Oct. 16, 1997 DURHAM, N.C. -- Duke University Medical Center researchers have found preliminary evidence suggesting a man's lifetime risk of prostate cancer may be linked to the amount of male hormone testosterone circulating in his body as early as puberty or even in utero, although direct evidence of this link remains to be shown.
The two possible risk factors they found -- high "free" testosterone levels in adulthood and a small shoulder span in relation to body size -- appear to be unrelated to one another. However, they are both tied to hormone levels at various stages of development, said Wendy Demark-Wahnefried, associate professor of surgery at Duke and lead author of two parts of a study that produced the findings.
While doctors won't be able to predict who will get the disease based on these two factors alone, the results suggest that "free" hormone levels and shoulder span could be benchmarks for determining who is at greater risk for the disease, Demark-Wahnefried said. Free testosterone refers to a type of hormone that is not bound to a protein and thus can freely enter cells throughout the body.
"We have to look at how hormone levels at different points in time actually determine the risk of prostate cancer," she said. "It is hypothesized that hormone levels throughout life -- ranging from in utero to old age -- drive such events as skeletal and muscle formation, fat deposition, baldness, and that these events may provide the initial stimuli and promotion for prostate cancer.
"By studying the tell-tale signs that hormones leave on the body, our goal was to clearly separate those men at risk for prostate cancer from those who are not."
Demark-Wahnefried's research, funded by the National Cancer Institute and the Cancer Research Foundation of America, set out to measure the link between prostate cancer and factors such as height, weight, musculature and baldness -- all of which are related to hormones. The two-year, blinded, case-controlled study compared a group of 159 men with prostate cancer to a control group of 156 men who had come to the urology clinic for prostate screenings and other concerns such as kidney stones. Subjects were aged 50 to 70 years.
In the first phase of the study, Demark-Wahnefried and her colleagues at the Duke Comprehensive Cancer Center found nearly a two-fold increase in the risk of prostate cancer among men with high "free" testosterone levels, the form of testosterone that can readily be used by cells throughout the body.
While the link between testosterone and prostate cancer has been made before, previous studies have measured "total" testosterone, a less active form of the hormone that is bound to specific protein and thus cannot enter the cells.
The researchers also found a link between high testosterone levels and vertex or "top of head" baldness. However, baldness was not linked to prostate cancer in the study subjects, probably because baldness is as much related to age as it is to other factors like testosterone, she said.
Demark-Wahnefried theorizes that baldness at a younger age, perhaps at 40, could be used to predict the later risk of prostate cancer, a theory that she plans to study next.
The part of the study that looked at baldness, testosterone levels and prostate cancer is published in the September/October issue of the Journal of Andrology. Co-authors of that study include Samuel M. Leski of Boston University School of Medicine and Mark R. Conaway, Cary N. Robertson, Richard V. Clark, Bruce Lobaugh, Barbara J. Mathias, Tara Smith Strigo, and David F. Paulson of Duke.
In the next phase of the study, published in the September issue of the Journal of Nutrition and Cancer, researchers found that men with prostate cancer were more likely to have a narrower shoulder span in proportion to their overall body size, a trait that earlier studies have shown to be determined during puberty.
Demark-Wahnefried said those earlier studies, although quite limited in their sample size, showed that men who go through puberty later have a broader shoulder span than men who go through puberty early. She said this finding suggests that hormone levels have a direct influence on shoulder span.
While the difference in shoulder span was less than a centimeter, Demark-Wahnefried said it was the only physical factor she studied that was significantly associated with prostate cancer.
"Shoulder span may provide us with a benchmark of past hormonal and/or nutritional status and help elucidate the etiology of this disease," she said.
While researchers have long believed that prostate cancer is linked to male hormone levels, Demark-Wahnefried said the existing research has yielded conflicting results, similar to the controversy surrounding estrogen as a risk factor for breast cancer.
The current studies provide strong evidence that risk of prostate cancer is, in fact, influenced by hormonal events that occur much earlier in life, such as the formation of skeletal frame, she said. However, Demark-Wahnefried said these events may originate in utero and continue to manifest themselves at developmental milestones throughout a man's life.
In her next phase of research, Demark-Wahnefried and colleagues Joellen Schildkraut and Philip Walhter will study the link between baldness and prostate cancer in younger men as well as hormonal differences between younger men, aged 18 to 35, who have a strong family history of prostate cancer versus those from families with no history of the disease.
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