Prostate, sex link intrigues scientists

The day may come when doctors ask a surprising question to evaluate a male patient’s risk for prostate cancer: “How’s your sex life?”

This spring, a pair of studies suggested that a man’s sexual habits and history might influence the likelihood that he would develop prostate cancer, which kills nearly 30,000 men in the United States each year. The research adds to a body of evidence gathered during the last four decades.

Scientists say that learning how sex affects the prostate gland (whose role is to produce secretions that make up part of semen) could lead to new ways to prevent and treat deadly tumors.

Researchers have been investigating the relationship between sexual behavior and prostate cancer since at least 1960, when a scientific journal, Annals of the New York Academy of Sciences, published a paper speculating that cultural differences in male sexual behavior may help explain ethnic disparities in rates of prostate cancer.

In the 1970s, researchers began to ask what behaviors and conditions might affect risk. In early interviews with prostate cancer patients, some men complained that they didn’t have sex as often as they would like. Soon, the “sexual frustration” theory was born: Lack of sexual release leads to stress, which is known to cause health problems, and may have increased the risk for prostate cancer.

Critics pointed out that this theory was flawed. A man’s sexual activity would likely diminish while being treated for a deadly disease, influencing how accurately he recalled his love life before the diagnosis.

Eventually, other researchers speculated that men who had too much sex were the ones at risk. To measure a man’s level of sexual activity, scientists have asked a variety of questions such as: How old were you the first time you had intercourse? Got married? How many times have you been married? How many children have you fathered? Do you have intercourse with prostitutes?

Although most of these questions yielded little useful information, a few intriguing trends emerged. Several (though not all) investigations have shown that a man’s risk for prostate cancer rises with the number of sex partners he has had in a lifetime.

Other studies have concluded that men who have contracted a sexually transmitted disease, or STD, appear to have an elevated risk for cancer of the prostate too.

University of Illinois researcher Karin Rosenblatt and several colleagues studied men in the Seattle area and found that those who had 30 or more sex partners in their lifetime more than doubled the risk of prostate cancer.

A 2000 National Cancer Institute study found that men who reported a history of syphilis were 2.6 times more likely to develop prostate cancer than other men.

In May, at the annual American Urological Assn. meeting, a team from the University of Michigan presented a study showing that men who had 25 or more sex partners in their lifetime were 2 1/2 times more likely to develop prostate cancer than men who had five or fewer. They also found that men who had been diagnosed with prostate cancer were significantly more likely to report a past bout with gonorrhea.

Research scientist Aruna Sarma, lead author of the Michigan study, said men who have had a high number of sex partners appeared to increase their risk for exposure to an STD. Sarma said that a sexually transmitted infection might set the stage for tumor growth by producing chronic inflammation in the prostate.

“That inflammation may trigger the proliferation of preexisting malignant cells,” she said.

Not all experts are as convinced that STDs can cause prostate cancer. “That interpretation is highly speculative,” said Dr. Howard Strickler, an associate professor of epidemiology at Albert Einstein College of Medicine in New York.

Studies of prostate tissue specimens by Strickler, Rosenblatt and others have shown that one prime candidate -- human papilloma virus, which is known to cause cervical cancer in women -- probably doesn’t cause prostate cancer.

Furthermore, Strickler said that if an infection -- sexually transmitted or otherwise -- is ever persuasively linked to prostate cancer, it will turn out to be the cause of a minority of cases.

Yet he considers the evidence compelling enough to continue studying whether STDs are linked to prostate cancer.

“If you can explain 10% to 20% [of cases], that’s huge,” said Strickler, noting that new screening tools and vaccines could be developed to help battle the disease.

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Testosterone theory

Another older theory about sex and prostate cancer that is largely disregarded today held that men who have frequent sexual encounters must have high testosterone levels, which not only boost their sex drive, but also increase their risk for cancer because the male hormone is believed to spur prostate tumor growth. This theory sank when research showed that men with high testosterone levels don’t necessarily have strong sexual desire or a higher risk for prostate cancer.

But, according to a controversial theory that made men uncomfortable when first discussed a few years ago, hormonal activity linked to sexual behavior may increase risk for prostate cancer after all, particularly later in life. In 2002, the journal Lancet Oncology featured an article by cancer biologist Mel Greaves, which argued that men who continue to have sex beyond traditional childbearing years may be exposing their prostates to stress that nature never intended.

Greaves, who describes his theory in greater detail in “Cancer: The Evolutionary Legacy” (Oxford Press, 2002), said he would never recommend decreasing sex to lower the risk for prostate cancer. “That’s nonsense,” he insists.

However, Greaves said sexual activity past midlife could be one of many factors that influence the development of the disease. He speculates that early human males who developed prostates that responded best to testosterone’s “signal” were most likely to remain fertile and survive. But today, most men stop fathering children by age 50 or so, making the need for what he calls “persistent prostate activity” unnecessary in middle age.

Unfortunately, the same gene mutation that makes prostate cells more sensitive to testosterone’s signal also appears to cause cells to proliferate, explains Greaves, which can lead to cancer. “More signaling, more risk,” he said.

Greaves concedes that his theory -- which he calls “sort of a horrible thought” -- is difficult to prove.

The author of a study published in the April 7 issue of the Journal of the American Medical Assn. said that middle-aged and older men should relax. Researcher Michael F. Leitzmann of the National Cancer Institute led a team that again looked at whether men who lead active sex lives have a greater risk for prostate cancer than less-amorous men.

The study, by far the largest of its kind, followed more than 29,000 men for eight years. But rather than asking the men indirect questions about their sexual activity, such as their age at first intercourse or marriage, Leitzmann and colleagues simply asked how often they ejaculated. The men were told to include sexual intercourse, masturbation and nocturnal emissions.

Unlike most previous studies, the JAMA paper failed to implicate carnality as a risk factor for prostate cancer. “Higher ejaculation frequency was not related to increased risk, which was really good news,” Leitzmann said.

In fact, he and his colleagues found that the opposite might be true: On average, a man decreased his risk for prostate cancer by 15% for every three times he ejaculated per week, which was true for subjects in all age groups. “Our data show that sexual activity, even at late ages, appears to protect against prostate cancer,” Leitzmann said.

So maybe the old sexual-frustration theory made sense after all? It’s possible, said Leitzmann, who notes that under stress, the body produces chemicals called growth factors that are known to promote growth of prostate cells, which might set the stage for tumor development. Leitzmann, however, backs a notion that might be called the “drain-the-ducts” theory.

“We believe ... that frequent ejaculation is helping to flush out retained chemical carcinogens that tend to accumulate in the prostate gland,” Leitzmann said. Studies have shown that environmental and industrial toxins can linger in the prostate, as can chemicals in cigarette smoke. “If you have incomplete drainage of the prostatic fluid ... you can imagine that these chemicals would have more time to affect the prostate tissue.”

Predictably, after the JAMA study appeared, a few newspaper headlines exclaimed “Sex May Prevent Prostate Cancer.” But Leitzmann isn’t ready to offer the ejaculation prescription just yet. “I wouldn’t go out and tell men to alter their sexual habits for the sake of preventing prostate cancer,” he said. Perhaps just as predictably, Leitzmann said it was not possible to reach conclusions about the link between sex and prostate cancer until more studies have been completed.

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Venereal disease link?

Some doctors say the link between venereal disease and prostate cancer is now worth talking about. Dr. Isaac Powell, a professor of urology at Wayne State University in Detroit, points out that sexually transmitted infections often cause prostatitis, or inflammation of the prostate. This condition can produce severe pain in the lower back or groin, along with other symptoms, though some men develop prostatitis and never know it.

What’s the connection? “There’s growing evidence that prostatitis is associated with prostate cancer,” said Powell, noting that trials are underway to determine whether prescription anti-inflammatory drugs (such as Vioxx) reduce the risk of prostate cancer. In his research, Powell helped lead a study (that has not been published) that detected high rates of prostatitis among African American males; in that same study, black men with prostatitis were more likely to develop prostate cancer than those who didn’t have prostatitis.

Powell advises his patients with prostatitis to undergo frequent screening for prostate cancer and suggests that men who have had an STD talk to their physicians about prostatitis.

However, neither he nor any other doctor or scientist contacted for this story thought that fear of prostate cancer should keep any man from enjoying a healthy, safe sex life.

“I think the jury is still out,” Greaves said. “Nobody, and certainly not me, is advocating celibacy.”