Posts Tagged ‘androgenic’

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:

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.


Testosterone Replacement Therapy Vs. Performance Enhancing Drugs: A Whole Different Ball Game

March 3, 2012


Recently, an appeals court ruled that Alberto Contador, the three-time winner of the Tour de France, was guilty of “doping,” the use of anabolic steroids to gain an athletic advantage.  This was an additional blow to a sport that has been repeatedly tarnished by doping scandals involving the most elite cyclists in the world.  The court ordered Contador to be stripped of his victory in the 2010 Tour de France as well as twelve subsequent victories.

Doping is by no means unique to cycling, as professional athletes in many different sports—weightlifting, bodybuilding, baseball, football, martial arts, etc.—have tested positive for performance-enhancing substances in the last few years. Doping is banned by all of the major sporting governing bodies.  Not limited to professional athletes, many amateur athletes and bodybuilders have used anabolic steroids to try to improve their game and gain a competitive edge.

Many years before Barry Bonds became involved with doping, it was recognized that the male sex hormone testosterone played a major role in muscle mass and strength.  In the early 1950’s, Soviet Union and other Eastern Bloc Olympic weightlifting teams made use of such androgens, isolated from the testicles of animals, in order to enhance their performance in Olympic events.  Over the subsequent 60 years, the use of synthetic anabolic steroids increased substantially.  Anabolic steroids mimic the effects of testosterone, increasing protein synthesis in cells, causing muscle growth and an increase in lean body mass that results in a gain in muscle strength and thus, a competitive edge.

Anabolic steroids have two different types of effects—anabolic and androgenic.  Anabolic refers to the promotion of cell growth and includes the following effects: increased appetite, increased muscle and bone growth and increased production of red blood cells by the bone marrow, all of which result in increased strength. Androgenic refers to the development of masculine characteristics including oil gland production, libido and sexuality, deep voice and male-pattern hair growth.  Many effects and side effects of anabolic steroids are dose-dependent, in other words, in proportion to the doses used.

Along with the escalating use of synthetic androgens in athletes, there has been a parallel increasing awareness of testosterone deficiency and its treatment, particularly over the last couple of years.  Since testosterone (T) and performance enhancing drugs (PEDs) are both classified as anabolic steroids and each increases muscle mass and strength, they are often incorrectly thought to be one and the same.

T and PEDs differ in structure, biochemistry and use.  The medical use of T is for men with testosterone deficiency, usually manifested by fatigue, diminished sex drive and a constellation of other symptoms.  The goal of treatment is to improve symptoms by getting the testosterone into a normal range.  There are a variety of means of testosterone replacement including gels, creams, trans-dermal patches, pellets and injections.  All of these formulations are FDA approved and provide testosterone that is identical to that of the testosterone that is present in our bodies under normal circumstances.  Testosterone levels are checked periodically to ensure that the testosterone is in the normal range.

PEDs are most often manufactured clandestinely at small labs to avoid FDA scrutiny; they are sometimes obtained through veterinarians, pharmacists or physicians, and are often procured on the black market.  They are intended solely to build muscle mass, strength and improve athletic performance, so their use is beyond the domain of standard medical practice.  PEDs favor anabolic (muscle building) over androgenic (pertaining to the development of male characteristics) effects.

The vast majority of the time, PEDs are provided illicitly by a trainer without special expertise in this area.  The goal is a super-high testosterone level, often ten times or more than normal levels.  Dopers often use the equivalent of 1000 mg or greater of T per week.  PEDs are not the chemical equivalent of T and there is no medical monitoring of users.   Popular PEDs include nandrolone and stanozolol, which were FDA approved years ago, but now have no medical indications.  “Designer” PEDs are often concocted by modifying T; their advantage is that monitoring organizations lack the wherewithal to detect them because of their unique chemical formulations.   The two common patterns of PED usage are stacking and cycling.  Stacking is using two or more PEDs simultaneously whereas cycling is an on—off schedule of use.

PEDs have no medical indications and a risk profile that includes the following: elevated blood pressure; abnormal cholesterol and lipid profiles; altered blood glucose; cardiac muscle enlargement; mood disorders including aggression and violence (“steroid rage”); increased rates of homicide and suicide; liver dysfunction; spontaneous tendon rupture; and endocrine issues including severe and irreversible testicular dysfunction. This contrasts with the use of T, which provides medical benefits and a relatively benign safety profile.  Adverse effects of testosterone may include the following: acne; male breast growth; high red blood cell counts; testicular atrophy; prostate enlargement; decreased sperm production; ankle swelling.

In summary, testosterone deficiency is a genuine problem that can cause a myriad of quality of life as well as quantity of life issues.  When deficiency symptoms are apparent and blood testing confirms the deficiency, testosterone replacement with careful physician monitoring is capable of improving or resolving these issues.  On the other hand, the use of performance enhancing drugs for purposes of achieving anabolic benefits and thus conferring a sports advantage or edge is a very risky business and is not recommended.

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food

Now available on Amazon Kindle

To view my ten-minute video on testosterone deficiency, go to the following link:

Credit to Dr. Abraham Morgentaler, Harvard Urologist and author of a good little book entitled Testosterone For Life, for providing much of the factual info for this blog.