The Association between Male Pattern Baldness and Prostate Cancer Risks Open Access
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Purpose: Male pattern baldness and prostate cancer seem to share common pathophysiologic mechanisms in terms of advancing age, hereditability and endogenous hormones (e.g., androgen receptor signaling pathway, insulin-growth factor signaling pathway, and hyperinsulinaemia). However, results from prior epidemiologic studies on associations between male pattern baldness and prostate cancer have been inconsistent. The majority of those studies are of case-control study design. Only two cohort studies have been published but were unable to perform subtype-specific analyses with statistical power. The purpose of this dissertation was to investigate the relationship between male pattern baldness and prostate cancer risks, in particular aggressive and lethal tumors, in an attempt to assess cumulative or early adulthood androgen exposure in relation to prostate cancer risks. Methods: We evaluated associations of male pattern baldness with overall and subtypes of incident prostate cancer or prostate cancer-specific mortality in three independent prospective US cohorts: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, the VITamins And Lifestyle (VITAL) Cohort Study, and the NHANES I Epidemiologic Follow-up Study (NHEFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional-hazards regression models with age as the time metric. Results: In the PLCO analysis, frontal with moderate vertex balding at age 45 years self-reported at supplemental questionnaire (age range=60-89 years) was associated with a 39% increased risk of aggressive prostate cancer (biopsy Gleason score≥7, and/or clinical stage≥III, and/or underlying cause of death as prostate cancer), compared with no balding (HR=1.39; 95%CI=1.07, 1.80). Conversely, male pattern baldness was unrelated to non-aggressive prostate cancer. Adjustment for covariates did not substantially alter the risk estimates. In the VITAL analysis, self-assessed male pattern baldness at age 30 years, age 45 years, and baseline (median age=60.5 years) were not associated with prostate cancer risks. The frontal with vertex balding category in the VITAL study combined what were three distinct classes of vertex balding in the PLCO analysis, which provided similarly null results when this set of district classes were collapsed into a single category in a sensitivity analysis of the PLCO data. In the NHEFS analysis, degrees of baldness (none/minimum/moderate/severe) were assessed by trained third-year dermatology residents in a standard procedure at NHANES I baseline. Any degree of baldness was associated with a 56% increased risk of prostate cancer-specific mortality (HR=1.56; 95%CI=1.02, 2.37) compared with no balding after the adjustment for potential confounders. Among three levels of baldness, moderate balding conferred the highest risk with an 83% increased risk estimate (HR=1.83; 95%CI=1.15, 2.92), compared with no balding after the adjustment for potential confounders.Conclusion: Our analyses collectively suggest male pattern baldness is positively associated with aggressive or lethal prostate cancer, supporting the hypothesis of overlapping pathophysiological mechanisms. Large studies are needed to replicate our findings, and further evaluate whether age of baldness onset or race modify the association of these two conditions.