Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors

Platinum Study Group

Research output: Contribution to journalArticle

Abstract

BACKGROUND: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. PATIENTS AND METHODS: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone-binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. RESULTS: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7-68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P= .003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P= .013), and to report erectile dysfunction (19.6% vs 11.9%; P= .018) or peripheral neuropathy (30.7% vs 22.5%; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P= .07) or anxiety/depression (14.8% vs 9.3%; P= .06) was observed. CONCLUSIONS: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.

Original languageEnglish (US)
Pages (from-to)459-468
Number of pages10
JournalJournal of the National Comprehensive Cancer Network : JNCCN
Volume17
Issue number5
DOIs
StatePublished - May 1 2019

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Hypogonadism
Testicular Neoplasms
Multicenter Studies
Drug Therapy
Survivors
Health
Odds Ratio
Sex Hormone-Binding Globulin
Erectile Dysfunction
Platinum
Single Nucleotide Polymorphism
Testosterone
Health Behavior
Peripheral Nervous System Diseases
Hypercholesterolemia
Cisplatin
Physical Examination
Prescriptions
Body Mass Index
Cardiovascular Diseases

ASJC Scopus subject areas

  • Oncology

Cite this

@article{95bb9d11bfaa47499774eead7da2694c,
title = "Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors",
abstract = "BACKGROUND: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. PATIENTS AND METHODS: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone-binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. RESULTS: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7-68.4 years), 38.5{\%} had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65{\%} vs 51{\%}; P= .003), to take medications for hypercholesterolemia (20.1{\%} vs 6.0{\%}; P<.001) or hypertension (18.5{\%} vs 10.6{\%}; P= .013), and to report erectile dysfunction (19.6{\%} vs 11.9{\%}; P= .018) or peripheral neuropathy (30.7{\%} vs 22.5{\%}; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8{\%} vs 2.6{\%}; P= .07) or anxiety/depression (14.8{\%} vs 9.3{\%}; P= .06) was observed. CONCLUSIONS: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.",
author = "{Platinum Study Group} and {Abu Zaid}, Mohammad and Dinh, {Paul C.} and Patrick Monahan and Chunkit Fung and Omar El-Charif and Feldman, {Darren R.} and Hamilton, {Robert J.} and Vaughn, {David J.} and Beard, {Clair J.} and Ryan Cook and Sandra Althouse and Shirin Ardeshir-Rouhani-Fard and Sesso, {Howard D.} and Robert Huddart and Taisei Mushiroda and Michiaki Kubo and Dolan, {M. Eileen} and Lawrence Einhorn and Fossa, {Sophie D.} and Travis, {Lois B.}",
year = "2019",
month = "5",
day = "1",
doi = "10.6004/jnccn.2018.7109",
language = "English (US)",
volume = "17",
pages = "459--468",
journal = "Journal of the National Comprehensive Cancer Network : JNCCN",
issn = "1540-1405",
publisher = "Cold Spring Publishing LLC",
number = "5",

}

TY - JOUR

T1 - Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy

T2 - A Multicenter Study of Testicular Cancer Survivors

AU - Platinum Study Group

AU - Abu Zaid, Mohammad

AU - Dinh, Paul C.

AU - Monahan, Patrick

AU - Fung, Chunkit

AU - El-Charif, Omar

AU - Feldman, Darren R.

AU - Hamilton, Robert J.

AU - Vaughn, David J.

AU - Beard, Clair J.

AU - Cook, Ryan

AU - Althouse, Sandra

AU - Ardeshir-Rouhani-Fard, Shirin

AU - Sesso, Howard D.

AU - Huddart, Robert

AU - Mushiroda, Taisei

AU - Kubo, Michiaki

AU - Dolan, M. Eileen

AU - Einhorn, Lawrence

AU - Fossa, Sophie D.

AU - Travis, Lois B.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - BACKGROUND: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. PATIENTS AND METHODS: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone-binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. RESULTS: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7-68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P= .003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P= .013), and to report erectile dysfunction (19.6% vs 11.9%; P= .018) or peripheral neuropathy (30.7% vs 22.5%; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P= .07) or anxiety/depression (14.8% vs 9.3%; P= .06) was observed. CONCLUSIONS: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.

AB - BACKGROUND: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. PATIENTS AND METHODS: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone-binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. RESULTS: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7-68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P= .003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P= .013), and to report erectile dysfunction (19.6% vs 11.9%; P= .018) or peripheral neuropathy (30.7% vs 22.5%; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P= .07) or anxiety/depression (14.8% vs 9.3%; P= .06) was observed. CONCLUSIONS: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.

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U2 - 10.6004/jnccn.2018.7109

DO - 10.6004/jnccn.2018.7109

M3 - Article

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AN - SCOPUS:85066282180

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EP - 468

JO - Journal of the National Comprehensive Cancer Network : JNCCN

JF - Journal of the National Comprehensive Cancer Network : JNCCN

SN - 1540-1405

IS - 5

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