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.

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.

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

Sustained inhibition of sperm production and inhibin secretion induced by a gonadotrophin-releasing hormone antagonist and delayed testosterone substitution in non-human primates (Macaca fascicularis)

1989 ◽  
Vol 123 (2) ◽  
pp. 303-310 ◽  
Author(s):  
G. F. Weinbauer ◽  
S. Khurshid ◽  
U. Fingscheidt ◽  
E. Nieschlag
Keyword(s):  
Sertoli Cell ◽  
Macaca Fascicularis ◽  
Gnrh Antagonist ◽  
Cell Activity ◽  
Serum Testosterone ◽  
Sperm Production ◽  
Entire Treatment Period ◽  
Releasing Hormone ◽  
Testosterone Substitution ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Since the concomitant administration of a gonadotrophin-releasing hormone (GnRH) antagonist and testosterone suppresses sperm production only incompletely, the feasibility of treatment with a GnRH antagonist and delayed testosterone supplementation for sustained suppression of sperm production in a non-human primate model was investigated. Adult cynomolgus monkeys (Macaca fascicularis; five/group) received daily s.c. injections of the GnRH antagonist [N-acetyl-d-2-naphthyl-Ala1,d-4-chloro-Phe2,d-pyridyl-Ala3,nicotinyl-Lys5,d- nicotinyl - Lys6, isopropyl-Lys8,d-Ala10]-GnRH of either 450 or 900 μg/kg for 18 weeks. During week 6 of the GnRH antagonist treatment, all monkeys were given a single i.m. injection of 40 mg of a long-acting testosterone ester (testosterone-trans-4-n-butylcyclo-hexanecarboxylate; 20-Aet-1). Within 1 week, serum LH bioactivity was suppressed in both groups and remained low throughout the entire treatment period. Similarly, concentrations of serum testosterone declined precipitously. During week 6, substitution with testosterone restored concentrations of serum testosterone into the pretreatment range. Concentrations of serum inhibin declined within 1 week and remained suppressed during the period of treatment with the GnRH antagonist. Testicular volumes were reduced to approximately 25% of pretreatment values in both groups by week 8 and stayed in that range during the remaining period of administration of the GnRH antagonist. During the first 6 weeks of administration of the GnRH antagonist, the ejaculatory response to electrostimulation and the volume of the ejaculates diminished with time. Supplementation with testosterone during week 6 restored the ejaculatory responses within 2–3 weeks. From week 9 of GnRH antagonist treatment onwards, all monkeys given 450 μg/kg and four monkeys given 900 μg/kg produced azoospermic ejaculates. The fifth animal in the latter group became azoospermic during week 13. Azoospermia persisted throughout the entire period of treatment with the GnRH antagonist and for a further 7–13 weeks. All suppressive effects of administration of GnRH antagonist were reversible. During the recovery phase the increase in testicular volumes paralleled an increase in concentrations of serum inhibin. The suppression of inhibin levels during the period of administration of testosterone indicates that Sertoli cell activity was not restimulated by testosterone. In conclusion, GnRH antagonist treatment with delayed supplementation with testosterone might serve as a model for further research towards the development of an endocrine male contraceptive. The recovery pattern of serum levels of inhibin suggests that inhibin could serve as a marker for Sertoli cell activity. Journal of Endocrinology (1989) 123, 303–310

scholarly journals Testosterone and cognitive function: current clinical evidence of a relationship

2006 ◽  
Vol 155 (6) ◽  
pp. 773-781 ◽  
Author(s):  
Olivier Beauchet
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Cognitive Ability ◽  
Cognitive Dysfunction ◽  
Clinical Evidence ◽  
Serum Testosterone ◽  
Older Men ◽  
Testosterone Levels ◽  
Testosterone Substitution ◽  
Low Testosterone

Background: Testosterone levels decline as men age, as does cognitive function. Whether there is more than a temporal relationship between testosterone and cognitive function is unclear. Chemical castration studies in men with prostate cancer suggest that low serum testosterone may be associated with cognitive dysfunction. Low testosterone levels have also been observed in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This paper reviews the current clinical evidence of the relationship between serum testosterone levels and cognitive function in older men. Methods: A systematic literature search was conducted using PubMed and EMBASE to identify clinical studies and relevant reviews that evaluated cognitive function and endogenous testosterone levels or the effects of testosterone substitution in older men. Results: Low levels of endogenous testosterone in healthy older men may be associated with poor performance on at least some cognitive tests. The results of randomized, placebo-controlled studies have been mixed, but generally indicate that testosterone substitution may have moderate positive effects on selective cognitive domains (e.g. spatial ability) in older men with and without hypogonadism. Similar results have been found in studies in patients with existing AD or MCI. Conclusions: Low endogenous levels of testosterone may be related to reduced cognitive ability, and testosterone substitution may improve some aspects of cognitive ability. Measurement of serum testosterone should be considered in older men with cognitive dysfunction. For men with both cognitive impairment and low testosterone, testosterone substitution may be considered. Large, long-term studies evaluating the effects of testosterone substitution on cognitive function in older men are warranted.

TRANSDERMAL TESTOSTERONE SUBSTITUTION THERAPY FOR MALE HYPOGONADISM

The Lancet ◽  
1986 ◽  
Vol 328 (8513) ◽  
pp. 943-946 ◽  
Author(s):  
Monika Bals-Pratsch ◽  
Yong-Dal Yoon ◽  
UlrichA. Knuth ◽  
Eberhard Nieschlag
Keyword(s):  
Male Hypogonadism ◽  
Substitution Therapy ◽  
Testosterone Substitution

scholarly journals Testosterone substitution with a new transdermal, hydroalcoholic gel applied to scrotal or non-scrotal skin: a multicentre trial

2005 ◽  
Vol 153 (2) ◽  
pp. 317-326 ◽  
Author(s):  
B Kühnert ◽  
M Byrne ◽  
M Simoni ◽  
W Köpcke ◽  
J Gerss ◽  
...  
Keyword(s):  
Multicentre Trial ◽  
Treatment Success ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Study Groups ◽  
Dose Titration ◽  
Scrotal Skin ◽  
Testosterone Levels ◽  
Testosterone Substitution ◽  
Patch Group

Objective: Testosterone-containing gels have improved testosterone substitution therapy, but they are associated with the risk of interpersonal transfer. Therefore, we tested a new hydroalcoholic 2.5% testosterone gel (TGW), which was removed by washing 10 min after administration. Design: The gel was applied to scrotal or non-scrotal skin in comparison to two 2.5 mg Androderm® patches in a randomised, three-arm, parallel-group, controlled multicentre trial over a period of 24 weeks. We included symptomatic hypogonadal men whose morning testosterone levels were <10 nmol/l. Either 1 g TGW was applied to scrotal skin (n = 54) or 5 g to non-scrotal skin (n = 56) once daily; the patch group (n = 52) applied two patches/day. Dose titration was allowed. Results: Whereas serum testosterone levels and the pre-post changes of the areas under the curve of testosterone and free testosterone between weeks 0 and 24 indicated equivalent treatment success for the patch and scrotal groups, the dermal gel group was significantly superior to the other two groups. Questionnaires on sexual function, mood and quality of life did not differ significantly between study groups, nor were prostate volume, prostate-specific antigen (PSA) levels and prostate symptoms different. However, tolerability was much better in the gel groups than the patch group. Conclusion: Efficacy, safety and tolerability suggest TGW as a favourable treatment for hypogonadal patients.

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

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

1986 ◽  
Vol 113 (1) ◽  
pp. 128-132 ◽  
Author(s):  
G. F. Weinbauer ◽  
G. R. Marshall ◽  
E. Nieschlag
Keyword(s):  
Aqueous Suspension ◽  
Serum Testosterone ◽  
Fertility Control ◽  
Rapid Decline ◽  
Moderate Increase ◽  
Testosterone Levels ◽  
Single Intramuscular Injection ◽  
Testosterone Substitution ◽  
Physiological Limit ◽  
Testosterone Ester

Abstract. 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.

Transdermal Testosterone Substitution Therapy for Male Hypogonadism

1987 ◽  
Vol 137 (6) ◽  
pp. 1328-1328
Author(s):  
M. Bals-Pratsch ◽  
U.A. Knuth ◽  
Y.D. Yoon ◽  
E. Nieschlag
Keyword(s):  
Male Hypogonadism ◽  
Substitution Therapy ◽  
Testosterone Substitution

SERUM TESTOSTERONE AS AN INDEX OF GONADOTROPHIN SECRETION IN ACROMEGALY AND PITUITARY DISEASE

1970 ◽  
Vol 65 (2) ◽  
pp. 302-308 ◽  
Author(s):  
Robert L. Rosenfield ◽  
Ira D. Goldfine ◽  
A. M. Lawrence
Keyword(s):  
Interstitial Cell ◽  
Sperm Count ◽  
Serum Testosterone ◽  
Substitution Therapy ◽  
Normal Response ◽  
Testosterone Levels ◽  
Pituitary Disease ◽  
Gonadotrophin Secretion ◽  
Lh Secretion ◽  
Stimulating Hormone

ABSTRACT Laboratory evidence for hypogonadism has been sought in 33 patients with acromegaly and pituitary disease. Low serum testosterone was found in 7 of the 15 males with acromegaly and 4 of 4 with chromophobe adenomas. Clomiphene administration caused no rise in testosterone in the acromegalic tested; a normal response to HCG, however, was determined in another. Disparity between testosterone levels and sperm count in three subjects suggests that dissociation of follicle stimulating hormone (FSH) secretion from interstitial cell stimulating hormone (LH) secretion may occur in association with hypothalamic-pituitary disease. This study indicates that gonadotrophic insufficiency is a commonly associated feature of acromegaly in the male. Testosterone levels were depressed in four of the five females with hypoadrenalism and/or hypogonadism secondary to pituitary disease who were not on oestrogen substitution therapy.

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