Global Environmental Influences

Ecological Study: Oral Contraceptives and Prostate Cancer Connection (Nov 2011, BMJ)

Article below is followed by Abstract and part of the Discussion section of the Full BMJ Text

[Comment: Medscape is definitely not prolife so this article is even more amazing. N Valko RN]

The Pill and Prostate Cancer: Is There a Link?
Countries where oral contraceptive use among women is high appear to have correspondingly higher rates of prostate cancer, according to a study published online [http://bmjopen.bmj.com/content/1/2/e000311.full]  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.
[Fran Lowry, November 16, 2011, From Medscape Medical News > Oncology, http://www.medscape.com/viewarticle/753667?sssdmh=dm1.734732&src=nldne]
BMJ Open. 2011;1:e000311 — BMJ Open 2011;1:e000311 doi:10.1136/bmjopen-2011-000311
Published 14 Nov 2011, Occupational & environmental medicine

Oral Contraceptive Use is Associated with Prostate Cancer: an Ecological Study

http://bmjopen.bmj.com/content/1/2/e000311.full

http://bmjopen.bmj.com/content/1/2/e000311.full

ABSTRACT
Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa).

Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality.

Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and

mortality. These analyses were performed by individual nations and by continents worldwide.

Results OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r=0.61 and r=0.53, respectively; p<0.05 for all). PCa incidence was also associated with OC use in Europe (r=0.545, p<0.05) and by continent (r=0.522, p<0.05). All other forms of contraceptives (ie, intra-uterine devices, condoms or vaginal barriers) were not correlated with prostate cancer incidence or mortality. On multivariable analysis the correlation with OC was independent of a nation's wealth.

Conclusion A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further investigation.

From Full Text:
Discussion

In this study we have shown a strong correlation between the country-specific female OC use and incidence of prostate cancer among worldwide, continent and even intra-European nations. This correlation appeared specific to OC as no association was demonstrated with other forms of contraception such as intrauterine devices, condoms or vaginal barriers. Furthermore, prostate cancer mortality was also associated with OC use when examined globally. The correlation to OC use was independent of GDP as a measure of a country's wealth, and strongest in Europe..

Another plausible explanation for the association between OC use and prostate cancer is the potential environmental impact of OCs. The last two decades have witnessed growing scientific concerns and public debate over the potential adverse effects that may result from exposure to a group of chemicals that have the potential to alter the normal functioning of the endocrine system in wildlife and humans.

These chemicals are typically known as endocrine disturbing compounds (EDCs).

Temporal increases in the incidence of certain cancers (breast, endometrial, thyroid, testis and prostate) in hormonally sensitive tissues in many parts of the industrialised world are often cited as evidence that widespread exposure of the general population to EDCs has had adverse impacts on human health.

OCs in use today can potentially act as EDCs as they frequently contain high doses of ethinyloestradiol, which is excreted in urine without degradation.

This can then end up either in the drinking water supply or passed up the food chain.11

OCs were made publicly available in the 1960s, and have been widely used since the 1980s, hence the exposure to these substances, even in small quantities, may be chronic enough (20–30 years) to have a clinically significant effect

[Note: 88 countries in 18 continental areas were analysed using data on prostate cancer from the International Agency for Research on Cancer, and the United Nations World Contraceptive Use 2007 report to retrieve data on contraceptive use.]

[http://bmjopen.bmj.com/content/1/2/e000311.full ; N Valko RN, 16 Nov 11]