so we changed the treatment to testosterone enanthate because of his symptoms with late-onset hypogonadism. Three months after testosterone replacement therapy (TRT), anemia and thrombocytopenia had improved, and mean platelet count and hemoglobin had significant increases from 2.36 ± 0.45 × 10(4) to 3.83 ± 0.78 × 10(4) /µL, and from 11.7 ± 0.81 to 15.2 ± 1.00 g/dL, respectively, which contributed to a decrease in platelet transfusion requirement. Since then, the patient has been on a good clinical course. The present case suggests that testosterone enanthate administration could be an alternative treatment for men with MDS, even in the case where treatment with anabolic-androgenic steroids is not successful, and suggests another interesting effect of TRT on platelets.

Urinary and serum hormones profiles after testosterone enanthate administration in male hypogonadism: Concerns on the detection of doping with testosterone in treated hypogonadal athletes

To describe serum and urinary hormones, androgens metabolites and testosterone/epitestosterone ratio profiles after testosterone administration in male hypogonadal volunteers, and to evaluate their possible usefulness in detecting doping with testosterone in treated hypogonadal athletes. Controlled open label design vs placebo; pharmacokinetic study. Ten male volunteers affected by severe hypogonadism (serum testosterone <2.31 ng/ml). Serum and urinary parameters were evaluated, by radioimmunoassay and gas chromatography-mass spectrometry, before and at different time points for 7/3 weeks after a single administration of testosterone enanthate (250 mg) or placebo, respectively. As partially known, testosterone administration increased, with great individual variability, urinary concentrations of glucuronide testosterone, androsterone, etiocholanolone, 5alpha-androstane- 3alpha,17beta-diol, 5beta-androstane-3alpha,17beta-diol, testosterone/ epitestosterone and testosterone/LH ratios; and decreased epitestosterone and 5alpha-androstane-3beta,17beta-diol/5beta-androstane- 3alpha,17beta-diol ratio. Serum testosterone and dihydrotestosterone increased in all volunteers, and concentrations higher than the upper reference limits were observed in many volunteers until 2 weeks after testosterone administration. Whereas the observed prolonged hyperandrogenism partially limited data interpretation, the report ed characteristics of variation of urinary parameters might be used to suspect testosterone misuse in hypogonadal athletes treated with testosterone enanthate. In this sense, while the actual threshold for tes tos terone/epites tos ter one ratio was confirmed to be of reduced usefulness, we suggest a contemporary evaluation of whole urinary androgen metabolites profile and serum androgens, at specific time points after testosterone enanthate administration. Moreover, an adequate tailoring of treatment, to avoid transitory hyperandrogenism, is highly advisable. Further studies on strategies for detecting doping with testosterone in hypogonadal athletes are warranted.

Carbon isotope ratio (δ 13C) values of urinary steroids for doping control in sport

The detection of steroids originating from synthetic precursors in relation to their chemically identical natural analogues has proven to be a significant challenge for doping control laboratories accredited by the World Anti-Doping Agency (WADA). Endogenous steroid abuse may be confirmed by utilising the atomic specificity of gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) that enables the precise measurement of differences in stable isotope ratios that arise as a result of fractionation patterns inherent in the source of steroids. A comprehensive carbon isotope ratio (δ 13C) profiling study ( n = 1262) of urinary ketosteroids is reported that demonstrates the inter-individual variation that can be expected from factors such as diet, ethnicity, gender and age within and between different populations (13 countries). This δ 13C distribution is shown by principal component analysis (PCA) to provide a statistical comparison to δ 13C values observed following administration of testosterone enanthate. A limited collection of steroid diol data ( n = 100; consisting of three countries) is also presented with comparison to δ 13C values of excreted testosterone to validate criteria for WADA accredited laboratories to prove doping offences.

Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats

High-dose testosterone enanthate (TE) may prevent hypogonadism-induced osteopenia. For this study, 3-mo-old male and female Fisher SAS rats underwent sham surgery, gonadectomy (GX), or GX plus 28 days TE administration (7.0 mg/wk). GX reduced serum sex hormones (i.e., testosterone, dihydrotestosterone, and estradiol) (P < 0.05) in both sexes and bone concentrations of testosterone (males only), and estradiol (females only). GX also elevated urine deoxypyridinoline/creatinine in both sexes and serum osteocalcin (females only), findings that are consistent with high-turnover osteopenia. GX reduced cancellous bone volume (CBV) and increased osteoid surfaces in tibia of both sexes. GX males also experienced reduced trabecular number and width and increased trabecular separation, whereas GX females experienced increased osteoblast and osteoid surfaces. Bone biomechanical characteristics remained unaffected by GX, except that femoral stiffness was reduced in females. In contrast, TE administration to GX rats elevated serum and bone androgens to supraphysiological concentrations in both sexes but altered neither serum nor bone estradiol in males. Additionally, TE did not prevent GX-induced reductions in serum or bone estradiol in females. TE also reduced markers of high-turnover osteopenia in both sexes. In males, TE prevented GX-induced changes in trabecular number and separation, CBV, and osteoid surfaces while diminishing osteoblast and osteoclast surfaces; however, these changes were not fully prevented in females. In both sexes, TE increased femoral length and femoral maximal strength to above that of Sham and GX animals while preventing the loss of femoral stiffness in females. In conclusion, TE administration appears protective of cancellous bone in male rats and augments cortical bone strength in both sexes.

Pharmacokinetics and Pharmacodynamics of Oral Testosterone Enanthate Plus Dutasteride for 4 Weeks in Normal Men: Implications for Male Hormonal Contraception

Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen.