Testosterone Levels Early In Life May Determine Later Risk Of Prostate Cancer

The two possible risk factors they found -- high "free" testosteronelevels in adulthood and a small shoulder span in relation to body size -- appearto be unrelated to one another. However, they are both tied to hormone levels atvarious stages of development, said Wendy Demark-Wahnefried, associate professorof surgery at Duke and lead author of two parts of a study that produced thefindings.

While doctors won't be able to predict who will get the disease based onthese two factors alone, the results suggest that "free" hormone levels andshoulder span could be benchmarks for determining who is at greater risk for thedisease, Demark-Wahnefried said. Free testosterone refers to a type of hormonethat is not bound to a protein and thus can freely enter cells throughout thebody.

"We have to look at how hormone levels at different points in timeactually determine the risk of prostate cancer," she said. "It is hypothesizedthat hormone levels throughout life -- ranging from in utero to old age -- drivesuch events as skeletal and muscle formation, fat deposition, baldness, and thatthese events may provide the initial stimuli and promotion for prostate cancer.

"By studying the tell-tale signs that hormones leave on the body, ourgoal was to clearly separate those men at risk for prostate cancer from thosewho are not."

Demark-Wahnefried's research, funded by the National Cancer Instituteand the Cancer Research Foundation of America, set out to measure the linkbetween prostate cancer and factors such as height, weight, musculature andbaldness -- all of which are related to hormones. The two-year, blinded,case-controlled study compared a group of 159 men with prostate cancer to acontrol group of 156 men who had come to the urology clinic for prostatescreenings and other concerns such as kidney stones. Subjects were aged 50 to70 years.

In the first phase of the study, Demark-Wahnefried and her colleagues atthe Duke Comprehensive Cancer Center found nearly a two-fold increase in therisk of prostate cancer among men with high "free" testosterone levels, the formof testosterone that can readily be used by cells throughout the body.

While the link between testosterone and prostate cancer has been madebefore, previous studies have measured "total" testosterone, a less active formof the hormone that is bound to specific protein and thus cannot enter thecells.

The researchers also found a link between high testosterone levels andvertex or "top of head" baldness. However, baldness was not linked to prostatecancer in the study subjects, probably because baldness is as much related toage as it is to other factors like testosterone, she said.

Demark-Wahnefried theorizes that baldness at a younger age, perhaps at40, could be used to predict the later risk of prostate cancer, a theory thatshe plans to study next.

The part of the study that looked at baldness, testosterone levels andprostate cancer is published in the September/October issue of the Journal ofAndrology. Co-authors of that study include Samuel M. Leski of Boston UniversitySchool of Medicine and Mark R. Conaway, Cary N. Robertson, Richard V. Clark,Bruce Lobaugh, Barbara J. Mathias, Tara Smith Strigo, and David F. Paulson ofDuke.

In the next phase of the study, published in the September issue of theJournal of Nutrition and Cancer, researchers found that men with prostatecancer were more likely to have a narrower shoulder span in proportion to theiroverall body size, a trait that earlier studies have shown to be determinedduring puberty.

Demark-Wahnefried said those earlier studies, although quite limited intheir sample size, showed that men who go through puberty later have a broadershoulder span than men who go through puberty early. She said this findingsuggests 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 wassignificantly associated with prostate cancer.

"Shoulder span may provide us with a benchmark of past hormonal and/ornutritional status and help elucidate the etiology of this disease," she said.

While researchers have long believed that prostate cancer is linked tomale hormone levels, Demark-Wahnefried said the existing research has yieldedconflicting results, similar to the controversy surrounding estrogen as a riskfactor for breast cancer.

The current studies provide strong evidence that risk of prostate canceris, in fact, influenced by hormonal events that occur much earlier in life, suchas the formation of skeletal frame, she said. However, Demark-Wahnefried saidthese events may originate in utero and continue to manifest themselves atdevelopmental milestones throughout a man's life.

In her next phase of research, Demark-Wahnefried and colleagues JoellenSchildkraut and Philip Walhter will study the link between baldness and prostatecancer in younger men as well as hormonal differences between younger men, aged18 to 35, who have a strong family history of prostate cancer versus those fromfamilies with no history of the disease.