BETHESDA, Md--Physicians have long hypothesized that natural variation
in sex hormones may influence prostate cancer risk, said Meir
Stampfer, MD, of the Harvard School of Public Health. Efforts
to prove this, however, have yielded unclear results. Now, by
examining the interrelationship of different sex hormones, Dr.
Stampfer and his colleagues have achieved what he calls the first
clear demonstration that circulating levels of sex hormones can
predict a man's risk of developing prostate cancer.
The finding further suggests the need for studies of how lifestyle
practices might change circulating hormone levels, he said at
the General Motors Cancer Research Foundation annual conference.
Previous studies failed to demonstrate a convincing link for a
variety of reasons, Dr. Stampfer said. Some were simply too small.
Often the blood used was collected after diagnosis of prostate
cancer, and concern lingered that the cancer therapy or the cancer
itself had altered sex hormone levels among the participants in
Dr. Stampfer and his colleagues, who included Peter H. Gann, MD,
ScD, turned to the Physicians' Health Study. In 1982, 14,916 of
the 22,071 male US physicians in the study, all with no prior
cancer, provided samples of their blood, which were frozen and
stored. Study participants answered follow-up questionnaires every
6 months. The Harvard team matched 222 physicians who developed
prostate cancer in the following decade with 390 healthy, cancer-free
Blood from each man was thawed and measured for testosterone;
DHT (dihy-drotestosterone, the active form of testosterone in
the prostate); AAG (3-alpha-androstanediol glucuronide, an androgenic
metabolite of testosterone); estradiol; prolactin; and SHBG (sex
hormone binding globulin).
"Our thinking was that the androgens--testosterone, DHT,
and AAG--would be associated with an increased risk of prostate
cancer and that estradiol would be associated with a decreased
risk," he said. Since SHBG "binds more to testosterone
than to estradiol, we thought that the net effect of SHBG would
be to reduce prostate cancer."