Short-term effect of pharmacologically induced alterations in testosterone levels on common blood biomarkers in a controlled healthy human model

TY - JOUR

T1 - Short-term effect of pharmacologically induced alterations in testosterone levels on common blood biomarkers in a controlled healthy human model

AU - Sahlin, K. Barbara

AU - Pla, Indira

AU - Sanchez, Aniel

AU - Pawłowski, Krzysztof

AU - Leijonhufvud, Irene

AU - Appelqvist, Roger

AU - Marko-Varga, György

AU - Giwercman, Aleksander

AU - Malm, Johan

PY - 2020

Y1 - 2020

N2 - Testosterone deficiency in males is associated with serious comorbidities such as cardiovascular disease, diabetes type two, and also an increased risk of premature death. The pathogenetic mechanism behind this association, however, has not yet been clarified and is potentially bidirectional. The aim of this clinical trial was to gain insight into the short-term effect of changes in testosterone on blood analytes in healthy young men. Thirty healthy young male volunteers were recruited and monitored in our designed human model. Blood sampling was performed prior to and 3 weeks after pharmacological castration with a gonadotropin-releasing hormone antagonist. Subsequently, testosterone replacement with 1000 mg testosterone undecanoate was given and additional blood samples were collected 2 weeks later. The alterations in the levels of 37 routine biomarkers were statistically analysed. Eight biomarkers changed significantly in a similar manner as testosterone between the time points (e.g. prostate specific antigen, creatinine and magnesium), whereas seven other markers changed in the inverse manner as testosterone, including sexual hormone-binding globulin, urea, aspartate aminotransferase and alanine aminotransferase. Most of our results were supported by data from other studies. The designed controlled human model yielded changes in known biomarkers suggesting that low testosterone has a negative effect on health in young healthy men.

AB - Testosterone deficiency in males is associated with serious comorbidities such as cardiovascular disease, diabetes type two, and also an increased risk of premature death. The pathogenetic mechanism behind this association, however, has not yet been clarified and is potentially bidirectional. The aim of this clinical trial was to gain insight into the short-term effect of changes in testosterone on blood analytes in healthy young men. Thirty healthy young male volunteers were recruited and monitored in our designed human model. Blood sampling was performed prior to and 3 weeks after pharmacological castration with a gonadotropin-releasing hormone antagonist. Subsequently, testosterone replacement with 1000 mg testosterone undecanoate was given and additional blood samples were collected 2 weeks later. The alterations in the levels of 37 routine biomarkers were statistically analysed. Eight biomarkers changed significantly in a similar manner as testosterone between the time points (e.g. prostate specific antigen, creatinine and magnesium), whereas seven other markers changed in the inverse manner as testosterone, including sexual hormone-binding globulin, urea, aspartate aminotransferase and alanine aminotransferase. Most of our results were supported by data from other studies. The designed controlled human model yielded changes in known biomarkers suggesting that low testosterone has a negative effect on health in young healthy men.

KW - comorbidities

KW - gonadotropin-releasing hormone

KW - gonadotropins

KW - healthy males

KW - hormone antagonists

KW - hypogonadism

KW - reproduction

KW - Testosterone

U2 - 10.1080/00365513.2019.1689429

DO - 10.1080/00365513.2019.1689429

M3 - Article

C2 - 31738571

AN - SCOPUS:85075239986

VL - 80

SP - 25

EP - 31

JO - Scandinavian Journal of Clinical & Laboratory Investigation

JF - Scandinavian Journal of Clinical & Laboratory Investigation

SN - 1502-7686

IS - 1

ER -