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

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.

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