Zhou Cindy Ke, Stanczyk Frank Z, Hafi Muhannad, Veneroso Carmela C, Lynch Barlow, Falk Roni T, Niwa Shelley, Emanuel Eric, Gao Yu-Tang, Hemstreet George P, Zolfghari Ladan, Carroll Peter R, Manyak Michael J, Sesterhenn Isabell A, Levine Paul H, Hsing Ann W, Cook Michael B
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Reproductive Endocrine Research Laboratory, Keck School of Medicine, University of Southern California, Los Angeles, California.
Prostate. 2017 Dec;77(16):1573-1582. doi: 10.1002/pros.23433. Epub 2017 Oct 2.
Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer.
We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (<7 vs ≥7) and race (European American vs. African American).
We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations.
This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ-specific sex hormone metabolism, implying that other sex steroid hormone-related factors (eg, androgen receptor) play important roles in organ-specific androgenic actions, and that other overlapping pathways may be involved in associations between the two complex conditions.
尽管动物研究和临床研究有相关证据，但关于循环性激素与前列腺癌风险的前瞻性队列研究并未得出一致的关联。然而，使用男性型秃发作为早年或累积雄激素暴露替代指标的研究报告称，其与侵袭性和致命性前列腺癌风险存在显著关联。鉴于雄激素是型脱发和胸毛发育的基础，我们评估了这两种皮肤特征是否与诊断为局限性前列腺癌的男性循环和前列腺内性激素浓度相关。
我们纳入了来自美国国立癌症研究所前列腺组织研究的248例前列腺癌患者，这些患者回答了调查问卷，并提供了治疗前血样以及新鲜冷冻的相邻正常前列腺组织。术前由经过培训的护士评估男性型秃发和胸毛密度。采用一般线性模型，通过皮肤表型估计每种激素变量的几何均值和95%置信区间（95%CI），并对潜在的混杂变量进行调整。按Gleason评分（<7 vs ≥7）和种族（欧美裔 vs 非裔美国人）进行亚组分析。
我们发现秃发状态与血清睾酮、二氢睾酮（DHT）、雌二醇和性激素结合球蛋白（SHBG）呈强正相关，与前列腺内睾酮升高呈弱相关。相反，循环性激素和前列腺内性激素均与胸毛密度无统计学显著关联。二元秃发状态与三级胸毛密度之间的年龄调整相关性较弱（r = 0.05）。几乎没有证据表明Gleason评分或种族会改变这些关联。
本研究提供的证据表明，在平均年龄60岁时评估的秃发状态可能是循环性激素浓度的临床标志物。秃发状态与前列腺内性激素之间的弱关联至无关联再次证实了器官特异性性激素代谢的差异，这意味着其他性激素相关因素（如雄激素受体）在器官特异性雄激素作用中起重要作用，并且其他重叠途径可能参与了这两种复杂情况之间的关联。
