androgens

Could Altered Vitamin A Metabolism Be Responsible for Endometriosis and Fibroid Growth?

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Yes, and increased use of environmental toxicants may be partially to blame. Over the last decade researchers have uncovered connections between tissue level vitamin A activity – the retinoic acid pathway – hormone metabolism, and the cell cycle overgrowth noted in fibroid tumor development, breast and ovarian cancer, and endometriotic tissue growth. Moreover, researchers from the environmental side have found that the popular glyphosate-based herbicides alter vitamin A or retinoic acid metabolism which in turn alters androgen and estrogen metabolism. Connecting the dots, we may have a first step to reducing cell growth in these conditions; remove the toxicant exposure and increase nutritional resources. A second step may be to develop locally absorbed vitamin A, applied directly to the aberrant tissues.

What is Vitamin A?

Vitamin A, (retinol, carotene) is a fat-soluble nutrient that we derive solely from dietary sources. It is responsible for a myriad of functions in a vast number of tissues from the eye, to the ovary, to the heart. Historically, nutrition from diet, coupled with the old wives’ tales of good health, carrots for eyesight, and cod liver oil for all that ails you, were all that were needed to maintain healthy levels of Vitamin A in most individuals. However, with the increase in processed foods, modern farming, intense use of herbicides and pesticides, and the general replacement of the old wives’ nutritional wisdom with pharmaceuticals, many men, women, and children are vitamin A deficient and likely do not even know it. The WHO estimates vitamin A deficiency in 19 million pregnant women and 150 million children worldwide. When Vitamin A deficiency reaches its nadir night blindness, maternal mortality, and difficulty fighting infections are common. In women, the first signs of vitamin A deficiency may be unrecognized and include fibroids or endometriosis. Earlier signs of vitamin A deficiency in women could also be menorrhagia (heavy menstrual bleeding) that often precedes fibroid or endometriosis diagnosis, but research is lacking here, or even genital warts of the common HPV strains.

Why Retinoic Acid, Hormones, and Cell Growth

Retinoic acid (RA), is the form of vitamin A stored in the body. RA is what is called a paracrine, perhaps even an intracrine hormone regulator. That means it turns hormone metabolism on or off in the cells within its immediate vicinity (paracrine) or within its own cell (intracrine). This is compared to endocrine control of hormone metabolism – where hormones and the factors that regulate hormone synthesis and metabolism travel vast distances through the blood to reach their targets tissues (the hypothalamus-pituitary – ovarian system is an example of endocrine regulation) or autocrine where the hormone leaves its own cell only to turn around and bind to a receptor on that cell. In contrast, retinoic acid stays close to home and regulates local cell behavior, both internally and proximally. The vitamin A deficiency leading to fibroids or endometriosis represents a cell and tissue level disruption of the retinoic acid pathway that in turn interrupts the normal cell cycle (differentiation, proliferation, and apoptosis -cell death) and elicits all sorts of problems from decreased estrogen metabolism (too much estradiol at the cells), to cell overgrowth, or more specifically, not enough cell death where needed. The results include aberrant cell growth as in fibroids, tumors, and endometriosis.

Retinoic Acid, Progesterone and Estrogen Metabolism

With many women’s health conditions too much estradiol at the tissue level is at the root. Estradiol is an excitatory hormone that tells our cells to go forth and prosper. Progesterone, depending upon the tissue and the relative values of each circulating hormone can work synergistically to enhance estradiol’s actions or it can shut it down entirely via the upregulation of a specific estradiol metabolizing enzyme called 17 beta-hydroxysteroid dehydrogenase type 2  (17B -HSD2).  When these enzyme levels are high, more estradiol is converted to estrone. Since estrone is a less potent estrogen than estradiol, metabolism of estradiol to estrone somewhat inactivates the estrogen and slows cell proliferation. When the enzyme levels are low, more estradiol remains, and cell growth is enhanced.  Vitamin A or retinoic acid mediates the progesterone-dependent activation of this enzyme, effectively regulating estradiol concentrations locally. Too little retinoic acid or a disrupted retinoic acid pathway and estradiol is not converted to estrone – e.g. it is not inactivated. Cell proliferation dominates, while normal cell death or apoptosis is reduced. Fibroids, tumors, or endometriosis ensue.

What Causes Low Retinoic Acid or Reduced Functioning?

Vitamin A is derived entirely from diet. Foods high in vitamin A include brightly colored vegetables, dark leafy greens, carrots, pumpkin, sweet potatoes, bell peppers, and fatty fish oils, like cod liver oil and organ tissues like the liver. Meat and dairy also have high concentrations of vitamin A. Diets high in processed food do not contain sufficient vitamin A to maintain the proper cell cycle balance and so we get too much proliferation and too little apoptosis. Tissues grow and grow and do not die.

Alcohol intake reduces the body’s ability to metabolize retinoic acid because alcohol and the retinoic acid pathway use the same enzymes – alcohol dehydrogenase (ADH1) and aldehyde dehydrogenase (ALDH1) for metabolism. Alcohol competes for the enzyme and so vitamin A from diet cannot be converted to the usable retinoic acid.

Can Toxins Disrupt the Vitamin A Pathway?

Yes, but here is where it gets complicated. Environmental toxins like glyphosate used in common weed killers such as Round-up have a complex relationship with the vitamin A pathway and hormone metabolism. These herbicides and many pesticides are endocrine disruptors, meaning they disrupt ‘normal’ hormone metabolism, often towards a hyper-estrogenic state. Similarly, plastics like BPA and a host of industrial chemicals are also endocrine disruptors that move us towards hyper-estrogenism – a key component of fibroid and endometriosis.

Glysophate activates an enzyme called retinaldehyde dehydrogenase which increases retinoic acid synthesis. This is argued to be the mechanism by which environmental exposures during pregnancy cause birth defects. However, glyphosate also inhibits vitamin A metabolism by a similar mechanism as alcohol, by competing for ADH1 availability, thereby having the ability to reduce vitamin A synthesis. Glyphosate also increases aromatase activity (the enzyme that converts testosterone to estradiol), creating a hyper-estrogenic state and depending upon the time course and the exposure concentration, completely wipes out aromatase activity. So like any true hormone system, that uses a complex chain of compensatory reactions to maintain homeostasis, the reactions to environmental toxins are complicated and non-linear. Nevertheless, they warrant attention, particularly when one is suffering from a condition affected by the environmental toxin in question.

Managing Vitamin A Levels

To determine if you are vitamin A deficient, seek out a lab that specializes in micronutrient testing. The recommended daily values of vitamin A can be found in the Dietary Supplement Fact Sheet.

Vitamin A is a fat-soluble vitamin, meaning that it will be stored in fat, and toxicity from too much vitamin A is possible. It is rare, but nevertheless, if supplementing, vitamin A levels should be monitored by micronutrient testing.

My Two Cents

Much of the research presented here linking local vitamin A deficiencies with endometriotic, fibroid, and cancer growth has not crossed over into clinical care. Moreover, it is complex and far from settled. Except for cancer trials, mostly in males and mostly with oral supplementation, the research regarding dietary vitamin A is limited and mixed. However, I think a local application of an absorbable form of vitamin A or retinoic acid should be investigated for the treatment of endometriotic and fibroid growth in women. Similarly, dietary supplementation within acceptable levels and changes combined with environmental ‘cleaning’ may be of use, if only to improve the overall health status of women currently suffering from fibroids or endometriosis.

Postscript: This article was published previously in August 2013. 

Photo by Tamanna Rumee on Unsplash.

Uterus and Ovaries: Fountain of Youth

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Numerous studies have shown a strong correlation between removal of both ovaries / bilateral oophorectomy (castration) and accelerated aging as measured by an increased risk of chronic health conditions. Hysterectomy / uterus removal with preservation of both ovaries is also associated with some of these chronic conditions. These include heart disease, stroke, metabolic syndrome, osteoporosis, hip fracture, lung cancer, colorectal cancer, dementia, Parkinsonism, impaired cognition and memory, mood disorders, sleep disorders, adverse skin and body composition changes, adverse ocular changes including glaucoma, impaired sexual function, more severe hot flushes and urogenital atrophy. Wow, that’s quite a list!

Ovaries: Health Powerhouses

This 2016 article titled “Study: Remove ovaries, age faster” sums up the findings of Mayo Clinic researchers proving yet again the harmful and unethical practice of ovary removal. The study found that ovary removal (oophorectomy) is associated with a higher incidence of 18 chronic conditions and should be discontinued in women who are not at high risk for ovarian cancer. Although this study cites the increase in chronic conditions in women who undergo oophorectomy before age 46, other studies have shown that oophorectomy even after menopause does more harm than good. Here is one that showed that to be true up to age 75.

The ovaries have both reproductive and endocrine functions as detailed in this International Menopause Society article. After menopause, the ovaries produce mostly androgens, some of which are converted into estrogen. Testosterone levels are more than 40% lower in women without ovaries compared to intact women. Women without their uterus likewise have lower levels but not as low as women without ovaries per this article. Estrogen therapy mitigates some but not all of the increased health risks of oophorectomy. But estrogen further reduces androgen levels increasing risk of osteoporosis and fracture. Nothing can replace the lifelong functions of the ovaries (and uterus).

The Uterus / Ovaries / Tubes Connection

The harms of ovary removal would also apply to ovarian failure that commonly occurs after hysterectomy and some other medical treatments. As previously cited, women who have had a hysterectomy have lower levels of testosterone. According to this 1986 publication, 39% of these women showed signs of ovarian failure. This study showed a nearly 2-fold increased risk of ovarian failure when both ovaries were preserved and nearly 3-fold when one was preserved. This likely explains the increased risk of heart disease and metabolic conditions as shown by multiple studies including this recent Mayo Clinic one. However, per this 1982 study, the uterus itself protects women from heart disease via the uterine substance prostacyclin. Loss of bone density is another harm of hysterectomy as shown by multiple studies such as this one.

Removal of even one ovary (unilateral oophorectomy) without hysterectomy is also harmful. Studies out of the Mayo Clinic showed increased risks of cognitive impairment or dementia and parkinsonism. Colorectal cancer is another increased risk according to this Chinese study and this Swedish one.

The Fallopian tubes appear to impair ovarian function to some degree as evidenced by Post Tubal Ligation / Sterilization Syndrome. This study shows an increase in Follicle Stimulating Hormone (FSH) after tube removal (salpingectomy).

Ovarian impairment after hysterectomy or salpingectomy is thought to be the mechanism of the reduced risk of ovarian cancer which is already rare.

The Uterus: Anatomy, Sex, Cancer Prevention

Hysterectomy is associated with other harms besides impaired ovarian / endocrine function. The uterus and its ligaments / pelvic support structures are essential for pelvic organ integrity as well as skeletal integrity. The effects on these structures and functions are detailed here and here. This article shows the many hysterectomized women lamenting their “broken bodies” – changes to their figures, back, hip and midsection pain, pelvic pain, bladder and bowel issues, and effects of severed nerves and blood vessels.

The uterus and associated nerves and blood vessels play a key role in sexuality and vibrancy. You can hear the desperation in women’s comments about the devastating sexual losses and feelings of emotional emptiness.

There is an increased risk of renal cell, thyroid, and colorectal cancers after hysterectomy. How ironic when cancer fear tactics are commonly used to market hysterectomy and/or oophorectomy.

Adhesions that commonly form after these surgeries can cause serious problems especially in the long term. Surgical complications – nerve injuries, bladder, bowel and ureter injuries, vaginal cuff dehiscence, a too short vagina, infections, hemorrhage – are more common than indicated by gynecologists.

Although “The Miraculous Uterus” article fails to mention the anatomical harms, it is otherwise “spot on.” It talks about the “ovarian conservation scam” and that “passion, love, ecstasy, the emotional essence that drives human achievement, forever after elude them.” This explains why “there’s no effective outrage against the barbarism of hysterectomy.”

Compelling Evidence of Harm

Clearly, there is compelling medical evidence that both hysterectomy and oophorectomy are destructive surgeries. Unfortunately, some hysterectomy forums censor negative posts giving a slanted view of the life shattering effects. Here is a sampling of women’s experiences on the Gyn Reform site.

The medical literature on the harms of these surgeries dates back over a century. Listed below are a small number of the numerous publications (minus the ovarian failure studies cited above). The Gyn Reform website has a fairly comprehensive list of resources on oophorectomy. Its Ovaries for Life sister site provides a good overview of the lifelong importance of our ovaries.

1912 – The Physiological Influence of Ovarian Secretion

1914 – Nervous and Mental Disturbances following Castration in Women

1958 – The controversial ovary

1973 – Osteoporosis after Oophorectomy for Non-malignant Disease in Premenopausal Women

“Oophorectomy before the age of 45 years was found to be associated with a significantly increased prevalence of osteoporosis within three to six years of operation.

1974 – Endocrine Function of the Postmenopausal Ovary: Concentration of Androgens and Estrogens in Ovarian and Peripheral Vein Blood

1978 – The emotional and psychosexual aspects of hysterectomy

1981 – Premenopausal hysterectomy and cardiovascular disease

1981 – Sexual response after hysterectomy-oophorectomy: Recent studies and reconsideration of psychogenesis

1981 – The role of estrogen and oophorectomy in immune synovitis

1982 – Prostacyclin from the uterus and woman’s cardiovascular advantage

1989 – The effects of simple hysterectomy on vesicourethral function

“The results show that simple hysterectomy is associated with a significant incidence of post-operative vesicourethral dysfunction and that there is an identifiable neurological abnormality incurred at operation which is pertinent to the subsequent disordered voiding.

1990 – Effects of bilateral oophorectomy on lipoprotein metabolism

1994 – The climacteric ovary as a functional gonadotropin-driven androgen-producing gland

1996 – Urinary incontinence in older women: who is at risk? Study of Osteoporotic Fractures Research Group

“Urinary incontinence is a common problem in older women, more common than most chronic medical conditions. Of the associated factors that are preventable or modifiable, obesity and hysterectomy may have the greatest impact on the prevalence of daily incontinence.

1997 – Bladder, bowel and sexual function after hysterectomy for benign conditions

1998 – Ovaries, androgens and the menopause: practical applications

1998 – Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function

1998 – Influence of bilateral oophorectomy upon lipid metabolism

1999 – Estrogen and movement disorders

2000 – The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis

2000 – Risk of myocardial infarction after oophorectomy and hysterectomy

2000 – Hysterectomy, Oophorectomy, and Endogenous Sex Hormone Levels in Older Women: The Rancho Bernardo Study

2005 – Ovarian conservation at the time of hysterectomy for benign disease

Ovarian conservation until age 65 benefits long-term survival…. There is sustained, but decreasing, benefit until the age of 75, when excess mortality for oophorectomy is less than 1%.

2007 – Ovarian conservation at the time of hysterectomy for benign disease

Approximately 78% of women between the ages of 45 and 64 years have prophylactic oophorectomy when hysterectomy is performed for benign disease. Therefore, the decision to perform prophylactic oophorectomy should be approached with great caution for the majority of women who are at low risk of developing ovarian cancer.”

2009 – Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses’ health study

In no analysis or age group was oophorectomy associated with increased survival.

2010 – Current indications and role of surgery in the management of sigmoid diverticulitis

A previous history of hysterectomy is a valuable clinical clue to the correct diagnosis as colovaginal and colovesical fistulas are rare in females with their uterus in place, as the uterus becomes a screen interposed between the inflamed colon and the bladder and vagina.”

2012 – Oophorectomy for whom and at what age? Primum non nocere

2016 – Study: Remove ovaries, age faster

2017 – Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study

A Harmful Practice That Won’t Die

Ovary removal / castration was introduced by Robert Battey in 1872 and “was practised widely for several decades….. Better insight into female physiology and ovarian function finally pushed the sinister operation of Robert Battey from the scene.” This publication refers to Battey’s operation as “barbaric.”

Despite the long-standing and compelling evidence of harm, these surgeries continue at alarming rates. Publications are misleading in that they report inpatient surgeries despite the large majority being outpatient (70% in 2014). This 2008 article reported that oophorectomies “more than doubled in frequency since the 1960’s.” According to results of a FOIA request by Ovaries for Life, there are over 700,000 oophorectomies every year despite there being only ~22,000 cases of ovarian cancer. Hysterectomy figures obtained by Ovaries for Life are also shocking at 830,000 in light of less than 70,000 cases of endometrial and cervical cancers.

Many media reports have questioned the high rate of these surgeries since gynecologic cancers are rare. The oldest one I could find was dated 1969. I found about three articles per decade in the mainstream media since then. According to the Athena Institute, half of U.S. medical schools in 1986 “had changed their suggestions and were now recommending a reconsideration of the common practice of ovariectomy.” Evidently, that never took hold.

Congress held two hearings on hysterectomy, one in 1976 and one in 1993. The 1993 transcripts state that the hysterectomy rate increased 250% in women ages 15 to 24 and 186% in ages 25 to 34 from 1965 to 1984! Despite these shocking statistics, it appears that no action was taken after either hearing.

According to this “Reassessing Hysterectomy” article, the Agency for Healthcare Research and Quality sponsored research and conferences on the overuse of hysterectomy in the 1990’s. This article is packed with information on the prevalence and harms of hysterectomy and oophorectomy as well as alternative treatment options. Yet, the high rate of hysterectomy has continued such that 45% of women will end up having one. Citing 2006 data, the oophorectomy rate was 73% of the hysterectomy rate.

How to End the Harm?

I’ve been researching this subject for over 10 years and sharing my experience and knowledge on various websites. It’s shocking how many women are misled and deceived into these surgeries. Age doesn’t seem to matter; younger and younger women are undergoing these surgeries. This appears to be the biggest surgical racket and women’s healthcare con as discussed here.

There are a number of issues that perpetuate the gross overuse of these harmful surgeries. These include:

  1. These surgeries and “forever after” care are very lucrative.
  2. The public has been led to believe that the female organs are disposable after childbearing is complete.
  3. Medical education and decades of practice have made these surgeries “a standard of care.”
  4. Informed consent is seriously lacking.
  5. Gynecology consent forms are open ended giving surgeons “carte blanche” to remove organs unnecessarily.
  6. We still live in a climate of gender disparity / male dominance.

As you can see from the list of publications above, some study authors have called out the practice of ovary removal as unethical. Numerous professional societies have issued guidelines discouraging its use in most women. But most have been silent on the overuse of hysterectomy despite its many harms.

Why has our government not stepped in to address this egregious harm? Women who have contacted their legislators have been met with indifference. Gyn Reform reported on their experiences with legislators and other authorities who can effect change. The non-profit HERS Foundation has been educating women and advocating for informed consent legislation since the 1980’s.

Why do insurance companies approve so many of these surgeries that are rarely necessary? Not only are the surgeries themselves expensive, treatments for the chronic after effects are costly. Reining in unnecessary treatments especially those that cause lifelong harm would go a long way towards making healthcare more affordable.

Why has Graduate Medical Education (GME) not changed their surgical requirements to favor organ preservation? Each resident must do at least 70 hysterectomies but there is no requirement for myomectomy (fibroid removal). Residents don’t need to do any cystectomies (cyst removals) either which is partly why so many women lose ovaries for benign ovarian cysts. Here are the GME ob/gyn requirements.

A popular mantra at Tufts in the 1970’s – “There’s no room in the tomb for the womb” – reflects this culture of the disposable uterus and gynecologists’ obsession with its removal. Insurance reimbursement rates are also to blame as they incentivize hysterectomy and oophorectomy over myomectomy and cystectomy. In many cases, medical management versus surgery is the appropriate course. The “Reassessing Hysterectomy” article cited above lists a number of treatment options for gynecologic problems. Revamping reimbursement rates to strongly favor organ preservation should eventually force GME to change their requirements. But how do we make that happen?

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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Lucas Cranach the Elder, Public domain, via Wikimedia Commons

Opioids, Chronic Pain and Low Testosterone in Men

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Does your guy suffer from chronic pain? Does he use opioid based pain-killers on a regular basis? Then he may also have low testosterone. Low testosterone or as the advertisers call it, Low T, is associated with a range of health issues beyond just reduced libido or sex drive. His low testosterone could be an important factor in his health and recovery.

Testosterone influences, muscle mass, bone density, cognition and memory, depression, and even insulin production. Many men with low testosterone are at risk of osteopenia and osteoporosis. Lower testosterone or hypogonadism has even been associated with an increased risk of heart attack. That means, in addition to worrying about managing chronic pain, the risks associated with long term opioid use, you and your guy now also should be aware of the critical hormone changes taking place. It is possible these hormone changes are compounding an already difficult recovery.

The study, published in the Clinical Journal of Pain, found that 53% of the men tested who were using daily opioids had low testosterone. Moreover, 74% of men using long-acting or time-released opioid pain killers had low testosterone compared to only 34% of those using short acting opioid pain-killers. Interestingly, the morphine-standardized equivalent dose (MSE),  a measure of how much pain-killer is circulating in the bloodstream, was not associated with the testosterone levels. This means that higher dose pain killers were not tied to lower testosterone, only the duration of the medication action was associated with the hormone change.  Long-acting (time release) pain-killers were linked to lower testosterone while short-acting pills were not.

 Long-acting Opioids

  • Buprenorphine
  • Fentanyl
  • Methadone
  • Morphine CR
  • Oxycodone

Short-acting Opioids

  • Oxycodone IR
  • Hydrocodone

If your guy is using is opioid pain-killers to manage a chronic pain from injury, have his doctor check his testosterone levels too.

Medical Disclaimer: All material on this web site is provided for your information only and may not be construed as, nor should it be a substitute for, professional medical advice. To read more about our health policy see Terms of Use.

Controversy, GMO Research & Women’s Health

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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.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Male Contraception

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How many women do you know that use birth control pills as their primary form of contraception? A recent analysis by the Guttmacher Institute reports that 18% of all women in the U.S use some form of oral contraception. Quite a few!

What would happen if there was an equivalent form of contraception for men? Would it be as popular? Would it be as reliable? Researchers are trying to develop the technology to answer these questions.

Anything but a Vasectomy!

Aside from condoms, other forms of male contraception have been around for a while. Some methods of contraception seek to physically block the vas deferens, or the path for sperm to exit the urethra. For example, the Pro-Vas clip is used as a mechanical block for sperm by clamping the vas deferens, essentially doing the same thing as a vasectomy – without physically severing the sperm duct.

Another method uses a chemical polymer to block the passage of sperm to the urethra. This polymer, known as styrene maleic anhydride, has entered phase III clinical trials in India. Lisbeth Prifogle goes into more detail about the exact mechanism used for this type of contraception in her article, Male Birth Control – Myth or Available Science.

Whether mechanical or chemical, these methods introduce drastic and potentially harmful changes to the male reproductive anatomy. Although the manufacturers claim that these treatments are completely reversible, as a male, I would be hesitant to adopt such measures as I suspect other men would be. Oral contraception is a more attractive method.

Oral Male Contraceptives

Oral contraception used by men is nothing new. Since the early 20th century, a natural product from the cotton plant known as gossypol, has been used as a male contraceptive, particularly in Asian countries. Due to concerns of toxicity and side effects, however, gossypol has never been approved as a contraceptive by the FDA.

Since the mid-1980s, research led by the World Health Organization to develop a hormone-based birth control pill for men has resulted in a better understanding of the male hormonal system, and what biological targets are most attractive for male contraceptives. Much like the female birth control pill, which works by controlling the levels of the hormones estrogen and progestin, these birth control pills also work by introducing exogenous hormones into the body. These types of pills have been called Male Hormonal Contraceptives (MHCs).

The primary form of MHC is a form of testosterone named testosterone undecanoate. Using testosterone as a contraceptive was counterintuitive for me because when I think of high testosterone I think of an increased libido. But as it turns out, an extra shot of the hormone results in a decrease of the signaling hormones responsible for spermatogenesis (sperm production). Although testosterone treatment does seem to induce azoospermia (the absence of motile/viable sperm), there is no MHC that is currently in clinical trials – it seems that this pill is quite a ways off.

A New Type of Pill

There have been a few other pills that have been proposed as male contraceptives that don’t use hormones – one of the most interesting new studies to come out was an anti-cancer drug that was accidentally discovered to have spermatogenic effects. Many of the compounds developed in these studies, including anti-cancer drug compounds, target and inactivate specific proteins that are necessary for biological function.

In this study, which was published in the journal Cell last August, the compound tested, which is called JQ1, binds and inactivates BRDT, a protein that is specific to the testes and is involved in an essential DNA-based process called chromatin remodeling. The result, as observed in mice, is that as long as the organism was administered the drug, although they mated, there was a complete and reversible contraception.

So it seems that many new technologies are being developed for men to share the responsibility of contraception. However the question still stands: Can they be trusted?

Neurogenesis – A Result of Hormones?

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Studies have shown that exercise promotes learning and neurogenesis, or the creation of new brain cells, but exactly what’s going on is still being worked out. One group of scientists, however, think they’re on the right track.

Researchers from the University of Tsukuba, the University of Tokyo, and The Rockefeller University considered a number of studies that have shown that hormones have more to do with our brains than previously imagined.

Hormones Produced in the Hippocampus

In the past, androgen hormones were thought to be produced solely in the testes and carried to the brain via circulation, but several studies have revealed that androgens can actually be made in the hippocampus, the part of the brain that is associated with forming and storing memories.

In 2010, Endocrinology published a study that found higher levels of sex hormones in the hippocampus than in the circulatory system of rats. Furthermore, even when the rats were castrated at birth, there was not a significant reduction of sex hormones in specific regions of the brain, leading scientists to believe that specific sex hormones are not only important for gender development, but for brain development as well.

Hormones Linked to Brain Plasticity

Recently, more scientists have been pursuing research that links hormones to brain development. In 2006, researchers from Yale discovered that androgens affect hippocampal synaptic plasticity.

There are billions of neurons in our bodies, and we rely on these cells to transmit information to other cells via synapses so that we can function. The more efficiently our neurons respond to messages, the more effectively our bodies function. Luckily (or unluckily) for us, scientists have discovered that this responsiveness can change – depending on how often we put our neurons to work.

The more we use certain synaptic pathways, or the structures that transmit information between neurons and other cells, the more they are strengthened – literally becoming engraved in our minds. Not engaging these synaptic pathways, however, results in slower responding neurons and cells.

The ability of synaptic pathways to become more or less responsive is referred to as synaptic plasticity. In the case of the neuron, the adage “practice makes perfect” or “use it or lose it” rings true. It’s no wonder that synaptic plasticity is associated with learning and memory.

But our ability to learn and remember is not solely based on how often we use certain synaptic pathways; the plasticity of the brain seems to be hinged on sex hormones, too.

The scientists from Yale found that when the testes were removed from rats, there was a significant decrease in the number of synaptic pathways. Yet these pathways were replenished when the castrated rats were treated with androgens. They found similar outcomes with ovariectomized female rats, but female rats rely more on endogenous estrogens, so weaker androgens were sufficient for rebuilding synaptic pathways.

Though scientists are still trying to understand the exact mechanisms involved with brain development, they have begun to recognize how important sex hormones are to brain development and our ability to learn.

Researchers Connect Exercise to Hormone Production

Building upon previous research, the scientists from Japan and New York proposed that exercise actually increases the production of androgenic hormones in the brain, and that this increase in sex hormones promotes neurogenesis. The study was published in the Proceedings of National Academy of Sciences, and the results sparked excitement.

In order to ensure that the androgen hormones were produced in the brain and not the testes, the researchers castrated some of the rats. Although the remaining test group of rats were not castrated, they still underwent a surgical procedure so that conditions and stress levels did not vary between the two groups.

There has already been research showing that the female sex hormone, estradiol, is involved in neurogenesis, so the scientists decided to focus on the male sex hormones. To ensure that testosterone was not being converted to estradiol, the researchers blocked the estrogen receptors with tamoxifen, a non-reactive binding agent, so estradiol could not be taken up in the brain.

The researchers found that after exercise, the androgen dihydrotestosterone increased significantly in the brains of the rats – even in the castrated rats. They also found an increase in the number of neurons in the hippocampus – and the results did not change in the rats that were treated with tamoxifen.

Some rats, however, had specific receptors blocked so that they could not use the dihydrotestosterone in the brain. The scientists were surprised to find that these rats did not experience neurogenesis, leading researchers to believe that dihydrotestosterone is not only produced as a result of exercise, but is also necessary for the production of new brain cells.

Though there is still much more research to be done (the researchers only experimented with male rats, for starters), the study demonstrates the complexity of our bodies and the hormones within us. As for me, I feel more compelled to exercise before I learn something new – hormones help me.