Dangers of Excess Estrogen in the Aging Male - Life Extension

Dangers of Excess Estrogen in the Aging Male - Life Extension

By William Faloon
 

William Faloon

We at Life Extension are sometimes asked why we check estrogen levels when testing the blood of our male members.

Long ago, we published data showing that estrogen levels are often elevated in aging men and discussed the insidious health risks associated with excess estrogen. Since it is so easy for men to correct estrogen overload, it made sense to test for it and recommend the appropriate corrective actions if blood results reveal excessive (or deficient) estrogen.

A presentation at a recent anti-aging conference suggested that higher estrogen levels are beneficial to aging men. This prompted us to search the published scientific literature to see if we had overlooked some recent findings.
What we uncovered not only confirmed our original recommendation, but revealed that excess estrogen in aging men is more dangerous than what we even thought.

Double the Stroke Risk

Stroke is the third leading cause of death and the leading cause of age-related disability. Abnormal blood clotting in the cerebral blood vessels is the most common cause of stroke. Excess estrogen promotes abnormal blood clots.1

In a study published just last year, blood levels of estradiol (a potent estrogen) were measured in a group of 2,197 men aged 71 to 93 years of age. Adjustment for age, hypertension, diabetes, adiposity, cholesterol, atrial fibrillation, and other characteristics were made. During the course of follow-up, men with the highest blood levels of estradiol had a 2.2-fold greater risk of stroke compared with those whose estradiol levels were lower.2

This study revealed that estradiol blood levels greater than 34.1 pg/mL resulted in this more than doubling of stroke incidence. Life Extension long ago warned men to keep their estradiol levels below 30 pg/mL, and this recent stroke study clearly validates our prior recommendation.

Excess Estrogen in Middle-Aged Men

One way to evaluate the health of the arterial system is to measure the inner and medial wall of the carotid artery using an ultrasound test.

In a study published two years ago, blood levels of estradiol were measured in 313 men whose average age was 58. Carotid artery intima-media thickness was measured at baseline and then three years later. After adjusting for other risk factors, men with higher levels of estradiol suffered a worsening thickening of their carotid artery wall. This led the researchers to conclude, “circulating estradiol is a predictor of progression of carotid artery intima-media thickness in middle-aged men.”3

This study of middle-aged men was initiated based on findings that treatment of men with prostate cancer using orally ingested estrogen drugs is associated with increased cardiovascular events and deaths.

Ultrasound measurement of the carotid artery wall provides an accurate prognostic indicator of arterial disease. The findings in this study show progression of carotid artery intima-media thickness in men with higher estradiol levels. Greater carotid artery intima-media thickness sharply correlates with increased risks of heart attack and stroke.

Estradiol Higher in Male Heart Attack Victims

A study published just last year compared blood levels of testosterone and estradiol in men suffering acute myocardial infarction (heart attack) with those who had previously suffered a heart attack.

Sex hormones were measured in patients presenting with acute heart attack, patients with old heart attack, and patients with normal coronary arteries. The results showed significantly higher levels of estradiol in both groups of heart attack patients compared with those without coronary disease.4 As would be expected from numerous prior studies, heart attack victims also had decreased testosterone levels.

The reason many men suffer from excess estradiol and deficient testosterone is that their aging bodies produce less testosterone while more of their beneficial testosterone is converted (aromatized) into estradiol. The pathological result is an altering of the ratio of testosterone to estrogen, creating estrogen dominance.5 This imbalance of estrogen overload and testosterone insufficiency is an often overlooked cause of cardiovascular disease.

Fortunately, there are safe methods to block the aromatase enzyme in order to lower excess estrogen while boosting free testosterone levels.

High Estrogen in Men With Coronary Atherosclerosis

An invasive diagnostic procedure known as a coronary angiogram can measure the degree of atherosclerosis present in the arteries feeding the heart muscle.

Researchers used angiogram-confirmed cases of coronary atherosclerosis to ascertain the effects of sex hormones and other metabolic factors in a group of men aged 40-60 years.

Compared with healthy age-matched controls, men with coronary atherosclerosis had low testosterone, higher levels of estrone (another potent estrogen), and a low level of testosterone in the presence of a high level of estradiol.6 These findings led the researchers to conclude their study by stating, “low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.”
In a study conducted a year later by another research group, angiograms were used to measure the extent of coronary atherosclerosis in a group of men with stable coronary artery disease. The finding showed significant positive correlations between estradiol levels and other known atherosclerotic risk factors.7 The scientists concluded their study by stating, “our results indicate a possible role of estradiol in promoting the development of atherogenic lipid milieu in men with coronary artery disease.”

These two recent studies validate other reports showing that excess estrogen promotes atherosclerosis in men.

Peripheral Artery Disease and Sex Hormones

Peripheral artery disease occurs when there is partial or total blockage of an artery, usually one leading to a leg or arm. Leg artery disease is usually due to atherosclerosis that impairs blood circulation. Those afflicted with this condition find that walking can bring on fatigue, cramping, and pain in the hip, buttock, thigh, knee, shin, or upper foot.

A study published last year sought to determine whether blood levels of testosterone and estradiol are associated with lower extremity peripheral arterial disease in elderly men.

The participants consisted of 3,014 men with peripheral artery disease who averaged 75.4 years of age. After factoring in age, current smoking, previous smoking, diabetes, hypertension, and body mass index, the findings showed that low levels of testosterone were independently and positively associated with peripheral artery disease as were high levels of estradiol.8

The doctors who conducted this study concluded, “this cross-sectional study shows for the first time that low serum testosterone and high serum estradiol levels associate with lower extremity peripheral artery disease in elderly men.”

The pharmaceutical industry makes a fortune treating those with peripheral artery disease. Common drugs prescribed include those that lower blood sugar, lower cholesterol (statins), lower blood pressure, and lower risk of blood clot. A popular drug called Plavix® has been heavily advertised to treat peripheral and other arterial diseases.

Based on what is known about the atherogenic and thrombotic risks of low testosterone and high estradiol, it is conceivable that men suffering from peripheral artery disease could discard many of their drugs if they restored their testosterone to youthful ranges and reduced excess estradiol.

High Estradiol Levels Seen in Male Chronic Inflammation Patients

Rheumatoid arthritis is a severe chronic inflammatory state that results in increased risks of heart attack, cancer, and stroke. A study of men with rheumatoid arthritis evaluated blood levels of sex hormones compared with healthy controls.9

Levels of estradiol in rheumatoid arthritis patients were higher and DHEA levels lower compared with subjects who were not suffering from chronic inflammation.9 This corresponds to studies showing that high estrogen levels (in women) can increase C-reactive protein, which is the most accurate marker for systemic inflammation.10-12 Elevated C-reactive protein is an independent risk factor for coronary heart disease in healthy individuals.

Another Lethal Mechanism of Excess Estrogen

The number one cause of death in persons over age 50 is the development of an abnormal blood clot (thrombus) in an artery that blocks blood flow to a critical region of the body such as the heart, lungs, or brain. Elevated estrogen predisposes people to these lethal thrombotic events.

It has been found that men admitted in hospitals with myocardial infarcts have elevated estradiol and lower testosterone levels.13 This was shown in an interesting study done on men admitted to the hospital with acute heart attacks whose levels of sex hormones were evaluated. Compared with control patients, estradiol levels in these heart attack patients were 180% higher, while bioavailable testosterone levels were nearly three times less than those of control patients.14

These findings reveal the higher heart attack incidences associated with high estrogen and low testosterone. It is possible, however, that these low levels of testosterone and high levels of estradiol occurred in response to the heart attack itself.14

Estrogen and Prostate Cancer

The role that estrogen plays in malignant prostate disease is contradictory and complex. Some studies indicate that estrogen and its toxic metabolites are a cause of prostate cancer.15,16 Yet once prostate cancer develops, certain estrogen compounds demonstrate anticancer effects.

This paradox can be explained by the mechanisms that estradiol (and its toxic metabolites) uses to damage prostate cell DNA,17 causing gene mutations that result in the loss of cell growth regulatory control, i.e. cancer. Interestingly, once a prostate tumor manifests, estrogen may exert anti-tumor effects, though cancer cells eventually become resistant to estrogen drugs and then even use endogenous estrogen to fuel their growth.

The fact that estrogen may temporarily exert anti-tumor effects in certain types of prostate cancer cells does not diminish the argument that estrogen may have contributed to the initiation of the same cancer. For example, in a study published two years ago, researchers discovered that when “estradiol is added to testosterone treatment of rats, prostate cancer incidence is markedly increased and even a short course of estrogen treatment results in a high incidence of prostate cancer.” These scientists hypothesize that metabolites of estrogens can be converted to reactive intermediates that can adduct to DNA and cause generation of reactive oxygen species; thus, estradiol is a weak DNA-damaging carcinogen that causes DNA damage to prostate cell genes.18 This kind of damage to DNA regulatory genes is what initiates prostate cancer.

Many published studies, however, show no association between high blood estradiol levels and diagnosed prostate cancers.19 One reason there are not more diagnosed prostate cancers in men with high estrogen may be that the high estradiol level that initiated DNA damage then serves to keep prostate cancer temporarily under control once it develops.

An interesting mechanism by which certain prostate cancer cells become resistant to estradiol therapy is the development of components in cancer cells that selectively remove estradiol from the tumor cells. If our normal cells were only as adaptive as cancer cells, we could possibly become biologically immortal.

Another reason why estradiol blood levels may not correlate with prostate cancer incidence is the ability of prostate cells to produce their own estradiol (by making their own aromatase enzyme). Although evidence is conflicting, there is a clear indication that local synthesis of estrogen in the prostate gland itself may be significant in prostate tumor development.16 All of this helps validate the importance of nutrients Life Extension male members take to block the carcinogenic effects of estrogen within the prostate gland.

An analogy to how excess estrogen can first damage DNA regulatory genes to cause cancer and then act as a prostate cancer suppressor can be seen with chemotherapy drugs. The mechanism by which most chemo drugs kill cancer cells is to inflict massive damage to cellular DNA. While chemo drugs kill cancer cells, they simultaneously damage healthy DNA and can increase the risk of future cancers. It appears that excess estrogen damages prostate cell DNA to initiate cancer, but then acts as a temporary prostate cancer suppressor. In presenting this analogy, I am not implying that estrogen in men is as dangerous as toxic chemo drugs. I am showing that something that suppresses cancer cell propagation (like estrogen) can also cause cancer.

Our Observations

We at Life Extension have often observed aged men with symptom-free prostate cancer who have startlingly high estradiol levels. It requires a needle biopsy to confirm these slow growing tumors that were identified by only modestly high PSA levels. In fact, we often look at aging men’s estradiol and free testosterone blood levels as a potential indicator of prostate cancer. Aging men with low free testosterone and high estradiol often have prostate cancer based on these observations. Many of these men, however, will die from vascular disease (possibly caused by their high estrogen levels) before their prostate cancer is diagnosed.

In fact, a study published just this year discusses potential initiating effect of estrogens in the development of prostate cancer.15 Tumor initiation is defined by the National Cancer Institute as a process in which normal cells are changed so that they are able to form tumors. Substances that cause cancer can be tumor initiators. The latest study on this subject suggests that estrogen is a prostate cancer initiator and that anti-estrogen therapies might be an overlooked prevention strategy.

An overlooked reason so many human studies fail to show a relationship between estrogen levels and prostate cancer is the fact that men with the highest estrogen levels may have perished from heart attacks and strokes before prostate cancer had a chance to clinically manifest. Based on the vascular disease risks discussed at the beginning of this article, men who suffered from estrogen overload early in their life would be expected to die sooner and, therefore not live long enough to develop clinically diagnosed prostate cancer. From a statistical standpoint, this would falsely make it appear that higher estradiol levels in aging men do not result in greater incidences of prostate cancer, since many men with the highest estrogen levels would not be alive to even participate in the study.

Misconceptions About Prostate Cancer

While prostate cancer is not usually diagnosed until men reach older ages, it can be initiated 15-25 years prior to clinical manifestation.20 In fact, there is convincing evidence that the initiating DNA damage inflicted by estrogen to prostate cells can occur before you are even born! Studies show that as early as the second and third trimester of life, exposure to elevated estrogens in the womb can initiate prostate cancer that may not manifest for 80 years.15,21-28 Please don’t feel overly helpless about this, as it requires more than mere initiation for cancer to fully develop. What you eat and other lifestyle factors have an enormous impact on whether you develop prostate cancer, even if you are strongly genetically predisposed.

Estrogen’s Role in Benign Prostate Enlargement

Unlike prostate cancer, estrogen’s role in the development and progression of benign prostatic hyperplasia (BPH) is clearly defined. Animal studies initially led to the hypothesis that estrogens can stimulate prostate growth, resulting in hyperplasia of the gland. A large body of subsequent human research confirms the initial findings.15,20,29-32

Estrogen stimulates proliferation of the stromal cells in the prostate gland that cause so many of the urinary discomforts associated with BPH. A study published just this year documents a specific mechanism by which estradiol causes rapid proliferation of prostate stromal cells.15
Another study also published this year provides further clarification on how estradiol increases the proliferation of stromal cells and how anti-estrogen compounds block this undesirable effect. The researchers concluded that “…these findings support the hypothesis that estrogens play a role in the pathogenesis of BPH, a disease characterized predominantly by stromal overgrowth.”20

In a study published last year, researchers evaluated the association of sex hormone levels in the blood with common BPH urinary tract symptoms. Study subjects consisted of 260 men, 60 years of age or older, whose blood levels of testosterone, estradiol, and other sex hormones were measured. Of these men, 128 cases had two to four symptoms (excessive urination at night, hesitancy, incomplete emptying, and weak stream). The 132 men in the control group had no urinary symptoms. Adjustments were made for age, race/ethnicity, waist circumference, cigarette smoking, alcohol consumption, and physical activity.33
The results showed that BPH sufferers had statistically significantly greater estradiol concentrations than symptom-free controls. Men suffering from BPH symptoms also had higher levels of a marker for a metabolite for dihydrotestosterone (DHT, another documented factor in the development of BPH).

After multivariate adjustments, men with the greater estradiol concentration had a 1.78 times higher incidence of urinary tract symptoms. An even greater incidence of urinary tract symptoms occurred in men with the highest levels of a dihydrotestosterone metabolite, whereas blood testosterone level showed no effect on urinary tract symptoms. The doctors who conducted this study concluded by stating, “in this cross-sectional study representative of older US men, circulating AAG, a metabolite of dihydrotestosterone, and estradiol were associated with an increased risk of having lower urinary tract symptoms.”33

These findings, reported over the past 18 months confirm what Life Extension told its members back in 1994 about estrogen’s role in benign prostatic hyperplasia (BPH). The encouraging news is that most Life Extension male members are already taking nutrients (and in some cases drugs like Arimidex® and Avodart®) that exhibit anti-estrogen and anti-DHT properties in the prostate gland itself. This is important because even when estrogen and DHT are lowered in the blood, prostate cells can compensate by synthesizing them in the prostate gland.

In males, the main biologically active estrogen is estradiol. The primary source of estradiol in men is from the conversion (aromatization) of testosterone. As men age, the production of androgens from the adrenals and gonads is decreased. The aromatization of testosterone to estradiol is often maintained, but due to a variety of factors, more testosterone is aromatized in fatty tissues, causing a further imbalance of the ratio of testosterone to estrogen, i.e. too much estradiol and not enough testosterone. The result is a deficiency of beneficial testosterone and an excess amount of estradiol.34 As men age, the amount of testosterone produced in the testes diminishes greatly. Yet estradiol levels remain persistently high. The reason for this is increasing aromatase activity along with age-associated fat mass, especially in the belly.5 Estradiol levels correlate significantly to body fat mass and more specifically to subcutaneous abdominal fat. The epidemic of abdominal obesity observed in aging men is associated with a constellation of degenerative disorders, including heart disease, diabetes, and cancer.9,35-38 Subcutaneous abdominal fat acts as a secretory gland, often producing and emitting excessive levels of estradiol into an aging man’s blood.39 One’s waist circumference is a highly accurate prognostic measurement of future disease risk, with excess estradiol secretion being at least one of the deadly mechanisms associated with the difficult-to-resolve problem of having too much abdominal fat.5,40 Symptoms of excess estrogen in aging men include the development of breasts, having too much abdominal weight, feeling tired, suffering loss of muscle mass, and having emotional disturbances. Many of these symptoms correspond to testosterone deficiency as well.41 Protecting Against Toxic Estrogen Metabolites It is not just excess estradiol that poses health risks. Specific estrogen metabolites may also initiate and promote hormone-related cancers. Daily consumption of cruciferous vegetables (broccoli, cauliflower, cabbage, Brussels sprouts),54-59 along with isoflavone-rich soy foods60-64 converts these dangerous estrogen metabolites (such as 16-alpha-hydroxyestrone) to safe ones (2-hydroxyestrone) that may protect against prostate cancer. For those who don’t eat these cancer-protective foods on a daily basis, low-cost supplements can supply the most active constituents of cruciferous vegetables (such as indole-3-carbinol and sulphoraphane)65-70 and soy (genistein and daidzein).71-74 Don’t Lower Your Estrogen Too Much! When reviewing the studies about the multiple pathological effects of excess estrogen in aging men, it may be tempting to take high doses of an aromatase-inhibiting drug (like Arimidex®) to slash estrogen levels as low as possible. Don’t do this, as men need estrogen to maintain bone density, cognitive function, and even to maintain the inner lining of the arterial wall (the endothelium).42 Most Life Extension members know that too little cholesterol (below 150 mg/dL) can be more dangerous than too much cholesterol (levels over 200 mg/dL). The same may hold true for estrogen. We have recommended that ideal ranges for estradiol for most aging men are between 20 and 30 pg/mL of blood. Below 18 pg/mL increases osteoporosis risk, while levels greater than 30 pg/mL increase heart attack and stroke incidence. The availability of low-cost blood tests enables aging men to optimize their estradiol levels using natural approaches and/or prescription drugs. Estrogen and Men’s Bones Osteoporosis is not just a risk for aging women. Men also suffer crippling fractures caused by loss of bone mineral density. When aged men suffer a bone fracture, their risk of dying is significantly higher than women.43,44 In a study published two years ago, doctors analyzed blood levels in three groups of men for estradiol only, testosterone only, and estradiol and testosterone together. In men with low estradiol (2.0-18.1 pg/mL of blood), hip fractures were more than three times higher compared with men who had estradiol levels of 18.2-34.2 pg/mL.45 Men with estradiol levels greater than 34.3 pg/mL had a slightly higher risk of hip fracture compared with those in the range of 18.2-34.2 pg/mL. This study helps confirm Life Extension’s recommended range for estrogen levels in aging men. Interestingly, this study also showed in the group of men whose blood was measured for estradiol and testosterone, those who were low in both these hormones suffered a startling 6.5 times greater incidence of hip fractures. The authors of this study concluded, “men with low estradiol levels are at an increased risk for future hip fracture. Men with both low estradiol and low testosterone levels seem to be at greatest risk for hip fracture.”45 Conflicting Data With the voluminous amount of scientific studies being published today, contradictions inevitably arise, and this is not always due to study design flaws. For the past decade, Life Extension has reported on dozens of studies showing that higher testosterone levels significantly reduce a man’s risk of cardiovascular disease. In fact, we just did a comprehensive database search and identified a total of 50 studies that document the protective effects of testosterone against cardiovascular disease in men. A study published two years ago, however, contradicts this. This study showed greater incidences of heart attacks in men with higher testosterone and lower heart attack risks in older men with higher estradiol. (In younger men, estradiol level had no impact on heart attack incidence in this study.) The authors of the study admitted a limitation to the study was only measuring baseline levels of hormones. This study nonetheless was used at the anti-aging conference to proclaim that estradiol protects against heart attack.46 There are scientific studies that demonstrate estrogen’s potential beneficial effects to a man’s vascular system. These protective mechanisms, however, have to be weighed against pathological damage the very same estrogen can induce. As I mentioned earlier, despite the documented dangers of excess estrogen, levels that are too low also present risks, not only to bone,45,47-49 but to the vascular system as well.46,50,51 If a man were to intentionally lower his estradiol too much, he could very well suffer vascular disease because estrogen is vital to proper endothelial function.52,53 This is why it is so important for aging men to have annual blood tests. If estrogen is too low (below 18-20 pg/mL), or too high (above 30 pg/mL), corrective action should be taken. How to Reduce Excess Estrogen In aging men, a large percentage of estradiol is synthesized in abdominal adipose (fat) tissues.42 Reducing waist circumference confers huge health benefits, one being a lowering of estradiol levels. One of the most effective ways for men to reduce belly fat is to restore their free testosterone to youthful ranges. Nutrients that inhibit the aromatase enzyme can help boost testosterone levels by preventing its conversion (aromatization) into estradiol. As men grow older, however, their testicular testosterone production declines precipitously. This means that inhibiting aromatase might not sufficiently maintain testosterone levels because not enough is being produced internally. Fortunately, low-cost compounded testosterone creams are available that can be rubbed on the skin for absorption into the bloodstream. For men with excess aromatase activity, this topically absorbed testosterone might convert into too much estradiol. If this happens, the use of very low-dose aromatase-inhibiting drugs (0.5 mg of Arimidex® twice a week) may be all that is needed to protect against estrogen overload. Some men don’t need these drugs and can use nutrient formulas that have aromatase-inhibiting properties. There is no need to guess what you need, as a blood test taken 30-45 days after initiating testosterone-replacement not only reveals a man’s estradiol level, but also ensures that the PSA has not spiked (indicating possible pre-existing prostate cancer), that the dose of testosterone cream is appropriate, and that there are no other side effects occurring. To view a wide range of estrogen-lowering strategies, one can view Life Extension’s Male Hormone Modulation Protocol by logging on to www.lef.org/MaleHormones What if Your Estrogen Level is Too Low? Some men are so deficient in aromatase that they do not make enough estrogen. If a blood test reveals estradiol below 20 pg/mL, which may occur if Arimidex®, for example, is being taken at too high a dose, one should consider reducing the dose. Alternatively, applying a tiny dose of a compounded topical estradiol cream to the skin several times a week may also help increase estradiol levels. Follow-up blood tests 30-45 days later can assess if too much or too little topical estradiol cream is being used. There is also evidence that consuming phytoestrogens from soy might provide similar benefits for the bone75-79 and vascular system.80-88 Summary It is hard to imagine that before 1906, doctors did not even know that a hormone (estrogen) was secreted by the ovaries in women. It was not until 1930 that the isolation of the estrogen complex in pure form was published. Less than 80 years later, scientists are debating what the optimal levels of estrogen should be in men. This exponential leap in scientific knowledge is a marvel in itself! The role that estrogen plays in men’s health is an important topic discussed at medical conferences today. As outlined in this article, testing one’s estradiol level is critical because it can be a serious problem if it is too high or if it is too low. I am pleased to announce that the everyday low price for the Male or Female Blood Test Panels has been reduced from $299 to $269. This price reduction is made possible by the large volume of blood testing Life Extension members have been ordering. In addition to estradiol, the Male Panel measures PSA, free testosterone, DHEA, C-reactive protein, homocysteine, along with cholesterol lipids, glucose, and blood cell counts and chemistries. I encourage any member who has not had this comprehensive blood test conducted over the past 12 months to take advantage of this new lower price. To order the Male or Female Panel by phone, call 1-800-208-3444. If the results reveal estradiol levels are too high or too low, corrective measures can easily be taken to protect your precious health.

References

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Rinsho Byori. 2004 Apr;52(4):291-4. 33. Rohrmann S, Nelson WG, Rifai N, et al. Serum sex steroid hormones and lower urinary tract symptoms in Third National Health and Nutrition Examination Survey (NHANES III). Urology. 2007 Apr;69(4):708-13. 34. Vermeulen A. Androgen replacement therapy in the aging male—a critical evaluation. J Clin Endocrinol Metab. 2001 Jun;86(6):2380-90. 35. Choi BG, McLaughlin MA. Why men’s hearts break: cardiovascular effects of sex steroids. Endocrinol Metab Clin North Am. 2007 Jun;36(2):365-77. 36. Kaneda Y, Ohmori T. Relation between estradiol and negative symptoms in men with schizophrenia. J Neuropsychiatry Clin Neurosci. 2005;17(2):239-42. 37. Zou B, Sasaki H, Kumagai S. Association between Relative Hypogonadism and Metabolic Syndrome in Newly Diagnosed Adult Male Patients with Impaired Glucose Tolerance or Type 2 Diabetes Mellitus. Metab Syndr Relat Disord. 2004;2(1):39-48. 38. Abu-Abid S, Szold A, Klausner J. Obesity and cancer. J Med. 2002;33(1-4):73-86. 39. Kula K, Walczak-Jedrzejowska R, Slowikowska-Hilczer J, et al. Important functions of estrogens in men—breakthrough in contemporary medicine. Przegl Lek. 2005;62(9):908-15. 40. Anderson LA, McTernan PG, Barnett AH, Kumar S. The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site. J Clin Endocrinol Metab. 2001 Oct;86(10):5045-51. 41. Lund BC, Bever-Stille KA, Perry PJ. Testosterone and andropause: the feasibility of testosterone replacement therapy in elderly men. Pharmacotherapy. 1999 Aug;19(8):951-6. 42. Gooren LJ, Toorians AW. Significance of oestrogens in male (patho)physiology. Ann Endocrinol (Paris). 2003 Apr;64(2):126-35. 43. Seeman E. The dilemma of osteoporosis in men. Am J Med. 1995 Feb 27;98(2A):76S-88S. 44. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999 Mar 13;353(9156):878-82. 45. Amin S, Zhang Y, Felson DT, et al. Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. Am J Med. 2006 May;119(5):426-33. 46. Arnlov J, Pencina MJ, Amin S, et al. Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006 Aug 1;145(3):176-84. 47. Nuti R, Martini G, Merlotti D, et al. Bone metabolism in men: role of aromatase activity. J Endocrinol Invest. 2007;30(6 Suppl):18-23. 48. Gennari L, Nuti R, Bilezikian JP. Aromatase activity and bone homeostasis in men. J Clin Endocrinol Metab. 2004 Dec;89(12):5898-907. 49. Khosla S, Melton LJ 3rd, Riggs BL. Estrogens and bone health in men. Calcif Tissue Int. 2001 Oct;69(4):189-92. 50. Phillips GB. Is atherosclerotic cardiovascular disease an endocrinological disorder? The estrogen-androgen paradox. J Clin Endocrinol Metab. 2005 May;90(5):2708-11. 51. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999 Jun 10;340(23):1801-11. 52. Sader MA, McCredie RJ, Griffiths KA, et al. Oestradiol improves arterial endothelial function in healthy men receiving testosterone. Clin Endocrinol (Oxf). 2001 Feb;54(2):175-81. 53. Sudhir K, Komesaroff PA. Clinical review 110: Cardiovascular actions of estrogens in men. J Clin Endocrinol Metab. 1999 Oct;84(10):3411-5. 54. Traka M, Gasper AV, Melchini A, et al. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS ONE. 2008;3(7):e2568. 55. Kirsh VA, Peters U, Mayne ST, et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst. 2007 Aug 1;99(15):1200-9. 56. Xiao D, Singh SV. Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res. 2007 Mar 1;67(5):2239-46. 57. Chan JM, Gann PH, Giovannucci EL. Role of diet in prostate cancer development and progression. J Clin Oncol. 2005 Nov 10;23(32):8152-60. 58. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003 Dec;12(12):1403-9. 59. Kristal AR, Lampe JW. Brassica vegetables and prostate cancer risk: a review of the epidemiological evidence. Nutr Cancer. 2002;42(1):1-9. 60. Grainger EM, Schwartz SJ, Wang S, et al. A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen. Nutr Cancer. 2008 Mar;60(2):145-54. 61. Heald CL, Ritchie MR, Bolton-Smith C, Morton MS, Alexander FE. Phyto-oestrogens and risk of prostate cancer in Scottish men. Br J Nutr. 2007 Aug;98(2):388-96. 62. Kurahashi N, Iwasaki M, Sasazuki S, et al. Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):538-45. 63. Holzbeierlein JM, McIntosh J, Thrasher JB. The role of soy phytoestrogens in prostate cancer. Curr Opin Urol. 2005 Jan;15(1):17-22. 64. Lee MM, Gomez SL, Chang JS, et al. Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol Biomarkers Prev. 2003 Jul;12(7):665-8. 65. Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005 Sep;4(9):1201-15. 66. Garikapaty VP, Ashok BT, Chen YG, et al. Anti-carcinogenic and anti-metastatic properties of indole-3-carbinol in prostate cancer. Oncol Rep. 2005 Jan;13(1):89-93. 67. Sarkar FH, Li Y. Indole-3-carbinol and prostate cancer. J Nutr. 2004 Dec;134(12 Suppl):3493S-8S. 68. Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH. Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene. 2001 May 24;20(23):2927-36. 69. Yao H, Wang H, Zhang Z, et al. Sulforaphane inhibited expression of hypoxia-inducible factor-1alpha in human tongue squamous cancer cells and prostate cancer cells. Int J Cancer. 2008 Sep 15;123(6):1255-61. 70. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood). 2007 Feb;232(2):227-34. 71. Zhang LL, Li L, Wu DP, et al. A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells. Acta Pharmacol Sin. 2008 Sep;29(9):1060-8. 72. Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008 May 18. 73. Kikuno N, Shiina H, Urakami S, et al. Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells. Int J Cancer. 2008 Aug 1;123(3):552-60. 74. Nagata Y, Sonoda T, Mori M, et al. Dietary isoflavones may protect against prostate cancer in Japanese men. J Nutr. 2007 Aug;137(8):1974-9. 75. Ma DF, Qin LQ, Wang PY, Katoh R. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2008 Feb;62(2):155-61. 76. Atkinson C, Compston JE, Day NE, Dowsett M, Bingham SA. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2004 Feb;79(2):326-33. 77. Harkness LS, Fiedler K, Sehgal AR, Oravec D, Lerner E. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. J Womens Health (Larchmt). 2004 Nov;13(9):1000-7. 78. Uesugi T, Fukui Y, Yamori Y. Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal japanese women: a four-week study. J Am Coll Nutr. 2002 Apr;21(2):97-102. 79. Droke EA, Hager KA, Lerner MR, et al. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease. J Inflamm (Lond). 2007;417. 80. Seok YM, Baek I, Kim YH, et al. Isoflavone attenuates vascular contraction through inhibition of the RhoA/Rho-kinase signaling pathway. J Pharmacol Exp Ther. 2008 Sep;326(3):991-8. 81. Si H, Liu D. Phytochemical genistein in the regulation of vascular function: new insights. Curr Med Chem. 2007;14(24):2581-9. 82. Colacurci N, Chiantera A, Fornaro F, et al. Effects of soy isoflavones on endothelial function in healthy postmenopausal women. Menopause. 2005 May;12(3):299-307. 83. Liang YL, Teede H, Dalais F, McGrath BP. The effects of phytoestrogen on blood pressure and lipids in healthy volunteers. Zhonghua Xin Xue Guan Bing Za Zhi. 2006 Aug;34(8):726-9. 84. Kapiotis S, Hermann M, Held I, et al. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2868-74. 85. Wenzel U, Fuchs D, Daniel H. Protective effects of soy-isoflavones in cardiovascular disease. Identification of molecular targets. Hamostaseologie. 2008 Feb;28(1-2):85-8. 86. Si H, Liu D. Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats. J Nutr. 2008 Feb;138(2):297-304. 87. Chan YH, Lau KK, Yiu KH, et al. Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden. Am J Clin Nutr. 2007 Oct;86(4):938-45. 88. Rimbach G, Boesch-Saadatmandi C, Frank J, et al. Dietary isoflavones in the prevention of cardiovascular disease--a molecular perspective. Food Chem Toxicol. 2008 Apr;46(4):1308-19.

Why Estrogen Balance is Critical to Aging Men – Life Extension

Why Estrogen Balance is Critical to Aging Men – Life Extension

By William Faloon

William Faloon

When we started offering comprehensive blood test panels back in 1996, men did not understand why we were checking their estrogen levels. Back in those days, estrogen was considered a hormone of importance only to women.

We tested estrogen based on published data indicating that when estrogen levels are unbalanced, the risk of degenerative disease in aging men skyrockets.1-7 Of concern to us 14 years ago were reports showing that excess estrogen contributes to the development of atherosclerosis.8,9 Human clinical studies conducted more than a decade later confirmed our suspicions. Men with even slightly elevated estrogen levels doubled their risk of stroke and had far higher incidences of coronary artery disease.10-12 Our early observations also revealed that men presenting with benign prostate enlargement or prostate cancer had higher blood estrogen levels (and often low free testosterone blood levels).13-16 Subsequent clinical studies help confirm our early observations.17-21


Insufficient estrogen, on the other hand, predisposes men to osteoporosis and bone fracture.22,23
The fact that 99% of men today have no idea what their blood estrogen levels are helps explain the epidemic of age-related disease that is bankrupting this nation’s medical system.

New Study Published in the Journal of the American Medical Association

Conventional doctors tend to ignore hard science until it appears in their own medical journals.
A study published in the Journal of the American Medical Association (JAMA) measured blood estradiol (a dominant estrogen) in 501 men with chronic heart failure. Compared to men in the balanced estrogen quintile, men in the lowest estradiol quintile were 317% more likely to die during a 3-year follow-up, while men in the highest estradiol quintile were 133% more likely to die.24
The men in the balanced quintile—with the fewest deaths—had serum estradiol levels between 21.80 and 30.11 pg/mL. This is virtually the ideal range that Life Extension® has long recommended male members strive for.

The men in the highest quintile who suffered 133% increased death rates had serum estradiol levels of 37.40 pg/mL or above. The lowest estradiol group that suffered a 317% increased death rate had serum estradiol levels under 12.90 pg/mL.

The dramatic increase in mortality in men with unbalanced estrogen (i.e., estradiol levels either too high or too low) is nothing short of astounding. It uncovers a gaping hole in conventional cardiology practice that is easily correctable.

This study revealing the lethal dangers of estrogen imbalance was published in conventional medicine’s Bastille of knowledge—the Journal of the American Medical Association. Physicians no longer have a basis to question male Life Extension® members who take aggressive approaches to maintain their serum estradiol levels in optimal ranges.

Low Estradiol and Testosterone Predict Mortality in Aging Men

Sales of testosterone replacement drugs have surged more than 20-fold in response to studies linking low testosterone to a host of common maladies.

In a recent study of 3,014 men aged 69-80 years, serum levels of testosterone and estradiol were measured during a mean follow-up of 4.5 years. Men with low testosterone had 65% greater all-cause mortality, while men with low estradiol suffered 54% more deaths.25

Those men low in estradiol and testosterone were almost twice as likely to die (a 96% increase in mortality) compared to men in the optimal ranges.25

This large study of aged men corroborates prior published reports linking imbalances of testosterone and/or estradiol with greater incidences of degenerative disease and death.26-36

How Do Men Naturally Make Estrogen?

Women synthesize most of their estrogen in their ovaries and other reproductive tissues.
Since men lack this female anatomy, they need to produce estrogen through a process involving an enzyme called aromatase that transforms testosterone into estradiol.
Aging men sometimes have too much aromatase activity, which causes their testosterone to convert to excess estradiol. This results in depletion of vital testosterone while spiking estradiol to unsafe ranges.
Some men lack aromatase and suffer an estrogen deficit. Other men produce so little endogenous testosterone that there is not enough to convert into estrogen, which causes low levels of both free testosterone and estradiol.

Fortunately, no matter what the underlying cause, aging men can easily achieve optimal free testosterone and estradiol serum levels.

Free testosterone is the unbound form that is biologically available to cell receptor sites throughout the body. Measuring free testosterone blood levels is the most accurate way of assessing testosterone status in aging men.

How Aging Men Can Control Their Estrogen Levels

An epidemic problem we at Life Extension observe in aging male members is insufficient free testosterone, i.e., less than 15-20 pg/mL of serum. When accompanied by excess estradiol (over 30 pg/mL of serum), this can signal excess aromatase enzyme activity.

Excess aromatase robs men of their testosterone while exposing them to higher than desirable estradiol.37 Aromatase can be suppressed with absorbable forms of chrysin (a plant flavonoid) and/or lignans such as those extracted from the Norway spruce tree (HMRlignan™).38-42

If these nutrients fail to reduce estradiol adequately, then we suggest that men ask their doctor to prescribe an aromatase-inhibiting drug like Arimidex® in the very low dose of 0.5 mg twice a week.
When aromatase is properly suppressed, estradiol levels are reduced to safe ranges, while free testosterone often increases, since less testosterone is being aromatized into estradiol.

Most testosterone in a man’s body emanates from the testes. Aging results in a decline in testicular output, thus necessitating the topical application of a testosterone cream to restore this vital hormone to youthful levels. Ideal free serum testosterone levels for most aging men are between 20-25 pg/mL. As you may surmise, a man who produces too little testosterone risks a lethal deficiency of both free testosterone and estradiol. That’s because men need testosterone to synthesize estradiol in their bodies. In the presence of insufficient testosterone production, some aging men are vulnerable to low free testosterone and low estradiol that according to the latest study almost doubles their risk of dying over a 4.5 year period!25 Critical Importance of Blood Testing Today’s conventional physicians prescribe blood tests to check glucose, cholesterol, and triglycerides, but rarely check their male patients’ free testosterone and estradiol levels. When looking at the horrific-ally high mortality rates associated with imbalances of these critical hormones, it becomes strikingly apparent that a significant number of heart attacks, strokes, bone fractures, and other degenerative diseases are easily preventable. One reason these hormone blood tests are not normally prescribed is their high retail cost, and the fact that many insurance companies refuse to pay for them. As a member of the Life Extension Foundation®, you don’t have to be victimized by conventional medical ignorance, high prices, or insurance company indifference. Take Charge of Your Health with Low-Cost Blood Testing An all-inclusive blood test panel that includes free testosterone and estradiol can retail for $1,000 at commercial labs. Life Extension members can obtain these same tests for only $269.   If your blood test result reveals an imbalance of free testosterone and/or estradiol, you are in a position to initiate immediate corrective action. Not only can restoring youthful hormone balance save your life, but men (and women) often experience an enhancement in their quality of life after their hormones are adjusted to optimal ranges. A complete description of the Male and Female Blood Test Panels can be found on this site. As you’ll readily see, these panels contain many important tests (such as homocysteine, C-reactive protein, and DHEA) that mainstream doctors seldom check for. When you order these tests, a requisition form is sent listing blood drawing stations in your local area. Appointments are usually not necessary, meaning you can have your blood drawn at your convenience. To order a comprehensive Male and/or Female Blood Test Panel, just call 1-800-208-3444. It is the single most important step you can take to ensure your continued good health.

References

1.Suzuki K, Ito K, Ichinose Y, Kurokawa K, Suzuki T. Endocrine environment of benign prostatic hyperplasia prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol. 1995 Mar;29(1):65-8. 2.Lindholm J, Eldrup E, Winkel P. Variability in plasma oestrogen concentrations in men with a myocardial Infarction. Dan Med Bull. 1990 Dec;37(6):552-6. 3.Usuki F, Nakazato O, Osame M, Igata A. Hyperestrogenemia in neuromuscular diseases. J Neurol Sci. 1989 Feb;89(2-3):189-97. 4.Zumoff B. Hormonal abnormalities in obesity. Acta Med Scand Suppl. 1988; 723:153-60. 5.Small M, MacRury S, Beastall GH. Oestradiol levels in diabetic men with and without a previous myocardial infarction. Q J Med. 1987 Jul;64(243):617-23. 6.Phillips GB. Evidence for hyperestrogenemia as the link between diabetes mellitus and myocardial infarction. Am J Med. 1984 Jun;76(6):1041-8. 7.Klaiber EL, Broverman DM, Haffajee CI, Hochman JS, Sacks GM, Dalen JE. Serum estrogen levels in men with acute myocardial infarction. Am J Med. 1982 Dec;73(6):872-81. 8.Jeppesen LL, Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K. Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):749-54. 9.Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994 May;14(5):701-6. 10.Abbott RD, Launer LJ, Rodriguez BL, et al. Serum estradiol and risk of stroke in elderly men. Neurology. 2007 Feb 20;68(8):563-8. 11.Dunajska K, Milewicz A, Szymczak J, et al. Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis. Aging Male. 2004 Sep;7(3):197-204. 12.Wranicz JK, Cygankiewicz I, Rosiak M, Kula P, Kareba W. The relationship between sex hormones and lipid profile in men with coronary artery disease. Int J Cardiol. 2005 May 11;101(1):105-10. 13.Krieg M, Nass R, Tunn S. Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J Clin Endocrinol Metab. 1993 Aug;77(2):375-81. 14.Gann PH, Hennekens CH, Longcope C, Verhoek-Oftedahl W, Grodstein F, Stampfer MJ. A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate. 1995 Jan;26(1):40-9. 15.Shibata Y, Ito K, Suzuki K, et al. Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition. Prostate. 2000 Jan;42(1):45-55. 16.Prins GS, Huang L, Birch L, Pu Y. The role of estrogens in normal and abnormal development of the prostate gland. Ann N Y Acad Sci. 2006 Nov;1089:1-13. 17.Prins GS, Korach KS. The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids. 2008 Mar;73(3):233-44. 18.Matsuda T, Abe H, Suda K. Relation between benign prostatic hyperplasia and obesity and estrogen. Rinsho Byori. 2004 Apr;52(4):291-4. 19.Ho CK, Nanda J, Chapman KE, Habib FK. Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen. J Endocrinol. 2008 Jun;197(3):483-91. 20.Singh PB, Matanhelia SS, Martin FL. A potential paradox in prostate adenocarcinoma progression: oestrogen as the initiating driver. Eur J Cancer. 2008 May;44(7):928-36. 21.Giton F, de la Taille A, Allory Y, et al. Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (PCa). J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):158-67. 22.Mellström D, Vandenput L, Mallmin H, et al. Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res. 2008 Oct;23(10):1552-60. 23.Pernow Y, Hauge EM, Linder K, Dahl E, Sääf M. Bone histomorphometry in male idiopathic osteoporosis. Calcif Tissue Int. 2009 Jun;84(6):430-8. 24.Jankowska EA, Rozentryt P, Ponikowska B. Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA. 2009 May 13;301(18):1892-901. 25.Tivesten A, Vandenput L, Labrie F, et al. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metab. 2009 Jul;94(7):2482-8. 26.Tang YJ, Lee WJ, Chen YT, et al. Serum testosterone level and related metabolic factors in men over 70 years old. J Endocrinol Invest. 2007 Jun;30(6):451-8. 27.Laaksonen DE, Niskanen L, Punnonen K, et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol. 2003 Dec;149(6):601-8. 28.Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A. Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann NY Acad Sci. 2002 Jun;966:131-42. 29.Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002 Nov;87(11):5001-7. 30.Hogervorst E, Combrinck M, Smith AD. Testosterone and gonadotropin levels in men with dementia. Neuro Endocrinol Lett. 2003 Jun;24(3-4):203-8. 31.Gouras GK, Xu H, Gross RS, et al. Testosterone reduces neuronal secretion of Alzheimer’s beta-amyloid peptides. Proc Natl Acad Sci USA. 2000 Feb 1;97(3):1202-5. 32.Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009 Jan-Feb;30(1):23-32. 33.Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007 Dec 4;116(23):2694-701. 34.Debing E, Peeters E, Duquet W, Poppe K, Velkeniers B, Van Den Branden P. Men with atherosclerotic stenosis of the carotid artery have lower testosterone levels compared with controls. Int Angiol. 2008 Apr;27(2):135-41. 35.Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004 May 4;109(17):2074-9. 36.Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab. 2002 Aug;87(8):3632-9. 37.Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrinol Metab. 2004 Mar;89(3):1174-80. 38.Ta N, Walle T. Aromatase inhibition by bioavailable methylated flavones. J Steroid Biochem Mol Biol. 2007 Oct;107(1-2):127-9. 39.Campbell DR, Kurzer MS. Flavonoid inhibition of aromatase enzyme activity in human preadipocytes. J Steroid Biochem Mol Biol. 1993 Sep;46(3):381-8. 40.Kellis JT Jr, Vickery LE. Inhibition of human estrogen synthetase (aromatase) by flavones. Science. 1984 Sep 7;225(4666):1032-4. 41.Saarinen NM, Warri A, Makela SI, et al. Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies). Nutr Cancer. 2000; 36(2):207-16. 42.Wang C, Makela T, Hase T, Adlercreutz H, Kurzer MS. Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. J Steroid Biochem Mol Biol. 1994 Aug;50(3-4):205-12.

Man vs. Estrogen: It's Not Just A Woman Thing! | Seasons of Farragut

Man vs. Estrogen: It's Not Just A Woman Thing! | Seasons of Farragut

Posted by Dr. Nathan Goodyear on June 5, 2012 · 1 Comment

Nathan Goodyear, M.D.

Testosterone is the defining hormone of a man. Estrogen is the defining hormone of a woman.
So when we talk about estrogen, it’s that word men whisper in secret when the women in their lives seem a little hormonal, right? When people find out that my wife and I have 3 daughters, the resulting comment is usually, “Wow, that’s a lot of estrogen in your household!” (Thankfully, I have a son, too, who helps balance the estrogen to testosterone ratio at our house!)

I’m sorry to burst your bubble, guys, but estrogen is not exclusive to women. We make estrogen, too. In fact, some of us make a LOT of estrogen. Too much, in fact. And it creates some serious problems.

But before we talk about estrogen, we need to talk about testosterone. Testosterone levels in American men are at an all-time low! There are four major reasons for that: stress, weight, endogenous estrogens, and xenoestrogens. In this post, I’ll address three of those – stress, weight, and endogenous estrogen.
So let’s get started learning four important facts about testosterone, estrogen, and men!

What problems do high estrogen levels create in men?


1. High estrogen = low testosterone. One of the primary causes of low testosterone is a high estrogen level. Estrogens can be endogenous (produced by your body) or exogenous (from the environment, also known as xenoestrogens). Estradiol and Estrone (two of the three kinds of estrogen produced by your body) feed back to the hypothalamus and pituitary and shut off testosterone production.

2. High estrogen = inflammation. Not only do high estrogen levels decrease testosterone in men, they also increase inflammation. And this is VERY significant. Inflammation, just like stress, is a biochemical process.



Inflammation is the natural result of the immune system. Remember the last time you got a paper cut?  It was incredibly painful, probably red, warm and swollen, all cardinal symptoms of inflammation. Inflammation, in the right setting, is actually the body protecting itself.  However, when the immune system becomes imbalanced or chronically activated, the immune system causes damage through inflammation. For example, chronically activated immune cells in the brain (glial cells) play a pivotal role in the development of Alzheimer’s, Parkinson’s, and Multiple Sclerosis.

Inflammation is a SERIOUS issue. Chronic inflammation has been linked to many of the chronic diseases of aging: Type II Diabetes, obesity, hypertension, and cancer. In fact, a new term has been coined to describe inflammation arising from the gut which results in many of the above listed disease states - metabolic endotoxemia.

We’ve established that high estrogen levels are bad for men, shutting down testosterone production and causing chronic inflammation leading to disease.

What causes high estrogen levels in men?

1. High aromatase activity = high estrogen. First, high endogenous estrogen levels in men come from high aromatase activity.  Aromatase is the enzyme that converts androstenedione and testosterone into estrone and estradiol respectively. Aromatase is present in many different tissues. But in men aromatase is highly concentrated in that mid-life bulge.

Unfortunately, aromatase activity in men increases as we age due to stress, weight gain, and inflammation. None of us are going to get away from aging (it’s right there with death and taxes). And who do you know that has NO stress? (Remember, it is estimated that 90% of doctor visits are stress-related.) Typically, as we age we gain weight and have more inflammation.

That “age-related” tire around the mid-section is more than just unsightly. It is a hormone and inflammation-producing organ. Remember metabolic endotoxemia, the disease-producing state I mentioned earlier? Metabolic endotoxemia is inflammation arising from the GI system which causes obesity and then turns right around and produces inflammation. It’s a vicious cycle!  And guess what is concentrated in fat? If you guessed aromatase activity, then you are absolutely correct. Aromatase activity in men accounts for 80% of estrogen production.



Hormones are not just about numbers, but balance and metabolism as well (read my recent post on the topic).

2. Overdosage of testosterone = high estrogen. As mentioned earlier, testosterone levels in men are at an all-time low. And the mass solution for this problem with most physicians is to increase testosterone without evaluating or treating the underlying causes for low testosterone. Unfortunately, this complicates the entire low testosterone problem. Overdosage of testosterone increases estrogen production.

What?  You mean you can dose too high on testosterone? Yes, and most of the patients I see who are being treated with testosterone have been, in fact, overdosed.

In fact, at Seasons Wellness Clinic and Seasons of Farragut, we have seen many men must donate blood due to excess production of hemoglobin and hematocrit, a by-product of testosterone overdosage. A 20-22 year old male normally produces 5-10 mg daily of testosterone. It is during this age range that men are at their physical peak of testosterone production. For me, this was during my college football years.

Does it make sense for 40-and-up men currently taking testosterone, that they did not need to donate blood monthly during their peak years of natural testosterone production, but are currently required to donate blood regularly with their current regimen of testosterone?  Of course not. So, if you didn’t have to donate blood with your peak testosterone production in your 20′s, you shouldn’t have to donate with testosterone therapy in your 40′s and beyond either. Something is wrong here, right?

The starting dosage for one of the most highly-prescribed androgen gels is 1 gram daily. Men, we didn’t need 1 gram of testosterone in our early 20′s, and we don’t need it in our 30′s and beyond.
80% of a man’s testosterone occurs from aromatase activity, and aromatase activity increases as we age. So high doses of testosterone don’t make sense. Doctors are just throwing fuel on the fire with these massive doses. More is not better if it’s too much, even when it is something your body needs.
Then, there is the delivery of testosterone therapy. The body’s natural testosterone secretion follows a normal diurnal rhythm.  Testosterone is known to be greatest in early morning and lowest in the evening.  But with many prescribing testosterone therapy today, it is very common to get weekly testosterone shots or testosterone pellets. This method of delivery does NOT follow the body’s natural rhythm. The shots and pellets delivery method of testosterone produce supra physiologic (abnormal) peaks. If the purpose of hormone therapy is to return the body to normal levels, then that objective can never be reached with this type of testosterone therapy.

The effects of Testosterone to estrogen conversion in men and women are different. That’s certainly no surprise. In men, high aromatase activity and conversion of testosterone to estrogen has been linked to elevated CRP, fibrinogen, and IL-6.

Are these important?  CRP is one of the best indicators of future cardiovascular disease/events (heart attacks and strokes), and is associated with metabolic syndrome. And yes, it is more predictive than even a high cholesterol level. Fibrinogen is another marker of inflammation that has been associated with cardiovascular disease and systemic inflammation. IL-6 is an inflammatory cytokine (immune signal) that has been implicated in increased aromatase activity (conversion of testosterone to estrogen) and at the same time is the result of increased testosterone to estrogen activity.

So, what’s the big deal? The studies are not 100% conclusive, but it is clear that inflammation increases the testosterone to estrogen conversion through increased aromatase activity. And the increased estrogen conversion is associated with increased inflammation in men. It’s a vicious cycle that will lead to disease states such as insulin resistance, hypertension, prostatitis, cardiovascular disease, autoimmune disease, and cancer, to name a few.

You may be thinking, “Is the testosterone I need leading me to disease?”

The answer is, “Yes, it sure can.” If your testosterone therapy includes prescription of supra physiologic levels of testosterone, lack of follow-up on hormone levels, and no effort to balance hormones and metabolism, then yes, it sure can.

Is there a safe and effective way to balance hormones, lower estrogen and increase testosterone for men?

Effectively administering hormone therapy requires the following:

• A physician with extensive training in hormones and body biochemistry.
• The best and most accurate testing possible to determine current hormone levels and to track hormone levels after therapy is administered.
• Hormones that most closely replicate the natural ones produced in your body — bioidentical hormones.
• A therapy plan with the objective of returning your body to normal, not super-charging the body with unnatural levels of testosterone or any other hormone.

At Seasons of Farragut, Nan Sprouse and I are fellowship-trained (or completing fellowship training) specifically in the areas of hormone therapy and wellness-based medicine.

Our patient experience begins with an initial consultation to evaluate symptoms and develop an evaluation plan.

The next step is testing. In the case of hormone imbalance, we evaluate hormones with state-of-the-art hormone testing via saliva, not just blood. As stated in a 2006 article, “plasma levels of estradiol do not necessarily reflect tissue-level activity.”  Saliva has been shown to reveal the active hormone inside the cell at the site of action.

After initial testing and a therapy program, hormone levels are re-evaluated to ensure the progression of treatment and necessary changes are made to the treatment program. Testing and follow-up are key to proper balance of hormones (read my recent post). At Seasons of Farragut, our approach to treatment and therapy is fully supported in the scientific research literature, and we’re happy to share that research with you if you’d like to educate yourself.

The way estrogens are metabolized plays an equally pivotol role in hormone risk and effect. At Seasons of Farragut, our system of testing, evaluating, and monitoring is the only way to ensure that testosterone therapy for men is raising the testosterone and DHT levels instead of all being converted to estrogen. Hormone therapy is safe, but for it to work effectively, it must be properly evaluated, dosed, followed, and re-evaluated.

If you have questions or comments, please post them below and I’ll respond as soon as possible. What is your experience with testosterone therapy? How has your physician tested and re-evaluated your therapy program?

For more information about the Seasons approach to wellness or to schedule an appointment, please contact our office at (865) 675-WELL (9355).

High Estrogen Causes Low Testosterone in men

High Estrogen Causes Low Testosterone in men

Posted by: By John Douillard | October 2, 2012

While men are lining up to get their testosterone injections, few doctors are testing their estrogen levels.

Men with even slightly elevated estrogen levels double their risk of stroke, have increased risk of coronary artery disease (1), benign prostatic hypertrophy, and prostate cancer (2).
 
As it turns out, it is incomplete to test only for testosterone levels in men and then fill the empty tank with testosterone injections. There is a complex balancing act that takes place between the two hormones, testosterone and estrogen.

In a study in the Journal of American Medicine (JAMA), 501 men with chronic heart failure were measured for levels of estradiol (a type of estrogen). Men with the lowest estradiol levels were 317% more likely to die, while the men with the highest estradiol were 133% more likely to die within 3 years (3).

So, both high and low male estrogen levels present a problem.

Of course, men cannot make estrogens, and therefore must convert testosterone into estrogen. Low testosterone may result in low estrogen levels, but not always. High amounts of the enzyme aromatase, which converts testosterone to estrogen, can deplete testosterone levels while raising estrogen levels dangerously high.

We all wish restoring hormonal balance was as easy as reading a blood test and prescribing more of the hormone that tested low – but it is not so!

The risk of testosterone supplementation is that, the more testosterone increases, the higher the risk of converting it into estrogen – which may present an even greater risk than low testosterone.

In Ayurveda, herbs to support natural hormonal function have been prescribed for thousands of years. Most of these herbs were used to bring balance back to a certain biological system, or set of hormones, rather than just to address one hormone or another.

Ashwagandha (also spelled ashwaganda), for example, has been shown to support healthy semen and stress-affected cortisol levels (4). Goksura (also spelled gokshura), another classic Ayurvedic herb for male hormonal support, has been shown to support a healthy libido and male hormone balance (5).
Sources:

1. Int J Cardiol. 2005 May 11;101(1):105-10
2. J Clin Endocrinol Metab. 1993 Aug:77(2):375-81
3. JAMA. 2009 May 13;301(18):1892-901
4. Evid Based Complement Alternat Med. 2009 Sep 29. PMID: 19789214
5. J Dent. 2008 Nov;36(11):900-6. Epub 2008 Sep 25. PMID: 12127159