The Pill and Prostate Cancer: Is There a Link?

Fran Lowry

November 16, 2011

November 16, 2011 — Countries where oral contraceptive use among women is high appear to have correspondingly higher rates of prostate cancer, according to a study published online November 14 in BMJ Open.

Several recent studies have suggested that estrogen exposure increases the risk for prostate cancer, David Margel, MD, from the Princess Margaret Hospital, University of Toronto, Ontario, Canada, told Medscape Medical News.

This could be because the residue of estrogen ends up in the water supply and the food chain, he said.

"We believe that this is due to an environmental effect," Dr. Margel said. "These oral contraceptives contain a small amount of estrogenic compounds, which are not biodegradable and are excreted in the urine. Although each woman takes these compounds at very minimal doses, when millions of women take them, and for a long period of time, there may be some effect on the environment."

Together with coauthor Neil E. Fleshner, MD, head of the division of urology at the University of Toronto Health Sciences Center, Dr. Margel decided to examine this association in an ecological study.

They used data from the International Agency for Research on Cancer to examine age-standardized rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report to determine the proportion of women taking the birth control pill or using other means of contraception, including condoms, intrauterine devices (IUDs), and vaginal barriers.

They then analyzed the data for 87 countries, and correlated the percentage of oral contraceptive use with the number of new cases of prostate cancer and the number of deaths due to prostate cancer in each country.

They found that the use of IUDs, condoms, and other vaginal barriers was not associated with an increased risk for prostate cancer.

However, throughout the world, oral contraceptive use was associated with a significantly increased incidence of prostate cancer (r = 0.61; P < .05) and death from prostate cancer (r = 0.53; P < .05).

The researchers controlled for each country's wealth, but found no correlation between wealth and prostate cancer risk or mortality. However, "wealth may be associated with prostate cancer, because the wealthier the country, the higher the likelihood of screening for prostate cancer, and with screening comes more prostate cancer," Dr. Margel said.

He stressed that these findings are observational and do not indicate a cause-and-effect relation between oral contraceptive use and prostate cancer.

Importantly, "we are in no way telling women to get off the Pill," he added.

"In the future, to help us understand this phenomenon, we want to look at water supplies and test the estrogenic levels. We also want to look at prostate tissue to see if there are differences in estrogenic levels between those with prostate cancer and those without," Dr. Margel said.

For now, the study is just meant to cause people to take note of a potential harmful effect that the use of estrogen-disruptive compounds might be having.

"We hope this provokes other people to become interested in this topic, not only for oral contraceptives but for other endocrine-disruptive compounds that may be in the environment and may affect our health," Dr. Margel said. "We don't have a solution; we just hope that this will open up more research in this area."

Hypothesis-Generating Study

"This study is hypothesis generating, but in terms of the evidence the authors present to support estrogen as a potential cause of prostate cancer, it is too early to say," said Jian-Min Yuan, MD, PhD, epidemiologist and newly appointed associate director of the University of Pittsburgh Medical Center (UPMC) Cancer Institute in Pennsylvania.

"They used aggregate data for each country's use of oral contraceptives to correlate with aggregate data of prostate cancer rates, but these are just correlations. There are no underlying biological mechanisms, at least not as yet, to show that oral contraceptives are a cause," explained Dr. Yuan, who also heads the cancer epidemiology, prevention, and control program at UPMC, and is professor of epidemiology at University of Pittsburgh's School of Public Health.

Dr. Yuan added that rates of prostate cancer in developing countries appear low, but this probably has nothing to do with the use, or lack thereof, of the Pill.

"There could be some kind of biological mechanism that we just don't understand yet. The belief that estrogen causes prostate cancer could be tested in animal models," Dr. Yuan noted.

Weighing in with his opinion about the study, Edwin van Wijngaarden, MD, from the University of Rochester Medical Center, in New York, told Medscape Medical News that the notion that men with more exposure to endocrine-disrupting chemicals, presumably from the drinking water, are at higher risk for prostate cancer seems speculative.

"All these data can tell you is that, on average, countries with higher oral contraceptive use have a higher prostate cancer incidence. This relationship could have many explanations, even at the country level, as they only controlled for gross domestic product per capita," Dr. van Wijngaarden said.

Like Dr. Yuan, Dr. van Wijngaarden believes that the study has generated an interesting hypothesis, "which is the only thing papers like this can do." However, he said, "it is far removed from being able to say that oral contraceptive use and prostate cancer are linked on a population level, let alone causally on an individual level."

Dr. Margel, Dr. Fleshner, Dr. Yuan, and Dr. van Wijngaarden have disclosed no relevant financial relationships.

BMJ Open. 2011;1:e000311. Full text

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