Archive for October, 2013

When Our Kidneys Go South

October 26, 2013

Andrew Siegel MD Blog #125

Our kidneys are paired, bean-shaped, fist-sized organs that work diligently and silently behind the scenes 24/7/365, filtering our blood free of toxins and waste products so that we can maintain a healthy existence. When they are working well, they are often taken for granted.  The renal arteries bring blood to the kidneys, the kidneys do their magic, and the cleansed and purified blood is returned into the renal veins, with the liquid waste—urine—excreted into the ureters that drain into the urinary bladder.

If the kidneys stop working properly, excessive fluid and toxic wastes build up rapidly, resulting in death within a matter of days to weeks. Death by kidney failure is described as “euphoric” because of the very abnormal blood chemistries and electrolyte disturbances that occur…not that death is something to be “giddy” about, but kidney failure just happens to be an easier, more peaceful way to exit the planet than many others.

Because of their critical importance to our healthy existence, it behooves us to take great care of these prized possessions, which nature gave us in duplicate. This “spare tire” is capable of sustaining life in the event of trauma, cancer requiring surgical removal, donating a kidney or other issues resulting in loss of one kidney.

The kidneys are multifunctional, not only filtering our blood to remove waste products, but also responsible for regulating fluid, electrolyte, acid-base balance and blood pressure.  They are in charge of maintaining the proper fluid volume within our blood stream. They regulate the levels of our electrolytes including sodium, potassium, chloride, etc. They keep our blood pH (indicator of acidity) at a precise level to maintain optimal function. They are key players in the regulation of blood pressure.  Furthermore—and unbeknownst to many—they are responsible for the production of several important hormones: calcitrol (calcium regulation), erythropoietin (red blood cell production), and renin (blood pressure regulation).

Kidney disease is a very common cause of serious illness with a prevalence of more than 25 million Americans. Each year approximately 110,000 new patients start dialysis treatments in the USA.  Kidney disease is responsible for nearly 100,000 American deaths annually. When the kidneys fail (end stage renal disease), the options are peritoneal dialysis, hemodialysis, kidney transplantation, or death. Peritoneal dialysis uses the peritoneal membrane that lines the abdomen as a filter to clear wastes and extra fluid from the body. Hemodialysis involves being hooked up to a machine that mimics the function of the kidneys; it requires three sessions weekly that take about 3-4 hours per session.

The unfortunate thing about kidney disease is that it typically causes few symptoms until it is advanced; however, simple tests are capable of detecting it.   Symptoms of kidney disease are non-specific and may include the following: fatigue; decreased energy; poor appetite; difficulty concentrating; insomnia; swollen ankles and feet; nighttime muscle cramping; puffiness around one’s eyes; dry and itchy skin; and the need for frequent urination, particularly at night

A definitive sign of kidney disease is the presence of protein in the urine, which is easily detectable on a urinalysis. Additionally, uncontrolled high blood pressure is highly suggestive of kidney disease, as is an elevated serum creatinine, detectable by a simple blood test.  Early detection is critical as it can help prevent kidney disease from progressing to kidney failure. The bottom line is that three simple tests can detect kidney disease:  blood pressure; serum creatinine; urine albumin (protein).

Under normal circumstances, the kidneys filter the blood, removing waste products and excessive fluid, returning into circulation the body’s important chemicals and constituents. When the filtration system is not working properly, one’s system is not cleared of the bad (waste products), resulting in electrolyte disturbances and proteinuria, a condition in which what is good for the body (protein) ends up being filtered out into the urine.

Risk factors for kidney disease are the following: African-American race; diabetes; high blood pressure; and family history of kidney disease.  The two leading causes of chronic kidney disease are hypertension and diabetes, responsible for about two thirds of cases.

Urologists are the specialists who deal with surgical kidney issues whereas nephrologists are the specialists who deal with medical kidney tissues including hypertension and impaired kidney function. If kidney disease is diagnosed, one will typically be referred to a nephrologist for further evaluation and management.  Nephrologists will typically measure the serum creatinine, and do blood and urine tests to assess the glomerular filtration rate, a quantitative test of kidney function.  Often a renal ultrasound is performed and in some cases it is necessary to do a renal biopsy to find the root cause of the kidney dysfunction

Treatment for progressive kidney disease includes interventions such as blood pressure control, often with the use of ACE inhibitors and angiotensin receptor blockers, and control of diabetes.   Nutritional interventions include dietary protein restriction that may slow the progression of chronic kidney disease.   High-protein intake can worsen the proteinuria and result in the accumulation of various protein breakdown products as a result of decreasing kidney function, which can cause toxic effects.

A truly unfortunate fact of life is that many of us are not responsible caretakers of our kidneys (or any of our other “precious physical valuables”); many seem to take better care of their automobiles than they do of their own health.  How many of us change our oil every 3000 miles, bring our cars in for regular service and proudly maintain shiny exteriors while at the same time neglecting our own health by living a harmful lifestyle.  This includes a sedentary existence, excessive stress, insufficient sleep and substance abuse—of alcohol, tobacco and food—with diets high in red and processed meats, sodium and fat laden concoctions, sugar-sweetened drinks, etc., and low in fruits, vegetables, legumes, nuts, whole grains, and low-fat dairy.  The result: obesity, high blood pressure, and elevated cholesterol, which oftentimes leads to diabetes, heart attack, stroke, cancer, and premature death. Sadly, the diabetic situation in our nation—often referred to as “diabesity”—has become epidemic and, as mentioned, is one of the leading causes of chronic kidney disease in the United States.

So how do we care for our kidneys?  The prescription for healthy kidneys is to maintain a healthy lifestyle and, if you have been neglectful in this department, to do a lifestyle remake through the following: good eating habits; maintaining a healthy weight; engaging in exercise; obtaining adequate sleep; consuming alcohol in moderation; avoiding tobacco; and stress reduction.  Additionally, being proactive by seeing a physician on a regular basis for “scheduled maintenance” is of paramount importance in order to detect kidney disease—or any other malady—as early as possible, no matter what the ivory tower pundits say about the ineffectiveness of annual physicals.

Bottom Line: Kidney disease is a debilitating—oftentimes deadly—condition, the risk for which can be greatly reduced by adopting a healthy lifestyle. Never neglect your health, for it is your greatest wealth. 

Andrew Siegel, M.D.

Facebook Page: Our Greatest Wealth Is Health

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Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

Available on Amazon in Kindle edition

Author of: Male Pelvic Fitness: Optimizing Sexual and Urinary Health; in press and available in e-book and paperback formats in January 2014.

Blog subscription: A new blog is posted every week.   On the lower right margin you can enter your email address to subscribe and receive notifications of new posts in your inbox.  Please feel free to avail yourself of these educational materials and share them with your friends and family.

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Pancreatic Cancer

October 19, 2013

 Pancreatic Cancer 

Andrew Siegel, M.D.  Blog #124

The pancreas is a vitally important organ that serves dual roles: as an endocrine organ that produces hormones including insulin and glucagon and as an exocrine organ that secretes digestive enzymes that help the process of fat, protein and carbohydrate breakdown and digestion.  It is located deep within the upper abdomen and is divided into a head, body and tail.  The head lies within the concavity of the duodenum (the first part of the intestine).  The body runs behind the stomach and the tail touches the spleen.  The fact that it is such a deep-seated organ makes it virtually impossible to examine on a physical exam (unlike superficial organs such as the breasts or testicles) and pathological problems of the pancreas are identifiable only on sophisticated imaging studies of the abdomen.

Cancer of the pancreas is an incredibly lethal malignant tumor.  Approximately 45,000 Americans will be diagnosed with pancreatic cancer in 2013 and more than 38,000 will die from the disease, with a five-year survival rate of only about 5%.   The greatest challenge is that there are no early detection tests and, unfortunately, most patients who have early and localized disease have no recognizable symptoms such that most are not diagnosed until late in the disease—after the cancer has spread (metastasized).

In spite of the dismal prognosis, there has been recent progress in pancreatic cancer with surgery becoming safer and less invasive, the availability of new drug combinations that have been shown to improve survival, and advances in radiation that have resulted in less side effects. Significant strides forward have been made in the understanding of the genetics of pancreatic cancer, and unlocking the molecular basis of this horrific disease hopefully will translate into better treatment options.

The most common form of pancreatic cancer is invasive ductal adenocarcinoma.  The second most common type is a pancreatic neuroendocrine tumor; this is less aggressive than the ductal carcinomas, but still has a 10-year survival rate of only 45%. Some of the neuroendocrine tumors manufacture hormones such as insulin that produce clinical syndromes.

A combination of inherited and environmental factors contributes to the development of pancreatic cancer. The most common environmental risk factor is tobacco; smokers having a more than double the risk of pancreatic cancer as compared to non-smokers.  The good news is that smoking cessation will substantially reduce the risk.  Other risk factors are long-standing type II diabetes, increased body mass index, heavy alcohol consumption, and chronic pancreatitis.   A strong family history of pancreatic cancer puts an individual at significant risk.  BRCA2 gene mutations also increase the risk. Additionally, patients who have hereditary pancreatitis have a 60-fold increased risk; this is so substantial that some patients with this disease opt for a prophylactic removal of the pancreas.

Now for Molecular Biology 101:  Genes are inherited bits of information that code for proteins.  When genes become mutated, the proteins that the genes code for become dysfunctional.  One can think of genes as the written recipe for a particular meal and their product as the meal itself—when the recipe is changed (mutated) the resultant meal is defective.  In the case of the human body, the altered genes code for altered proteins that damage cellular function and replication in such a way as to alter the normal orderly process of cellular reproduction, resulting in unrestrained, disorderly cell replication, aka cancer.  Scientists have identified numerous genetic mutations responsible for cancers and they are named with bizarre combinations of letters and numbers—do not be daunted by their names as follow.

So, on a molecular level, cancer is caused by inherited and acquired mutations in genes. The sequencing of the genetic material of the pancreatic ductal adenocarcinomas has demonstrated that four specific genes are each altered in more than 50% of these cancers.  KRAS, an oncogene (a gene with the potential to cause cancer), becomes activated in 95% of pancreatic cancers—the protein coded for by this gene plays an important role in cell signaling, a complex system of communication that governs basic cellular activities and coordinates cell actions. The p16/CDKN2A gene, a tumor suppressor gene (a gene that protects a cell from cancer that, when mutated, would allow the cell to progress to cancer), becomes inactivated in 95% of pancreatic cancers.  The protein product of this gene plays an important role in the regulation of the cell cycle and its loss promotes unrestricted cell growth. The TP53 tumor suppressor gene is inactivated in 75% of pancreatic cancers. Loss of its function through mutation promotes pancreatic cancer through the loss of a number of critical cell functions.  The SMAD4 tumor suppressor gene has a protein product in the cell signaling pathway that when interfered with is associated with a very poor prognosis and widely metastatic disease. In addition to these 4 major genes, there are numerous other genes that are mutated in pancreatic cancer at lower frequencies.

Unfortunately, most pancreatic cancers do not cause specific symptoms and are not diagnosed in a timely manner. Typical non-specific symptoms include upper abdominal pain radiating to the back; unexplained weight loss; nausea; jaundice; clay colored stools; and in a small percentage of people, migratory thrombophlebitis (multiple blood clots appearing in a variety of veins). At times, it can present with diabetes, symptoms of pancreatitis, or depression. Diagnosis is predicated upon imaging tests including CT, MRI, and endoscopic ultrasound.  Standard cancer staging is stage I through stage IV, with stages I an II being localized, III being locally advanced, and IV being metastatic. In the absence of metastatic disease, the ability to surgically remove the cancer is predicated on the relationship of the tumor to the adjacent major blood vessels.

Pancreatic cancer is a complex disease and is best treated by a multidisciplinary team including a surgeon, medical oncologist, and radiation oncologist. In general, patients with stage I/II disease should undergo surgery followed by adjuvant therapy (chemotherapy and/or radiation).  Patients with stage III locally advanced disease should be treated with chemotherapy and/or chemo-radiation.  Patients with stage IV and good performance status may receive systemic therapy and those with poor health should be given supportive therapy.

The best chance of long-term survival of a patient with localized pancreatic cancer is surgical removal. However, because pancreatic cancer is often beyond the confines of the pancreas at presentation and due to the potentially negative impact of surgery on quality of life as well as the low chance of long-term survival, surgery is often non-curative. Certainly, the risk of local and systemic recurrence after surgery is very high.

Bottom Line: Pancreatic cancer is a wickedly lethal cancer.  In terms of minimizing one’s risk, avoid tobacco, obesity and heavy alcohol consumption. So, don’t smoke, eat a healthy diet, maintain a good weight, and be moderate with alcohol.  Despite the dismal prognosis, there have been recent advances on many fronts, particularly in terms of the genetics of the cancer, wherein the key to treating this miserable cancer most likely lies.

“Sometimes life hits you in the head with a brick. Don’t lose faith. I’m convinced that the only thing that kept me going was that I loved what I did. You’ve got to find what you love. And that is as true for your work as it is for your lovers. Your work is going to fill a large part of your life, and the only way to be truly satisfied is to do what you believe is great work. And the only way to do great work is to love what you do. If you haven’t found it yet, keep looking. Don’t settle. As with all matters of the heart, you’ll know when you find it. And, like any great relationship, it just gets better and better as the years roll on. So keep looking until you find it. Don’t settle.” 

Steve Jobs, who died of neuroendocrine cancer of the pancreas

Reference: Recent Progress in Pancreatic Cancer, Wolfgang, Herman, Laheru, Klein, Erdek, Fishman and Hruban

CA CANCER J CLIN 2013;63:318-348 September/October 2013

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

Available on Amazon in Kindle edition

Author of: Male Pelvic Fitness: Optimizing Sexual and Urinary Health; in press and available in e-book and paperback formats in January 2014.

Blog subscription: A new blog is posted every week.   On the lower right margin you can enter your email address to subscribe and receive notifications of new posts in your inbox.  Please feel free to avail yourself of these educational materials and share them with your friends and family.

Sugar Substitutes

October 12, 2013

Andrew Siegel, M.D.  Blog #123

For many of us who have a “sweet tooth,” sweet tastes are delightful and we actively seek them out in accordance with our evolutionary drives. The first bite of that sugary Cinnabon is pure bliss. The brain’s reward pathway squirts out the neurotransmitter dopamine and we get a jolt of near ecstasy—the mind-body connection in action. Hopefully, within a matter of minutes, leptin—our satiety hormone that regulates appetite—will counteract the dopamine, making subsequent bites less rewarding and stopping us from gorging.

Sugar is ubiquitous in our diets, not just in the places you expect it, but also “stealth” sugar in breads, crackers, pretzels, chips, salad dressings, sauces, etc.  If you read food labels you might be shocked about the presence of sugar in many unexpected destinations. Sugar (sucrose) is clearly unhealthy and processing and refinement “advances” have permitted its consumption in unreasonable, immoderate and unwarranted amounts, contributing to America’s expanding waistlines and derrières.  So what’s the skinny on sugar substitutes?  Are they helpful in terms of losing weight? Are they better for our dental health than sugar? Are they helpful for diabetics?  Do they have risks?

Sugar substitutes duplicate the sweetness of sugar, but without the caloric (energy) load. Natural sugar substitutes originate from nature and include the following: agave nectar; date sugar; fruit sugar concentrate; honey; maple syrup; and molasses. Synthetic substitutes are concocted by chemists in a lab and are known as artificial sweeteners.   There are 6 “super-sweet” high-intensity substitutes approved for use by the FDA. The super-sweet sugar substitutes are the following: stevia (Truvia); aspartame (NutraSweet; Equal); sucralose; neotame (manufactured by the NutraSweet company); acesulfame (Nutrinova); and saccharin (Sweet’N Low).  Aspartame is the most popular artificial sweetener in United States and sucralose is not far behind.

Sugar substitutes are widely prevalent in our food supply—in processed foods, baked goods, dietary foods, dietary soft drink beverages, powdered drink mixes, canned foods, jams and jellies, dairy products, toothpastes, chewing gums, sugar-free desserts such as ice cream, yogurts, and puddings, and in vitamins and medicines including cough drops.

In terms of weight loss, sugar substitutes can be an effective and attractive means of consuming less calories since the substitutes are non-nutritive and have virtually no calories, while retaining the sweet taste of food substances.    This is in contrast to sucrose that has 4 calories per gram.  Additionally, sugar substitutes are dental friendly, as they—unlike sucrose—are not fermented by the bacterial flora that lives on the teeth and thus do not produce acidy waste products that cause tooth decay.   Sugar substitutes can be effective for diabetics who have trouble regulating blood glucose levels since sugar substitutes do not elevate blood sugar levels the way sucrose does.

Sugar substitutes, while providing a sweeter taste than sugar, contain few or no calories, which is why using them has been thought to aid weight management. Our food-reward system plays a critical role in regulating eating behavior and controlling the number of calories consumed. When the tongue perceives sweetness, the brain expects a glucose infusion, which increases levels of dopamine and stimulates reward centers in the brain.  Without the energy kick provided by actual sucrose, sugar substitutes cannot fool our brains into feeling satisfied. Sugar imposters yield no such reward and cravings can persist and cause more rebound consumption than eating sugar in the first place.

The Food and Drug Administration (FDA) is the governmental body responsible for the regulation of sugar substitutes. Over the years, health concerns have been raised with respect to the use of substitutes and they have been the subjects of intense scrutiny. The general consensus is that there is no sound evidence that any of the substitutes approved for use in the United States cause serious health problems and that they are generally safe in limited quantities. However, there is ongoing and unsettled controversy regarding whether substitute usage is problematic in terms of health risks. We remain muddled in a debate about the health implications of substitutes and whether they might be linked to obesity, cancer, Alzheimer’s disease, ADD, autism, etc.  Search on the Internet and you will learn about the “conspiracy theories” concerning artificial sweeteners.

Saccharin (Sweet’N Low) was the first artificial sweetener, originally synthesized in 1879.  It is 400 times as sweet as sugar.  Although saccharin was previously considered hazardous when it was discovered to cause cancer in rats and carried a warning label, the warning label was subsequently repealed and saccharin has been removed from the hazardous list.  Cancer in laboratory rats has not been found to necessarily correlate with cancer in humans.

Aspartame (Equal; NutraSweet) was discovered serendipitously in 1965 when a scientist at Searle was working on a drug for peptic ulcer disease and spilled some of the chemical on his hand. He accidentally noted its sweet taste, and the rest is history.  It is 200 times as sweet as sugar and derives from 2 amino acids, aspartic acid and phenylalanine.  It is undesirable as a baking sweetener because, when heated, it breaks back down into its constituent amino acids.  It has sometimes been linked to headaches.

Stevia is a natural sweetener that is derived from the stevia plant; its leaves have been used as a sweetener in South America for centuries. It is 300 times as sweet as sucrose.  It was discovered by botanist Petrus Jacobus Stevus, which is why it was named Stevia.

Sucralose (Splenda) is a chemically modified form of sugar that was discovered in 1976 and is about 600 times as sweet as sucrose. It is stable when heated, so is appropriate for use in cooked foods.   Most of consumed sucralose passes out of the body unchanged, with only a small amount getting absorbed.

Neotame (from NutraSweet) is chemically similar to aspartame, but is significantly sweeter, being the sweetest of the group.  It is the only artificial sweetener deemed safe by the Center for Science in the Public Interest (CSPI).

Acesulfame is calorie-free and 200 times as sweet as sucrose; it is formed by adding potassium to aceto-acetic acid.  It is not metabolized by the body, but is excreted unchanged.  Because it is heat stable, it can be used in cooking and baking.

Sugar alcohols are carbohydrates that occur naturally in certain fruits and vegetables, but can also be synthesized.   They do contain calories but they are lower in calories than sucrose. They are used in many processed foods and household items including chocolate, candy, frozen desserts, chewing gum, toothpaste, mouthwash, baked goods and fruit spreads.

Bottom Line: The take-away message is “everything in moderation.” Whether you indulge in items sweetened with sugar derived from sugar beet or sugar cane, sugar alcohols, or any of the natural or artificial sweeteners, consumption should always be kept in check.

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

Available on Amazon in Kindle edition

Author of: Male Pelvic Fitness: Optimizing Sexual and Urinary Health, in press. Will be available in e-book and paperback formats in later 2013.

Blog subscription: A new blog is posted every week.   On the lower right margin you can enter your email address to subscribe to the blog and receive notifications of new posts in your inbox.  Please avail yourself of these educational materials and share them with your friends and family.

Testosterone: Not Just For Men; Estrogen: Not Just For Women

October 5, 2013

Andrew Siegel MD Blog # 122

What’s going on with the unrelenting direct–to-consumer television advertising for medications?  On television and radio we are bombarded with ads for drugs for the “ABC” diseases—ED (erectile dysfunction), OAB (overactive bladder), low T (testosterone).  What’s all this hubbub about T (testosterone) anyway?  Why is T suddenly so special, so hot and trendy, the hormone de jour, the “new” Viagra?  Is this for real or mere media hype?

Medicine is truly in its “infancy” with respect to its understanding of the male and female sex hormones, testosterone (T) and estrogen (E), respectively. Not too long ago it was dogma that T was solely the male hormone and that E was solely the female hormone.  As is often the case in science, “dogma” turns to “dog crap” with time, research, and progressive understanding.

Dr. Joel Finkelstein, in the September 13, 2013 New England Journal of Medicine, disrupted the endocrine status quo and provided the scientific basis for the major importance of both T and E for male health and wellness (and there is little doubt that both E and T are also equally crucial for female health and wellness). His study clearly demonstrated that muscle size and strength are controlled by T; fat accumulation is primarily regulated by E; and sexual function is determined by both T and E.

Some basics about T:

In the life of the male embryo, T is first produced during the mid-first trimester, and this hormonal surge causes the male external genitalia (penis and scrotum) and internal genitalia (prostate, seminal vesicles, etc.) to develop. In the absence of T, the fetus becomes a female, making the female gender the “default” sex. Dihydrotestosterone (DHT) is the activated form of T required by the fetus to initiate the development of male physical characteristics. In the absence of DHT, male genitalia do not develop.  DHT is far more potent than T and is the hormone that also gives rise—much later in life—to male pattern baldness and the condition of benign prostate enlargement.

T is produced mostly in the testes, although the adrenal glands also manufacture a small amount. T has a critical role in male development and physical characteristics. It promotes tissue growth via protein synthesis, having “anabolic” effects including building of muscle mass, bone mass and strength, and “androgenic” (masculinizing) effects at the time of puberty.  With the T surge at puberty many changes occur: penis enlargement; development of an interest in sex; increased frequency of erections; pubic, axillary, facial, chest and leg hair; decrease in body fat and increase in muscle and bone mass, growth and strength; deepened voice and prominence of the Adam’s apple; occurrence of fertility; and bone and cartilage changes including growth of jaw, brow, chin, nose and ears and transition from “cute” baby face to “angular” adult face.  Throughout adulthood, T helps maintain libido, masculinity, sexuality, and youthful vigor and vitality. Additionally, T contributes to mood, red blood cell count, energy, and general “mojo.

Thanks to the advertising of Big Pharma, patients now come to the office requesting—if not demanding—to know what their T levels are. Prescriptions for T have increased exponentially over the last five years, creating a $2 billion industry with numerous pharmaceutical companies competing for a piece of the lucrative T pie, as the cost of the product is minimal and the markup is prodigious.  Little did Butenandt and Hanisch—who earned the Nobel Prize in chemistry for their synthesis of testosterone from cholesterol way back in 1939—know of what their discovery would lead to 70 years later!

Who Knew? Humans manufacture T using cholesterol as a precursor, so don’t be under the delusion that all cholesterol is bad. However, don’t get carried away consuming cholesterol-laden foods reasoning that the Big Mac with cheese will raise your T.

T can bind to specialized receptors that are present in many cells in the body and exert numerous anabolic and androgenic effects; alternatively, T can be converted to 5-DHT  (the active form of T) or can be converted to estradiol—a form of E—by the chemical process of aromatization. More than 80% of E in men is derived from T as a source. When levels of T are low, there is a decline in E levels. E deficiency is important in terms of osteopenia (bone thinning) in both men and women.

Dr. Finkelstein’s study was really a more sophisticated and quantitative take on the original study by organic chemist Professor Fred Koch at the University of Chicago in 1927, this time using humans instead of animals, and quantitating the effect of the T replacement as opposed to a qualitative assessment. Professor Koch used capons—roosters castrated surgically (having their testes removed) at a young age.  He then injected them with a substance obtained from bull testicles—readily available from the Chicago stockyards—which essentially was T.   After injecting the capons with this extraction, the capons crowed like roosters, a feat that capons are incapable of.  When the study was repeated in castrated pigs and rats, the substance was found to re-masculinize them as well.  Unlike Professor Koch, who used surgically castrated animals, Dr. Finkelstein used humans who were temporarily “castrated” via a reversible medication.

In Dr. Finkelstein’s study, as reported in the NEJM, there were 2 groupings of 5 populations of men. Both groupings had their T production blocked chemically. One population was given no replacement T, another 1.25 grams T daily, another 2.5 grams T daily, another 5 grams T daily, and the last group 10 grams T daily. The average serum T and E levels of each population were the following: no testosterone replacement: 44/3.6; 1.25 grams: 191/7.9; 2.5 grams: 337/11.9; 5 grams: 470/18.2; 10 grams 805/33. The second grouping of 5 populations had their E blocked as well.  Testing was done to see the effects of T and E levels on lean mass, muscle size and strength, fat mass, and sexual function.

By looking at the aforementioned numbers, one can see a direct relationship between T dose and serum level of both T and E.  The higher the T dose, the greater is the serum T and E.  The study concluded that lean mass, muscle size and strength were T dose-dependent, meaning the higher the T, the more the lean mass, muscle size and strength.  Additionally, fat mass was seen to be E dose-dependent and sexual function was both T and E responsive.

Dr. Finkelstein concluded that E deficiency in men is a manifestation of severe T deficiency and is remediable by T replacement. Fat accumulation seems to occur with a mild T deficiency (T measurements in the 300-350 range); muscle mass and muscle strength are preserved until a more marked T deficiency (T <200) occurs.   E was shown to have a fundamentally important role in the regulation of body fat and sexual function and evidence from previous studies demonstrated a crucial role for E in bone metabolism. Therefore, low T is not just about low T, but is also about E deficiency, which is responsible for some of the key consequences of T deficiency. Measuring levels of E are helpful in assessing sexual dysfunction, bone loss, and fat accumulation in men with low T.

The amount of T made is regulated by the hypothalamus-pituitary-testicular axis, which acts like a thermostat to regulate the levels of T.  Healthy men produce 6-8 mg testosterone daily, in a rhythmic pattern with a peak in the early morning and a lag in the later afternoon. T levels can be low based upon testicular problems or hypothalamus/pituitary problems, although the problem most commonly is due to the aging testicle’s inability to manufacture sufficient levels of T.  T levels gradually decline—approximately a 1% decline each year after age 30—sometimes giving rise to symptoms.  These symptoms may include the following: fatigue; irritability; decreased cognitive abilities; depression; decreased libido; ED; ejaculatory dysfunction; decreased energy and sense of well-being; loss of muscle and bone mass; increased body fat; and abnormal lipid profile. A simple way to think about the effect of low T is that it accelerates the aging process.

T is commonly prescribed for T deficiency when it becomes symptomatic. There are many means of testosterone replacement therapy (TRT).  Oral replacement is not used because of erratic absorption and liver toxicity. Injections are not the first-line means of TRT because of wide fluctuations in testosterone levels and injection site reactions. There are a number of testosterone gel formulations that are commonly used. There are also skin patches, pellets that are injected into the fatty tissue of the buttocks, and a formulation that is placed in the inner cheek or gum. Currently in the works is a long-acting injection.

Men on replacement T need to be followed carefully to ensure that the TRT is effective, adverse effects are minimal, and blood levels are in-range. Periodic digital rectal exams are important to check the prostate for enlargement and irregularities, and, in addition to T levels, other blood tests are obtained including a blood count and PSA (Prostate Specific Antigen).  Potential complications of TRT include acne and oily skin, increased hematocrit (thicker, richer blood), worsening of sleep apnea, hair loss, and suppression of fertility.

Bottom Line: T and E levels are of vital importance to men (as well as women), greatly impacting physical development, sexuality, mood, energy levels, etc. So while T advertisements may be annoying and confusing, it is wise nonetheless to assess and monitor T levels, particularly if one is experiencing any of the myriad of symptoms associated with low T.

Reference: “Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men by Joel Finkelstein, M.D., et al:  ”The New England Journal of Medicine (September 12, 2013)

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

Available on Amazon in Kindle edition

Author of: Male Pelvic Fitness: Optimizing Sexual and Urinary Health;  book is in press and will be available in e-book and paperback formats in November 2013.

Blog subscription: A new blog is posted every week.   On the lower right margin you can enter your email address to subscribe to the blog and receive notifications of new posts in your inbox.  Please feel free to avail yourself of these educational materials and share them with your friends and family.