Indiana University, Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
University of Rochester Medical Center, James P. Wilmot Cancer Institute, Rochester, New York.
J Natl Compr Canc Netw. 2019 May 1;17(5):459-468. doi: 10.6004/jnccn.2018.7109.
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.
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.
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.
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.
本研究旨在探讨北美睾丸癌幸存者（TCS）在接受现代铂类化疗后，性腺功能减退症的患病率、其临床和遗传危险因素，以及其与不良健康结局（AHOs）的关系。
合格的 TCS 在诊断时年龄<55 岁，且接受一线铂类化疗。参与者接受了体检，并完成了关于 15 种 AHOs 和健康行为的问卷。性腺功能减退症定义为血清睾酮水平≤3.0ng/mL 或使用睾酮替代疗法。我们研究了两个单核苷酸多态性（rs6258 和 rs12150660）在性激素结合球蛋白（SHBG）基因座中的作用，该基因座与一般人群中增加性腺功能减退症风险有关。
在 491 名 TCS（评估时的中位年龄为 38.2 岁；范围为 18.7-68.4 岁）中，38.5%患有性腺功能减退症。多变量二项逻辑回归分析确定了性腺功能减退症的危险因素，包括临床评估时的年龄（每增加 10 岁，比值比[OR]为 1.42；P=.006）和身体质量指数为 25 至<30kg/m2（OR，2.08；P=.011）或≥30kg/m2（OR，2.36；P=.005）与<25kg/m2 相比。SHBG 单核苷酸多态性的风险等位基因≥2 的 TCS 性腺功能减退症风险略有增加（OR，1.45；P=.09）。剧烈强度的体育活动似乎具有保护作用（OR，0.66；P=.07）。顺铂类化疗方案的类型和社会经济因素与性腺功能减退症无关。与无性腺功能减退症的 TCS 相比，有性腺功能减退症的 TCS 更有可能报告≥2 种 AHOs（65% vs 51%；P=.003），服用降脂药（20.1% vs 6.0%；P<.001）或降压药（18.5% vs 10.6%；P=.013），并报告勃起功能障碍（19.6% vs 11.9%；P=.018）或周围神经病（30.7% vs 22.5%；P=.041）。观察到糖尿病（5.8% vs 2.6%；P=.07）或焦虑/抑郁（14.8% vs 9.3%；P=.06）处方药使用的显著趋势增加。
在相对年轻的中位年龄，超过三分之一的 TCS 患有性腺功能减退症，这与心血管疾病风险因素的增加显著相关，且与勃起功能障碍有关。医生应筛查 TCS 的性腺功能减退症并治疗有症状的患者。
