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Male pattern baldness increased risk for aggressive prostate cancer

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October 17, 2014

Men who exhibited frontal plus moderate vertex baldness by age 45 years were at increased risk for developing aggressive prostate cancer, according to study findings.

“Male pattern baldness seems to share pathologic mechanisms with prostate cancer in terms of advancing age, hereditability, and endogenous hormones,” the researchers wrote. “The fact that the age of observable hair loss coincides with the age of microscopic evidence for prostate cancer in autopsy studies, and that male pattern baldness represents cumulative exposures, as opposed to a single serum measurement, may help elucidate prostate cancer etiology.”

To examine the association between male pattern baldness prostate cancer risk, researchers extracted data for 39,070 men enrolled in the PLCO Cancer Screening Trial, a multicenter, randomized, two-arm study evaluating the effect of cancer screenings on disease-specific mortality.

Participants in this study, who had no cancer diagnosis at baseline, were randomly assigned to a screening group, consisting of annual PSA screening and digital rectal examination for the first 4 years, or a standard care group. At approximately the time of randomization, the researchers of the present study mailed the participants a sex-specific baseline questionnaire.

Men who continued to be actively followed between 2006 and 2008 also were mailed a supplemental questionnaire to further investigate possible risk factors, asking patients to recall and categorize their hair-loss patterns at age 45 years.

The categories were taken from a modified Norwood-Hamilton scale, and included:

  • No baldness;
  • Frontal baldness only;
  • Frontal plus mild vertex baldness;
  • Frontal plus moderate vertex baldness; and
  • Frontal plus severe vertex baldness.

The researchers followed the patients for diagnosed cancers and deaths through annual mailed update questionnaires, as well as through linkage to the National Death Index. Medical records were abstracted to confirm cancer diagnoses. The researchers used Cox proportional hazards regression models, with age as the time metric, to estimate HRs and 95% CIs of the association between male pattern baldness and risk for prostate cancer.

Michael B. Cook

The researchers found that during the median 2.78-year follow-up, 1,138 incident cases of prostate cancer were diagnosed, and 571 of these were aggressive (Gleason score ≥7, and/or clinical stage III or greater).

According to study results, compared with men who exhibited no baldness, men with frontal plus moderate vertex baldness at age 45 years did not have a higher risk for overall (HR=1.19; 95% CI, 0.98-1.45) or nonaggressive (HR=0.97; 95% CI, 0.72-1.3) prostate cancer, but had a significantly increased risk for aggressive prostate cancer (HR=1.39; 95% CI, 1.07-1.8).

“Our study found an increased risk for aggressive prostate cancer only in men with a very specific pattern of hair loss, baldness at the front and moderate hair-thinning on the crown of the head, at the age of 45. But we saw no increased risk for any form of prostate cancer in men with other hair-loss patterns,” researcher Michael B. Cook, PhD, an investigator in the division of cancer epidemiology and genetics at the NCI, said in a press release. “While our data show a strong possibility for a link between the development of baldness and aggressive prostate cancer, it’s too soon to apply these findings to patient care.”

Disclosure: The researchers report no relevant financial disclosures.

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Tanya Dorff

Tanya Dorff

The relationship between testosterone and development of prostate cancer is surprisingly complex and not fully defined. Yes, men who are castrated early in life or who lack 5-alpha reductase will never develop prostate cancer, but there have otherwise been inconsistent associations between circulating androgen levels and the lifetime risk for prostate cancer. Further, although prostate cancer is more common in Western countries and affluent populations — in parallel with the finding that these men have higher testosterone levels (though only early in life) — these populations also suffer higher rates of diabetes and obesity, which may underpin some of the risk described. Male pattern baldness, as a reflection of cumulative androgen exposure, has been associated with prostate cancer risk in some but not all previously published studies. Additionally, it has become clear from such studies that focusing on aggressive or fatal prostate cancer may be a more important endpoint than on absolute prostate cancer incidence.
In the current report, Zhou and colleagues reviewed data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer prevention trial — a very well-described prospective clinical trial — and there was no overall association between male pattern baldness at age 45 years and overall prostate cancer risk. However, a significant association was described, specifically between frontal plus moderate vertex hair loss and the risk for aggressive — including fatal — prostate cancer.
In their conclusions, the authors focus on the fact that this association may reflect shared biology, and the most obvious suspect is 5-alpha reductase and its metabolite dihydrotestosterone. 5-alpha reductase is an increasingly topical subject in prostate cancer, as men with congenital deficiency of 5-alpha reductase develop neither prostate cancer nor male pattern baldness. Therapy with 5-alpha reductase inhibitors prevents hair loss in men with male pattern baldness. It also reduces the incidence of biopsy-proven prostate cancer, as well as the rate of cancer progression in men pursuing active surveillance. However, this story is likely to be further complicated by genomic variations in androgen production and bio-availability, including levels of steroid hormone binding globulin, CYP17, the androgen receptor and the androgen receptor response elements.
For men, and the families who are concerned about them, the looming question is whether prostate cancer screening and prevention recommendations should be affected by the presence of early onset frontal plus moderate vertex baldness. The results of the PLCO trial have contributed significantly to the current recommendations issued by the US Preventive Services Task Force against PSA screening in the general population; however, in an era of increasingly individualized recommendations, it is important to consider the potential performance of PSA screening in this subgroup of men who may have higher risk to develop aggressive and possibly fatal prostate cancer.

Tanya Dorff, MD
USC Norris Comprehensive Cancer Center

Disclosure: Dorff reports no relevant financial disclosures.