Mg Of Testosterone Enanthate Research Articles

The Effect of Eight Weeks of Resistance Training and Testosterone Enanthate Consumption on TNF-α and IL-6 Genes’ Expression in the Kidney Tissue of Female Wistar Rats

Objectives: This study aimed to evaluate the effect of a testosterone enanthate anabolic steroid on the gene expression of inflammatory factors in the kidney tissue of female rats following eight weeks of resistance training. Methods: Twenty-one female Wistar rats weighing 200 ± 20 g, aged eight weeks, were prepared from the Iran Pasture Institute. Following a week for acclimatization, the rats were randomly divided into three groups: control (n = 7), training + placebo (n = 6), and training + testosterone enanthate (n = 8). Resistance training included five days a week of climbing a 1-meter ladder with 26 stairs while bearing weights and two days of rest. In the first week, the weights were equal to 40% of the rats’ body weight. In the following weeks, the weight was increased by 20% per week. The rats were weighed two times a week. In the testosterone group, the rats were injected with 20 mg of testosterone enanthate thrice a week. Forty-eight hours following the last training session and testosterone injection, kidney tissue samples were collected to determine the gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) using real-time PCR. Results: The results showed that testosterone consumption significantly increased the gene expression of TNF-α and IL-6 in female rats undergoing resistance training (P = 0.001). Conclusions: The findings of this study demonstrated that using testosterone increased inflammatory factors in the kidney tissue of all female Wistar rats.

Presence of ovarian stromal aberrations after cessation of testosterone therapy in a transgender mouse model†.

Some transmasculine individuals may be interested in pausing gender-affirming testosterone therapy and carrying a pregnancy. The ovarian impact of taking and pausing testosterone is not completely understood. The objective of this study was to utilize a mouse model mimicking transmasculine testosterone therapy to characterize the ovarian dynamics following testosterone cessation. We injected postpubertal 9-10-week-old female C57BL/6N mice once weekly with 0.9mg of testosterone enanthate or a vehicle control for 6 weeks. All testosterone-treated mice stopped cycling and demonstrated persistent diestrus within 1 week of starting testosterone, while control mice cycled regularly. After 6weeks of testosterone therapy, one group of testosterone-treated mice and age-matched vehicle-treated diestrus controls were sacrificed. Another group of testosterone-treated mice were maintained after stopping testosterone therapy and were sacrificed in diestrus four cycles after the resumption of cyclicity along with age-matched vehicle-treated controls. Ovarian histological analysis revealed stromal changes with clusters of large round cells in the post testosterone group as compared to both age-matched controls and mice at 6 weeks on testosterone. These clusters exhibited periodic acid-Schiff staining, which has been previously reported in multinucleated macrophages in aging mouse ovaries. Notably, many of these cells also demonstrated positive staining for macrophage markers CD68 and CD11b. Ovarian ribonucleic acid-sequencing found upregulation of immune pathways post testosterone as compared to age-matched controls and ovaries at 6 weeks on testosterone. Although functional significance remains unknown, further attention to the ovarian stroma may be relevant for transmasculine people interested in pausing testosterone to carry a pregnancy.

EP136: An exploration of the impact of Hormonal Replacement Therapy (HRT) upon vocabulary skills in males with 49,XXXXY

49,XXXXY is a rare variant of 47,XXY, Klinefelter syndrome, that occurs in approximately 1 in 100,000 live male births. It is the most uncommon and complex X and Y chromosomal variation consisting of neurodevelopmental, physical, and medical complications. These boys are at an increased risk for musculoskeletal abnormalities and health difficulties. Intellectual disability, motor deficits, and severe speech dysfunction are common to this population. Specifically, receptive language skills are typically more advanced than expressive language skills, with some individuals being nonverbal. Childhood Apraxia of Speech (CAS) is thought to be the origin of speech and expressive language dysfunction in these boys suggesting that the core challenge is rooted in motor planning deficiency. Challenges in expressive language typically affect all aspects of daily life for males with 49,XXXXY, as it is difficult for them to convey their thoughts and feelings. This often leads to difficulties expressing themselves, social communication challenges, and peer isolation. Males with 49,XXXXY have androgen deficiency that benefits from hormonal replacement therapy (HRT). HRT has been found to have positive effects on neurodevelopmental capabilities in males with 49, XXXXY. Specifically, treated individuals have been found to have improved neurodevelopmental function than the untreated and may therefore have a potential beneficial impact on social skills. Two types of HRT are common during infancy and the childhood years: early hormonal treatment (EHT) and hormonal booster therapy (HBT). EHT is often administered during the “mini-puberty” period, ideally given at 4, 5, and 6 months old, but can be given up until 2 years of age. HBT may be recommended during the school-aged population, often beginning around 5 years old and given up until 11years old. The current study explores the effect of HRT upon expressive and receptive vocabulary skills in males with 49,XXXXY. One hundred and one participants with a diagnosis of 49,XXXXY were evaluated for this study (CA: 88.9 months). Participants completed the Expressive One-Word Picture Vocabulary Test 4th Edition (EOWPVT-4) and the Receptive One-Word Picture Vocabulary Test 4th Edition (ROWPVT-4). Subjects were segregated into four different groups according to their HRT status: no-T, EHT, HBT, and EHT&HBT. EHT consisted of 3 intramuscular injections of 25 mg of testosterone enanthate, once monthly, for three months given between 4 and 24 months of age. HBT consisted of 3 intramuscular injections of 50 mg of testosterone enanthate, once monthly for three months administered between the ages of 5 and 11. Two-tailed t-tests were completed to assess the differences within HRT groups between performance on the EOWPVT-4 and ROWPVT-4. The no-T group (CA: 90.3 months, N = 20) showed a significant difference between EOWPVT-4 and ROWPVT-4 scores (p = .00888) with receptive capabilities being higher than their expressive skills. The EHT group (CA: 79.3 months, N = 44) approached significance with greater skills on the ROWPVT-4 in comparison to the EOWPVT-4 (p = .0556). Finally, the HBT (CA: 104.5 months, N = 8) and EHT&HBT groups (CA: 98.1 months, N = 29) showed no differences between their receptive and expressive capabilities (p = .532; p = .700). The current study expands on the neurocognitive profile of boys with 49,XXXXY and the impact of HRT on their expressive and receptive vocabulary skills. Individuals with 49,XXXXY typically present with severely depressed expressive capabilities in comparison to their receptive skills. The no-T group had this typical presentation with higher receptive language abilities in comparison to expressive capabilities while the EHT, HBT, and EHT&HBT groups showed no differences between receptive and expressive vocabulary skills. Participants who received EHT, HBT, or a combination performed higher on the EOWPVT-4 and presented with commensurate and higher receptive and expressive vocabulary skills than those who had not been treated. These results suggest a positive treatment effect of both EHT and HBT on expressive vocabulary capabilities in boys with 49,XXXXY.

Klinefelter Syndrome and Turner Syndrome.

1. Carole Samango-Sprouse, EdD*,†,‡ 2. Sophia Q. Song, BA‡ 3. Angela E. Lin, MD§ 4. Cynthia M. Powell, MD¶ 5. Andrea L. Gropman, MD*,** 1. *George Washington University, Washington, DC 2. †Florida International University, Miami, FL 3. ‡Department of Research, The Focus Foundation, Davidsonville, MD 4. §Massachusetts General Hospital for Children, Boston, MA 5. ¶University of North Carolina at Chapel Hill, Chapel Hill, NC 6. **Children’s National Medical Center, Washington, DC Sex chromosome aneuploidy (SCA) syndromes refer to disorders with an abnormality of sex chromosome number. The most common are Klinefelter syndrome (KS), resulting from the gain of an X chromosome in males, and Turner syndrome (TS), reflecting the loss of an X chromosome or the presence of a structurally different X chromosome in females. Whereas most patients with KS have nonmosaic 47,XXY, only 40% of women with TS have 45,X; the remainder have a variety of mosaicisms. The syndromes also contrast in that males with KS are characteristically tall, whereas females with TS are typically short unless they receive hormonal treatment. Despite efforts to increase awareness, KS and TS are often underdiagnosed, leading to delayed care. Only 25% of men with KS are ever diagnosed, with fewer than 10% detected prenatally, and with a median age of 27 years for those identified later in life. For TS, the median age at diagnosis is 6.6 years. Although not exclusively, optimal neurocognitive outcomes depend on the timing of diagnosis and access to early targeted treatment, so fortunately the recent development of noninvasive prenatal screening is increasing the early identification of these disorders dramatically. Pediatricians should be aware of signs that allow for early detection, and the importance of prompt referral for testing and therapy. KS occurs in 1 in 660 live births, representing the most common SCA. Affected males have androgen deficiency, which affects endocrine, central nervous system, and neurodevelopmental function. Characteristics include increased height, clinodactyly of the fifth finger, pes planus, and hypogonadism manifesting as …

Pharmacokinetics of Testosterone Enanthate After Intramuscular Injection for Transgender Men

Aim: To clarify the pharmacokinetics (PKs) of testosterone enanthate intramuscular injection in transgender men. Materials and Methods: This is a single-center nonblind single-drug administration study. After screening, 10 Japanese transgender men were administered 250 mg of testosterone enanthate intramuscularly. If the subjects had already received testosterone treatment, a screening test was carried out after washout for at least 4 weeks. The total testosterone (TT) and free testosterone (FT) and estradiol (E2) levels were examined for 4 weeks. At days 0 and 28, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were examined. Results: Mean age was 31.1 ± 7.2 years, and four subjects received first-time testosterone administration. Mean TT level at baseline was under the cutoff value in hypogonadal men. Mean time to reach its maximum level was 1.7 days, and in all cases within 3 days. Then, the level decreased and reached <3.0 ng/mL at day 21. Mean time to maximum level of FT was 3.4 days, but in three cases it was at day 7. The coefficient of variation in apparent total clearance and distribution volume for TT was large. The PK parameters of E2 could not be calculated in four cases. In the remaining six, E2 gradually decreased and reached the nadir at day 21. LH and FSH were not different before and after injection. No specific adverse event associated with testosterone administration was observed. Conclusions: PK profiles in transgender men after testosterone enanthate 250 mg single injection were clarified.

SAT-037 Effect of Weight on Serum Testosterone with Subcutaneous Testosterone Enanthate in Men with Testosterone Deficiency

BACKGROUND: In men, obesity is often associated with low testosterone (T) levels, but information is limited as to how body weight affects the pharmacokinetic profile or dosing of testosterone therapy (TTh) in men with T deficiency. Historically, men with body mass index (BMI) >32.4 kg/m2 required higher doses of T 2% gel to achieve physiological T levels than men with BMI ≤29.1 or 29.2–32.4 kg/m2.(1) In a phase 3 trial (N=150) of subcutaneous (SC) testosterone enanthate (TE) administered weekly, concentration-guided dosing raised T levels to within physiological range in 92.7% of patients.(2) Here, we report a post hoc analysis evaluating the association between body weight and serum T levels attained with SC TE. Methods: SC TE was evaluated in an open-label, single-arm, dose-blinded, 52-week phase 3 trial (NCT02159469). Patients self-administered 75 mg SC TE weekly during the titration phase; blinded dose-adjustments in 25 mg increments occurred at pre-defined time points beyond the sixth dose. The primary endpoint of this study was the percentage of patients achieving an average serum T concentration (Cavg0-168h) of 300 to 1,100 ng/dL at week 12. For this post hoc analysis, a linear regression model with weight and dose as independent variables was used to assess differences in mean minimum T concentration (Cmin) and Cavg0-168h at week 12. Results: For this analysis, 137 patients were included. Doses were 50 mg (n=25), 75 mg (n=93), and 100 mg (n=19). The mean weight was 84.4 kg, 102.2 kg, and 112.0 kg for the 50 mg, 75 mg, and 100 mg dose groups, respectively (range, 49.9–146.5 kg). The dose-normalized T Cmin was 9.2 ng/dL, 5.7 ng/dL, and 4.3 ng/dL per 1 mg of SC TE for the 50 mg, 75 mg, and 100 mg groups, respectively. The dose-normalized T Cavg0-168h was 12.0 ng/dL, 7.2 ng/dL, and 5.7 ng/dL per 1 mg of SC TE. In an overall linear regression model, 48.2% (P<0.0001) and 55.0% (P<0.0001) of the total variance in Cmin and Cavg0-168h, respectively, can be predicted from the independent weight and dose variables. Conclusion: Our results show an inverse relationship between body weight and T exposure. Men with higher mean body weights required higher doses of SC TE to achieve physiologic T levels compared with men with lower mean body weights. The available doses provide effective options to reach target exposures. These findings highlight the impact of weight and dose selection on SC TE exposure.

Summative Usability Evaluation of the SCTE-AI Device: A Novel Prefilled Autoinjector for Subcutaneous Testosterone Administration

BackgroundThe subcutaneous testosterone enanthate (TE) autoinjector (SCTE-AI) is a single-use, pre-filled, disposable autoinjector intended for testosterone (T) self-administration in adult males with T deficiency. AimTo evaluate the usability of the market configuration of the SCTE-AI, including packaging and instructions for use (IFU), in order to identify and mitigate any preventable patterns of use errors that could result in harm. Methods4 groups of participants (injection-naïve or injection-experienced patients or caregivers) were randomized to 1 of 3 doses (50, 75, and 100 mg) of TE and either trained (ie, reviewed the IFU and shown how to properly inject) or not trained (only given the IFU). After simulated at-home use, participants were asked questions regarding the comprehensibility of the IFU and the intuitiveness/usability of the device. All tasks were measured as success, use error, or close call (participant initiated an error but recovered in time). Main Outcome MeasureUsability (success rates, errors, and close calls) of the drug/device combination by adult males with T deficiency or their caregivers. Results65 patients received 1 dose of TE, and 59 patients received 2 doses. Overall, 99 of 123 (80.5%) attempted injections resulted in administration of 1 full dose. Injection success rates were high and comparable among the various user groups. The most common use error (21 of 24) was due to not holding the autoinjector on the abdomen long enough (at least 8 seconds). Few critical drug delivery and safety errors or close calls were observed. No unmitigated use errors by patients or caregivers were apparent that could result in harm or have a negative impact on treatment. SCTE-AI was well tolerated. Clinical ImplicationsThe SCTE-AI development process resulted in a subcutaneous, TE autoinjection device that is intuitive to use, with clear labeling and packaging and an easy-to-understand IFU, providing an option for T-deficient adult males to self-inject subcutaneously at home. Strength & LimitationsThe strengths of the study include use of a patient-ready drug/device combination for self-administration and inclusion of both injection-naïve and injection-experienced patients and caregivers. The main limitation of the study is the presence of observers/cameras that may have distracted or created performance anxiety, potentially contributing to errors. ConclusionResults of this usability validation study indicate that the SCTE-AI device is safe and intuitive to use, with a low potential for harm and is associated with a high rate of injection success, regardless of prior training or experience.Arora S, Moclair B, Murphy K, et al. Summative Usability Evaluation of the SCTE-AI Device: A Novel Prefilled Autoinjector for Subcutaneous Testosterone Administration. J Sex Med 2018;15:1707–1715.

Muscles of the trunk and pelvis are responsive to testosterone administration: data from testosterone dose–response study in young healthy men

Testosterone dose-dependently increases appendicular muscle mass. However, the effects of testosterone administration on the core muscles of the trunk and the pelvis have not been evaluated. The present study evaluated the effects of testosterone administration on truncal and pelvic muscles in a dose-response trial. Participants were young healthy men aged 18-50years participating in the 5α-Reductase (5aR) Trial. All participants received monthly injections of 7.5mg leuprolide acetate to suppress endogenous testosterone production and weekly injections of 50, 125, 300, or 600mg of testosterone enanthate and were randomized to receive either 2.5mg dutasteride (5aR inhibitor) or placebo daily for 20weeks. Muscles of the trunk and the pelvis were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The dose effect of testosterone on changes in the psoas major muscle area was the primary outcome; secondary outcomes included changes in paraspinal, abdominal, pelvic floor, ischiocavernosus, and obturator internus muscles. The association between changes in testosterone levels and muscle area was also assessed. Testosterone dose-dependently increased areas of all truncal and pelvic muscles. The estimated change (95% confidence interval) of muscle area increase per 100mg of testosterone enanthate dosage increase was 0.622cm2 (0.394, 0.850) for psoas; 1.789cm2 (1.317, 2.261) for paraspinal muscles, 2.530cm2 (1.627, 3.434) for total abdominal muscles, 0.455cm2 (0.233, 0.678) for obturator internus, and 0.082cm2 (0.003, 0.045) for ischiocavernosus; the increase in these volumes was significantly associated with the changes in on-treatment total and free serum testosterone concentrations. In conclusion, core muscles of the trunk and pelvis are responsive to testosterone administration. Future trials should evaluate the potential role of testosterone administration in frail men who are predisposed to falls and men with pelvic floor dysfunction.

Codeine influences the serum and urinary profile of endogenous androgens but does not interact with the excretion rate of administered testosterone.

Today's doping tests involve longitudinal monitoring of urinary steroids including the testosterone glucuronide and epitestosterone glucuronide ratio (T/E) in an Athlete Biological Passport (ABP). The aim of this study was to investigate the possible influence of short-term use of codeine on the urinary excretion of androgen metabolites included in the steroidal module of the passport prior to and after the co-administration with testosterone. The study was designed as an open study with the subjects being their own control. Fifteen healthy male volunteers received therapeutic doses of codeine (Kodein Meda) for 6 days. On Day 3, 500 mg or 125mg of testosterone enanthate (Testoviron®-Depot) was administered. Spot urine samples were collected for 17 days, and blood samples were collected at baseline, 3, 6, and 14days after codeine intake. The circulatory concentration of total testosterone decreased significantly by 20% after 3days' use of codeine (p=0.0002) and an atypical ABP result was noted in one of the subjects. On the other hand, the concomitant use of codeine and testosterone did not affect the elevated urinary T/E ratio. In 75% of the individuals, the concentration of urinary morphine (a metabolite of codeine) was above the decision limit for morphine. One of the participants displayed a morphine/codeine ratio of 1.7 after codeine treatment, indicative of morphine abuse. In conclusion, our study shows that codeine interferes with the endogenous testosterone concentration. As a result, the urinary steroid profile may lead to atypical findings in the doping test.

Effects of testosterone administration (and its 5-alpha-reduction) on parenchymal organ volumes in healthy young men: findings from a dose-response trial.

Animal data shows that testosterone administration increases the volume of some parenchymal organs. However, the effects of exogenous testosterone on solid abdominal organs in humans remain unknown. The present study evaluated the effects of testosterone administration on the volume of liver, spleen and kidneys in a dose-response trial. Young healthy men aged 18-50years participating in the 5α-Reductase (5aR) Trial. All participants received monthly injections of 7.5mg leuprolide acetate to suppress endogenous testosterone secretion and weekly injections of 50, 125, 300 or 600mg of testosterone enanthate, and were randomized to receive either 2.5mg dutasteride (5 α-reductase inhibitor) or placebo daily for 20weeks. Liver, spleen and kidney volumes were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The dose-effect of testosterone on changes in the volume of parenchymal organs was evaluated by linear regression model. The association between changes in total testosterone (TT) levels and changes in organ volumes were assessed. Testosterone administration increased liver volume dose-dependently (17.4cm3 per 100mg of weekly testosterone enanthate; p=0.031); the increase in liver volume was positively associated with changes in TT levels (R2 =0.08, p=0.024). A dose-dependent, but non-significant, increase in kidney volumes was also seen. Inclusion of dutasteride use into the models showed an independent association of randomization to dutasteride group with liver volume increase. In conclusion, Testosterone administration increased the liver volume in a dose-dependent manner. The potential changes in parenchymal organs should be considered when interpreting apparent changes in lean mass in response to anabolic interventions.

Effects of testosterone replacement therapy on metabolic syndrome among Japanese hypogonadal men: A subanalysis of a prospective randomised controlled trial (EARTH study).

We investigated the effects of testosterone replacement therapy (TRT) on metabolic factors among hypogonadal men with a metabolic syndrome. From the study population of the EARTH study, which was a randomised controlled study in Japan, 65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n=32) and controls (n=33), were included in this study analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4weeks for 12months. Waist circumference, body mass index, body fat volume and blood pressure were measured in all patients at baseline and at 12months. In addition, blood biochemical data, including total cholesterol, triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels, were also evaluated. Changes in these categories from baseline to 12months were compared between the TRT and control groups, with significant differences observed in waist circumference, body fat percentage, FPG, TG and HbA1c levels. No significant differences were observed in other parameters. TRT for 1year was associated with improvements in some metabolic factors among Japanese men with hypogonadism and metabolic syndrome.

Effects of testosterone replacement therapy on nocturia and quality of life in men with hypogonadism: a subanalysis of a previous prospective randomized controlled study in Japan

Objective: We investigated the effects of testosterone replacement therapy (TRT) on nocturia and general health among men with hypogonadism and nocturia.Methods: From our previous EARTH study population, 64 patients with a clinical diagnosis of nocturia (two or more times per one night) and hypogonadism, comprising the TRT group (n = 31) and controls (n = 33), were included in this analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 6 months. All patients responded to the following questionnaires: International Prostatic Symptoms Score (IPSS), Aging Male Symptoms (AMS) score and Short Form-36 health survey at baseline and 6-month visit. These categories were compared based on changes from baseline to the 6-month visit between TRT and control groups.Results: At the 6-month visit, the TRT group had a significant decrease in IPSS question no. 7 and AMS question no. 4, whereas no significant changes were observed in the control group. Additionally, role limitation because of health program, vitality and mental health domains were significantly improved in the TRT group.Conclusions: Six-month TRT may improve nocturia, sleep conditions and quality of life among men with hypogonadism and nocturia.

Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men.

AimsTo study the effect and time profile of different doses of testosterone enanthate on the blood lipid profile and gonadotropins.Experimental designTwenty-five healthy male volunteers aged 27–43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses of Testoviron® Depot. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), blood lipid profile (total cholesterol, plasma [p-] low-density lipoprotein, p-high-density lipoprotein [HDL], p-apolipoprotein A1 [ApoA1], p-apolipoprotein B, p-triglycerides, p-lipoprotein(a), serum [s-] testosterone, and 25-hydroxyvitamin D3) were analyzed prior to, and 4 and 14 days after dosing. Testosterone and epitestosterone in urine (testosterone/epitestosterone ratio) were analyzed prior to each dose after a washout period of 6–8 weeks.Results and discussionAll doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic–pituitary–gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile.ConclusionThe single doses of testosterone produced a dose-dependent increase in serum testosterone concentrations together with suppression of s-LH and s-FSH. Alterations in ApoA1 and HDL were observed after the two highest single doses. It is possible that long-time abuse of anabolic androgenic steroids will lead to alteration in vitamin D status. Knowledge and understanding of the side effects of anabolic androgenic steroids are important to the treatment and care of abusers of testosterone.

Testosterone dose-response relationships in hysterectomized women with or without oophorectomy

This study aims to determine the dose-dependent effects of testosterone on sexual function, body composition, muscle performance, and physical function in hysterectomized women with or without oophorectomy. Seventy-one postmenopausal women who previously underwent hysterectomy with or without oophorectomy and had total testosterone levels less than 31 ng/dL or free testosterone levels less than 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were randomized to receive weekly intramuscular injections of placebo or 3, 6.25, 12.5, or 25 mg of testosterone enanthate for 24 weeks. Total and free testosterone levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. The primary outcome was change in sexual function measured by the Brief Index of Sexual Functioning for Women. Secondary outcomes included changes in sexual activity, sexual distress, Derogatis Interview for Sexual Functioning, lean body mass, fat mass, muscle strength and power, and physical function. Seventy-one women were randomized; five groups were similar at baseline. Sixty-two women with analyzable data for the primary outcome were included in the final analysis. The mean on-treatment total testosterone concentrations were 19, 78, 102, 128, and 210 ng/dL in the placebo, 3-mg, 6.25-mg, 12.5-mg, and 25-mg groups, respectively. Changes in composite Brief Index of Sexual Functioning for Women scores, thoughts/desire, arousal, frequency of sexual activity, lean body mass, chest-press power, and loaded stair-climb power were significantly related to increases in free testosterone concentrations; compared with placebo, changes were significantly greater in women assigned to the 25-mg group, but not in women in the lower-dose groups. Sexual activity increased by 2.7 encounters per week in the 25-mg group. The frequency of androgenic adverse events was low. Testosterone administration in hysterectomized women with or without oophorectomy for 24 weeks was associated with dose and concentration-dependent gains in several domains of sexual function, lean body mass, chest-press power, and loaded stair-climb power. Long-term trials are needed to weigh improvements in these outcomes against potential long-term adverse effects.

Effects of varying doses of testosterone on atherogenic markers in healthy younger and older men

Whether exogenous testosterone is proatherogenic remains controversial. We assessed the effects of graded doses of testosterone on serum markers of oxidative stress, chemotaxis, adhesion, and inflammation in healthy younger and older men. In a double-blind, randomized trial, 121 eugonadal men (n = 61, 18-35 years of age and n = 60, 60-75 years of age) were randomized to one of five groups to receive weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk, respectively, along with a long-acting gonadotropin-releasing hormone (GnRH) agonist. Energy and protein intakes were standardized and no resistance training was allowed. We measured plasma levels of the atherogenic biomarkers monocyte chemotactic protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1), 8-isoprostane-PGF(2α) (8-iso-PGF(2α)), and high-sensitivity C-reactive protein (hs-CRP) before and after the intervention. Administration of increasing doses of testosterone led to reduction in total 8-iso-PGF(2α) in the younger (p-trend(Younger) = 0.01), but not older (p-trend(Older) = 0.79) men. No significant linear associations were observed between testosterone dose and MCP-1, sICAM-1, or hs-CRP (all p-trend >0.20). In apparently healthy men, over a wide dose range, testosterone did not adversely affect atherogenic biomarkers. Long-term studies with larger sample sizes are warranted to determine whether testosterone supplementation affects atherosclerosis progression and cardiovascular risk.

Non-Steroidal Anti-Inflammatory Drugs Do Not Influence the Urinary Testosterone/Epitestosterone Glucuronide Ratio

The UDP Glucuronosyl Transferase (UGT) enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including non-steroidal anti-inflammatory drugs (NSAIDs) as well as anabolic androgenic steroids (AAS). Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug–drug interaction that may influence the doping tests for AAS. In vitro studies show inhibitory potential on UGT2B7, 2B15, and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG) as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test. The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 male healthy volunteers, with either two, one or no allele (ins/ins, ins/del, or del/del) of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac) for 6 days. On day three, 500 mg of testosterone enanthate was administered. Spot urine samples were collected for 17 days. After a wash-out period of 4 months the volunteers received 500 mg testosterone enanthate only, with subsequent spot urine collection for 14 days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs.

Change of aging males' symptoms (AMS) rating scale in Japanese late-onset hypogonadism (LOH) patients administered androgen replacement therapy

Background We examined changes in the Aging Males' Symptoms (AMS) rating scale in Japanese late-onset hypogonadism (LOH) patients during the administration of androgen replacement therapy (ART), and evaluated whether the AMS rating scale is a useful tool for the diagnosis of LOH or the determination of ART efficacy. Methods Eighty-two Japanese LOH patients who had been given ART and who completely answered their AMS rating scale questionnaires were enrolled. The ART consisted of intramuscular injections of 250 mg of testosterone enanthate every three weeks. Subjective effectiveness of ART made sure at three months after administration. The answers to the AMS rating scale were obtained prior to ART, at 3, and 6 months after administration. Results The patients' mean age was 55.8 years. Prior to ART, the total and subscales (psychological, somatic and sexual) AMS scores were 51.0, 13.0, 20.5, and 16.0, respectively. There were no significant correlation between AMS score and age or testosterone levels. At 3 months from administration, all AMS scores had decreased significantly (total: 41.5, psychological: 9.0, somatic: 18.0, sexual: 13.5, p < 0.001), and maintained after 3 months. Statistically significant variations in AMS score during ART were not observed between patients judged effective and ineffective. Conclusions The AMS rating scale improved significantly after the administration of ART in Japanese LOH patients, although the choice of ART method remains limited. The AMS rating scale never predicted the patient's testosterone levels, and it is impossible to judge the subjective efficacy of ART by the changes in AMS score during ART.

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

Purpose. We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH).Methods. Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment.Results. Forty-six patients (ART group, n = 23; control, n = 23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7 ± 8.7 vs. 12.5 ± 9.5; p < 0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p < 0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p < 0.05), whereas no significant changes were seen in the controls.Conclusion. ART improved LUTS in hypogonadal men with mild BPH.

Distribution of testosterone in plasma proteins during replacement therapy with testosterone enanthate in patients suffering from hypogonadism.

In five hypogonadal men treated with 250 mg of testosterone enanthate once every three weeks, total testosterone, "free" testosterone and the percent of testosterone bound to the sex hormone-binding globulin (SHBG) and albumin were determined during three weeks. Immediately after the injection total plasma testosterone rapidly increased about four times the starting level closely paralleled by the concentration of "free" testosterone. We found that if the concentration of SHBG had been reached albumin took over the surplus of the testosterone. Whereas in the first and second week after the injection, high and sufficient levels of testosterone were determined, both total and "free" testosterone approached the lower limit of the normal male range in the third week, i.d. 300 ng/dl, or 5 ng/dl, respectively. In one patient with hypalbuminemia, "free" testosterone decreased during the third week below 3 ng/dl though his total testosterone remained sufficient high. This patient complained about symptoms of androgen deficiency. We explained this with his impaired capacity to bind the excess of testosterone by albumin. We concluded that though the concentration of total testosterone may be sufficient high, "free" testosterone can decrease to very low levels due to disturbance in the distribution of the androgen between the plasma proteins.

Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss

Testosterone increases fat-free mass (FFM) in men infected with human immunodeficiency virus (HIV), but its effects on muscle performance, physical function, mood, and quality of life are poorly understood. Sixty-one HIV-infected men with weight loss were randomized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk. The primary outcome of interest was physical function (walking speed, stair-climbing power, and load-carrying ability). Secondary outcome measures included body weight and composition, muscle performance, sexual function, mood, and quality of life. Serum nadir free and total testosterone levels increased (+188.0 +/- 29.6 and +720 +/- 86 ng/dl) in the testosterone, but not placebo, group. Testosterone administration was associated with increased FFM (2.8 +/- 0.5 kg), which was significantly greater than in the placebo group (P < 0.0001). Leg press strength increased significantly in testosterone-treated (P = 0.027), but not placebo-treated, men; the difference between groups was not significant. Other measures of muscle performance and physical function did not change significantly in either group. Men receiving testosterone demonstrated significantly greater improvements in mental health and quality-of-life scores than those receiving placebo and improvements in fatigue/energy and mood scores that were not significantly different from those receiving placebo. Sexual function scores did not change in either group. In HIV-infected men with weight loss, a supraphysiological dose of testosterone significantly increased FFM but did not improve self-reported or performance-based measures of physical function. Improvements in mood, fatigue, and quality-of-life measures in the testosterone group, although clinically important, need further confirmation.