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.

Cisplatin causes erectile dysfunction by decreasing endothelial and smooth muscle content and inducing cavernosal nerve senescence in rats

“…However, there are still problems to be resolved ( 22 ). Several studies have demonstrated that platinum-based chemotherapy can induce ED ( 10 , 12 , 13 , 23 , 24 ), but ED has not gained the attention of clinicians as a complication. Some scholars have found that oxaliplatin can induce ED in rats by inducing damage to the endothelium of the corpus cavernosum ( 11 ).…”

Chemotherapy‐induced toxicity in patients with testicular germ cell tumors: The impact of physical fitness and regular exercise

“…It may also be associated with muscle weakness, depression, osteoporosis, as well as decreased sexual function and fertility 3,75 . Hypogonadism rate of 38.5% has been reported in a study on 491 North American testicular cancer survivors 76 . Hypogonadism in this population could be related to orchiectomy, chemotherapy, radiotherapy, and testicular dysgenesis syndrome (which comprises testicular cancer) 3,77 .…”

“…3,75 Hypogonadism rate of 38.5% has been reported in a study on 491 North American testicular cancer survivors. 76 Hypogonadism in this population could be related to orchiectomy, chemotherapy, radiotherapy, and testicular dysgenesis syndrome (which comprises testicular cancer). 3,77 Hypogonadism severity is directly linked to the intensity of treatment.…”

Malignant ovarian and testicular germ cell tumors: Common characteristics but different prognoses

“…Late effects after treatment may, to some extent, be caused by lower levels of sex hormones after orchiectomy or oophorectomy as well as being caused by the chemotherapy given. In testicular cancer patients, endocrine hypogonadism is prevalent in 5%-13% of patients after orchiectomy, increasing to 11%-27% after chemotherapy [115,116]. Patients treated for testicular GCT should be followed with regular hormonal assessments according to guidelines, and testosterone replacement therapy is recommended for patients with low testosterone levels and clinical symptoms of hypogonadism [68].…”