Administration Of Testosterone Enanthate Research Articles

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.

The sudden and unexpected death of a female-to-male transsexual patient

A 32-year-old woman, who was intramuscularly injected with testosterone enanthate (125 mg) once or twice a month over a two-year period for female-to-male transsexualism, died suddenly. A forensic autopsy was performed to investigate the cause of death. Concentric cardiac hypertrophy was macroscopically observed. In the left and right coronary arteries, atherosclerosis was generally observed within the endothelium. In particular, there was severe stenosis (>90%) at the start of the left descending branch. In the myocardium, both coagulation necrosis and contraction band necrosis were microscopically observed. Moreover, myocardial fibrosis and myocardial calcification were diffusely detected, respectively. The cause of death was diagnosed as ischemic heart disease due to coronary stenosis. There is some debate as to whether cross-hormone replacement is related to the occurrence of coronary artery disease or not, however, it is possible that the development of ischemic heart disease was aggravated by the administration of testosterone enanthate in the current case.

231 Natural killer cell numbers and natural killer cytotoxic activity after six weeks of testosterone enanthate administration in healthy young males

231 Natural killer cell numbers and natural killer cytotoxic activity after six weeks of testosterone enanthate administration in healthy young males

Retention of Performance Gains following Testosterone Enanthate Administration

Introduction: There are many anecdotal reports of the length of time that performance enhancement persists after cessation of androgenic anabolic steroid use. The first controlled study to show the performance enhancement of the anabolic androgenic steroids was carried out by Bhasin and co-workers in 1996, however controlled studies of the length of time that performance enhancement persists have not been performed. This study reports on the performance gains after cessation of steroid use. Methods: Twenty-one weight training male subjects between the ages of 19 and 43 completed a randomised, double-blind, placebo-controlled study. Subjects were given weekly injections for 12 weeks (either 3.5 mg/kg body weight testosterone enanthate or saline placebo) while undertaking a supervised weight training program with a 12-week controlled follow-up phase with continued supervised weight training (post steroid phase). One repetition maximal bench press, 30m sprint, 6 s cycle test and counter-movement jump performance measures were made prior to testosterone dosage, after 12 weeks of administration and at 6 weeks and 12 weeks of the post steroid phase. T/E ratios were determined both during the testosterone administration and during the post-steroid phase. Results: After 12 weeks of testosterone administration there were significant (p < 0.05) increases in the bench press results of the testosterone group compared to the placebo group of 22% v 9%. 30m Sprint times decreased from 4.42 ± 0.17s to 4.33 ± 0.23s for the testosterone group with no decrease for the placebo group. No significant differences were found for the 6s cycle test or the counter movement jump. In the post steroid phase, the bench press improvements decreased after 6 weeks to an increase over pre steroid administration of only 12% v 9% for the placebo whilst 12 weeks in the post steroid phase both groups recorded 8% increases over the initial measures. The increases in the 30m sprint times recorded at the conclusion of testosterone administration were maintained after 12 weeks of no drug. The T/E ratios of the placebo group did not alter during the period of the study. The testosterone administration group increased T/E ratios from 0.96 ± 0.64 to 15.12 ± 13.13 after 12 weeks. This declined after drug dose ceased with a T/E ratio of 10.59 ± 9.27 at the second week of the post-steroid phase and a return to 1.19 ± 0.65 at the conclusion of the 12 weeks without testosterone administration. Discussion: As with the study of Bhasin et al (1996) significant increases in performance measures were found following the 12 weeks testosterone administration period. Muscular strength improved by 13% with use of testosterone. However 6 weeks after cessation of steroid use the muscular strength improvement had declined to only 3% whilst there were no gains remaining after 12 weeks without drug. Indications appear that the gains in the bench press were lost at a rate the reverse of their gain. 30m Sprint performance, a measure of muscular power did not follow the pattern of the bench press as it was retained during the 12 weeks post-steroid phase. However T/E ratios followed the pattern of the bench press measures by declining to baseline levels after the 12 weeks. Overall this study indicates that steroid enhanced strength “improvements” are lost when steroids are no longer used even though weight training was maintained. However sprint gains appear to be maintained which are associated with the acceleration phase rather than the later stages of the sprint. The sprint gains may be due to improved neuromuscular co-ordination occurring during the training and be maintained by the training regime. It will be of interest to repeat the study without the weight training during the post-steroid phase.

Characterization of exogenous testosterone in livestock by gas chromatography/combustion/isotope ratio mass spectrometry: influence of feeding and age

The detection of exogenous testosterone in bovine urine was investigated by using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The carbon isotopic ratio measurement of epitestosterone, etiocholanolone (testosterone metabolite) and DHEA (testosterone precursor) in female bovine urines after testosterone enanthate administration was carried out. An important modification in the 13C/12C ratio of testosterone metabolites was observed, such that significant differences between precursor and metabolites of testosterone occurred until three weeks after intramuscular administration of testosterone enanthate. The factors influencing the 13C/12C of endogenous steroids were studied especially through cattle feeding and age. The DHEA mean δ13C value was found to vary between −25 and −26‰ when hay and concentrate diet were used for fattening. On the other hand the δ13C value observed when maize silage was used increased to −20‰. Testosterone metabolites showed the same δ13C increase as their precursor. Moreover, we observed a clear relationship between age and efficiency of misuse determination. Indeed, because of the lower concentration of natural hormones in young animals, the contribution of exogenous molecules increases significantly compared with older subjects. Consequently, demonstration of administration is easier to achieve in calves than in mature animals. Copyright © 2000 John Wiley & Sons, Ltd.

Characterization of exogenous testosterone in livestock by gas chromatography/combustion/isotope ratio mass spectrometry: influence of feeding and age.

The detection of exogenous testosterone in bovine urine was investigated by using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The carbon isotopic ratio measurement of epitestosterone, etiocholanolone (testosterone metabolite) and DHEA (testosterone precursor) in female bovine urines after testosterone enanthate administration was carried out. An important modification in the 13C/12C ratio of testosterone metabolites was observed, such that significant differences between precursor and metabolites of testosterone occurred until three weeks after intramuscular administration of testosterone enanthate. The factors influencing the 13C/12C of endogenous steroids were studied especially through cattle feeding and age. The DHEA mean delta13C value was found to vary between -25 and -26/1000 when hay and concentrate diet were used for fattening. On the other hand the delta13C value observed when maize silage was used increased to -20/1000. Testosterone metabolites showed the same delta13C increase as their precursor. Moreover, we observed a clear relationship between age and efficiency of misuse determination. Indeed, because of the lower concentration of natural hormones in young animals, the contribution of exogenous molecules increases significantly compared with older subjects. Consequently, demonstration of administration is easier to achieve in calves than in mature animals.

Oral Testosterone Administration Detected by Testosterone Glucuronidation Measured in Blood Spots Dried on Filter Paper

Blood sampling is not a common practice for sports drug testing. Our aim was to investigate whether dried blood spots on filter paper could be an alternative to plasma samples for monitoring steroid profiles in dope testing. We collected dried blood spots and plasma from six healthy Caucasian subjects after an oral 120-mg dose of testosterone undecanoate (TU). Nonconjugated testosterone, testosterone glucuronide (TG), androsterone glucuronide (AG), and etiocholanolone glucuronide (EtG) were measured by gas chromatography-mass spectrometry in both matrices. 17alpha-Hydroxyprogesterone (17alphaOHP) and luteinizing hormone (LH) also were measured in the plasma samples. For comparison, similar measurements were done on samples obtained from the same subjects given 25 mg of testosterone propionate (TP) plus 110 mg of testosterone enanthate (TE) intramuscularly after a wash-out period. After oral TU intake, TG, AG, and EtG increased sharply, whereas nonconjugated testosterone did not change significantly. Results on dried blood spots correlated well with those on plasma. The TG/testosterone ratio in blood or plasma was verified to be a sensitive and specific marker (significantly increased for up to 8 h after intake; P <0.05) for oral TU intake but not for intramuscular administration of TP plus TE. Little suppression of plasma LH and 17alphaOHP was observed after a single oral dose of TU. One subject did not show a significant increase of blood TG after oral TU intake. The measurement of glucuronide conjugates in blood and plasma samples is relevant for sports drug testing when analyzing the steroid profile. Dried blood spots collected on filter paper are a suitable alternative to plasma for detecting testosterone abuse.

Effects of long-term use of testosterone enanthate. II. Effects on lipids, high and low density lipoprotein cholesterol and liver function parameters.

The present study was designed to evaluate the effects of long-term administration of testosterone enanthate (TE) on lipid and liver function parameters in rhesus monkeys (n = 9) maintained under controlled dietary conditions. Bimonthly administration of 50 mg of TE increased serum testosterone into the supraphysiological range one day after injection and peak levels were seen on day 3, followed by a decrease to above baseline values by day 14. High density lipoprotein cholesterol (HDL-C) levels decreased gradually; compared to baseline values, the decline was significant from the 19th month of injection until the first month of recovery. The increase in low density lipoprotein cholesterol (LDL-C) levels and the LDL-C/HDL-C ratio during the treatment period was not significant compared to baseline values; however, when compared to control animals, HDL-C and LDL-C levels and the LDL-C/HDL-C ratio were significantly elevated from the 12th month until the end of the treatment period. All lipid parameters recovered by the end of the treatment period. Control animals (n = 9) did not show significant changes in HDL-C and LDL-C levels and the LDL-C/HDL-C ratio during the study period. Total cholesterol levels decreased in control (n = 9) and treated animals from 6 to 15th months of the treatment period, coinciding with the feeding of sprouted grams to animals. TE injections did not change the levels of triglycerides, alkaline phosphatase or bilirubin in control and treated animals. However, transaminase (SGOT and SGPT) levels increased following TE injections and remained elevated until the end of injections followed by a return to baseline values or below during the recovery period. These effects could be due to the pharmacokinetic profile of TE in which testosterone levels were elevated to supraphysiological values after injections. The recovery of the TE-induced changes in lipid parameters and liver transminases is reassuring but the changes in these parameters during TE injections indicate the need for long-acting androgens with better pharmacokinetic properties.

Androgen receptor expression of proliferating basal and luminal cells in adult murine ventral prostate.

Maintenance of the size and differentiated function of the adult prostate is dependent on testicular androgens. In this study, simultaneous androgen receptor (AR) immunohistochemistry and [(3)H]thymidine labelling was used to characterise the proliferating epithelial cells of the murine ventral prostate. Proliferation in the adult prostate was more prevalent in the basal cell population with 1.8&percent; AR-negative cells labelled with [(3)H]thymidine as compared with 0.7% AR-expressing luminal cells. Three weeks following castration of mice, the atrophied prostate contained rudimentary glands composed of both luminal and basal cells with the proportion of AR-expressing basal cells reduced from 50 to 25%. Administration of testosterone enanthate to castrated mice induced a recapitulation of the prostate gland that was preceded by up-regulation of AR expression in basal cells to normal adult levels (50% AR-positive cells) by 12 h following testosterone injection. Proliferation of AR-positive luminal cells peaked at 48 h (22.8%) while proliferation of AR-negative basal cells peaked at 96 h (6.1%) following testosterone administration. These results suggest that distinct populations of luminal and basal cells are resistant to castration-induced involution of the prostate but remain responsive to direct or indirect testosterone effects and recapitulate the gland following administration of testosterone.

Effects of long-term treatment with testosterone enanthate in rhesus monkeys: I. Pharmacokinetics of testosterone, testicular volume and liver metabolism of testosterone.

The effects of long-term administration of testosterone enanthate on the pharmacokinetics and bioavailability of testosterone were studied in adult male rhesus monkeys (n = 9), injected with 50 mg of testosterone enanthate (TE) once every 14 days for a total of 32 months. Control animals were injected with 0.2 mL olive oil. Serum testosterone levels increased sharply within 24 h of the first injection of TE and reached a peak on day 3 followed by a sharp decline, but baseline values were not reached even by day 14. Subsequent injections of TE caused a similar pharmacokinetic profile until the 55th injection; testosterone levels on day 3 declined from the 56 to 58th injection and remained in a lower range until the last injection. Repeated injections of TE increased the bioavailability of testosterone as shown by the Area Under the Curve. The nocturnal (22.00 h) surge in testosterone levels during the pretreatment phase was abolished by TE injections. TE injections altered the metabolism of testosterone by the liver, as studied in vitro; while liver from control animals converted testosterone to androstenedione as the major metabolite, androsterone was the major metabolite in chronically TE-treated animals. Spermatogenesis and the associated increase in testicular volume observed in control animals in winter were suppressed in TE-treated animals. The results indicate that repeated TE injections elevate serum testosterone to supra-physiological levels with marked fluctuations in circulating testosterone levels after each injection. Possibly in response to these elevated levels, there was a change in the metabolism of testosterone by the liver as observed in vitro.

Effects of long term administration of testosterone enanthate on glucose metabolism in rhesus monkeys

The effects of long term administration of testosterone enanthate (TE) on glucose metabolism including glucose tolerance test (GTT) and fasting serum insulin levels were evaluated in adult rhesus monkeys kept under controlled dietary conditions. Adult male rhesus monkeys (n = 9) were administered 50 mg of TE bimonthly for 32 months, whereas control animals were injected the vehicle only. Glucose concentration reached a maximum 5 min after an intravenous glucose load and thereafter decreased gradually to reach near baseline values within 60 min. Significant changes in GTT or t 1/2 of glucose were not seen in animals treated with TE, throughout the treatment period. However, serum insulin levels decreased significantly from months 27–32 of TE treatment and returned to baseline values within 3 months of recovery.

Changes in structure and functions of prostate by long-term administration of an androgen, testosterone enanthate, in rhesus monkey (Macaca mulatta).

The increasing use of androgens in clinical trials for developing a safe, effective, and reversible male contraceptive has necessitated a critical evaluation of the effects of their long-term use on the structure and functions of the prostate gland, which is androgen dependent. Combination regimens using progestogens, gonadotropin-releasing hormone antagonists, or antiandrogens along with androgens are undergoing clinical evaluation as antispermatogenic agents. The majority of these regimens have used testosterone enanthate (TE) as the androgen of choice, but very limited information is available on the side effects of long-term androgen use. The present study is the first report that critically evaluates the effects of long-term use of TE on prostate structure and functions. Adult male rhesus monkeys received intramuscular injections of 50 mg of TE once in 14 days for 33 months. The cranial and caudal lobes of the prostate, which were removed under ketamine anesthesia, were processed for the preparation of semithin sections to evaluate histological changes. The DNA distribution in the cells was studied in single cell suspensions of cranial and caudal lobes of the prostate by using flow cytometry. Changes in the levels of testosterone, estradiol, prostate-specific acid phosphatase (PAP), and prostate-specific antigen (PSA) in samples collected during the pretreatment period and at the time of removal of the prostate were estimated by using conventional procedures. Control samples were processed simultaneously. The administration of TE for 33 months caused the following changes: 1) significant increase in the weight of both lobes of the prostate, 2) cellular hypertrophy and increase in secretory material in the cells and in the lumen of the acini in the central and peripheral zones of the two lobes of the prostate, 3) cellular hyperplasia indicated by flow cytometric analysis of DNA content, 4) significant increase in the secretion of PAP and levels of estradiol, and 5) a marked increase in fibromuscular stroma in the central and peripheral zones of both the lobes of the prostate. The present study is the first report to provide evidence that long-term androgen treatment has caused hypertrophy of the prostatic epithelial cells, which showed increased secretory activity. The hyperplastic changes indicate a need for the development of new androgens with a better pharmacokinetic profile for use in male contraceptive regimens.

Langur prostate and its hormonal modulation.

The normal histoarchitecture of langur prostate of different growth phases, viz., juvenile, sub-adult, and adult, and the hormonal modulation of adult prostate were studied in order to explore its suitability of a surrogate for human prostate. The histological observations revealed that the langur prostate is histoarchitecturally homogeneous. The volumetric composition of stroma (%) was found to be decreased significantly from juvenile to adult and that of epithelium and lumen was found to be increased significantly. The absolute volume (c.c.) of stroma, epithelium, and lumen increased significantly from juvenile to adult. A marked depletion in the various prostatic fluid biochemical parameters was observed in castration groups, which were recovered to control level following testosterone enanthate administration. The castration induced significant increase in volumetric composition of stroma; conversely that of the epithelium and lumen decreased significantly. The absolute volume of stroma did not show any appreciable variation, while that of epithelium and lumen decreased significantly. The inter acinar stroma decreased from juvenile to adult, while the lumen diameter increased significantly from juvenile to adult. Castration increased the inter acinar and lumen diameter; conversely the epithelial height decreased. The testosterone supplementation restored the prostate. However, the volumetric composition of stroma remained high, while the luminal volume remained low. Various prostatic parameters in normal and under altered hormonal conditions suggest that the langur prostate is similar to the human and therefore could be used as surrogate for the human prostate.

Testosterone replacement increases fat-free mass and muscle size in hypogonadal men.

This open‐label nonrandomized study evaluated the effect of intramuscular testosterone enanthate administration on body composition, protein dynamics, and serum hormone concentrations in seven healthy hypogonadal adults 19 to 47 years old. The subjects had been previously treated with androgen replacement therapy (testosterone or gonadotropins) but underwent a 12‐week washout period off all androgenic therapy prior to study. During the 10‐week treatment period, testosterone enanthate (100 mg IM) was administered weekly in the Clinical Research Center. Subjects were instructed to refrain from moderate to heavy exercise for 4 weeks before study and during the treatment period. All were instructed to consume a standardized daily diet of 36 kcal/kg/d and 1.5 g/ kg/d protein and 100% of the recommended dietary allowance for vitamins.Study endpoints were determined before and after testosterone therapy. The primary outcome measure was fat‐free mass determined by underwater weighing. Body composition (fat‐free mass, total body water, and fat mass) was also estimated with use of the deuterium water dilution method. Muscle size was evaluated with use of magnetic resonance imaging (MRI) of the arm and thigh muscles, with cross‐sectional areas of the limb, the subcutaneous tissue, and the muscle compartment computed. Muscle strength was assessed by a one‐repetition‐maximum method for supine bench press and parallel squat exercises. Serial blood hormone measurements included total and free testosterone, luteinizing hormone, follicle‐stimulating hormone, and sex‐hormone binding globulin determined during weeks 4, 2, and 1 before treatment and an additional eight times during hormone therapy. Finally, the labeled‐leucine technique was used to determine protein dynamics (leucine flux, oxidation, and nonoxidative disappearance) before and at the end of treatment.The etiology of hypogonadism in four subjects was Klinefelter's syndrome (hypergonadotropic hypogonadism), and one each had idiopathic hypogonadotropic hypogonadism, panhypopopituitarism (after resection of a craniopharyngioma), and autoimmune polyglandular failure. There were no significant changes in hemoglobin, hematocrit, serum creatinine, and transaminases before or during testosterone treatment. Serum total testosterone levels increased significantly from baseline values of 2.5 ± 1.0 to 17.7 ± 3.2 nmol/L (mean ± SEM) on day 15, and were maintained in the normal male range for the duration of treatment. Free testosterone levels increased from a baseline of 66 ± 24 to 257 ± 69 pmol/L on day 29 of treatment and were maintained at this level throughout treatment. Blood liver function tests, hematocrit, and creatinine were unaltered by hormone administration.Body weight and fat‐free mass increased significantly from baseline to the posttreatment study. The average weight gain during hormonal treatment was 4.5 ± 0.6 kg or 6% of body weight. The percent body fat did not change with treatment; however, fat‐free mass measured by underwater weighing increased significantly from 56 ± 2.5 to 60.9 ± 2.2 kg (or 9% increase). Similar effects on fat‐free mass were detected with use of the deuterium‐water dilution method. Total body water increased from 40.9 ± 3.3 to 46.0 ± 3.9 kg with testosterone, but percent body water did not change significantly.Muscle size increased significantly with testosterone for 10 weeks. The triceps muscle area increased by 12% from baseline and the quadriceps musculature increased by 8%, while the amount of subcutaneous fat in arm and thigh did not change. Muscle strength increased significantly with testosterone over the 10 weeks of treatment, as evidenced by a 22% increase in the bench press and a 31% increase in the squat strength measurements. Whole‐body leucine flux, oxidation, and nonoxidative disappearance rates did not change with treatment. Testosterone treatment was clinically well tolerated in these hypogonadal men.

Confirming testosterone administration by isotope ratio mass spectrometric analysis of urinary androstanediols

A gas chromatographic combustion isotope ratio mass spectrometric (GC/C/IRMS) method was used for studying the incorporation of exogenous testosterone enanthate into excreted urinary 5α- and 5β-androstane-3α,17β-diols. A multistep but straightforward work-up procedure produced a simple GC chromatogram of urinary steroid acetates composed principally of two androstanediols and pregnanediol. It is anticipated that such a method may form the basis of a doping control test for testosterone that could be used as a primary method during major sporting events or alternatively as a verification technique. Urine samples from five individuals were collected before and after administration of testosterone enanthate (250 mg). The δ 13 C 0/00 value of androstanediols was around −26 to −28 during the baseline period and decreased to about −29 to −30 in the days following synthetic testosterone administration. One of the other major steroids in the chromatogram, pregnanediol, was utilized as the “internal standard,” because its δ 13 C 0/00 values did not markedly change following testosterone administration, remaining at −25 to −27. In all subjects studied, the δ 13 C 0/00 values for androstanediols were reduced sufficiently over 8 days to confirm administration of synthetic testosterone. Although steroids isolated from urine of normal individuals from 12 different countries gave values between −24 and −28, this seemed not to be related to nationality or region. The most likely variable is the proportion of plants with low and high carbon 13 content in the diet. This variable is likely to be more affected by individual food preferences than broad ethnic food divisions. In this paper, we propose a ratio of δ 13 C 0/00 for androstanediols to pregnanediol as a useful discriminant of testosterone misuse, a value above 1.1:1.0 being indicative of such misuse. The work-up procedure was designed for batch analysis and to use only simple techniques, rather than employ further instrumentation, such as high-performance liquid chromatography (HPLC), in purifying steroids for GC/C/IRMS.

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate.

Hormonal suppression of spermatogenesis is currently being investigated as a method of reversible male contraception. However, administration of exogenous testosterone (T) induces azoospermia in only 40-70% of Caucasian men, whereas the remainder suppresses to severe oligozoospermia (< 5 x 10(5)/mL). The reason(s) for the heterogeneity in the spermatogenic response is not clear. We have prospectively investigated the possibilities that higher plasma concentrations of T and/or differences in the extent and rate of gonadotropin suppression could maintain a low level of spermatogenesis in subjects taking part in a clinical efficacy trial of hormonal male contraception. Thirty-three healthy adult men, aged 21-41 yr, were given 200 mg T enanthate (TE), im, weekly for up to 18 months. Azoospermia was achieved in 18 men (55%) after 20 weeks of treatment, at which time the remaining 15 (45%) stabilized at a mean sperm density of 2.0 +/- 0.8 (+/- SD) x 10(6)/mL. These 15 subjects remained oligozoospermic for the rest of the efficacy study. To compare the pharmacokinetics and pharmacodynamics of TE between the azoospermic and oligozoospermic responders, plasma samples were obtained immediately before and 1, 2, 4, and 7 days after the 1st and 16th TE injections. Further samples were taken after 2, 4, 8, and 12 weeks of treatment. Plasma concentrations of total, free, and non-sex hormone-binding globulin (non-SHBG)-bound T, estradiol, LH, and FSH were measured. Compared to baseline, preinjection levels of total T increased 2.5-fold, reaching a steady state around 12 weeks of treatment. Peak concentrations of total T increased by 5-fold, but free and non-SHBG-bound T levels were increased by 10-fold after 16 weeks. The plasma levels of estradiol showed similar changes as T. However, neither T (bound or free) nor estradiol was significantly different between azoospermic and oligozoospermic responders. Plasma SHBG was reduced to a similar degree in both groups of men after 16 weeks of TE treatment. Plasma concentrations of both LH and FSH decreased rapidly after the first TE injection; a significant decline in LH was detectable after 24 h. Mean levels of both gonadotropins decreased to less than 0.5 U/L by the end of 4 weeks and to below the limit of sensitivity of the assays (0.05 IU/L) by 12 weeks. There were no significant differences in plasma concentrations of LH or FSH or in the rates of suppression between azoospermic and oligozoospermic responders. We conclude that the polymorphism of spermatogenic suppression in response to exogenous T is unlikely to be due to differences in the pharmacokinetics or pharmacodynamics of TE or in the sensitivity of the hypothalamo-pituitary-testicular axis to sex steroid inhibition. Measurements of total plasma T considerably underestimate the increase in bioavailable T during the weekly TE regimen.

Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study

To evaluate the secondary impact of a prototype androgen contraceptive regimen on physical, metabolic and behavioral variables. Prospective, open, noncomparative contraceptive efficacy study. International multicenter study comprising 10 centers in seven countries. Two hundred seventy-one healthy men, age 31.8 +/- 5.4 years (mean +/- SD), range 21 to 45 years. Weekly IM injections of 200 mg T enanthate. Adverse effects and discontinuations; biochemical and hematologic changes and interpopulation differences. Chinese subjects were shorter and lighter and their baseline hemoglobin, plasma lipid, and liver enzyme levels were lower than in non-Chinese subjects. The most common side effects were painful injections, acne, fatigue, and weight gain. Gynecomastia and prostate problems were detected in 24 and 9 men, respectively, though no men stopped injections for such reasons. Testosterone enanthate increased body weight, hemoglobin, and urea but decreased testicular volume and creatinine. Plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol were unchanged; high-density lipoprotein cholesterol decreased by 14% to 18% in non-Chinese but was unchanged in Chinese men. Liver transaminases were increased by 36% to 51% in Chinese but were unchanged in non-Chinese subjects. These T enanthate-induced effects were reversible within 6 months of stopping injections and were not related to the duration of T exposure. Testosterone enanthate administration in a contraceptive trial produced significant but reversible effects on skin, muscle, liver, lipid metabolism, and hemopoietic functions that varied between population groups. These effects reflect the relatively high peak levels and fluctuations of plasma T produced by the weekly T enanthate regimen rather than an inherent feature of hormonal male contraception. The results highlight the need for long-acting preparations of T with more stable delivery kinetics.

Testosterone enanthate at a dose of 200 mg/week decreases HDL‐cholesterol levels in healthy men

The concept that androgen alone can provide an effective male contraceptive has been tested in a multicentre, multiphase trial by the World Health Organization. Results from this trial showed that an ester of testosterone, testosterone enanthate (TE), administered at a dose of 200 mg/week, has a very high contraceptive efficacy, and suggested that, at least in some populations, androgen alone might provide a viable option for the control of male fertility. It has been claimed that testosterone represents one of the gender-related risk factors for coronary artery disease (CAD) in men. Epidemiological and interventional studies have failed to establish a convincing relationship between testosterone and high density lipoprotein cholesterol (HDL-C). Therefore, there is concern about possible negative effects on lipoprotein asset of an androgen-alone male contraceptive. In this study we analysed the effects of long-term (12 months) administration of TE (200 mg/week) in normal healthy men. Blood samples (six men > 10 h fast = Group 1; 30 men > 4 h fast = Group 2) were drawn from 36 men, monthly before the beginning of the injections (control), every 3 months throughout the study period (treatment), and 1 month after stopping TE injections (recovery). Total cholesterol (chol), triglycerides, HDL-C and LDL-C levels were measured in these samples. Biochemical parameters were also monitored. TE administration induced a significant decrease (15-20%) in HDL-C levels that was of comparable magnitude in men from both groups (fasting and non-fasting) and occurred regardless of basal HDL-C levels. No statistically significant effect on other lipoproteins was detected. Considering all men together, HDL-C levels were decreased in 78% of the men by month 3, 83% by month 6, 94% by month 9 and 97% by month 12 of treatment. In all men the HDL-C decrease was reversible within 1 month of stopping TE administration. It is concluded that: (1) injection of 200 mg TE/week causes a 15-20% decrease in HDL-C in normal men with no effect on other lipoproteins, (2) the suppressive effect of TE is maintained throughout the 1-year-injection period, and a direct relationship between the duration of TE administration and the proportion of men showing decreased HDL-C levels, was observed. (3) The HDL-C decrease was reversible within 1 month of stopping TE administration. These data will be important in designing further studies on male contraception, and in interpreting the relationship between testosterone levels, HDL-C levels and potential cardiovascular risk.

Sperm function in Indonesian men treated with testosterone enanthate.

This study was undertaken to assess the fertilizing capacity (sperm function) of residual spermatozoa produced by groups of men (n = 7) rendered oligozoospermic by treatment with weekly intramuscular injection of 50 or 100 mg testosterone enanthate (TE). The treatment was continued for 6 months and the effects compared with a control group (n = 6) in which men received weekly intramuscular injections of sesame oil (1 ml). Sperm function was assessed by tests of membrane integrity (supravital stain and hypoosmotic swelling [HOS] test) and sperm penetration (artificial cervical capillary tube test). The quality of sperm movement was also assessed. These parameters of sperm function were all reduced consistently in a dose-dependent manner with maximal suppression occurring between weeks 15 and 25 of treatment, and full recovery to baseline levels by 12 months after cessation of treatment. The decrease in sperm function was correlated with the degree of suppression of sperm output with the proportion of morphologically normal spermatozoa and the degree of suppression of gonadotrophin levels. The weekly dose of 50 mg TE induced severe oligozoospermia (concentration < 5 million/ml) in four of seven men, whereas 100 mg TE induced azoospermia in all seven men by week 20. It is concluded that, unlike published observations on men of European background, the administration of TE at 100 mg per week may achieve adequate contraceptive efficacy in Indonesian men.