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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.

SUBMITTER: Abu Zaid M

PROVIDER: S-EPMC6712564 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Abu Zaid Mohammad M Dinh Paul C PC Monahan Patrick O PO Fung Chunkit C El-Charif Omar O Feldman Darren R DR Hamilton Robert J RJ Vaughn David J DJ Beard Clair J CJ Cook Ryan R Althouse Sandra S Ardeshir-Rouhani-Fard Shirin S Sesso Howard D HD Huddart Robert R Mushiroda Taisei T Kubo Michiaki M Dolan M Eileen ME Einhorn Lawrence H LH Fossa Sophie D SD Travis Lois B LB

Journal of the National Comprehensive Cancer Network : JNCCN 20190501 5

<h4>Background</h4>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.<h4>Patients and methods</h4>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 behav ...[more]

PMID: 31085753

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Project description:BackgroundFew data exist on the relationship of cisplatin-related adverse health outcomes (AHOs) with disability, unemployment, and self-reported health (SRH) among testicular cancer survivors (TCS).MethodsA total of 1815 TCS at least 1 year postchemotherapy underwent clinical examination and completed questionnaires. Treatment data were abstracted from medical records. A cumulative burden of morbidity score (CBMPt) encompassed the number and severity of platinum-related AHOs (peripheral sensory neuropathy [PSN], hearing loss, tinnitus, renal disease). Multivariable regression assessed the association of AHOs and CBMPt with employment status and SRH, adjusting for sociodemographic and clinical characteristics. Unemployment was compared with a male normative population of similar age, race, and ethnicity.ResultsAlmost 1 in 10 TCS was out of work (2.4%, disability leave; 6.8%, unemployed) at a median age of 37 years (median follow-up = 4 years). PSN (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 1.01 to 8.26, grade 3 vs 0, P = .048), renal dysfunction defined by estimated glomerular filtration rate (OR = 12.1, 95% CI = 2.06 to 70.8, grade 2 vs 0, P = .01), pain (OR = 10.6, 95% CI = 4.40 to 25.40, grade 2 or 3 vs 0, P < .001), and CBMPt (OR = 1.46, 95% CI = 1.03 to 2.08, P = .03) were associated with disability leave; pain strongly correlated with PSN (r 2 = 0.40, P < .001). Statistically significantly higher percentages of TCS were unemployed vs population norms (age-adjusted OR = 2.67, 95% CI = 2.49 to 3.02, P < .001). PSN (OR = 2.44, 95% CI = 1.28 to 4.62, grade 3 vs 0, P = .006), patient-reported hearing loss (OR = 1.82, 95% CI = 1.04 to 3.17, grade 2 or 3 vs 0, P = .04), and pain (OR = 3.75, 95% CI = 2.06 to 6.81, grade 2 or 3 vs 0, P < .001) were associated with unemployment. Increasing severity of most cisplatin-related AHOs and pain were associated with statistically significantly worse SRH.ConclusionsOur findings have important implications regarding treatment-associated productivity losses and socioeconomic costs in this young population. Survivorship care strategies should include inquiries about disability and unemployment status, with efforts made to assist affected TCS in returning to the workforce.

Project description:Background: Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. Patients and Methods: TCS were aged <55 years at diagnosis and received first-line chemotherapy. Patients underwent physical examination, and had lipid panels, testosterone, and soluble cell adhesion molecule-1 (sICAM-1) evaluated. A single nucleotide polymorphism in rs523349 (5-?-reductase gene, SRD5A2), recently implicated in MetS risk, was genotyped. Using standard criteria, MetS was defined as ?3 of the following: hypertension, abdominal obesity, hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol level, and diabetes. Matched controls were derived from the National Health and Nutrition Examination Survey. Results: We evaluated 486 TCS (median age, 38.1 years). TCS had a higher prevalence of hypertension versus controls (43.2% vs 30.7%; P<.001) but were less likely to have decreased HDL levels (23.7% vs 34.8%; P<.001) or abdominal obesity (28.2% vs 40.1%; P<.001). Overall MetS frequency was similar in TCS and controls (21.0% vs 22.4%; P=.59), did not differ by treatment (P=.20), and was not related to rs523349 (P=.61). For other CVD risk factors, TCS were significantly more likely to have elevated low-density lipoprotein (LDL) cholesterol levels (17.7% vs 9.3%; P<.001), total cholesterol levels (26.3% vs 11.1%; P<.001), and body mass index ?25 kg/m2 (75.1% vs 69.1%; P=.04). On multivariate analysis, age at evaluation (P<.001), testosterone level ?3.0 ng/mL (odds ratio [OR], 2.06; P=.005), and elevated sICAM-1 level (ORhighest vs lowest quartile, 3.58; P=.001) were significantly associated with MetS. Conclusions and Recommendations: Metabolic abnormalities in TCS are characterized by hypertension and increased LDL and total cholesterol levels but lower rates of decreased HDL levels and abdominal obesity, signifying possible shifts in fat distribution and fat metabolism. These changes are accompanied by hypogonadism and inflammation. TCS have a high prevalence of CVD risk factors that may not be entirely captured by standard MetS criteria. Cancer treatment-associated MetS requires further characterization.

Project description:Recent increasing trends in breast cancer incidence and survival have resulted in unprecedented numbers of cancer survivors in the general population. A cancer diagnosis may have a profound psychological impact, and breast cancer treatments often cause long-term physical sequelae, potentially affecting women's mental health. The aim of this systematic review is to identify and summarise all studies that have compared mental health outcomes in breast cancer survivors, versus women who did not have cancer.This study will be a systematic review of the literature. Four databases, including MEDLINE and PsycINFO, will be searched to identify potentially relevant studies. The search expressions will use a Boolean logic, including terms for the target population (women who have had breast cancer), outcomes (psychiatric disorders) and comparators (e.g. risk, hazard). All mental disorders will be eligible, except those with onset normally occurring during childhood or strong genetic basis (e.g. Huntington disease). The eligibility of the studies will be assessed in two phases: (1) considering the information provided in the title and abstract; (2) evaluating the full text. Studies including women diagnosed with breast cancer 1 year or more ago and that provide original data on mental health outcomes will be eligible. Studies in which all women were undergoing surgery, chemotherapy or radiotherapy, or hospitalised or institutionalised, will be excluded, as well as studies that include patients selected on the basis of symptomatology. Two investigators will do the screening of the references and the data extraction independently, with results compared and discrepancies resolved by involving a third investigator when necessary. Study quality and risk of bias will be assessed across six broad domains. Results will be summarised by outcome, and summary measures of frequency and/or association will be computed if possible.This review will summarise the evidence on the mental health outcomes of women who have been diagnosed with breast cancer. This information can be used to motivate further research and increase understanding of the most common mental health conditions affecting this growing population of women.PROSPERO CRD42017056946.

Dataset Information

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

Publications

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

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