Testosterone Oenanthate Research Articles

Aescin Protects against Experimental Benign Prostatic Hyperplasia and Preserves Prostate Histomorphology in Rats via Suppression of Inflammatory Cytokines and COX-2.

Background: Benign prostatic hyperplasia (BPH) is the most common urogenital condition in aging males, while inflammation and tissue proliferation constitute the main pathophysiological factors. The adverse effects of currently available BPH medications limit patient compliance. We tested the protective effect of aescin against the development of BPH in rats. Methods: A total of 18 male Wistar rats were divided into 3 groups: control (sesame oil 1 mL/kg, s.c.); BPH (testosterone oenanthate 3 mg/kg, s.c., in sesame oil), and BPH-aescin rats (testosterone oenanthate 3 mg/kg, s.c. + aescin 10 mg/kg/day, p.o.). All treatments continued for 4 weeks. Serum and prostatic samples were harvested for biochemical and histopathological examination. Results: Induction of BPH by testosterone increased the prostate weight and prostate weight index, serum testosterone, prostate expression of inflammatory (IL-1β, TNF-α, and COX-2), and proliferative markers (PCNA and TGF-β1). Concurrent treatment with aescin decreased the testosterone-induced increase in prostatic IL-1β, TNF-α, and COX-2 expression by 47.9%, 71.2%, and 64.4%, respectively. Moreover, aescin reduced the prostatic proliferation markers TGF-β1 and PCNA by 58.3% and 71.9%, respectively, and normalized the prostate weight. Conclusion: The results of this study showed, for the first time, that aescin protected against the development of experimental BPH in rats via its anti-inflammatory and antiproliferative effects. These findings warrant further studies to clinically repurpose aescin in the management of BPH.

Cardiac Lesions Induced by Testosterone: Protective Effects of Dexrazoxane and Trimetazidine

Further to our previous observation of post-mortem cardiac lesions after sudden death in several athletes with a history of anabolic steroid abuse, this study was intended to reproduce these lesions in rabbits administered testosterone oenanthate, a prototypic anabolic steroid abused by athletes, and to provide evidence for the protective effects of trimetazidine and dexrazoxane that are used as antianginal and cardioprotective drugs, respectively. Groups of six rabbits each were administered saline, testosterone, or a combination of testosterone and either trimetazidine or dexrazoxane for 3 months. Histologic cardiac lesions including necrosis, misshapen cell nuclei, interstitial and endocardial fibrosis, lymphocytic infiltrates, and vascular dystrophies were observed in testosterone-treated rabbits. In contrast, no significant lesions were observed in the animals treated with testosterone combined with either trimetazidine or dexrazoxane. This is the first study providing evidence for testosterone cardiotoxicity following sub-chronic exposure in laboratory animals. In addition, these results suggest the protective role of trimetazidine and dexrazoxane.

Demonstration of the Reversibility of Spermatozoa Suppression by Testosterone Oenanthate

Long-term treatment with testosterone oenanthate in seven healthy young men was conducted with the aim of inducing reversible inhibition of spermatogenesis. During the observation period following discontinuation of the therapy spermatogenesis showed a gradual recovery. In three cases, however, the sperm counts did not reach pre-treatment levels. The subjects were re-examined 3 years after the start of the study, i.e. 2.5 years after the last injection of testosterone oenanthate. This examination confirmed that the testosterone treatment had had no recognizable negative influence on testicular function--on the contrary, in three cases analysis of the seminal fluid yielded higher sperm counts than previously.

Effect of administration of a single dose of testosterone oenanthate on constituents of human seminal plasma and serum gonadotropins.

Testosterone oenanthate was administered intramuscularly in six infertile men with oligozoospermia and its effects on serum gonadotropins and some constituents in the seminal plasma were studied. One week after injection the mean serum FSH level was decreased to about 50%. Serum LH levels did not change. The mean ornithine decarboxylase activity in human semen was increased by 100% after the testosterone administration. The androgen dependent nature of ODC, fructose and sialic acid have been demonstrated.

Effect of administration of a single dose of testosterone oenanthate on human serum and seminal plasma inhibin concentration.

The effect of a single administration of testosterone oenanthate (250 mg, intra-muscularly) on serum and seminal plasma inhibin concentrations were studied in four adult human volunteers. A significant decrease in serum FSH and LH levels were observed by day 6 when the serum testosterone levels were high. These were followed by a sharp increase in serum and seminal plasma inhibin concentration by day 8 and day 12 respectively. The present investigations also suggest the existence of a positive relationship between the serum and seminal plasma inhibin concentrations.

Short-term, high-dose testosterone treatment fails to reduce adult height in boys with constitutional tall stature.

Height predictions based on three different methods (Bayley-Pinneau [BP], Tanner-Whitehouse Mark II [TW II], Roche-Wainer-Thissen [RWT]) were compared to adult heights in 19 males with constitutional tall stature previously treated with high-dose testosterone oenanthate for 6 months (group A) and 25 untreated tall males (group B). Their chronological ages (CA) at the initial evaluation of tall stature ranged from 12.1 to 16.6 years in group A and from 10.4 to 15.7 years in group B; at the time of assessment of adult height ages ranged from 18.0 to 26.5 years and from 18.4 to 25.1 years, respectively. Height measurements and predicted adult heights were expressed as height standard deviation scores (height SDS) for chronological age using the tables of Reinken and van Oost [14]. Height SDS in group A were 2.8 (range = 1.8-5.4) before testosterone treatment, 3.0 (range = 2.0-4.8) thereafter and finally 3.0 (range = 2.1-4.2) (P = NS) and in group B 2.7 (range = 0.5-4.3) and 2.4 (range = 1.3-3.5) (P = NS). A significant difference between adult height SDS and predicted height SDS according to BP was detected both in group A (3.0; range = 2.1-4.2 vs 3.6; range = 2.4-5.0. P < or = 0.004) and group B (2.4; range = 1.3-3.5 vs 3.0; range = 2.0-4.9; P < or = 0.0002), whereas no significant difference between adult height SDS and predicted height SDS according to TW II and RWT was found in either group. These data indicate that BP height predictions overestimated adult height in our patient group of treated and untreated males with constitutional tall stature. In contrast, the TW II and RWT methods were more accurate in predicting adult height in these patients, but also failed to demonstrate that testosterone therapy in boys with constitutional tall stature can be limited to a 6-month period in order to reduce adult height. The widely used height prediction method of BP is inaccurate in boys with constitutional tall stature. High dose testosterone treatment fails to reduce adult height in these individuals when discontinued before complete closure of the epiphyses.

Sensitivity to testosterone varies with strain, sex, and site of action in chickens

Day-old chicks (cockerels and pullets) of two strains of chicken (a commercial breed and strain of feral fowl) were treated intramuscularly with 25 mg/0.1 ml of testosterone oenanthate on day 1 posthatching. Controls received 0.1 ml of the vehicle. Attack and copulatory behavior were scored from days 7 to 14 using standard hand-thrust tests, which rank the responses from 1 to 10. The sizes of the comb and testes were also measured. All measures showed strain and sex differences. Copulation and attack scores were highest in males of the feral strain. Even untreated males of the feral strain had high scores, and these were further elevated by the testosterone treatment. In fact, the attack scores of feral males were marginally higher than those of the males of the commercial strain treated with testosterone. Testosterone treatment of the feral females also elevated attack and copulation to a much greater extent than in the commercial strain. Opposite effects occurred for the development of the comb. Comb volume, absolute and adjusted for body weight, was much greater in treated chicks of the commercial strain than in those of the feral strain. These results indicate that chicks of the feral strain may have more central and fewer peripheral receptors for testosterone or that their receptors for testosterone are more sensitive than those of the commercial strain. Alternatively, there may be strain, as well as sex, differences in the metabolism of testosterone.

Haemostatic Effects of Supraphysiological Levels of Testosterone in Normal Men

The effects of exogenous testosterone on the haemostatic system were studied in a group of 32 healthy men undergoing a clinical trial of hormonal male contraception. The men received 200 mg testosterone oenanthate (TE) weekly i.m., and plasma samples were taken pretreatment, at defined time points up to 52 weeks of treatment, and 4 and 8 weeks after discontinuing TE. This dose of TE caused a 2-fold increase in trough plasma testosterone levels. TE caused a fall in plasma fibrinogen concentration after 16 weeks of treatment. This was sustained for the duration of TE treatment and recovered to pretreatment levels during the recovery phase. There was also a sustained fall in the level of C4b binding protein which showed a rebound to levels above pretreatment during recovery. Levels of antithrombin III and prothrombin fragment F1.2 rose initially during TE treatment, and levels of protein C, protein S (free) and plasminogen activator inhibitor fell, but the concentrations of these factors all returned to pretreatment levels during continued treatment. There was no change in the plasma concentrations of beta-thromboglobulin, tissue plasminogen activator, protein S (total), or D-dimer. There was a sustained increase in haemoglobin concentration and haematocrit, without any change in platelet count. The observed changes were consistent with mild activation of the haemostatic system during initial treatment with testosterone. After several months the raised activation markers had returned to pretreatment levels indicating that a new equilibrium had been established which did not appear to be prothrombotic.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Treatments by Calcium and Sex Hormones on Vertebral Fracturing in Osteoporosis

Lateral radiographs of the thoracic and lumbar spine were taken periodically in 49 patients with osteoporosis. Thirty patients were postmenopausal, and 19 nonmenopausal with osteoporosis due to steroids, male hypogonadism, alcoholism, thyrotoxicosis or unknown cause. Patients were studied before, during and after treatment with high calcium alone, or with combined calcium and sex steroids. Calcium was given as effervescent calcium lactate gluconate, and sex hormones as oestradiol valerate, testosterone oenanthate, or methenolone oenanthate. A total of 964 films covering 409 patient-years were available for measurement. On each vertebra, deformity due to loss of anterior height was measured and assigned to one of four grades. For the time interval between each consecutive pair of films, a patient's vertebral fracture rate score was calculated and expressed per thousand patient-years. In comparison with the corresponding pretreatment fracture rate score, both the postmenopausal and the nonmenopausal groups who had not received sex hormones previously, failed to show significant changes (p = 0.144; p = 0.017) on high calcium alone during mean periods of 4.3 and 2.8 years respectively. If the first 2 years on high calcium were excluded for the postmenopausal group, they still failed to show a reduction in fracture rate score (observed for a mean period of 5.0 years; p = 0.04). When treated with combined calcium and sex hormones, both postmenopausal and nonmenopausal groups showed a lower fracture rate score of 20 and 207 respectively when compared with the pretreatment levels of 1500 and 1697 (in mean treatment periods of 3.2 and 4.4 years; p less than 0.001 in each case). When given high-dose calcium alone, but after treatment with sex hormones as well, the postmenopausal group showed no change in fracture rate score from pretreatment (in a mean of 3.1 years; p = 0.069); however the nonmenopausal group still showed a significant reduction in fracture rate score from 1697 to 42 over a mean period of 2.3 years (p = 0.001). The postmenopausal group, after stopping all treatment, showed a higher fracture rate score of 1286 (in a mean of 2.6 years) than did those on combined calcium and sex hormones, in whom the fracture rate score was 20 (in a mean of 3.2 years; p = 0.008). A subgroup of 11 patients with osteoporosis of both the menopausal and nonmenopausal types, had data both before (in a mean of 5.5 years) and during (for a mean of 2.5 years) treatment with calcium alone; the fracture rate scores were 1473 and 918 (p = 0.247).(ABSTRACT TRUNCATED AT 400 WORDS)

EFFECT OF LONG‐TERM ADMINISTRATION OF TESTOSTERONE OENANTHATE ON SYMPATHETIC NEUROTRANSMISSION TO RAT ISOLATED SEMINAL VESICLES

1. The effects of prolonged administration of testosterone oenanthate (TE) on sympathetic neurotransmission to the rat isolated seminal vesicle were examined. 2. TE was administered at either 1.2 or 2.4 mg/kg subcutaneously (s.c.) thrice weekly for 8 weeks. A separate group of rats was administered the vehicle, sesame oil, 0.5 mL/kg, s.c. at the same regime and used as controls. TE administration increased plasma testosterone and dihydrotestosterone levels and seminal vesicle weights. TE 2.4 mg/kg suppressed fertility in male rats. 3. The mean -log EC50 values of adrenalin and noradrenaline in seminal vesicles from the control group were 5.30 (95% confidence limits: 5.14, 5.58; d.f. = 14) and 4.92 (95% confidence limits: 4.56, 5.49; d.f. = 14) respectively. Neither of these estimates were modified by TE administration. 4. The mean noradrenaline content (microgram/tissue) in seminal vesicles from control rats was 0.88 +/- 0.09 microgram/tissue. This did not change with TE treatment. Tissue noradrenaline concentration (microgram/g tissue), on the other hand, decreased by more than 50% in preparations from rats treated with TE. This was paralleled by a decrease in the density of catecholamine fluorescence. 5. Mean responses to field stimulation (20 pulses, 60 V dial setting, 2 ms, 1-70 Hz) appeared to decrease in preparations from TE treated groups; this decrease was, however, not statistically significant (P greater than 0.05; d.f. = 15). 6. It is concluded that prolonged administration of testosterone oenanthate to rats, at doses sufficient to suppress fertility, decreases the density of sympathetic innervation to the seminal vesicle by increasing smooth muscle mass. Treatment does not, however, modify the responses of this preparation to exogenously added catecholamines.

Effect of depot medroxyprogesteroneacetate and testosteroneoenanthate on serum lipoproteins in man

Ten normal men were given three monthly intramuscular injections of 200mg of depot medroxyprogesterone acetate (DMPA) and 250mg of testosterone oenanthate (TE) as part of a male contraceptive trial. During the three months of treatment, serum high density lipoprotein cholesterol (HDL-C) and the HDL-C:LDL-C (low density lipoprotein cholesterol) ratio were significantly depressed compared to baseline. Although the long-term effect of this alteration in lipoprotein cholesterol metabolism in normolipidaemic men is currently uncertain, these results suggest that the potential cardiovascular risks of progestagen-containing regimens for male contraception will have to be seriously considered.

THE EFFECT OF SHORT TERM HIGH DOSE TESTOSTERONE THERAPY ON BONE AGE (BA) AND HEIGHT IN TALL BOYS

We have prospectively evaluated the effect of a short term high dose testosterone therapy on height and BA in tall boys. BA was assessed according to the Greulich-Pyle method. Adult height was predicted with the tables of Bayley-Pinneau. Treatment consisted of intramuscular injections of 500 mg testosterone oenanthate every 2 weeks for 6 months. Height and BA were determined before, at the end of and 3, 6 and 12 months after therapy. 34 boys have been followed for at least 6 months after therapy. ΔBA/ΔCA accelerated by 2.46 ± 0.82 years (mean ± SD) during therapy and by 2.99 ± 1.14, 2.23 ± 0.78 and 1.58 ± 0.46 years 3, 6 and 12 months thereafter, thus demonstrating, that BA-acceleration persists for several months after treatment.12 boys were measured 2.50 ± 0.34 years after therapy. Their initial bone age was 14.02 ± 0.52 years with a predicted height of 204.99 ± 4.25 cm. At the end of therapy height was 193.61 ± 5.59 cm and bone age 15.67 ± 0.58 years. Height at the time of the last evaluation was 197.38 ± 4.11 cm, which is 7.61 ± 5.6 cm less than predicted. The reduction of 50.26 ± 14.55 % is similar to the one observed in 115 boys treated for 14.25 ± 4.14 months with the same therapeutic regimen.We conclude, that with the persistent acceleration of BA after treatment only 6 months of high dose testosterone therapy are needed to effectively reduce height in boys with tall stature.

TESTOSTERONE THERAPY IN BOYS WITH DELAYED PUBERTY

Delayed puberty, often associated with short stature is a common problem in the paediatric clinic. These boys' retarded growth and sexual development causes considerable distress during adolescence. Because testosterone is widely believed to accelerate bone maturation disproportionately and thus reduce final height this treatment is often withheld. 36 boys, aged 12.0-17.7 (mean 14.8) yrs, were treated with testosterone oenanthate 125mg intramuscularly for 3 months. They were seen half yearly and heights (Harpenden stadiometer), skeletal maturation (Tanner RUS (TW2)) and pubertal status (Tanner and Whitehouse) were measured. At 6 months there was a distinct advance in pubertal status and an increase in height velocity from 4.4 to 9.8cm/year. The boys' morale and confidence increased impressively. No serious side-effects were seen. The effects of treatment on height prediction and height standard deviation score for bone age are shown below: Treatment with testosterone effectively alleviates the main problems of delayed puberty and our data suggest that at this dosage it has no significant effect on final height.

Oestrogen dependent suppression of mitogen response in rat lymphocytes.

Female Fischer rats have a significantly (P less than 0.01) lower response to mitogens (phytohaemagglutinin and pokeweed mitogen) in whole blood cultures, than do male. In vitro cultures were carried out in 96-well micro-test plates with 5% blood over a period of 64 h, with a pulse of [3H]thymidine at 48 h. Ovariectomy resulted in a significant (P less than 0.01) increase in mitogen response, raising it to the level of normal males. Orchidectomy caused a small, but consistent rise in response. Injection of oestradiol valerate (at 0.5 mg/week, to yield physiological levels) suppressed the response of gonadectomized animals of both sexes to the level of normal female rats. Testosterone oenanthate had little effect unless administered in conjunction with oestradiol valerate, when a much greater depression of response was noted. Suppressor cells, or suppressive serum factors, could not be detected in the blood of normal females or oestrogen-treated animals during in vitro mixing experiments. Although it required 3 weeks for the ovariectomized animals' response to rise to the level of normal males, only 3 days of oestradiol valerate treatment was necessary to suppress the response again. Whereas it seems clear that oestradiol is responsible for the suppressed response of female Fischer rats, its mechanism of action has not been revealed by our experiments.

TREATMENT WITH HIGH DOSES OF ESTROGENS AND ANDROGENS INDUCES MARKED CHANGES NOT ONLY ON GONADAL AND ADRENAL STEROIDS AND THEIR BINDING GLOBULINS BUT ALSO ON THE THYROID HORMONES AND ON THYROXIN BINDING GLOBULIN

Little is known about the influence of high doses of sexual steroids on other hormones and their binding globulins. We studied 28 children treated for tall stature: 14 boys treated with 500 mg testosterone oenanthate every two weeks; 14 girls treated with 0.5 mg ethinyestradiol from day 1 to 25 and 15 mg norethisterone day 20 to 25. Results boys: TBG reduced (19.03 ± 0.9 (SE) mg/1), T4 and T4/TBG-ratio markedly reduced (51.4 ± 6.4 (SE) ug/1 and 2.65 ± 0.25 (SE)). T3 variable, basal TSH levels and TSH-rise in TRH-test normal. Cortisol normal, CBG slightly reduced and C/CBG-ratio slightly increased. SHBG levels markedly reduced and T/SHBG-ratio extensively increased. Results girls: TBG markedly increased (36.6 ± 2.3 (SE) mg/1) but T4 only slightly elevated (94.9 ± 7.4 (SE)), reduction of the T4/TBG-ratio (2.55 ± 0.17 (SE)). T3 variable, TSH in TRH-test normal. Cortisol and CBG increased, but C/CBG-ratio unchanged. T increased slightly, SHBG increased markedly, T/SHBG decreased distinctly. We conclude that high doses of sexual steroids induce profound changes in hormone levels which are either compensated or aggravated by simultaneous changes of their binding globulins.

Sex differences and reversal of brain asymmetry by testosterone in chickens

The study examined the effect of testosterone on the asymmetry of visual discrimination performance of young chicks. Two-week-old chicks were tested on the pebble floor visual discrimination task. Male chicks were found to have brain asymmetry for visual discrimination learning, since chicks tested binocularly, or tested monocularly using their right eye system, have superior learning performance compared to chicks tested monocularly using their left eye system. Control female chicks were not found to have brain asymmetry. Testosterone treatment (12.5 mg of testosterone oenanthate on day 2 posthatch) reversed the pattern of brain asymmetry observed in control males but not females. In addition, asymmetry of visual discrimination learning is demonstrated in both male and female chicks after unilateral intracranial treatment with monosodium glutamate.

Effect of testosterone oenanthate on spermatogenesis and serum testosterone concentrations in adult mice.

Administration of 80 or 160 micrograms testosterone oenanthate s.c. three times per week for 8 or 12 weeks reduced testis weight and increased seminal vesicle weight in mice. Radioimmunoassay indicated that treatment increased serum testosterone concentrations. Treatment with testosterone oenanthate decreased the number of step 16 and step 7 spermatids, pachytene spermatocytes and type A spermatogonia, and particularly reduced the proportion of step 7 spermatids which matured to form step 16 spermatids.

New injectable testosterone ester maintains serum testosterone of castrated monkeys in the normal range for four months.

Two groups of four long-term orchidectomized cynomolgus monkeys, Macaca fascicularis, weighing 2.8-4.6 kg received either a single intramuscular injection of 40 mg of a new testosterone ester, testosterone-trans-4-n-butylcyclohexyl-carboxylate (20 Aet-1) in an aqueous suspension or 32.8 mg testosterone oenanthate dissolved in sesame oil. Both preparations contained equal amounts of testosterone, namely 23.6 mg. Testosterone oenenthate injections resulted in supraphysiological serum testosterone levels for eight days followed by a rapid decline so that the lower physiological limit was reached after three weeks. In contrast, 20 Aet-1 produced a moderate increase of serum testosterone levels into the physiological range. Serum testosterone remained in this range for a period of 18 weeks. Thus it appears that the 20 Aet-1 may provide a long desired, new modality of testosterone substitution for hypogonadal men as well as for methods of male fertility control.

Gonadal and adrenal steroids and their binding globulins SHBG and CBG in patients treated with ethinylestradiol and testosterone oenanthate

Gonadal and adrenal steroids and their binding globulins SHBG and CBG in patients treated with ethinylestradiol and testosterone oenanthate

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency: gender reassignment in early infancy.

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) deficiency has a high prevalence within the Arab population of the Gaza strip and is characterised by marked virilization at puberty, leading in many cases to the spontaneous adoption of a male gender role. As a result of this, parents of 7 affected male infants (aged 1-10 months) born with female phenotype requested early gender reassignment. Diagnosis was suspected in 5 on the basis of a positive family history, but confirmed in all cases by the finding of low to normal testosterone levels (30-184 ng/dl) with high delta 4-androstenedione levels (188-808 ng/dl), after hCG. Treatment with im testosterone oenanthate (25-50 mg/dose) was given in one to three 3-months courses and penile size was increased into the normal range without evoking a significant increase in height velocity or skeletal maturation. Five patients underwent the first stage of male genitoplasty between 2 and 3 years of age. This consisted of bilateral orchidopexy, chordee release and penile lengthening - yielding finally an anatomically normal-sized and shaped penis. Androgen responsive male pseudohermaphroditism due to 17 beta-HSD deficiency or a similar defect and diagnosed in infancy should be treated as soon as possible with systemic testosterone before considering any sex change, and in preparation for male genitoplasty. Early gender reassignment according to genetic and gonadal sex is probably the management of choice for these cases since this may result in a normal adjustment to the male gender role, particularly after puberty.