liver disease Archives - Hormones Matter

More Side Effects from Birth Control- The Liver and the Gallbladder

Published on December 3, 2018

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birth control liver and gallbladder damage

This time of year, the holiday season, can be a time of overindulgence for many of us. And how can we talk about overindulgence without taking a look at the liver? To say the liver is important is an understatement. It is the body’s largest gland and while estimates of the number of functions of the liver vary, many textbooks generally cite around 500. Nearly everything we ingest, from drugs and alcohol to vitamins and nutrients, is metabolized by the liver. The vital role it plays in the functioning of our bodies makes the testimony from the 1970 Nelson Pill Hearings about the effects of oral contraceptives on the liver that much scarier.

Research Presented at the Nelson Pill Hearings

Dr. Victor Wynn was one of the first physicians to testify about the effects of hormonal birth control on the liver.

On page 6341 he states, “if you will take cells out of the liver and examine them under the electromicroscope of women taking oral contraceptive medication, you will find some extraordinary changes.” Of these and other changes caused by the pill, he says: “When I say these changes occur, I mean they occur in everybody, more in some than in others, but no person entirely escapes from the metabolic influence of these compounds. It is merely that some manifest the changes more obviously than others.”

Later to testify was Dr. William Spellacy who was specifically called upon to speak about the metabolic effects on the liver. His testimony about the liver begins, “The biochemical effects of the sex hormones on the liver are legion.” Below is a list of liver functions that, based on the research presented in Dr. Spellacy’s testimony, are altered or impaired (NPH 6427):

Lowering of total plasma protein level
Decrease in the albumin and gamma globulin and increases in other fractions
Tests may be abnormal in women on oral contraceptives without disease being present
Estrogen (including that in oral contraceptives) interferes with liver function and varies with dosage
Some women taking oral contraceptives have abnormally high blood bilirubin levels
1/3 of women who have jaundice on oral contraceptives will get it when pregnant
Discontinuation of oral contraceptives “cures” jaundice

He summed up his thoughts on the liver damage caused by hormonal birth control:

“The immediate effects include the alteration of several of the laboratory tests used in medical diagnoses. Aggravation of existing liver disease, if present, to the point where jaundice may be seen has also been shown. There is no answer to the query of will permanent liver damage result from the use of the oral contraceptives.”

The honorary Chairman of the Population Crisis Committee, a “pro-pill” organization focused on population control added his two cents about the effects of oral contraceptives on the women using them. “While metabolic alterations affecting the liver and other organs do result from use of the pill, there is no evidence at this time that they pose serious hazards to health;” General William Draper, Page 6705.

Of course, we shouldn’t assume that just because a medication causes a “legion” of biochemical effects on the livers of otherwise healthy women that there will be any lasting problems, right?

Research Since the Hearings

“Women more commonly present with acute liver failure, autoimmune hepatitis, benign liver lesions, primary biliary cirrhosis, and toxin-mediated hepatotoxicity,” according to a 2013 article in Gastroenterology and Hepatology.

Like I mentioned in my piece about rheumatoid arthritis, whenever a health issue affects women disproportionately, there is often a connection with hormonal birth control. While this study doesn’t specifically mention that, it does call for further studies assess the role of sex hormones and other behaviors on liver problems in women.

These connections were well-documented at the 1970 Nelson Pill Hearings but the subsequent research gets more confusing.

Timeline of Liver Research

1980: Lancet published an article showing the connection between malignant liver tumors and women using oral contraceptives.

1989: The British Journal of Cancer found “confirmation in this population of the association between oral contraceptives and hepatocellular carcinoma” and “the relative risk was significantly elevated in long-term users [of oral contraceptives].”

1992: “This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.”

2006: “Long-term use of oral contraceptives (OCs) and anabolic androgenic steroids (AASs) can induce both benign (hemangioma, adenoma, and focal nodular hyperplasia [FNH]) and malignant (hepatocellular carcinoma [HCC]) hepatocellular tumors.”

Yet a 2015 meta-analysis concluded that “oral contraceptive use was not positively associated with the risk of liver cancer.” However, the analysis also conceded that “a linear relationship between oral contraceptives use and liver cancer risk was found.” And the authors noted the need for further research into specific formulations of oral contraceptives and the duration of usage.

It makes you wonder how we went from pretty convincing and highly damning connections between oral contraceptives and liver cancer to no positive association at all. Did all the scientists from the 1960s to 2006 get it wrong? Or is something else going on here?

What About the Gallbladder?

Perhaps we can look at the liver’s little buddy, the gallbladder, for some more information. The two are intimately connected in that the liver is constantly making bile and sending it to the gallbladder for storage and dispensation. Like problems with the liver, women are more likely to develop gallstones than men. According to the National Institute of Diabetes and Digestive and Kidney Diseases, “Extra estrogen can increase cholesterol levels in bile and decrease gallbladder contractions, which may cause gallstones to form. Women may have extra estrogen due to pregnancy, hormone replacement therapy, or birth control pills.”

This was proven shortly after the Nelson Pill Hearings. According to the revised edition of The Doctors’ Case Against The Pill by Barbara Seaman:

“The Pill also has serious adverse effects on the gallbladder, and women who take the Pill face an increased risk of someday facing surgery for gallstones. Pill use causes higher levels of cholesterol saturation in the bile, according to a study reported in the New England Journal of Medicine in 1976. This high level of fate in the bile is considered ‘an early chemical stage of gallstone disease,” according to Dr. Donald Small of the Boston University School of Medicine… The risk of gallbladder disease rises with the length of time a woman has been on the Pill… In some studies, Pill users are two and a half times as likely to suffer from gallstones as comparable women.”

A meta-analysis conducted in 1993 found “Oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease” and “Considering…the rapidly changing formulas of oral contraceptives, the authors suggest that the safety of new oral contraceptives be evaluated by studying bile saturation and biliary function rather than by waiting for gallbladder disease to develop.”

A much more recent study (2011) found that there was even more risk of gallbladder disease with the newer formulations:

Long-term use of an oral contraceptive is associated with an increased risk of gallbladder disease compared with no use
There was a small, statistically significant increase in the risk of gallbladder disease associated with the use of desogestrel, drospirenone and norethindrone compared with levonorgestrel
Both estrogen and progesterone have been shown to increase the risk of gallstones
Estrogen has been shown to increase cholesterol production in the liver, with excess amounts precipitating in bile and leading to the formation of gallstones
Progesterone has been shown to decrease gall-bladder motility, which impedes bile flow and leads to gallstone formation

The gallbladder shows us that these hormones are damaging the body.

What Now?

So what do you do when you have a gallbladder that’s not functioning properly? The current practice is to take it out! Of course, removing the gallbladder is not the quick fix many think it is and often leads to other health complications like irritable bowel syndrome, acid reflux, and Sphincter of Oddi Dysfunction.

What about when your liver isn’t functioning properly? That’s not as simple. You can’t just take a liver out. How can the gallbladder, an organ so fundamentally connected to the liver, experience drastic and dangerous changes from hormonal birth control but the liver is supposedly unaffected? Have we researched ourselves out of that problem by declaring that it isn’t a problem? Has there been some spin-doctoring going on when it comes to the liver?

As Dr. Wynn said at the hearings, “There are more than 50 ways in which the metabolic functions of the body are modified, and to say therefore that normal physiological function has been demonstrated in the years of oral contraception is to overlook a very large amount of information.”

I think a very large amount of information has indeed been overlooked.

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This article was first published December 15, 2016.

Controversy, GMO Research & Women’s Health

by Chandler Marrs, PhD

Published on October 8, 2012

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If you’ve been on the internet at all over the last several weeks, you’ve likely come across these pictures- the white rats with grotesquely large mammary tumors warning of the dangers of GMO foods. A controversial and not yet even officially published study out of France on the Long term toxicity of Roundup herbicide and a Roundup-tolerant genetically modified maize is responsible.

In this 2 year study (compared to the 90-120 days for most previous protocols) researchers purportedly demonstrated the ill-effects of glyphosate (active ingredient in Roundup herbicide) and its adjuvants (putatively inactive ingredients that enhance the absorption, distribution or metabolism of the active ingredient), but also inadvertently, and despite the rampant criticism of the study, may have identified a mechanism of action for the growth of these tumors; a disruption of the estrogen pathway perhaps linked to primary kidney and liver damage. Moreover, and again perhaps inadvertently, the research points to a possible player in the development of fibroid type tumors.

How GMO Research is Conducted

There is great debate over the safety of herbicide rendered or engineered, genetically modified organisms (GMO) within the food and water supply. Studies on the side of industry, suggest no major ill-effects, while those on the side of environmentalist indicate differently. Research design likely contributes to the disparate findings. Much research to date has been short-term (90-120 days) and/or has limited the analysis to testing or manipulating only the active ingredient in the herbicide (glyphosate) and not the variety adjuvants found in the total herbicide formulation and that would be dispersed into the natural environment (food, water) post herbicide use.

The current study sought to remedy some of those short-comings and approximate what humans might be exposed to with current regulatory standards in place and in an ‘natural environment’ where exposure rates and types would necessarily vary. (Whether lab rats can approximate human physiology or the lab can be considered a ‘natural environment’ are debates for another day).

The Seralini GMO Study

Using healthy male and female Sprague-Dawley rats, the researchers evaluated the long-term (two years), across a life-span effects, of eating Roundup treated foods (maize) and water with Roundup residue at levels below the currently parts per billion standard and consistent with what humans might be exposed to in the current environment. Control rats were fed non-GMO diets and the test rats were fed varying levels of GM maize (11%, 22% and 33% of the total diet) and water with Roundup – well below the approved levels found in the environment.

Tumors, Toxicity, Death and the GM Diet

Compared to control rats fed a non-GM diet, those fed the GM-maize and Roundup water, died five times sooner and developed huge tumors, often greater than 25% of their body weight and requiring euthanasia to reduce suffering. There were distinct differences between the male and female treated animals. The females died more quickly and developed primarily mammary tumors, followed by a lower percentage of pituitary tumors and kidney and liver toxicity. While the males, demonstrated more severe kidney and liver disease along with skin tumors. The females were more susceptible to the Roundup in the water and both groups were equally susceptible to both the lower and higher percentage (11% and 33%) exposure to GM food, suggesting a threshold effect for disease initiation rather than a cumulative or additive effect.

Endocrine Disruption

The endocrine effects were also telling and pointed to sex-dependent differences in the tumor and disease expression. The ratio of testosterone to estradiol was disrupted in both males and females. Males in the highest Roundup treatment group (33% of total feed maize), demonstrated double the levels of circulating estradiol (see Evolution or Extinction of Men for details on male endocrine disruption) when compared to the control group. Whereas the exposed females showed increased testosterone levels.

Potential Fibroid Connection

The explosive growth of tumors in the female treated rats is notable both because of the large size and location of the tumors (mammary and pituitary) but more so perhaps because of the nature and physiology of the tumors themselves. In all but two cases, the tumors were non-cancerous, non-infective or non-metastatic. The tumors were benign adenomas and fibroadenomas, those commonly found in human women as they age (also common in this strain of lab rat as it ages). Fibroadenomas are comprised of fibrous and glandular tissue located in the breast. Fibroids are similar in tissue composition, but are found in the uterus. In the present study, fibroadenomas were found in the mammary tissue and adenomas in the pituitary gland. There was no mention of uterine fibroids or adenomas in other female reproductive regions. Similarly, although, the authors make no such claim regarding the expression of fibroid type tumors, relative to hormone changes and concurrent liver dysfunction (where the enzymes and proteins involved in the hormone regulation reside), I surmise that perhaps there is a connection there as well. It is conceivable that the combined insult of aging and environmental toxins on liver function alters hormone pathways sufficiently to promote this type of tumor growth.

Controversy and Criticism

As this study was released both pro- and anti-GMO factions got their pants in a bunch. On the anti-GMO side, this study represented proof-positive that GMO foods were bad. The results of this study, and in particular, the pictures of the tumor-ridden rats went viral on the internet. On the pro-GMO side, the criticism was as swift as it was vitriolic, with claims ranging from poor methodology, to outright scientific fraud. I suspect the truth lay somewhere in between.

My Take

Releasing to press first. This merited all sorts of criticism, most of which has no bearing on the actual study but does suggest a less than forthright approach to media relations. However, given the politics surrounding this topic, one can understand this PR approach.

Sprague-Dawley rats are prone to tumors. Yes, they are and as they age, tumors become more frequent. But here we have a little pot and kettle action going on. Sprague-Dawley and other outbred strains of rats and mice, all have predilections for certain diseases and tumors, but are nevertheless what is used in all industry supported (even the studies supporting the safety of GMO) and academic research. The choice of lab rat/mice is important, but even within specific strains there is huge variability. Nullifying the study because the researchers used the same strain of lab rats that other researchers also use, is a weak criticism at best and more than a little disingenuous. Perhaps a better criticism would be the use of lab rats in general to extrapolate human physiology.

Sprague-Dawley rats are prone to tumors as they age. Well guys, so are women. By the time a woman reaches age 50, upwards of 70% of women have fibroid type tumors. And frankly, aging, whether in animals or humans, increases disease expression. Our bodies just don’t work as well when we are older. Simply measuring the effects of a toxin for a short period of time in youthful animals does not, in any way, mirror the real life of the animal or a human, where effects are cumulative over time and sometimes even multiplicative and synergistic.

The study was too long and the control rats were dying too. Life is longer than adolescence. If one wants to evaluate how a treatment or toxin affects an organism over time and as it ages, one has to evaluate across that life span. This study compared tumor progression, disease and death rates between the non-GM controls and the GM fed groups, across the rodent’s life span, which is about 2+/- years. As the rodents aged, both groups developed tumors and some died, but there were more tumors and earlier deaths in the experimental group.

Failure to observe or measure is not synonymous with non-existence. Neglecting to measure a particular toxin or analyte, a specific symptom or disease process, or failing to evaluate long term effects does not mean that the toxin, analyte, symptom or disease process in question did not happen or does not exist. It simply means that you chose not to measure it. So claiming that a 3-month study in youthful rodents nullifies results from a longer study, regardless of any other methodological issues with either study, is an utterly false, and more than a little dishonest argument.

The dose response-curve was not linear. Damn it, how dare our complex physiology not conform to the simplicity of linear statistics. A common dose-response reaction is highly linear, where a small dose elicits a similarly small response and a larger dose increase the response size. This is not case when dealing with endocrine disruptors. Hormone systems are complex and highly non-linear. Hormone reactions occur at extremely low doses and often interact synergistically with other factors and respond differently over time and with cumulative exposures. This was the case in the current study.

In spite of the flaws with this study and contrary to the criticism, the Seralini study represents one of the only, if not the only, long term evaluation of the effects of Roundup and GM feeding on health. Long term studies, even in rodents, are not common place. They should be.

The next long term study (and there should be many more) should include different strains of rodent, measure additional hormones and steroidogenic proteins altered with liver disease and if they want to be really ingenious, look at the estrogen, androgen and progesterone receptor densities in the tumors.