Men with moderate pattern baldness on the front and the crown of the head at age 45 had a 40% increased risk, compared to men with no baldness at that age, of developing prostate cancer later in life, according to a study led by researchers from the National Cancer Institute (NCI) and published in the Journal of Clinical Oncology.¹ The study’s senior author, Michael B. Cook, PhD, of the NCI’s Hormonal and Reproductive Epidemiology Branch, and other experts not involved in the study have commented in press statements and reports that the study presents strong evidence for a link between pattern baldness and aggressive prostate cancer, but say that these results are not yet practice-changing.

“Previous research linking baldness and prostate cancer has been inconclusive, but this large study suggests a significant link between high risk prostate cancer and hair loss—and suggests that men with hair loss may need to be followed more closely. More evidence is needed, however, before we can routinely consider baldness in prostate cancer screening recommendations,” said Charles J. Ryan, MD, Professor of Clinical Medicine and Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, in a statement released by ASCO.²

In a follow-up interview with The ASCO Post, Dr. Ryan stressed, “The study is suggestive, not definitive. It doesn’t alter how we approach screening at this point, and it doesn’t alter how we approach the active disease at this point. It just raises some interesting questions in the population.” Among those interesting questions are: what roles do hormones and genetics play in baldness and increased risk of prostate cancer, and why do men with moderate, but not severe, pattern baldness have an increased risk of prostate cancer?

The Balding Question

The study looked at data from a cohort of men aged 55 to 74 years at the time they enrolled in the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, between 1993 and 2001. To be eligible, men could have no history of prostate, lung, or colorectal cancer, or be receiving treatment for any kind of cancer, except nonmelanoma skin cancer.

Eligible men were randomly assigned to screening with prostate-specific antigen (PSA) for the first 6 years and annual digital rectal examination for the first 4 years, or to usual care. The men received a baseline questionnaire at the time of randomization, and from 2006 to 2008, those who remained under active follow-up received a supplemental questionnaire.

On that questionnaire, men were asked to recall their hair loss patterns at age 45 and given a number of options, from no baldness to frontal and severe vertex baldness. The questionnaire included illustrations of the different patterns, which are reprinted in the JCO article.¹ The 39,070 men “who responded to the balding question,” the article noted, were included in the analytic cohort. Information on cancer diagnoses and deaths was obtained from updated questionnaires, as confirmed by death certificates and medical documents.

Male pattern baldness at age 45 years was reported by 53.4%, and among those, 46.4% reported frontal baldness only, 23.5% frontal plus mild vertex baldness, 18.1% frontal plus moderate vertex baldness, and 12.0% frontal plus severe vertex baldness. During a median follow-up of 2.78 years, 1,138 incident prostate cancer cases were diagnosed, including 571 aggressive cases.

Compared with no baldness, frontal plus moderate vertex baldness was significantly associated with an increased risk of aggressive prostate cancer (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.07–1.80), but not overall or nonaggressive prostate cancer. None of the other classes of baldness were associated with prostate cancer.

Risk Is Not Linear

Dr. Ryan noted that the finding that the risk of aggressive prostate cancer didn’t increase with severe baldness represents “one of the potential gaps in these data. It doesn’t quite follow a linear course. You would expect,” he said, that if the risk of aggressive prostate cancer is higher in men with moderate than in those with mild pattern baldness, the risk would be even higher with severe than with moderate pattern baldness, but that is not what the study showed.

The study authors proposed a number of possible explanations for why they found no significant association between the highest class of male pattern baldness (frontal plus severe vertex baldness) and prostate cancer risk. These included measurement errors of recalled hair loss and different biologic mechanisms of balding patterns or extent.

Dr. Cook has reported that his research team is currently conducting two additional cohort analyses exploring the relationship between male pattern baldness and the risk of developing and dying from prostate cancer. One of these studies is using a baseline dermatologic assessment of male pattern baldness, which would eliminate any recall errors.

Underlying Health Issues

“Male pattern baldness of various different types has been associated with a variety of health conditions, including cardiac disease and prostate cancer,” Dr. Ryan said, so there is “the potential for there to be underlying health issues in some of these patients, but not all patients. The last thing we want to do is make every man who is losing his hair panic, but certainly there is that potential in some patients,” he added.

“With respect to prostate cancer, there is a link biologically between the two processes,” Dr. Ryan said. “Essentially, think of it as a chronic exposure to testosterone or a chronic exposure to androgens and that when that is happening in the scalp or in the skin, it leads to hair loss, but when that is happening in the prostate, it can actually promote the progression of the cancer.”

“Besides androgenic action, circulating insulin-like growth factors and hyperinsulinemia may also play roles in prostate carcinogenesis and baldness either directly or via interactions with androgen,” the study authors wrote.

“That is one of the other issues,” Dr. Ryan agreed. “Baldness is actually associated with heart disease and with diabetes.”

Different Genetic Predispositions

“Baldness is highly variable among men of different genetic predispositions,” Dr. Ryan said. “It is very relatively rare among Asians, for example. It is very common—about 50%—among men of European descent.”

The study cohort was predominantly white (89.3%). In the discussion portion of the JCO article, the authors noted that “the paradox that black men are less likely to have male pattern baldness than their white counterparts but have higher risk for prostate cancer requires further elucidation.”

Risk Down the Road

“The other key point is that this finding had to do with baldness at the age of 45, and the diagnosis of the prostate cancer was occurring at about the age of 70, so it was about 20 years or more later. The baldness is actually something that preceded the prostate cancer,” Dr. Ryan said.

“We have a dilemma about whether PSA screening is useful for the population as a whole, and now we have a situation where there is a physical finding that is present in one’s mid-40s that might be a red flag for risk down the road. It is possible that those individuals could be identified for screening and one could test whether screening is effective in that group. That is a big process to undertake, and I don’t know if anyone is actually advocating that.” A smaller, incremental step that might be considered, Dr. Ryan said, is to integrate that physical finding of baldness into the patient’s medical record.

Dr. Ryan stated that he is not advocating general PSA screening for men in their 40s with the type of pattern baldness identified in the study. “I am asking the question whether or not that is a reasonable response to these data. I think you have to look at the magnitude of the risk. This is something that epidemiologists would have to do, look at the magnitude of the risk associated with baldness.”

“To take this to the next level, you would have to do a prospective study, where you identify people at the age of 45, follow them for 20 years. That would cost multiple millions of dollars, and the question is, would that be worth our tax dollars and our research money? I don’t know.” ■

Disclosure: Drs. Cook and Ryan reported no potential conflicts of interest.

References

1. Zhou CK, Pfeiffer RM, Cleary SD, et al: Relationship between male pattern baldness and the risk of aggressive prostate cancer: An analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. J Clin Oncol. September 15, 2014 (early release online).

2. Blackburn KL: Certain form of baldness at age 45 linked to higher risk of aggressive prostate cancer. ASCO News Digest. September 15, 2014.