A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

Michael Kreiberg; Niels Jørgensen; Anders Juul; Jakob Lauritsen; Peter Oturai; Jørn Wulff Helge; Jesper Frank Christensen; Lise Aksglaede; Tim Schauer; Thomas Wagner; Josephine Rosenvilde; Emma Grunwald; Christian Dehlendorff; Gedske Daugaard; Mikkel Bandak

doi:10.1016/j.clgc.2022.04.017

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

Michael Kreiberg^*, Niels Jørgensen, Anders Juul, Jakob Lauritsen, Peter Oturai, Jørn Wulff Helge, Jesper Frank Christensen, Lise Aksglaede, Tim Schauer, Thomas Wagner, Josephine Rosenvilde, Emma Grunwald, Christian Dehlendorff, Gedske Daugaard, Mikkel Bandak

^*Corresponding author for this work

2 Citations (Scopus)

Abstract

INTRODUCTION: Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors.

PATIENTS AND METHODS: This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www.

CLINICALTRIAL: gov (NCT02991209) and ended June 2019.

RESULTS: Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n = 35, 51%) or placebo (n = 34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)).

CONCLUSION: In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.

Original language	English
Journal	Clinical Genitourinary Cancer
Volume	20
Issue number	5
Pages (from-to)	404-414
Number of pages	11
ISSN	1938-0682
DOIs	https://doi.org/10.1016/j.clgc.2022.04.017
Publication status	Published - Oct 2022

Keywords

Double-Blind Method
Glucose/metabolism
Humans
Insulin
Leydig Cells/metabolism
Luteinizing Hormone/metabolism
Male
Metabolic Syndrome/drug therapy
Neoplasms, Germ Cell and Embryonal
Survivors
Testicular Neoplasms/therapy
Testosterone
Testicular germ cell cancer
Glucose
Metabolic syndrome
Testosterone deficiency
Randomized trial

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10.1016/j.clgc.2022.04.017

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Kreiberg, M., Jørgensen, N., Juul, A., Lauritsen, J., Oturai, P., Helge, J. W., Christensen, J. F., Aksglaede, L., Schauer, T., Wagner, T., Rosenvilde, J., Grunwald, E., Dehlendorff, C., Daugaard, G., & Bandak, M. (2022). A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention). Clinical Genitourinary Cancer, 20(5), 404-414. https://doi.org/10.1016/j.clgc.2022.04.017

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention). / Kreiberg, Michael ; Jørgensen, Niels ; Juul, Anders et al.

In: Clinical Genitourinary Cancer, Vol. 20, No. 5, 10.2022, p. 404-414.

Research output: Contribution to journal › Journal article › Research › peer-review

Kreiberg, M , Jørgensen, N , Juul, A , Lauritsen, J , Oturai, P, Helge, JW, Christensen, JF , Aksglaede, L , Schauer, T, Wagner, T, Rosenvilde, J, Grunwald, E, Dehlendorff, C, Daugaard, G & Bandak, M 2022, 'A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)', Clinical Genitourinary Cancer, vol. 20, no. 5, pp. 404-414. https://doi.org/10.1016/j.clgc.2022.04.017

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title = "A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)",

abstract = "INTRODUCTION: Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors.PATIENTS AND METHODS: This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www.CLINICALTRIAL: gov (NCT02991209) and ended June 2019.RESULTS: Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n = 35, 51%) or placebo (n = 34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)).CONCLUSION: In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.",

keywords = "Double-Blind Method, Glucose/metabolism, Humans, Insulin, Leydig Cells/metabolism, Luteinizing Hormone/metabolism, Male, Metabolic Syndrome/drug therapy, Neoplasms, Germ Cell and Embryonal, Survivors, Testicular Neoplasms/therapy, Testosterone, Testicular germ cell cancer, Glucose, Metabolic syndrome, Testosterone deficiency, Randomized trial",

author = "Michael Kreiberg and Niels J{\o}rgensen and Anders Juul and Jakob Lauritsen and Peter Oturai and Helge, {J{\o}rn Wulff} and Christensen, {Jesper Frank} and Lise Aksglaede and Tim Schauer and Thomas Wagner and Josephine Rosenvilde and Emma Grunwald and Christian Dehlendorff and Gedske Daugaard and Mikkel Bandak",

year = "2022",

month = oct,

doi = "10.1016/j.clgc.2022.04.017",

language = "English",

volume = "20",

pages = "404--414",

journal = "Clinical Genitourinary Cancer (Online)",

issn = "1938-0682",

publisher = "Elsevier",

number = "5",

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TY - JOUR

T1 - A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

AU - Kreiberg, Michael

AU - Jørgensen, Niels

AU - Juul, Anders

AU - Lauritsen, Jakob

AU - Oturai, Peter

AU - Helge, Jørn Wulff

AU - Christensen, Jesper Frank

AU - Aksglaede, Lise

AU - Schauer, Tim

AU - Wagner, Thomas

AU - Rosenvilde, Josephine

AU - Grunwald, Emma

AU - Dehlendorff, Christian

AU - Daugaard, Gedske

AU - Bandak, Mikkel

PY - 2022/10

Y1 - 2022/10

N2 - INTRODUCTION: Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors.PATIENTS AND METHODS: This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www.CLINICALTRIAL: gov (NCT02991209) and ended June 2019.RESULTS: Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n = 35, 51%) or placebo (n = 34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)).CONCLUSION: In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.

AB - INTRODUCTION: Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors.PATIENTS AND METHODS: This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www.CLINICALTRIAL: gov (NCT02991209) and ended June 2019.RESULTS: Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n = 35, 51%) or placebo (n = 34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)).CONCLUSION: In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.

KW - Double-Blind Method

KW - Glucose/metabolism

KW - Humans

KW - Insulin

KW - Leydig Cells/metabolism

KW - Luteinizing Hormone/metabolism

KW - Male

KW - Metabolic Syndrome/drug therapy

KW - Neoplasms, Germ Cell and Embryonal

KW - Survivors

KW - Testicular Neoplasms/therapy

KW - Testosterone

KW - Testicular germ cell cancer

KW - Glucose

KW - Metabolic syndrome

KW - Testosterone deficiency

KW - Randomized trial

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U2 - 10.1016/j.clgc.2022.04.017

DO - 10.1016/j.clgc.2022.04.017

M3 - Journal article

C2 - 35701334

VL - 20

SP - 404

EP - 414

JO - Clinical Genitourinary Cancer (Online)

JF - Clinical Genitourinary Cancer (Online)

SN - 1938-0682

IS - 5

ER -

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

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