Male Pattern Baldness in Relation to Prostate Cancer–Specific Mortality

A Prospective Analysis in the NHANES I Epidemiologic Follow-up Study

Cindy Ke Zhou; Paul H. Levine; Sean D. Cleary; Heather J. Hoffman; Barry I. Graubard; Michael B. Cook

Disclosures

Am J Epidemiol. 2016;183(3):210-217. 

In This Article

Abstract and Introduction

Abstract

We used male pattern baldness as a proxy for long-term androgen exposure and investigated the association of dermatologist-assessed hair loss with prostate cancer–specific mortality in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. From the baseline survey (1971–1974), we included 4,316 men who were 25–74 years of age and had no prior cancer diagnosis. We estimated hazard ratios and used Cox proportional hazards regressions with age as the time metric and baseline hazard stratified by baseline age. A hybrid framework was used to account for stratification and clustering of the sample design, with adjustment for the variables used to calculate sample weights. During follow-up (median, 21 years), 3,284 deaths occurred; prostate cancer was the underlying cause of 107. In multivariable models, compared with no balding, any baldness was associated with a 56% higher risk of fatal prostate cancer (hazard ratio = 1.56; 95% confidence interval: 1.02, 2.37), and moderate balding specifically was associated with an 83% higher risk (hazard ratio = 1.83; 95% confidence interval: 1.15, 2.92). Conversely, patterned hair loss was not statistically significantly associated with all-cause mortality. Our analysis suggests that patterned hair loss is associated with a higher risk of fatal prostate cancer and supports the hypothesis of overlapping pathophysiological mechanisms.

Introduction

In US men, prostate cancer is the most frequently diagnosed nonskin cancer and the second leading cause of cancer deaths, with an estimated 238,590 new cases and 29,720 deaths in 2013.[1] Established risk factors for prostate cancer are limited to older age, black race, family history of prostate cancer,[2] and certain genetic polymorphisms,[3] which collectively explain only a fraction of the disease occurrence. More studies are needed to better understand the etiology of prostate cancer, especially lethal malignancies, given that the current screening tests for prostate cancer lead to substantial overdiagnosis.[4]

Male pattern baldness (also known as androgenic alopecia) is progressive scalp hair loss due to androgenic miniaturization of hair follicles. Generally, 3 zones of the scalp are preferentially affected: the bitemporal, frontal, and vertex areas. The prevalence and extent of baldness increase with increasing age.[5] Evidence has suggested that male pattern baldness and prostate cancer might share similar pathophysiological mechanisms in terms of heritability and endogenous hormones. For example, heritable factors contribute to approximately 42% of prostate cancer risk[6] and 81% of male pattern baldness.[7] Regarding endogenous hormones, androgenic action has been shown to play integral roles in hair loss and prostate cancer progression; both hair follicles and the prostate gland are androgen responsive. However, results from prior epidemiologic studies of circulating sex steroid hormones in relation to prostate cancer risks have been inconsistent.[8–12] All of such prior studies only quantitated sex steroid hormones at a single time point, mainly at midlife or older. Thus, intra-individual variation and/or the etiologically relevant time window of exposure[13,14] might not have been adequately captured. Male pattern baldness might be a marker of long-term androgen exposure and thus could be useful in aiding our understanding of prostate cancer etiology.

Prior studies of male pattern baldness in relation to prostate cancer risks have been inconsistent in the methods used and the conclusions drawn. In most prior studies, investigators have used a case-control study design, and a meta-analysis of 7 such studies suggested a 25% higher risk of prostate cancer (odds ratio = 1.25; 95% confidence interval (CI): 1.09, 1.44) for men with any vertex balding compared with men with no balding.[15] In prospective studies, researchers have found somewhat similarly positive associations between these 2 conditions. An analysis of the Melbourne Collaborative Cohort Study (MCCS) suggested that vertex balding (Norwood-Hamilton scale types III vertex–VII) at 40 years of age might predict earlier onset of prostate cancer.[16] In our prior analysis of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort, we found that men with frontal plus moderate vertex balding (Norwood-Hamilton scale types V–VI) at age 45 years had a 39% higher risk of aggressive prostate cancer (hazard ratio (HR) = 1.39; 95% CI: 1.07, 1.80).[17] However, we did not observe associations between classes of baldness and prostate cancer risks in the cohort of Vitamins and Lifestyle (VITAL) Study,[18] although vertex balding was captured as a single exposure class—a categorization that produced a similarly null result when assessed in our PLCO analysis. Lastly, results from a former prospective analysis in the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), which included follow-up until 1992, suggested a 50% higher risk of incident prostate cancer for men with any baldness at baseline compared with men with no balding.[19] In that prior analysis of NHEFS data, investigators could not assess the association of baldness with fatal prostate cancer because too few deaths from prostate cancer occurred.[19] With an additional 20 years of follow-up, we used the unique resource of the NHEFS, which has the major advantage of data on dermatologically assessed baldness at baseline, to investigate the relationship between male pattern baldness and prostate cancer–specific mortality.

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