Why You Might Want to Refuse the PSA Test for Prostate Cancer Screening

If you are a man of a certain age (say, over 40-45), you have likely had at least one prostate screen in your regular exams (and if you haven't, DO IT NOW). The old school test is the digital rectal exam (DRE), you know, the one where the doc inserts a gloved, lubricated finger into your arse and feels for the size of the prostate gland. Most men dread this part of the physical. Once prostate specific androgen was discovered (by Richard Ablin, in 1970) and a blood test was developed, PSA screens became the most popular diagnostic tool.

The problem is that PSA screening is not a very effective tool. Dr. Ablin, and a lot of other researchers, worry that "the use of the PSA test has led to overdiagnosis and overtreatment, with millions of unnecessary surgeries, complications and deaths." There is considerable research to support this concern.

This is from "Prevention of Prostate Cancer" (Algotar, AM, Stratton, MS, Harryman, WL, and Cress, AE); Fundamentals of Cancer Prevention, D. Alberts, L.M. Hess (eds.), 2014.

Treatment of clinically silent cancers is termed “overtreatment” (Klotz 2012 ). Estimates place the cost of this phenomenon in excess of $31 and $55 million respectively (Heijnsdijk et al. 2009 ).

After extensive review of literature, the United States Preventive Services Task Force (USPTF) has issued a grade D recommendation (“discourage the use of this service”) for screening with PSA (Force 2012 ). This means that the USPTF believes there is moderate or high certainty that screening with PSA has no net benefit or that the harm outweighs the benefit. This grade D recommendation applies to healthy men of all ages, regardless of race or family history. (p. 495-496)

Perhaps the most scathing review of PSA testing in recent months comes from Dr. Ablin himself, in a New York Times editorial, The Problems with Prostate Screening (Nov. 25, 2014).

In this editorial, he dissects some serious issues with two major studies - European Randomized Study of Screening for Prostate Cancer, and the so-called Swedish Goteborg study - both of which support the use of PSA tests to reduce prostate cancer deaths. These studies appeared in highly prestigious journals, The New England Journal of Medicine and Lancet Oncology, respectively.

The researchers in the European Randomized Study of Screening for Prostate Cancer (ERSPC) have refused to make their data available to outside researchers, despite government and charity funding of the project. This is a HUGE red flag. More troubling, however, is that this project transferred 60% of the data from the Swedish Goteborg Study, which is unique "among country-specific studies in showing an almost 50 percent reduction in prostate cancer deaths for screening recipients." Without this data (which is an outlier in PSA research), there would not have been any clinically relevant survival rate in the ERSPC study.

Another HUGE red flag is that several of primary researchers in the European study have interests in the PSA screening industry. This is from Dr. Ablin's editorial:

Finally, several senior authors of the European trials, and their American supporters, have potential conflicts of interest that relate to payments from companies involved in marketing PSA tests, or in holding patents in the PSA and prostate cancer diagnostic space — relationships documented by the International Committee of Medical Journal Editors, in the forms that accompany the PSA-study publications and in disclosures found in CA: A Cancer Journal for Clinicians.

None of this serves the men who rely on prostate cancer screening to protect them and identify possible tumors as early as possible (early detection = much higher survival rates).

In the end, the decision to get a prostate cancer screen (of whatever type) should be made by the man in discussion with his physician. For men who are not in high-risk groups (high risk groups include African-Americans, first-degree relative with prostate cancer before age 65, and so on), the American Cancer Society does not recommend prostate cancer screens.

For myself, I have chosen to go with the DRE in my physicals, and I made this choice in conversation with one of the leading researchers in prostate cancer, Dr. Anne Cress of the UA Cancer Center (and a friend of mine). This feels like the best choice for me.

Movember To Support Men's Mental Health (in addition to prostate and testicular cancers)

Okay, first an admission, I wrongly believed that Movember was beard growing, not just mustaches. But that is because I confused it with another men's health meme, part of the same Movember fund-raising effort, No Shave November. There's also Novembeard.

If you can grow it, let it grow! It's for a good cause (or causes).

Movember To Support Men's Mental Health

Trending News: There's A New Reason To Grow A 'Mo' This Movember

© Getty


Joel Balsam | November 1, 2014

Why Is This Important?

Because too many men suffer from mental illness and they could use a helping hand.

Long Story Short

This year, donations from guys who grow out their ‘stache for Movember will go towards fundraising and raising awareness about male mental health in addition to prostate and testicular cancers.

Long Story

The hairy truth is that too many men suffer from mental illness. According to data released on Movember’s website, a total of 38,364 Americans died by suicide in 2010 and over three quarters of them (79%) were men.

To make matters worse, men aren’t talking about it. According to researchers in the UK, almost a third of men are too embarrassed to seek help for a mental problem and less than a quarter talk to their doctor if they felt down for more than two weeks in comparison to a third of women.

Justin Coughlan, the Australian co-founder of Movember told the BBC that this is a huge issue men need to combat. “It’s the last piece of the puzzle,” he said. “It’s just so big and there’s such a need for it.”

For the 11 years since it began in 2003, the month-long campaign has asked men to grow out their moustaches for charity and awareness about prostate cancer and then testicular cancer. This year, men’s mental illness will be added to the list.

It’s hard to think of too many other annual charity campaigns that have caught on as well as Movember. Every year, millions of “Mos” can be found on street corners and in offices worldwide and the charity’s success is undeniable. Well over four million Mo Bros and Mo Sistas have registered to fundraise since the charity began and $559 million has been raised. Immeasurable is the amount of conversations people have had about men’s mental health and in the case of prostate cancer, how many have gotten checked. According to Movember, 75% of those who participate were more aware of the health risks they face and 50% told someone they should take action to improve their health.

If you haven’t done Movember before, all you need to do is have a fresh shave at the beginning of the month (you’re a little late, but today will do) and sign up for an account. Then, try and get funds to support your Mo and talk about men’s health. Easy peasy.

The stigma about mental illness, especially for men is something that absolutely needs to go, and if Movember can help take it down it will be doing a great service to men everywhere.

Own The Conversation

• Ask The Big Question: Will you be growing your mustache out for Movember this year?
• Disrupt Your Feed: Are there more worthy causes that Movember could be supporting?
• Drop This Fact: Around 15 million American adults are diagnosed with depression each year.

Expand Your Expertise

• Movember founder: Men can end up 'mentally broken' [BBC]
• A Spectator's Guide to Movember and No Shave November [Boston.com]

More Conversation Ammo On AskMen

• Movember Moustaches
• Movember Moustache Monikers
• Kate Upton And Movember
• Moustache Styles

Two New Studies on Prostate Cancer with a Surprising Link

Two new studies on prostate cancer have been released in the last couple of days. The first one shows a 3.3 times greater risk of fatal cardiac events (heart attacks) in men who undergo androgen depletion therapy (ADT) for the treatment of prostate cancer (ADT eliminates testosterone from the body).

The new information supports previous studies suggesting that ADT increases risk of cardiovascular disease, risk of depression, induces muscle loss, decreases bone density (leading to osteoporosis), and results in an overall lower quality of life. I'd rather die of the disease than go through any of that. And in the long term, ADT does not stop progression of the disease, it only slows it down for about 6 months. After ADT the risk of a highly aggressive tumor is increased considerably, at which point it is untreatable.

The other study suggests that men who have had more than 20 female sexual partners have a 1/3 lower risk of developing prostate cancer. Strangely, men who sleep with 20 or more male partners are twice as likely to develop prostate cancer. That is a curious result that may be an anomaly, further studies are needed.

The connection between these two studies is testosterone. Men who have more sexual partners tend to have higher testosterone levels, and despite the prevailing belief that ADT is a useful treatment, there is mounting evidence that testosterone provides some protection against developing the most severe prostate cancers (which tend to be estrogen dependent, which makes ADT the most wrong choice possible).

Anyway, here are the press releases for the new studies.

Prostate cancer treatment linked to cardiac death risk 

An increased risk of dying from heart-related causes has been linked with a mainstay treatment of prostate cancer in a subgroup of men who have had prior heart attacks or congestive heart failure.

Written by David McNamee | 10.29.2014

The authors say that the findings of their study should be carefully weighed against larger controlled trials that demonstrate benefits of ADT.

One of the main treatments for prostate cancer, androgen deprivation therapy (ADT) reduced male hormone levels in an effort to prevent them from stimulating cancer cells. However, previous studies have found some adverse effects to be associated with ADT, including increased risk of diabetes, coronary heart disease, heart attacks and sudden cardiac death.

To further investigate this link, a group of researchers from Brigham and Women's Cancer Center and Harvard Medical School - both in Boston, MA - analyzed data from 5,077 prostate cancer patients who were treated between 1997 and 2006. About 30% of the participants had been treated with ADT.

No link was found between ADT and heart-related deaths among men with no risk factors for heart problems after a median follow-up of 4.8 years.

However, among men with congestive heart failure or prior heart attacks, there was a 3.3-times increased risk of death from heart problems. Heart-related deaths occurred in 7.01% of men in this subgroup who were receiving ADT, compared with 2.01% of men not receiving ADT.

The researchers explain that this increased risk works out as one cardiac death for every 20 at-risk men who receive this therapy.

"While androgen deprivation therapy can be a life-saving drug for men with prostate cancer and [can] significantly increase the cure rates when used with radiation for aggressive disease," says Dr. Paul Nguyen, of Brigham and Women's Cancer Center, "this study also raises the possibility that a small subgroup of men who have significant heart disease could experience increased cardiac death on ADT."

Further research should examine different types and durations of ADT

However, the researchers also warn that, as the study - which is published in the journal BJU International - was a retrospective analysis, its findings should be carefully weighed against larger controlled trials that demonstrate benefits of ADT.

It is also possible that changing the type or duration of ADT may reduce cardiac harm, and the researchers suggest that future studies should examine this.

The authors also consider that a longer follow-up period in future studies may reveal associations between ADT and cardiac harms in lower risk subgroups, such as among men with diabetes.

Dr. Nguyen says:

"I would still say that for men with significant heart problems, we should try to avoid ADT when it is not necessary - such as for men with low-risk disease or men receiving ADT only to shrink the prostate prior to radiation. However, for men with high-risk disease, in whom the prostate-cancer benefits of ADT likely outweigh any potential cardiac harms, ADT should be given even if they have heart problems, but the patient should be followed closely by a cardiologist to ensure that he is being carefully watched and optimized from a cardiac perspective."

In March, a study published in the Journal of Clinical Oncology found that prostate cancer patients who received ADT as their primary treatment instead of surgery or radiation therapy did not live any longer than patients who received no treatment.

The authors, from Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, said that their study - which analyzed data from 15,170 patients - "mitigates against any clinical or policy rationale for use of primary androgen deprivation therapy in these men."

* * * * *

Prostate Cancer Risk Reduced By Having More Sex

Trending News: This New Study Suggests The Weirdest Reason You Should Sleep Around

Paul Watson October 28, 2014

© danrocha/Flickr

Why Is This Important?

Because it may now be medically advisable for men to sleep around.

Long Story Short

Research has revealed that men who have slept with more than 20 women have reduced their risk of prostate cancer by almost a third, but men who have slept with 20 men have doubled their risk.

Long Story

A revolutionary new study has shown that sleeping with more than 20 women can reduce a man’s chances of developing prostate cancer by 28 percent. Conversely, men who sleep with more than 20 male partners are twice as likely to get prostate cancer than a man who has never had sex with another man.

Researchers at the University of Montreal and the Institut Armand-Frappier published their discovery in the journal Cancer Epidemiology after a survey of 3,208 men between 2005 and 2009.

It is suggested that intercourse can protect men from prostate cancer and those who are more promiscuous have more regular sex than those in long-term relationships.

“It is possible that having many female sexual partners results in a higher frequency of ejaculations, whose protective effect against prostate cancer has been previously observed,” lead researcher Dr. Marie-Elise Parent is quoted as saying by The Telegraph.

However, the reason for the reverse effect in homosexual male relationships where men who have slept with 20 male partners have double the chance of getting prostate cancer and a staggering 500% greater chance of developing a less aggressive prostate cancer, is still not clear.

“It could come from greater exposure to STIs, or it could be that anal intercourse produces physical trauma to the prostate,” Parent said, but she stressed that was a “highly speculative" analysis.

This is the first study to find a link between the number of sexual partners and prostate cancer, but it has previously been suggested that intercourse may help guard against prostate cancer because it reduces the concentration of carcinogenic substances in the fluid of the prostate.

Still, many men will be disappointed to hear that Dr. Parent was unwilling to recommend men should be told to sleep with more women, insisting we were “not there yet.”

Own The Conversation

• Ask The Big Question: Does sleeping with more women really help men avoid prostate cancer?
• Disrupt Your Feed: I always knew it was medically responsible to sleep with as many women as possible... Kidding.
• Drop This Fact: Prostate cancer is the most common cancer in Europe for males and the third most common cancer overall.

Expand Your Expertise

• Prostate cancer risk reduced by sleeping with many women, but increased with many men [Eureka Alert]
• Sex with 21 women lowers risk of prostate cancer, academics find [The Telegraph]
• Men who sleep with multiple women REDUCE their risk of prostate cancer [Daily Mail]

Fitness Friday - Fitness News and Information You Can Use

It's time for another Fitness Friday. We start off with two articles from Chad Waterbury (partly as a promotion for his new book), one from his own blog and one from Eric Cressesy's sight. After that we have an article on running from T-Nation. Finally, a nutrition article on the Western diet and its impact on the immune system, then two articles debunking the health risks associated with testosterone replacement therapty (good news for men on T replacement).

Full-Body Training for Mass Rules

Chad Waterbury

 

The best trigger for muscle growth across your entire body is a full-body workout. The combination of an upper-body pull, push and squat/deadlift/lunge is a powerful stimulus to upregulate the anabolic hormones and ramp up protein synthesis.

I’ve written extensively about full-body training over the years, and I keep experimenting with ways to make it better. Here’s what I’ve learned over the years that you can do to make full-body training your go-to strategy for fast muscle gains....

* * * * *

What Cirque du Soleil Can Teach You About How to Build Muscle

Written by Chad Waterbury on June 28, 2014 | by Eric Cressey

I'm in Chicago to speak at the Perform Better Summit this weekend, but fortunately, my good friend Chad Waterbury provided this guest post for today. Enjoy! -EC

In 2001, I went with a buddy to Vegas. I wish I could say the trip was replete with all the temptations that Sin City had to offer, but it was strictly business.

At the time, I had a packed personal training calendar that kept me busy from dawn to dusk. Most of my clients were guys that wanted to build muscle, so I had them do a combination of heavy and high-rep training to failure.

That’s how bodybuilding protocols worked back then, and most of them still do today. I made my clients work hard and they trained each major muscle group about twice per week.

Now this is where my Vegas trip comes in.

That year I went to see the Cirque du Soleil show, Mystere. Many of my clients had seen the popular show and they mentioned that I should make a point to attend, mainly because of two heavily-muscled gymnastics that display mind-blowing feats of strength: the Alexis Brothers.

* * * * *

Running Doesn't Suck

by Max Shank   
07/01/14

Here's what you need to know...

• The anti-running movement has gone too far when it says that running is stupid or that it will eat up all of your muscle.
• The weight-lifter-who-moves-like-garbage and bashes running is becoming a tiresome cliché.
• Short distances like 10-40 meters, 40 to 100 meters, and 100 to 800 meters, in addition to hill sprints and shuttle runs, all have varying benefits ranging from increases in GH and Testosterone to increases in leg strength, coordination, and bone and soft tissue integrity.
• If the endurance nutballs would start doing repeats of 400-800 meters at high effort, they might forget what a thruster is.

The fact that there's been a revolt against "jogging" as a fitness modality is terrific and I'm happy we're moving more towards the center. However, one thing that's gone too far is this whole idea of how running is stupid, or will somehow eat up all of your muscle. I've even heard trainers tell people that running is the worst thing you can do to stay in shape.

Now I'm all for the execution of "jogging" in general, but to make a blanket statement that all running is worthless is extreme. Running sucks? Really? Seriously? Humans are literally built for running. As far as the hierarchy of things you need to do for survival, running is right smack dab at the top of the list, next to keeping your heart beating at all times. Frankly, the weight-lifter-who-moves-like-garbage and bashes running is becoming a tiresome cliché.

Running offers several benefits including, but not limited to:

• Increase in growth hormone and Testosterone production
• Increase in leg strength
• Increase in coordination
• Increase in bone and soft tissue integrity
• Prevention of injuries

Now when I advocate that you run, it's not for 26 miles, but for varying distances up to 800 meters at a time. Here's a short list of the different modalities I use and their benefits....

* * * * *

Next up we have two nutrition/supplement studies. One looks at the impact of the Western diet on the immune system, the other is a new testosterone study that fails to confirm a study from earlier this year that suggested testosterone replacement cause cardiac damage.

Fast food fever: reviewing the impacts of the Western diet on immunity

Ian A Myles

Nutrition Journal; 2014, 13:61 doi: 10.1186/1475-2891-13-61

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

While numerous changes in human lifestyle constitute modern life, our diet has been gaining attention as a potential contributor to the increase in immune-mediated diseases. The Western diet is characterized by an over consumption and reduced variety of refined sugars, salt, and saturated fat. Herein our objective is to detail the mechanisms for the Western diet’s impact on immune function. The manuscript reviews the impacts and mechanisms of harm for our over-indulgence in sugar, salt, and fat, as well as the data outlining the impacts of artificial sweeteners, gluten, and genetically modified foods; attention is given to revealing where the literature on the immune impacts of macronutrients is limited to either animal or in vitro models versus where human trials exist. Detailed attention is given to the dietary impact on the gut microbiome and the mechanisms by which our poor dietary choices are encoded into our gut, our genes, and are passed to our offspring. While today’s modern diet may provide beneficial protection from micro- and macronutrient deficiencies, our over abundance of calories and the macronutrients that compose our diet may all lead to increased inflammation, reduced control of infection, increased rates of cancer, and increased risk for allergic and auto-inflammatory disease. 

* * * * *

Latest Testosterone Study Finds No Heart Attack Risk

Nancy A. Melville
July 03, 2014

In the latest addition to the ongoing debate over the safety of testosterone treatment, researchers report no significant increased heart attack risk in older men treated with an intramuscular form of the therapy.

The study, published online this week in the Annals of Pharmacotherapy, compared 6,355 Medicare beneficiaries treated with testosterone with 19,065 who were not, between January 1997 and December 2005, and showed no increased risk of myocardial infarction (MI) in the treatment group (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.69 - 1.02).

“In this matched double-cohort study of more than 24,000 Medicare beneficiaries, we found that use of intramuscular testosterone therapy was not associated with an increased risk of MI,” say the authors.

Furthermore, "a dose–response analysis demonstrated no increased risk in MI according to estimated cumulative dose of testosterone. These findings were robust across a range of sensitivity analyses that addressed eligibility criteria, exposure thresholds, follow-up periods, and covariate adjustment,” they add.

* * * * *

Testosterone Therapy Does Not Cause Prostate Cancer

NEW YORK, NY--(Marketwired - Jul 3, 2014) 

What are the dangers of testosterone therapy? Does long-term hormone replacement therapy increase prostate cancer risk? Testosterone replacement therapy is on the rise, though recent reports suggest that low testosterone (Low T) diagnoses may be too prevalent and that excessive treatment pose risks to men. However, according to a recent German study, long-term testosterone therapy does not increase a man's risk of developing prostate cancer.

Some experts caution that testosterone therapy is overused. Evidence shows that the treatment increases prostate size, elevates prostate-specific antigen (PSA) levels, and permanently impairs the body's ability to produce natural testosterone. Leading New York robotic prostate surgeon, David B. Samadi, MD, Chairman of Urology and Chief of Robotic Surgery at Lenox Hill Hospital, encourages men to seek a second opinion before beginning a testosterone therapy regimen.

"For some men, Low T is very real and can cause loss of energy, reduced sex drive, weight gain, and depression," said Dr. Samadi. "Men with truly low testosterone levels can experience tremendous benefits from testosterone therapy and may opt for long-term treatment. For them, this is good news. Their risk of prostate cancer is no higher than that of other men."

Statins and Prostate Cancer - Don't Believe What You Read

Every few years, it seems, there is renewed interest in using statins (hydroxy-methyl-glutaryl CoA reductase inhibitors - drugs that lower cholesterol) to treat (or prevent) prostate cancer. WebMD reported on a 2009 study suggesting an almost 2/3 reduction in death rate with the use of statins:

Statins and Prostate Cancer Death

The new study involved 380 men ages 55 to 79 who died from prostate cancer between 1999 and 2001 and who had living spouses who could verify their medical histories. They were compared to 380 married men in the same age group who were still alive.

A total of 63 men who died from prostate cancer had taken statins, as had 109 of the men who were alive.

After taking into account other risk factors for dying from prostate cancer, men taking statins were 63% less likely to die from the disease than men not taking statins.

Stephen Marcella, MD, assistant professor of epidemiology at the University of Medicine and Dentistry of New Jersey in Piscataway, presented the findings at the 2009 Genitourinary Cancers Symposium.

Further analysis showed that high-potency statins like Lipitor, Zocor, and Crestor were linked to a lower risk of dying from prostate cancer even more than weaker statins like Mevacor, Pravachol, and Lescol.

"The high-potency statins were about 2.5 times more effective at preventing prostate cancer death than the weak statins," Marcella says.

"That makes sense," Klein says. "The more potent the drug, the bigger the biologic effect."

That doesn't mean high-potency statins are better than weaker statins, he stresses. "Their primary purpose is for cholesterol lowering and you typically want to use the least aggressive therapy you can to achieve the desired effect," Klein says.

While the studies were not designed to examine how statins might protect against dying from prostate cancer, Klein notes that they are potent anti-inflammatory drugs. "There's a lot of evidence that inflammation contributes to the development of prostate cancer." Alternately, statins may directly kill cancer cells, Klein says.

The anti-inflammatory model of the reduction of cancer severity in those who use statins may be true for some patients. We don't know. But we do that a diet rich vegetables, antioxidants, fruits (especially berries), and anti-inflammatory herbs (curcumin, olive leaf extract, oregano oil), combined with regular exercise and an avoidance of too much red meat (or, more precisely, flame-cooked meat) and too much sugar and other simple carbs, all work in synergism to reduce inflammation, which is the primary driver of cancer growth.

Why use statins when we can get the same benefit (and may others as well) from a proper diet?

In a 2010 paper (Di Stasi, MacLeod, Winters, and Binder-Macleod¹) on how physical therapists can be useful for those taking statins, the authors outline some of the issues with statins and muscle damage:

Approximately 25 million Americans use statins,¹³ and 5% to 18% of these patients report some form of myalgia.¹⁴ Skeletal muscle side effects that are associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death (ie, rhabdomyolysis).^15,16 Side effects have been associated with all commonly used statins and are dose dependent.^17,18

Other research has suggested the percentage of people who experience side effects (especially in muscle) is not really so tiny. Parker, Capizzi, Grimaldi, Clarkson, et al. (2013²) found that even non-symptomatic patients express increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects.

However, this is not the most serious with statins and prostate cancer. 

Earlier this year, the research surfaces again. This is a lengthy article, and I am including all of it - it comes via the Prostate Cancer Foundation.

Statins and Prostate Cancer

As the science comes together, risk of aggressive disease may be abated with use, but little effect on indolent, early prostate cancers

March 4, 2014 -- Statins are a group of widely prescribed drugs used to lower cholesterol levels in the body. Common statin medications include well-known brands such as Zocar, Lipitor, and Crestor. Statins work by inhibiting an enzyme in our bodies (HMG-CoA reductase) that is used to manufacture cholesterol, and the drugs can also help clear already formed cholesterol from the bloodstream. High cholesterol is a known cause of cardiovascular disease, and it’s well-established that statins reduce the rate of death and illness caused by cardiovascular disease. And while statins can help prevent the risk of heart attack or stroke, some studies have also suggested that statins may have an effect on prostate cancer.

Whether the effect would be beneficial or harmful has been the subject of ongoing studies for some time. When statins first became widely available to the public in the 1980s, concerns erupted that these drugs might spur some cancers. Those fears are now widely dispelled, and this past year, a massive meta-analysis of 135 randomized studies that included over a quarter million study participants, found that statin use did not increase the risk of developing cancer.

Statins and Prostate Cancer

However, whether or not statins had a positive impact on cancer risk remained an open question. Research has suggested that statins can slow cancer cell growth in certain cancer types such as breast, colorectal, and skin cancers, and may lower the risk for the latter two. And some research has also suggested that statins might lower the overall risk for prostate cancer, but because of inconsistent findings, it was clear more research was needed. From such ongoing research, what is emerging is that statins may indeed reduce the risk of death from prostate cancer, but likely have little effect on whether or not a man develops prostate cancer in the first place.

Statins and Advanced Prostate Cancer



Dr. Elizabeth A. Platz of the Johns Hopkins Bloomberg School of Public Health and a Prostate Cancer Foundation-funded researcher.
Dr. Platz and colleagues have twice found that individuals with lower levels of cholesterol (within the normal ranges, not the super low ranges) had a lower risk of developing more aggressive disease, as defined by high Gleason scores. This is yet another reason for men to put aside that plate of fried chicken and head for the salad bar, in order to naturally lower their cholesterol levels.

This January, research out of Canada published in the Journal of Clinical Oncology found that men who used statins after a diagnosis of prostate cancer had a 24% decreased risk of death from the disease compared to men who did not take statins. The longer the men took statins, the greater the protective effect. For example, men who took statins for less than one year post-diagnosis had a 1% lower risk of death from prostate cancer compared to non-users. But men who had taken statins for three or more years post-diagnosis lowered their risk of death from their cancer by 39%.

Interestingly, the study also found that statin use prior to a diagnosis of prostate cancer was even more protective to the men, in terms of both mortality specifically from prostate cancer, or from any other cause. Pre-diagnostic statin use reduced the men’s risk of death from prostate cancer by 45%, and conferred a 34% reduced risk of death from any cause, compared to men not taking statins.

All the men in the study had been newly diagnosed with non-metastatic prostate cancer at the time of their enrollment into the study; men who used statins after their diagnosis were 23% less likely to develop distant metastatic cancer spread during the study period.

This study adds to other recent research showing reduced prostate cancer-specific mortality among men who used statins. Dr. Janet Stanford, of the Fred Hutchinson Cancer Research Center in Seattle and a Prostate Cancer Foundation-funded researcher, and colleagues published a study this past summer in The Prostate demonstrating that men who took statins prior to their diagnosis of prostate cancer experienced an 81% reduced risk of prostate cancer-specific mortality compared to men who did not take statins. At 10 years of follow-up, only 1% of statin users had succumbed to prostate cancer, compared to 5% of non-users. However, that study also found that statin use prior to prostate cancer diagnosis did not affect whether or not prostate cancer recurred or progressed. At the time the study was published, Stanford called for confirmation study to validate her findings, and suggested that such research could pave the way for a large, randomized, placebo-controlled study that will yield the most definitive results on whether or not men with prostate cancer should or should not be prescribed statins to lessen their risk of death from the disease.

In response to last month’s study in the Journal of Clinical Oncology (JCO), Drs. Lorelei A. Mucci and Meir J. Stampfer from the Harvard School of Public Health and both Prostate Cancer Foundation-funded researchers, penned an editorial on the subject: Mounting Evidence for Prediagnostic Use of Statins in Reducing Risk of Lethal Prostate Cancer. In this article, Mucci and Stampfer point out that much of the inconsistency among studies on statins and prostate cancer “disappears" when the research distinguishes between risk of overall incidence of prostate cancer and risk of advanced or lethal disease. In reviewing the current “mounting" evidence, Mucci and Stampfer pointed to Stanford and colleagues findings of lower risk of death from prostate cancer in statin users, as well as a Danish study showing lower rates of death for statin users, and a Norwegian study finding that risk of lethal prostate cancer also dropped with statin use.

The authors noted that Prostate Cancer Foundation researchers were the first to focus on risk of lethal disease and statin use in a prospective, observational study published in the Journal of the National Cancer Institute (JNCI) , in 2006. (Men at risk for prostate cancer were observed over the course of several years; their use of statins was recorded, as was their incidence of prostate cancer.) That study, with first author Dr. Elizabeth A. Platz of the Johns Hopkins Bloomberg School of Public Health and a PCF-funded researcher, found that men diagnosed with prostate cancer who used statins halved their risk of developing advanced disease during the study period, and lowered their risk of lethal disease (having metastatic disease at time of diagnosis or succumbing to prostate cancer during the study’s follow up period) by 61 percent. Furthermore, the study found that the risk of developing advanced prostate cancer was lower with longer durations of statin use.

Dr. Mucci says that the Canadian study was a particularly good study for a number of reasons. “It is one of the larger studies to date with the ability to study lethal cancer during the follow-up period," says Mucci, referring to the fact that a large number of men in the study developed lethal disease during the study’s follow-up. Because smaller studies may pick up outcomes that happen just by chance rather than due to the effect of the drug, this study allows far greater confidence in the findings that statin use did have a positive effect on risk of dying from prostate cancer. Also, says Mucci, “A really unique feature of this study is that the researchers looked at statin use both before and after diagnosis." That may be important in helping to determine the mechanism of action statins have on prostate cancer. “One can think about statin use after a diagnosis, and that the drug will probably influence tumor cells after they’ve left the prostate, whereas, statin use before diagnosis could influence the tumor itself," says Mucci.

Knowing when and where statins act on prostate cancer can help determine which patients are most likely to benefit, as well as lead to new drug development specific to prostate cancer once the cellular pathways of action are determined.

Dr. Mucci and colleagues are now working out how statins may affect genes and other molecular pathways for better or worse in prostate cancer patients. They will examine prostate tissue samples taken from men who’ve just undergone radical prostatectomy. “We want to determine if there are differences in gene expression between men who use statins and those who don’t," says Mucci. They examine both tumor tissue samples and normal tissue samples taken from the prostate of each man in their study.

Statins and Overall Risk of Prostate Cancer – unlikely to work as chemopreventive agent

While statin use may have an effect on survivability of prostate cancer in some men, the evidence to date does not point to a protective effect from the drug in terms of overall risk of prostate cancer. In the 2006 JNCI study by Platz and colleagues, while risk of lethal disease was lowered among statin users, there was no risk reduction for the overall occurrence of prostate cancer in men who were taking statins.

On the heels of that study, Platz and colleagues decided to further investigate overall risk of prostate cancer and statin use. “Most of overall prostate cancer is early stage disease, and we did not see an association between statin use and prostate cancer overall" says Platz, “and we were worried maybe we might be missing an association because of a particular study bias—detection bias." Men who regularly seek care through their primary-care doctor are more likely to be screened for both high cholesterol and PSA levels. “If a man has high cholesterol he may well be prescribed a statin to lower his cholesterol levels, and if his PSA levels are elevated, his doctor might recommend a biopsy," says Platz. Regular screening can lead to both a high incidence of statin use and prostate biopsy. And because biopsy if quite sensitive to picking up early prostate cancer, this can create a false association between statin use and prostate cancer, says Platz.

“We wanted to study early prostate cancer in a setting where such detection bias is very unlikely to be operating," said Platz.

To that end, her group studied statin use in a group of men enrolled in the Prostate Cancer Prevention Trial, a study that called for annual PSA screening and digital rectal exams for prostate cancer. This eliminated the variability in screening that likely colored other studies. And, because Platz wanted to focus on early cases of prostate cancer, a setting where all men are screened equally also favored early disease detection that gave the researchers a more homogenous group of diagnosed men, weeding out most cases of late stage disease. In a study just published online in the Journal of Urology, Platz and colleagues again found no association between statin use and early prostate cancer among some 10,000 men enrolled in the Prostate Cancer Prevention Trial who were followed for a period of seven years.

“Overall," says Platz, “if you take all of the literature together, it appears as though statin drugs may be inversely associated with aggressive disease—meaning the cancer progresses to the point of distant metastatic spread, or death of the patient—but not associated with the development of the most common form of prostate cancer in men, which is very early disease."

Why and how might statin use affect development of aggressive prostate cancer?

Clearly this needs to be better understood, but there are several likely avenues of action statins can exert on cancer cells. Pre-clinical research has shown that these cholesterol-lowering drugs can inhibit prostate cancer cell growth, and may encourage cancer cell death and prevent tumor blood vessel growth as well as modulate immune system factors. Additionally, it has been suggested that statins may tamp down the activity of certain oncoproteins. Dr. Mucci’s team, in their work just beginning on tumor tissue samples and statin use, will help suss out such molecular activity and pathways involved.

Dr. Platz and colleagues have now twice found, in two different study groups of men, that individuals with lower levels of cholesterol (within the normal ranges, not the super low ranges) had a lower risk of developing more aggressive disease, as defined by high Gleason scores. (This is yet another reason for men to put aside that plate of fried chicken and head for the salad bar, in order to naturally lower their cholesterol levels.)

Moving forward to better answers

And while the indications are fairly ripe for an interventional randomized clinical study of statins as one agent in the treatment of men with advanced prostate cancer, it is very important to do the groundwork to best determine which subset of men and at what time in their treatment scope, statin use may yield the best results, says Dr. Howard Soule, chief science officer at PCF. Large randomized studies are very costly and if not properly set up, may not bring forth the best information.

From a public health standpoint, it doesn’t make sense to give healthy men, who do not have elevated cholesterol levels, statins for prevention of cancer, says Platz. “Even though these drugs are quite safe, they are not without side effects," she says.

Dr. Jonathan Simons, president and CEO of the Prostate Cancer Foundation, says, “This tantalizing possibility that statins may be used in conjunction with other therapeutics to lower a man’s risk of death from aggressive prostate cancer is well worth further exploration." Simons adds: “Finding that subset of men who might most benefit from statin use in order to hold their cancer in check, or discovering what genes and molecular pathways might be targeted with other new drugs, is a definite goal." And with the recent advent of blood tests that use genetic signatures to help separate out risk of less aggressive from risk of more aggressive disease, and the discovery of constellations of single point mutations—changes in DNA sequence called SNPs—that add up to a higher risk of lethal disease , it may be that evaluating statin use in men who are deemed at higher risk of aggressive disease may be ideal candidates in whom to study statin use as a treatment option. In fact, says Platz, such a research strategy would be feasible because in a high-risk group of men the likelihood of having an event of aggressive prostate cancer is higher, so the study would be more manageable in term of size and duration—fewer men would need to be enrolled and follow up time could be shorter in order to get actionable data.

If you noticed in the article, these studies were conducted on non-metastatic cancer patients, and the studies did not progress far enough to see if any of the patients did suffer from metastasis. Although in one of the studies mentioned, "men who used statins after their diagnosis were 23% less likely to develop distant metastatic cancer spread during the study period." But how long was the study period?

Statins, Metastasis, and Red Blood Cells

One of the emerging theories for the metastasis of prostate cancer is that the cancer stem cells have found a way to "hijack" red blood cells, which allows them to move through the body undetected by the immune system and to eventually hide out in bone morrow, where they are safe from radiation and chemotherapies, and where they also have a steady blood flow to keep them alive.

So the question, then, is how do they get into the red blood cells?

Research (Honda, Yamada, Endo, Ino, Gotoh, et al., 1998³) demonstrates that regulation of the actin cytoskeleton of erythrocytes (red blood cells) likely plays a central role in cell motility and cancer invasion. These authors believe that nonmuscle actinin-1 associates with cell adhesion molecules, such as integrin β1 and α-catenin, and is plays an important role in stabilizing cell adhesion and regulating cell shape and cell motility (Otey et al., 1990, 1993; Glück et al., 1993; Glück and Ben-Ze'ev, 1994; Knudsen et al., 1995).

Their research found that cytoplasmic actinin-4 (a novel isoform of nonmuscle α-actinin) regulates the actin cytoskeleton and increases cellular motility. However, it becomes inactivated when it is transferred to the cell nucleus, which "abolishes the metastatic potential of human cancers." So, in essence, activation of actinin-4 increases cell motility. But how?

It's long been known that inflammatory substances in the immune system can damage erthrocytes, which creates an opening for cancer stem cells to enter. The above study showed that actinin-4 was markedly induced in cells along the edges of a wound to the cytoskeleton.  

Actinin-4 was expressed in a limited population of normal cells, including erythrocytes, endothelial cells, and epithelial cells in various tissues at their border with stromal connective tissue.

So where I am going with all of this?

Simvastatin (Zocor), one of the more common statins, has been shown (Clapp, Ellsworth, Sprague, and Stephenson, 2013⁴) to increase erythrocyte deformability, which means red blood cells are more easily deformed, as in the research above. It is highly likely that other statins produce the same risks.

Deformed erthrocyes, whether from cytokines or statins, increase the risk that cancer cells, including prostate cancer, can invade the damaged blood cells and metastasize throughout the body.

So when you read that statins might be an effective treatment for prostate cancer, please keep this in mind.


References

1. Di Stasi, SL, MacLeod, TD, Winters, JD, and Binder-Macleod, SA. (2010, Oct). Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists. Physical Therapy; 90(10): 1530–1542.
2. Parker, BA, Capizzi, JA, Grimaldi, AS, Clarkson, PM, Cole, SM, et al. (2013). Effect of Statins on Skeletal Muscle Function. Circulation; 127: 96-103. doi: 10.1161/​CIRCULATIONAHA.112.136101 
3. Honda, K, Yamada, T, Endo, R, Ino, Y, Gotoh, M, Tsuda, H, Yamada, Y, Chiba, H, and Hirohashi, S. (1998, Mar 23). Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion. Journal of Cell Biology; 140(6):1383-93.
4. Clapp, KM, Ellsworth, ML, Sprague, RS, and Stephenson, AH. (2013, Mar 1). Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O2 tension-induced ATP release. Am J Physiol Heart Circ Physiol.; 304(5): H660–H666.

Plastics Are Unsafe in Any Form for Foods

We have known for a long time that bisphenol A (BPA) is a dangerous endocrine disruptor, but now we also know it is associated with prostate cancer.  Here is the introduction to the press release of the new study published in PLoS ONE, which is open access.

BPA linked to prostate cancer, study shows

March 4, 2014CINCINNATI—Findings by Cincinnati Cancer Center researchers show that levels of bisphenol A (BPA) in men's urine could be a marker of prostate cancer and that low levels of BPA exposure can cause cellular changes in both non-malignant and malignant prostate cells. 

This research, published in the March 3 edition of PLOS ONE, provides the first evidence that urinary BPA levels may help predict prostate cancer and that disruption of a cell duplication cycle through exposure to low-dose BPA may cause cancer development in the prostate.

BPA, an environmental pollutant with estrogen activity, is used to make hard, clear plastic and is common in many food product containers. It has been linked to neurological defects, diabetes and a number of cancers, including breast and prostate.

Many of us who care about our health have tried to eliminate BPA from our lives and hoped that would be good enough to protect us somewhat. Not so much.

In a new article from Mother Jones, it seems all of those BPA-free plastics have a lot of different, and sometimes even more toxic, endocrine disrupting chemicals. Oh joy!

The Scary New Evidence on BPA-Free Plastics

And the Big Tobacco-style campaign to bury it.

—Mariah Blake | March/April 2014 Issue


Photographs by Evan Kafka

Update (3/3/14): After this story went to press, the US Food and Drug Administration published a paper finding that BPA was safe in low doses. However, the underlying testing was done on a strain of lab rat known as the Charles River Sprague Dawley, which doesn't readily respond to synthetic estrogens, such as BPA. And, due to laboratory contamination, all of the animals—including the control group—were exposed to this chemical. Academic scientists say this raises serious questions about the study's credibility. Stay tuned for more in-depth reporting on the shortcomings of the FDA's most recent study.

EACH NIGHT AT DINNERTIME, a familiar ritual played out in Michael Green's home: He'd slide a stainless steel sippy cup across the table to his two-year-old daughter, Juliette, and she'd howl for the pink plastic one. Often, Green gave in. But he had a nagging feeling. As an environmental-health advocate, he had fought to rid sippy cups and baby bottles of the common plastic additive bisphenol A (BPA), which mimics the hormone estrogen and has been linked to a long list of serious health problems. Juliette's sippy cup was made from a new generation of BPA-free plastics, but Green, who runs the Oakland, California-based Center for Environmental Health, had come across research suggesting some of these contained synthetic estrogens, too.

He pondered these findings as the center prepared for its anniversary celebration in October 2011. That evening, Green, a slight man with scruffy blond hair and pale-blue eyes, took the stage and set Juliette's sippy cups on the podium. He recounted their nightly standoffs. "When she wins…every time I worry about what are the health impacts of the chemicals leaching out of that sippy cup," he said, before listing some of the problems linked to those chemicals—cancer, diabetes, obesity. To help solve the riddle, he said, his organization planned to test BPA-free sippy cups for estrogenlike chemicals.

The center shipped Juliette's plastic cup, along with 17 others purchased from Target, Walmart, and Babies R Us, to CertiChem, a lab in Austin, Texas. More than a quarter—including Juliette's—came back positive for estrogenic activity. These results mirrored the lab's findings in its broader National Institutes of Health-funded research on BPA-free plastics. CertiChem and its founder, George Bittner, who is also a professor of neurobiology at the University of Texas-Austin, had recently coauthored a paper in the NIH journal Environmental Health Perspectives. It reported that "almost all" commercially available plastics that were tested leached synthetic estrogens—even when they weren't exposed to conditions known to unlock potentially harmful chemicals, such as the heat of a microwave, the steam of a dishwasher, or the sun's ultraviolet rays. According to Bittner's research, some BPA-free products actually released synthetic estrogens that were more potent than BPA.

Estrogen plays a key role in everything from bone growth to ovulation to heart function. Too much or too little, particularly in utero or during early childhood, can alter brain and organ development, leading to disease later in life. Elevated estrogen levels generally increase a woman's risk of breast cancer.

Estrogenic chemicals found in many common products have been linked to a litany of problems in humans and animals. According to one study, the pesticide atrazine can turn male frogs female. DES, which was once prescribed to prevent miscarriages, caused obesity, rare vaginal tumors, infertility, and testicular growths among those exposed in utero. Scientists have tied BPA to ailments including asthma, cancer, infertility, low sperm count, genital deformity, heart disease, liver problems, and ADHD. "Pick a disease, literally pick a disease," says Frederick vom Saal, a biology professor at the University of Missouri-Columbia who studies BPA.



BPA exploded into the headlines in 2008, when stories about "toxic baby bottles" and "poison" packaging became ubiquitous. Good Morning America issued a "consumer alert." The New York Times urged Congress to ban BPA in baby products. Sen. Dianne Feinstein (D-Calif.) warned in the Huffington Post that "millions of infants are exposed to dangerous chemicals hiding in plain view." Concerned parents purged their pantries of plastic containers, and retailers such as Walmart and Babies R Us started pulling bottles and sippy cups from shelves. Bills banning BPA in infant care items began to crop up in states around the country.

Today many plastic products, from sippy cups and blenders to Tupperware containers, are marketed as BPA-free. But Bittner's findings—some of which have been confirmed by other scientists—suggest that many of these alternatives share the qualities that make BPA so potentially harmful.

Those startling results set off a bitter fight with the $375-billion-a-year plastics industry. The American Chemistry Council, which lobbies for plastics makers and has sought to refute the science linking BPA to health problems, has teamed up with Tennessee-based Eastman Chemical—the maker of Tritan, a widely used plastic marketed as being free of estrogenic activity—in a campaign to discredit Bittner and his research. The company has gone so far as to tell corporate customers that the Environmental Protection Agency (EPA) rejected Bittner's testing methods. (It hasn't.) Eastman also sued CertiChem and its sister company, PlastiPure, to prevent them from publicizing their findings that Tritan is estrogenic, convincing a jury that its product displayed no estrogenic activity. And it launched a PR blitz touting Tritan's safety, targeting the group most vulnerable to synthetic estrogens: families with young children. "It can be difficult for consumers to tell what is really safe," the vice president of Eastman's specialty plastics division, Lucian Boldea, said in one web video, before an image of a pregnant woman flickered across the screen. With Tritan, he added, "consumers can feel confident that the material used in their products is free of estrogenic activity."

Eastman's offensive is just the latest in a wide-ranging industry campaign to cast doubt on the potential dangers of plastics in food containers, packaging, and toys—a campaign that closely resembles the methods Big Tobacco used to stifle scientific evidence about the dangers of smoking. Indeed, in many cases, the plastics and chemical industries have relied on the same scientists and consultants who defended Big Tobacco. These efforts, detailed in internal industry documents revealed during Bittner's legal battle with Eastman, have sown public confusion and stymied US regulation, even as BPA bans have sprung up elsewhere in the world. They have also squelched debate about the safety of plastics more generally. All the while, evidence is mounting that the products so prevalent in our daily lives may be leaching toxic chemicals into our bodies, with consequences affecting not just us, but many generations to come.

THE FIGHT OVER THE SAFETY of plastics traces back to 1987, when Theo Colborn, a 60-year-old grandmother with a recent Ph.D. in zoology, was hired to investigate mysterious health problems in wildlife around the Great Lakes. Working for the Washington, DC-based Conservation Foundation (now part of the World Wildlife Fund), she began collecting research papers. Before long, her tiny office was stacked floor to ceiling with cardboard boxes of studies detailing a bewildering array of maladies—cancer, shrunken sexual organs, plummeting fertility, immune suppression, birds born with crossed beaks and missing eyes. Some species also suffered from a bizarre syndrome that caused seemingly healthy chicks to waste away and die.

While the afflictions and species varied widely, Colborn eventually realized they had two factors in common: The young were hardest hit, and, in one way or another, all of the animals' symptoms were linked to the endocrine system, the network of glands that controls growth, metabolism, and brain function, with hormones as its chemical messengers. The system also plays a key role in fetal development. Colborn suspected that synthetic hormones in pesticides, plastics, and other products acted as "hand-me-down poisons," with parents' exposure causing affliction in their offspring. Initially, her colleagues were skeptical. But Colborn collected data and tissue samples from far-flung wildlife populations and unearthed previously overlooked studies that supported her theory. By 1996, when Colborn copublished her landmark book Our Stolen Future, she had won over many skeptics. Based partly on her research, Congress passed a law that year requiring the EPA to screen some 80,000 chemicals—most of which had never undergone any type of safety testing—for endocrine-disrupting effects and report back by 2000.

Around this time, the University of Missouri's vom Saal, a garrulous biologist who previously worked as a bush pilot in Kenya, began studying the effects of synthetic estrogens on fetal mouse development. The first substance he tested was BPA, a chemical used in clear, hard plastics, particularly the variety known as polycarbonate, to make them more flexible and durable. (It's also found in everyday items, from dental sealants and hospital blood bags to cash register receipts and the lining of tin cans.) Naturally occurring estrogens bind with proteins in the blood, limiting the amount that reaches estrogen receptors. But vom Saal found this wasn't true of BPA, which bypassed the body's natural barrier system and burrowed deep into the cells of laboratory mice.

Vom Saal suspected this would make BPA "a hell of a lot more potent" in small doses. Working with colleagues Susan Nagel and Wade Welshons, a professor of veterinary biology, he began testing the effects of BPA at amounts 25 times lower than the EPA's safety threshold. In the late 1990s, they published two studies finding that male mice whose mothers were exposed to these low doses during pregnancy had enlarged prostates and low sperm counts. Even in microscopic quantities, it seemed, BPA could cause the kinds of dire health problems Colborn had found in wildlife. Before long, other scientists began turning up ailments among animals exposed to minute doses of BPA.

These findings posed a direct threat to plastics and chemical makers, which fought back using tactics the tobacco makers had refined to an art form. By the late 1990s, when tobacco companies agreed to drop deceptive marketing practices under a settlement agreement with 46 states, many of the scientists and consultants on the industry's payroll transitioned seamlessly into defending BPA.

Plastics and chemical interests worked closely with the Weinberg Group, which had run Big Tobacco's White Coat Project—an effort to recruit scientists to create doubt about the health effects of secondhand smoke. Soon Weinberg, which bills itself as a "product defense" firm, was churning out white papers and lobbying regulators. It also underwrote a trade group with its own scientific journal, Regulatory Toxicology and Pharmacology, which published studies finding BPA was safe.

The industry also worked hand in glove with the Harvard Center for Risk Analysis, a think tank affiliated with the university's school of public health that has a history of accepting donations from corporations and then publishing research favorable to their products. In the early 1990s, its founder, John D. Graham—who was later tapped as George W. Bush's regulatory czar—lobbied to quash an EPA finding that secondhand smoke caused lung cancer, while soliciting large contributions from Philip Morris.



In 2001, as studies on BPA stacked up, the American Chemistry Council enlisted the center to convene a panel of scientists to investigate low-dose BPA. The center paid panelists $12,000 to attend three meetings, according to Fast Company. Their final report, released in 2004, drew on just a few industry-favored studies and concluded that the evidence that low-dose BPA exposure harmed human health was "very weak." By this point, roughly 100 studies on low-dose BPA were in circulation. Not a single industry-funded study found it harmful, but 90 percent of those by government-funded scientists discovered dramatic effects, ranging from an increased breast cancer risk to hyperactivity. Four of the 12 panelists later insisted the center scrub their names from the report because of questions about its accuracy.

Chemical interests, meanwhile, forged deep inroads with the Bush administration, allowing them to covertly steer the regulatory process. For decades, the Food and Drug Administration has assured lawmakers and the public that BPA is safe in low doses. But a 2008 investigation by the Milwaukee Journal Sentinel revealed that the agency had relied on industry lobbyists to track and evaluate BPA research, and had based its safety assessment largely on two industry-funded studies—one of which had never been published or peer reviewed.

The panel the EPA appointed to develop guidelines for its congressionally mandated endocrine disruptor screening was also stocked with industry-backed scientists. It included Chris Borgert, a toxicology consultant who had worked closely with Philip Morris to discredit EPA research on secondhand smoke. He later served as the president of the International Society of Regulatory Toxicology and Pharmacology, the Weinberg Group-sponsored outfit, which met in the offices of a plastics lobbyist.

Members of the EPA panel say Borgert seemed determined to sandbag the process. "He was always delaying, always trying to confuse the issue," recalls one participant. And the screening approach the EPA settled on came straight from the industry's playbook. Among other things, the chemicals would be tested on a type of rat known as the Charles River Sprague Dawley—which, oddly, doesn't respond to synthetic hormones like BPA.

How best to test for estrogenic activity would become a key front in the fight over plastic safety. The American Chemistry Council joined forces with an unlikely ally, PETA, to fight large-scale chemical-safety testing on animals. At the same time, Borgert and other industry-funded scientists made the case that the other common method for testing—using cells that respond in the presence of estrogen—did not necessarily tell us how a substance would affect animals or humans. In fact, a massive, ongoing NIH-run study has found that cell-based tests track closely with animal studies, which have accurately predicted the effects of synthetic estrogens, particularly DES and BPA, on humans.

Stanton Glantz, who directs the Center for Tobacco Control Research and Education at the University of California-San Francisco, argues the chemical industry's real aim in challenging specific testing methods is to undermine safety testing altogether. "Like the tobacco companies, they want to set up a standard of proof that is unreachable," he says. "If they set the standard of proof, they've won the fight."

DURING THE HEIGHT of the battle over BPA, vom Saal periodically traveled to Texas and huddled around the dining table with his old friend George Bittner, whose home overlooks a walnut grove on the outskirts of Austin. Bittner, who holds a Ph.D. in neuroscience from Stanford, is quirky and irascible. But he has a brilliant mind for science and an interest in applying it to real-world problems—in his lab at UT-Austin, he had developed a nerve-regeneration technique that had helped crippled rats walk within days. And he had taken a keen interest in vom Saal's research on endocrine disruption. "It struck me as the most important public health issue of our time," Bittner told me when we met at his lab. "These chemicals have been correlated with so many adverse effects in animal studies, and they're so pervasive. The potential implications for human health boggle the mind."

In the late 1990s, Bittner—a squat, ruddy man with thinning red hair and Napoleon Dynamite glasses who had made a tidy sum investing in real estate and commodities—began mulling the idea of launching a private company that worked with manufacturers and public health organizations to test products for endocrine disruptors. He believed this approach could help raise awareness and break the regulatory logjam—while also reaping a profit.

In 2002, armed with a $91,000 grant from the National Institutes of Health, Bittner launched a pair of companies: CertiChem, to test plastics and other products for synthetic estrogens, and PlastiPure, to find or develop nonestrogenic alternatives. Bittner then enlisted Welshons to design a special test using a line of breast cancer cells, which multiply rapidly in the presence of estrogen. It features a robotic arm, which is far more precise than a human hand in handling microscopic material.



But before long Bittner began butting heads with Welshons and vom Saal. Bittner wanted the researchers to sign over the rights to the test Welshons had developed, while they insisted it belonged to the University of Missouri. Eventually, they had a bitter falling out. Welshons and vom Saal filed a complaint with the NIH, alleging that Bittner had misrepresented data from Welshons' lab in a brochure. (Bittner maintains that he merely excluded data from contaminated samples; the institute found no evidence of wrongdoing.) Bittner, meanwhile, enlisted V. Craig Jordan, a pharmacology professor at Georgetown University with an expertise in hormones—he discovered a now-common hormone therapy that blocks the spread of breast cancer—to refine the testing protocol. By 2005, Bittner had opened a commercial lab in a leafy office park in Austin. He managed to attract some big-name clients, including Whole Foods, which hired CertiChem to advise it on endocrine-disrupting chemicals and test some of its products.

At this point, BPA was among the most studied chemicals on the planet. In November 2006, vom Saal and a top official at the National Institute of Environmental Health Sciences convened a group of 38 leading researchers from various disciplines to evaluate the 700-plus existing studies on the subject. The group later issued a "consensus statement" that laid out some chilling conclusions: More than 95 percent of people in developed countries were exposed to levels of BPA that are "within the range" associated with health problems in animals, from cancer and insulin-resistant diabetes to early puberty. The scientists also found that there was "great cause for concern with regard to the potential for similar adverse effects in humans," especially given the steep uptick in these same disorders.

At the same time, a new body of research was finding that BPA altered animals' genes in ways that caused disease. For instance, it could switch off a gene that suppresses tumor growth, allowing cancer to spread. These genetic changes were passed down across generations. "A poison kills you," vom Saal explains. "A chemical like BPA reprograms your cells and ends up causing a disease in your grandchild that kills him."

Scientists were also uncovering links between endocrine-disrupting chemicals known as phthalates and health problems, including genital abnormalities and infertility in humans. These chemical additives were commonly found in soft, pliable plastics, such as those used in pacifiers and baby bottle nipples. In 2008, Congress passed a law banning six types of phthalates in children's products. As concerns about BPA hit the mainstream, Congress also launched an investigation into the industry's efforts to manipulate science and regulation, and a number of states proposed BPA bans.

In 2009, the BPA Joint Trade Association—which included the American Chemistry Council, Coca-Cola, and Del Monte, among others—gathered at the Cosmos Club, a members-only retreat in Washington, DC's Dupont Circle. According to meeting minutes leaked to the Milwaukee Journal Sentinel, the group explored messaging strategies, "including using fear tactics (e.g., 'Do you want to have access to baby food anymore?')." The "'holy grail' spokesperson," attendees agreed, was a "pregnant young mother who would be willing to speak around the country about the benefits of BPA."

Even as the industry crafted defensive talking points, some companies began offering BPA-free alternatives. But they often didn't bother testing them for other potentially toxic compounds or synthetic hormones. Nor did they have to: Under US law, chemicals are presumed safe until proven otherwise, and companies are rarely required to collect or disclose chemical-safety data. Michael Green, the Center for Environmental Health director who worried about his daughter's sippy cup, says this results in a "toxic shell game": Corporations that come under pressure to root out toxins often replace them with untested chemicals, which sometimes turn out to be just as hazardous. "It's an unplanned science experiment we're doing on our families," Green told me when I visited him at his Bay Area home, where Juliette, now 5, was padding around in a pink princess costume.

One of the most popular BPA-free options, especially among companies catering to families and health-conscious consumers, was Tritan, a clear, sturdy, heat-resistant plastic that Eastman rolled out in 2007. (Eastman also produces the chemical that sullied the drinking water of 300,000 West Virginians in January.) A company founded by alternative medicine guru Dr. Andrew Weil launched a line of Weil Baby bottles made from Tritan, which it touted as "revolutionary" and "ultra-safe" material. Thermos began churning out Tritan sippy cups, decorated with Barbie and Batman. With more and more consumers demanding BPA-free products, Nalgene, CamelBack, Evenflo, Cuisinart, Tupperware, Rubbermaid, and many other companies also worked Tritan into their production lines.



Eastman, a $7 billion company that was spun off from Eastman Kodak in the 1990s, assured its corporate customers that it had done extensive safety testing on Tritan. But its methods were questionable. According to internal Eastman documents, in 2008 Eastman signed a two-year contract with Sciences International, another product defense firm that had played a key role in the tobacco industry's scientific misinformation campaign. On Sciences' advice, Eastman then commissioned a study that used computer modeling to predict whether a substance contains synthetic estrogens, based on its chemical structure. The model suggested that one of Tritan's ingredients—triphenyl phosphate, or TPP—was more estrogenic than BPA.

Eastman, which never disclosed these findings to its customers, later commissioned another study, this one involving breast cancer cells. Again, the initial results appeared positive for estrogenic activity. In an email to colleagues, Eastman's senior toxicologist, James Deyo, called this an "oh shit moment."

Read the whole article.