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

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.

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Substitution therapy of hypogonadal men with transdermal testosterone over one year

Acta Endocrinologica ◽

10.1530/acta.0.1180007 ◽

1988 ◽

Vol 118 (1) ◽

pp. 7-13 ◽

Cited By ~ 37

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.

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

Acta Endocrinologica ◽

10.1530/eje.0.1320514 ◽

1995 ◽

Vol 132 (4) ◽

pp. 514-519 ◽

Cited By ~ 38

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

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Faculty Opinions recommendation of Serum testosterone levels in male hypogonadism: Why and when to check-A review.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.731791457.793556541 ◽

2019 ◽

Author(s):

Suks Minhas ◽

Tharu Tharakan ◽

Saiful Miah

Keyword(s):

Serum Testosterone ◽

Male Hypogonadism ◽

Testosterone Levels

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Zinc Status and Serum Testosterone Levels of Healthy Adults

Nutrition ◽

10.1016/s0899-9007(96)00064-0 ◽

1996 ◽

Vol 12 (5) ◽

pp. vi

Author(s):

A Prasad

Keyword(s):

Serum Testosterone ◽

Healthy Adults ◽

Zinc Status ◽

Testosterone Levels

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The Association between Serum Testosterone Levels and Erythrocyte Count in Male Rats Exposed to Oil Paint Vapor

International Journal of Advances in Chemical Engineering and Biological Sciences ◽

10.15242/ijacebs.a0915010 ◽

2015 ◽

Vol 2 (1) ◽

Keyword(s):

Serum Testosterone ◽

Erythrocyte Count ◽

Male Rats ◽

Testosterone Levels

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Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-021-00359-8 ◽

2021 ◽

Author(s):

Eun-Young Shin ◽

Seah Park ◽

Won Yun Choi ◽

Dong Ryul Lee

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Male Hypogonadism ◽

Testosterone Levels ◽

Sequence Of Events ◽

Short Period ◽

Molecular Compounds

Abstract Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

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Testosterone in Female Depression: A Meta-Analysis and Mendelian Randomization Study

Biomolecules ◽

10.3390/biom11030409 ◽

2021 ◽

Vol 11 (3) ◽

pp. 409

Author(s):

Dhruba Tara Maharjan ◽

Ali Alamdar Shah Syed ◽

Guan Ning Lin ◽

Weihai Ying

Keyword(s):

Mendelian Randomization ◽

Meta Analysis ◽

Menopausal Status ◽

Serum Testosterone ◽

Serum Levels ◽

Testosterone Levels ◽

Mendelian Randomization Analysis ◽

The Difference ◽

Diagnostic Capabilities ◽

Randomization Analysis

Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.

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Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0280 ◽

2018 ◽

Vol 31 (1) ◽

pp. 21-24 ◽

Cited By ~ 8

Author(s):

Andrea Albrecht ◽

Theresa Penger ◽

Michaela Marx ◽

Karin Hirsch ◽

Helmuth G. Dörr

Keyword(s):

Growth Hormone ◽

Side Effects ◽

Adverse Effects ◽

Side Effect ◽

Serum Testosterone ◽

Low Flow ◽

Effect Rate ◽

Testosterone Levels ◽

Testicular Pain ◽

Prepubertal Boys

AbstractBackground:Despite the fact that priming with sex steroids in prepubertal children before growth hormone (GH) provocative tests is recommended, there is an ongoing controversial discussion about the appropriate age of the children, the drug used for priming, the dose and the period between priming and the GH test. Interestingly, there is no discussion on the safety of this procedure. To date, only little data have been available on the possible side effects of priming with testosterone.Methods:We analyzed the outcome in 188 short-statured prepubertal boys who had been primed with testosterone enanthate (n=136: 50 mg; n=51: 125 mg, and accidentally one boy with 250 mg) 7 days prior to the GH test. Serum testosterone levels were measured on the day of the GH test in 99 boys.Results:Overall, only five boys developed adverse side effects. Two boys (dose 125 mg) showed severe low-flow priapism and had to undergo decompression of the corpora cavernosa. One boy suffered from self-limiting priapism and testicular pain (dose 50 mg). Two patients reported testicular pain (each dose 50 mg). The single patient with 250 mg testosterone did not show any adverse effects. The total side effect rate was 2.7%. The serum testosterone levels of the boys with side effects were not different from the testosterone levels of the boys without any side effects.Conclusions:Parents and patients should be informed about the possible side effects of priming with testosterone such as priapism and testicular pain. However, the overall side effect rate is low. We found no correlation between the outcome and the testosterone dose used and/or the level of serum testosterone.

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