Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate

1995 ◽  
Vol 132 (4) ◽  
pp. 514-519 ◽  
Author(s):  
Carl-Joachim Partsch ◽  
Gerhard F Weinbauer ◽  
Ruiying Fang ◽  
Eberhard Nieschlag
Keyword(s):  
Body Weight ◽  
Serum Testosterone ◽  
Pharmacokinetic Analysis ◽  
Male Hypogonadism ◽  
Androgen Deficiency ◽  
Testosterone Enanthate ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Testosterone Undecanoate ◽  
Testosterone Levels

Partsch C-J, Weinbauer GF, Fang R, Nieschlag E. Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate. Eur J Endocrinol 1995;132:514–19. ISSN 0804–4643 Testosterone preparations producing constant physiological testosterone serum levels are desirable for long-term treatment of androgen deficiency. However, all injectable testosterone esters used clinically for substitution of male hypogonadism are characterized by unfavourable pharmacokinetics. We therefore tested two groups of five long-term orchidectomized cynomolgus monkeys (Macaca fascicularis), which received a single intramuscular injection of 10 mg/kg body weight of an injectable testosterone undecanoate (TU) preparation or testosterone enanthate (TE) in a preclinical study to assess the pharmacokinetic and pharmacodynamic characteristics of TU in comparison to TE. The dose was equivalent to 6.3 and 7.2 mg of pure testosterone per kilogram body weight in the TU and TE group, respectively. Following injection of TU, mean serum testosterone rose to 58 ± 18 nmol/l on day 1 and remained at moderately supraphysiological levels of 40–68 nmol/l for 45 days. Thereafter, testosterone levels were maintained in the normal range of intact monkeys for another 56 days. The TE injection resulted in highly supraphysiological levels of 100–177 nmol/l from immediately after the injection to day 5. A rapid decline followed and testosterone levels reached the lower limit of normal after 31 days. Serum testosterone levels were significantly higher in the TEthan in the TU-treated animals on days 0.5–7 (p < 0.05). Significantly lower testosterone levels were seen in the TE than in the TU group on days 16, 22, 25 and 31 (p < 0.05). Pharmacokinetic analysis of serum testosterone levels showed a significantly higher area under the curve for TU (4051 ± 939 vs 1771 ±208 nmol·h/l; p < 0.045), a longer residence time (40.7 ±4.1 vs 11.6 ±1.1 days; p <0.00012), a longer terminal half-life (25.7 ± 4.0 vs 10.3 ± 1.1 days; p < 0.0069), and a lower maximal testosterone concentration (73 ± 12 vs 177 ± 21 nmol/l; p < 0.0027). Following TU injection, oestradiol levels increased from 48 ± 8 pmol.l to a plateau of 80–118 pmol/l from day 1 to day 59. In contrast, TE injection resulted in a rapid increase of oestradiol levels to a maximum of 166 ± 29 pmol/l after 4 days (p < 0.05 vs TU- treated group). In the TU and TE groups levels below 80 pmol/l were reached after 66 and 16 days, respectively. Ejaculatory response was induced for 14 weeks in the TU animals in contrast to 7 weeks in the TE animals. Ejaculate weight reached a maximum of 533 ± 163 mg at day 52 in the TU group (p < 0.05 vs TE group). In the TE animals, the maximal ejaculate weight of 41 ± 17 mg was seen at day 16. Thus, with respect to androgen substitution therapy, TU showed pharmacokinetic and pharmacodynamic properties clearly superior to those of TE and may provide an important improvement in the substitution of male androgen deficiency and also for male contraception. E Nieschlag, Institute of Reproductive Medicine of the University, Steinfurter Str. 107, D-48149 Münster, Germany

Why Do We Need New Markers for Male Hypogonadism and How Seminal Proteomics Might Solve the Problem?

2020 ◽  
Vol 27 (12) ◽  
pp. 1186-1191
Author(s):  
Giuseppe Grande ◽  
Domenico Milardi ◽  
Silvia Baroni ◽  
Andrea Urbani ◽  
Alfredo Pontecorvi
Keyword(s):  
Serum Testosterone ◽  
Clinical Syndrome ◽  
Testosterone Replacement ◽  
Total Testosterone ◽  
Male Hypogonadism ◽  
Grey Zone ◽  
Testosterone Levels ◽  
Normal Number ◽  
Replacement Treatment

Male hypogonadism is “a clinical syndrome that results from failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic– pituitary–testicular axis”. The diagnostic protocol of male hypogonadism includes accurate medical history, physical exam, as well as hormone assays and instrumental evaluation. Basal hormonal evaluation of serum testosterone, LH, and FSH is important in the evaluation of diseases of the hypothalamus-pituitary-testis axis. Total testosterone levels < 8 nmol/l profoundly suggest the diagnosis of hypogonadism. An inadequate androgen status is moreover possible if the total testosterone levels are 8-12 nmol/L. In this “grey zone” the diagnosis of hypogonadism is debated and the appropriateness for treating these patients with testosterone should be fostered by symptoms, although often non-specific. Up to now, no markers of androgen tissue action can be used in clinical practice. The identification of markers of androgens action might be useful in supporting diagnosis, Testosterone Replacement Treatment (TRT) and clinical follow-up. The aim of this review is to analyze the main findings of recent studies in the field of discovering putative diagnostic markers of male hypogonadism in seminal plasma by proteomic techniques. The identified proteins might represent a “molecular androtest” useful as a seminal fingerprint of male hypogonadism, for the diagnosis of patients with moderate grades of testosterone reduction and in the follow-up of testosterone replacement treatment.

Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates

1990 ◽  
Vol 122 (4) ◽  
pp. 432-442 ◽  
Author(s):  
Gerhard F. Weinbauer ◽  
Bettina Jackwerth ◽  
Yong-Dal Yoon ◽  
Hermann M. Behre ◽  
Ching-Hei Yeung ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Half Life ◽  
Rhesus Monkeys ◽  
Serum Testosterone ◽  
Testosterone Enanthate ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Elimination Phase ◽  
Cynomolgus Monkeys ◽  
Ejaculate Size ◽  
Testicular Size

Abstract. The pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosteroneenanthate were compared in orchidectomized cynomolgus monkeys (Macaca fascicularis) and in intact GnRH agonist-suppressed rhesus monkeys (Macaca mulatta). Following a single im injection of 32.8 mg testosterone enanthate or 32.7 mg dihydrotestosteroneenanthate, i.e. 23.6 mg of pure steroid, in the orchidectomized cynomolgus monkeys, serum testosterone and dihydrotestosterone levels rose to 400 and 800% of baseline, respectively, within 24 h. Androgen levels remained in that range for 3-5 days followed by a continuous decline until baseline values were attained after 4-5 weeks. The areas under the testosterone- and dihydrotestosterone-curves did not differ significantly 2290±340 (dihydrotestosterone-enanthate) vs 2920±485 (testosteroneenanthate) suggesting that similar amounts of steroid had been released from the respective ester preparation. Mean half-life estimates of the terminal elimination phase were 4 and 7 days for testosterone-enanthate and dihydrotestosterone-enanthate, respectively. In a second experiment rhesus monkeys received, at 4-weekly intervals, sc implantation of a biodegradable polylactic:polyglycolide rod loaded with the GnRH agonist buserelin. The last injection was given during week 20. GnRH agonist treatment suppressed serum bioactive LH, testosterone and dihydrotestosterone levels, testicular size, sperm production, and seminal carnitine content. The ejaculatory response to electrostimulation and the masturbatory behaviour were abolished. Testosterone or dihydrotestosterone injections at the same doses as above were given in week 10, 14, 17 and 20 of GnRH agonist treatment. Serum testosterone and dihydrotestosterone levels were stimulated 9- and 4-fold, respectively. Mean half-life estimates for testosterone-enanthate and dihydrotestosterone were 5 and 7 days, respectively. Both ester preparations completely restored the ejaculatory response, ejaculate size, masturbatory behaviour, and seminal carnitine levels. In conclusion, androgen substitution with dihydrotestosterone-enanthate, in equivalent doses, is as effective as testosterone-enanthate in restoring reproductive functions in hypogonadal monkeys.

Correction of Androgen Deficiency in Men with Type 2 Diabetes

2021 ◽  
Vol 16 ◽  
Author(s):  
Volodymyr Pankiv ◽  
Tetyana Yuzvenko ◽  
Nazarii Kobyliak ◽  
Ivan Pankiv
Keyword(s):  
Type 2 Diabetes ◽  
Replacement Therapy ◽  
Testosterone Replacement ◽  
Control Group ◽  
Total Testosterone ◽  
Testosterone Replacement Therapy ◽  
Androgen Deficiency ◽  
Testosterone Undecanoate ◽  
Testosterone Levels

Background: In men with low levels of testosterone in the blood, it is believed that the symptoms can be regarded as an association between testosterone deficiency syndrome and related comorbidities. Aim: to investigate the effectiveness of testosterone therapy in patients with type 2 diabetes (T2D) and androgen deficiency. Materials and methods: Testosterone replacement therapy was carried out in 26 men with T2D and clinically or laboratory-confirmed androgen deficiency. The age of the subjects ranged from 35 to 69 years old. Laboratory studies included determinations of the concentration of the hormones estradiol, luteinizing hormone (LH), and prostate-specific antigen (PSA). The observation period was 9 months. Results: The average level of total blood testosterone in the subjects before treatment was 9.4 mol/l and was likely lower than that of the control group (19.3 ± 1.6 nmol/l). The levels of total testosterone in the subjects ranged from 3.9 nmol/l to 10.7 nmol/l, and hormone levels measuring less than 8.0 nmol/l were observed in only 11 patients. After a course of testosterone replacement therapy, a stabilization in total testosterone levels at the level of reference values (as compared to the start of treatment) was observed in the blood of men with T2D after 9 months of observation and the administration of the fourth injection (16.83 ± 0.75 nmol/l). Conclusion: The use of long-acting injectable testosterone undecanoate leads to normalization of total testosterone levels in the blood of men with T2D and androgen deficiency, and LH levels in these patients are unlikely to change.

scholarly journals Decreased Serum Testosterone Levels in Long-Term Adult Survivors with Fatty Liver after Childhood Stem Cell Transplantation

2012 ◽  
Vol 18 (7) ◽  
pp. 1119-1127 ◽  
Author(s):  
Hiromi Hyodo ◽  
Hiroyuki Ishiguro ◽  
Yuichiro Tomita ◽  
Hiromitsu Takakura ◽  
Takashi Koike ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Fatty Liver ◽  
Cell Transplantation ◽  
Serum Testosterone ◽  
Adult Survivors ◽  
Testosterone Levels

scholarly journals Serum testosterone levels in male hypogonadism: Why and when to check-A review

2017 ◽  
Vol 71 (11) ◽  
pp. e12995 ◽  
Author(s):  
Mark Livingston ◽  
Anura Kalansooriya ◽  
Andrew J. Hartland ◽  
Sudarshan Ramachandran ◽  
Adrian Heald
Keyword(s):  
Serum Testosterone ◽  
Male Hypogonadism ◽  
Testosterone Levels

Substitution therapy of hypogonadal men with transdermal testosterone over one year

1988 ◽  
Vol 118 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Monika Bals-Pratsch ◽  
Klaus Langer ◽  
Virgil A. Place ◽  
Eberhard Nieschlag
Keyword(s):  
Clinical Chemistry ◽  
Day Treatment ◽  
Treatment Phase ◽  
Serum Testosterone ◽  
Male Hypogonadism ◽  
Substitution Therapy ◽  
Entire Treatment Period ◽  
Testosterone Levels ◽  
Physiological Range ◽  
Testosterone Substitution

Abstract. Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3–5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment. Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.

Effects of Methanol Vapors on Testosterone Production and Testis Morphology in Rats

1991 ◽  
Vol 7 (4) ◽  
pp. 261-275 ◽  
Author(s):  
E. Lee ◽  
A.N. Brady ◽  
M.J. Brabec ◽  
T. Fabel
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Weight Ratio ◽  
Serum Testosterone ◽  
Exposure Period ◽  
Body Weight Ratio ◽  
Testosterone Levels ◽  
Age Related ◽  
Testosterone Synthesis ◽  
Testicular Degeneration

Potential toxic effects of methanol vapors on testicular produc tion of testosterone and the morphology of testes were investi gated using normal or methanol-sensitive folate-reduced rats. Methanol inhalation at the level of the current permissible expo sure limit, 200 ppm, for up to six weeks (8 hours/day, 5 days/ week), did not reduce serum testosterone levels in normal rats. Testes isolated from methanol-exposed (200 ppm) rats had the same capability as those from air-exposed rats in synthesizing testosterone whether testes were incubated in the absence or pres ence of hCG. The testes-to-body weight ratio of rats exposed up to 800 ppm methanol for up to 13 weeks (20 hours/day, 7 days/ week) were not different from those of the air-exposed rats. Fur thermore, methanol had no adverse effect on testicular morphol ogy at the end of the 13 week exposure period at 800 ppm in either normal rats or folate-reduced methanol-sensitive rats when they were 10 months old at the time of examination. Thus, these data indicate that low level methanol may not cause an inhibi tory effect on testosterone synthesis contrary to previous litera ture reports. However, a greater incidence of testicular degeneration was noticed in the 18 month old folate-reduced rats exposed to 800 ppm for 13 weeks (20 hours/day, 7 days/week), suggesting that methanol may have a potential to accelerate the age-related degeneration of the testes.

scholarly journals Breast Tissues in Transsexual Women–A Nonprostatic Source of Androgen Up-Regulated Production of Prostate-Specific Antigen

1999 ◽  
Vol 84 (9) ◽  
pp. 3313-3315
Author(s):  
Victor H. H. Goh
Keyword(s):  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Androgen Therapy ◽  
Testosterone Levels ◽  
The Mean ◽  
Breast Tissues ◽  
Serial Measurements

The present study made use of the female transsexual model and sought to evaluate the contributions of the ovarian, endometrial, and breast tissues to the androgen up-regulated production of prostate specific antigen (PSA). Serum levels of PSA were significantly raised in female transsexuals before surgery, after long-term androgen therapy (mean ± se = 35.3 ± 6.2 pg/mL) when compared with female transsexuals before surgery, but with no androgen therapy (mean ± se = 1.53 ± 0.25 pg/mL). In addition, in androngenized female transsexuals, after surgery, concentrations of PSA (mean ± se = 14.5 ± 2.8 pg/mL) were significantly lowered compared with androngenized female transsexuals after surgery, but the levels were, nevertheless, significantly higher than in normal females. Monthly im injection of 250 mg Sustanon-250 to female transsexuals had raised serum testosterone levels to within the male range. In five subjects, in whom serial measurements were taken, serum testosterone levels were greatly raised 24 h after the testosterone therapy; the mean level (±se) was 19.5 ± 2.1 ng/mL. But in spite of these high testosterone levels, serum PSA levels (mean ± se= 2.2 ± 0.9 pg/mL) were not significantly raised. However, after 12 months of androgen therapy, the mean (±se) PSA level in these five subjects was 47 ± 11.6 pg/mL and was significantly higher than the mean level in nonandrogenized female transsexuals. The present study confirmed that high levels of testosterone were able to up-regulate PSA production in women. This up-regulation of PSA production is both a dose- and time-dependent process. Furthermore, the evidence indicates that breast tissues are possibly a nonprostatic source of androgen up-regulated production of PSA women.

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