Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: A multicenter study of North American testicular cancer survivors (TCS).

Abstract

LBA10012 Background: HG affects a substantial percentage of TCS and can contribute to significant morbidity, but few studies have examined the relationship between HG and adverse health outcomes (AHO), taking into account genetic variation. Methods: Eligible TCS were < 55 y at diagnosis and treated with only first line chemotherapy after 1990. TCS underwent physical exams and genotyping, and completed questionnaires regarding 16 AHO and health behaviors. HG was defined as serum testosterone ≤ 3.0 ng/mL or the use of testosterone replacement therapy. Results: We evaluated 491 TCS. Median age at evaluation was 38 y (range 19-68). 38.5% had HG. Two SNPs in the sex-hormone-binding globulin ( SHBG) locus previously implicated in increased HG risk in the general population (Ohlsson et al, PLOS Genetics 2011) displayed effect sizes consistent with prior reports (rs6258, OR = 1.3; rs12150660, OR = 0.79), but were not statistically significant. However, TCS with ≥ 2 risk alleles for the two SNPs in the SHBG locus vs no risk alleles had 2-fold increased risk for HG (OR = 2.2, P = .12). Multivariate analysis identified risk factors for HG including: age (OR = 1.4 per 10 year increase, P = .007), and BMI ≥ 25 kg/m2 (OR = 2.2, P = .003). Vigorous-intensity physical activity appeared protective (OR = 0.6, P = .06). Type of chemotherapy regimen and socioeconomic factors did not correlate with HG. Only 35% of TCS with HG vs 49% of those without HG reported none or 1 AHO ( P = .003). TCS with HG were more likely to take medications for dyslipidemia (20% vs 6%, P < .001), hypertension (19% vs 11%, P = .01), erectile dysfunction (ED) (20% vs 12%, P = .02), diabetes (6% vs 3%, P = .07), or anxiety/depression (15% vs 10%, P = 0.06) compared to TCS with normal levels, and also to have peripheral neuropathy (PN) (31% vs 23%, P = .04). HG status did not correlate with oto- or renal toxicity. Conclusions: Over a third of TCS have HG at a relatively young age. HG was associated with increased cardiovascular disease risk factors, ED, and PN. SHBG polymorphisms appear important in TCS, but our study was underpowered to confirm an association. Providers should screen TCS for HG and treat those who are symptomatic.