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

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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; P5.006) and body mass index of 25 to ,30 kg/m2 (OR, 2.08; P5.011) or $30 kg/m2 (OR, 2.36; P5.005) compared with ,25 kg/m2 . TCS with $2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P5.09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P5.07). 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%; P5.003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P,.001) or hypertension (18.5% vs 10.6%; P5.013), and to report erectile dysfunction (19.6% vs 11.9%; P5.018) or peripheral neuropathy (30.7% vs 22.5%; P5.041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P5.07) or anxiety/ depression (14.8% vs 9.3%; P5.06) 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.











Conclusions

At a relatively young age, there is a high prevalence of hypogonadism among North American TCS treated with modern cisplatin-based chemotherapy. Major risk factors include increasing age and obesity. Hypogonadism was strongly associated with risk factors for CVD. The clinical value of assessing possible genetic variants in the role of hypogonadism requires further study before these are recommended for use in the clinic. In the meantime, TCS should be encouraged to maintain a normal body weight and a healthy lifestyle. Although there are currently no evidence based guidelines, Bhasin et al recommend that healthcare providers screen for hypogonadism by surveying TCS for the classic symptoms of hypogonadism (decreased energy, depressed mood, decreased sexual desire and performance, and night sweats) and prescribe testosterone replacement therapy to survivors who have low testosterone levels on 2 occasions and have symptoms related to low testosterone.
 

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  • MAY17-TCS-HYPOGONADISM-[15401413 - Journal of the National Comprehensive Cancer Network] Adver...pdf
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