Testosterone

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A Critical Hormone for Men and Women
by Jeffry S. Life, M.D. Ph.D.

Men and Testosterone

Testosterone is a hormone that has been intimately tied throughout time to a man’s virility and sexuality. It is the major steroid hormone of the testicles. However, testosterone is much more than just a sex hormone. With testosterone receptor sites in the brain and heart, and in fact throughout the entire body, testosterone plays a critical role in maintaining a healthy immune system, insuring proper cardiac output, and regulating mood and cognition, controlling blood sugars, regulating healthy cholesterol levels, controlling blood pressure, preventing heart attacks, and even reducing the risk for prostate cancer (Steiner & Raghow. World J Urol. 2003 May; 21(1): 235-41).

Testosterone production in the male begins when the pituitary gland, located deep inside the brain, secretes lutenizing hormone (LH), which in turn, stimulates the Leydig cells in the testicles to produce testosterone. It is estimated that men are born with 700 million Leydig cells and they begin losing 6 million each year after their twentieth birthday. In spite of these losses, studies have found that testosterone levels peak in men at about age 30. After this, testosterone levels begin declining an average of 2% a year.

Declines in testosterone production are due to several factors besides decreases in Leydig cell numbers. Diminished testicular response to pituitary signals that initiate testosterone production and a poor coordination of the release of these pituitary signals play the most important role in testosterone decline. Another reason for testosterone declines is because most of the testosterone that is secreted into the bloodstream attaches to a protein called sex hormone binding globulin (SHBG). Testosterone that is not bound to SHBG is called free testosterone and it is only in this form that testosterone can exert its powerful effects on all of the body’s cells. An increase of SHBG occurs in many men as they age, especially if they are obese. As SHBG levels increase, the amount of testosterone that is available to act on cells diminishes even further.

These age-related declines in total and free testosterone levels in men are associated with easily identifiable, classic signs and symptoms called andropause. Andropause can cause significant problems that include negative attitudes about life in general, a loss of focus and drive, a questioning of one’s values and accomplishments, loss of goals and directions in life, decreased libido, depression, and even cognitive impairments. Declines in sex drive, frequency of sexual thoughts, and erectile dysfunction are additional problems that are directly related to falling levels of free testosterone and these can have a profoundly negative impact on the male psyche and relationships.

Physical changes also occur and are characterized by thinning hair, a decline in lean muscle tissue, and an increase in body fat (particularly abdominal and pectoral fat). As muscle mass declines, strength declines and risk for falls and fractures increases. A decrease in bone mass is another major problem associated with declining levels of testosterone. Osteoporosis is not just a woman’s disease—up to 30% of men aged 60 and over become osteoporotic. One out of every six men will fracture a hip at some point in their life as a result of decreased bone density. Declines in stamina and exertional performance are also a direct result of inadequate levels of testosterone as are declines in cognitive skills, concentration, and memory.

Testosterone can be converted, by enzymes, into other hormones. One of these enzymes is called 5-alpha reductase. It is found in especially high concentrations in the prostate gland where it converts testosterone into dihydrotestosterone (DHT). Another enzyme, called aromatase, is found in skin, brain, fat, and bone. Aromatase converts testosterone into estradiol, the human form of estrogen. As men age, more of the testosterone they produce is converted into estradiol. When there is too much estradiol it competes with testosterone and negative consequences can develop. These include prostate cancer, heart disease, and stroke. Abnormal increases of estradiol are caused by excess amounts of aromatase enzyme, impaired liver function (often caused by excessive alcohol or certain drug interactions), obesity (which increases aromatase enzyme), and zinc deficiency (zinc is a natural aromatase enzyme inhibitor). In addition to declining levels of testosterone and increasing levels of estradiol, growth hormone and DHEA levels fall during andropause. As these levels decline, profound changes occur with growth and metabolism that affect men both physically and mentally and add to their testosterone deficiency problems.

Today the signs and symptoms of andropause should not be accepted as an inevitable consequence of the aging process. By utilizing bio-identical hormones and accurate monitoring techniques, replacement therapy is now possible (Katznelson L. Neuroendocrine Center Bulletin. Winter 2000; vol 6, Issue 2). Hormone optimization programs offered by Age Management Medicine physicians have rapidly moved into the forefront of preventive medical care and have greatly contributed to the enhancement of quality of life as men and women age.


Women and Testosterone

Testosterone may be well known as a hormone that has been tied to a man’s virility and sexuality, but few realize that it is also a very important hormone for women. As women age, estradiol and progestin levels begin falling as they enter menopause. Testosterone (produced in the ovaries and adrenal glands) and growth hormone levels also decline during this time. As the levels of these key hormones diminish, profound degenerative changes begin occurring with growth and metabolism that affect the breasts, vagina, bones, blood vessels, gastrointestinal tract, urinary tract, cardiovascular system, skin, brain, and energy levels (Davis et al. Maturitas. 1995; 21: 227-236).

We now know testosterone is critically important for a woman’s libido, sexual responsiveness, mood, and generalized feelings of well-being. Women, like men, also need adequate testosterone levels for peak mental acuity and the maintenance of healthy bone density and muscle tissue. Maintaining bone density is absolutely critical for women. Unsupplemented women have a 50% chance of experiencing a pathological fracture of their hip or vertebra at some point in their life. This is a frightening statistic because a hip fracture carries with it a 25% six-month mortality rate, and a 50% two-year mortality. Testosterone also plays a key role in the prevention of the accumulation of unwanted body fat, heart disease, and loss of cognitive function in women. Testosterone replacement therapy is now recommended for women with suboptimal blood levels. Like men, women must have all of their hormones at optimal levels and be followed with laboratory studies on a regular basis.

Testosterone Measurement

Clinical signs and symptoms are important indicators that an individual needs testosterone replacement therapy. However, objective laboratory measures must be obtained to properly institute and manage therapy. These lab measurements are also necessary to rule out or address any accompanying medical problems. To adequately measure testosterone levels, both total and free testosterone studies should be obtained. For males, a level of 260-1,000 ng/dL is given as the normal laboratory range for men aged 20-70. For females, this range is 15-70 ng/dL. Free testosterone levels average approximately 2% of the total.

Obviously, the fifty-year span from age 20 through 70 with the same normal range is not a useful guide to determine optimal testosterone levels for older individuals. A decline of 70% from the more youthful levels to the levels typically seen after age 40 will produce most, if not all, of the problems associated with low testosterone levels described above. Yet a level that falls in this broad range is declared "within the normal range" by today’s laboratory standards. A more accurate approach would be to use the 60th percentile values of a 44-year-old man or woman as an optimal range. This is 700-900 ng/dL of total testosterone for men and 50-70 ng/dL for women. It should be stressed that these levels represent the upper 25th percentile for a 70-year-old man or woman, so we are talking about optimizing normal hormone levels, not pushing levels into supraphysiological ranges (Dotson A. “Methods of Testosterone Supplementation for Men and Women”. Cenegenics Testosterone Medical Information Gateway. 2004; www.testosterone-articles.com).

The decision to institute testosterone replacement therapy should always be made in the context of other hormonal and laboratory studies. Prostate Specific Antigen (PSA) measurement and a digital rectal exam of all men must accompany testosterone blood levels at the time of the initial evaluation to screen for any pre-existing prostate disease and need to be followed at regular intervals. Other studies, such as thyroid hormones, growth hormone (hGH), leutinizing hormone (LH), dehydroepiandrosterone (DHEA), estradiol, progesterone, blood count, lipid profiles, and other laboratory and metabolic markers (such as body composition and bone density) all play important roles in maximizing a testosterone replacement program in both men and women. Once therapy is initiated, follow up hormone levels and other markers must be monitored over time at regularly scheduled intervals in order to maximize success and assure safety.



Testosterone Therapy

Before any testosterone supplementation program is started, all key hormone levels must be evaluated and therapy should be based on the augmentation of all hormones with suboptimal levels. After the decision has been made to optimize hormone levels, the next step is to decide on the best means of delivery. The best method of testosterone delivery varies from individual to individual, and is dependent upon several factors. Optimally, a testosterone delivery method should be clinically effective in correcting the signs and symptoms of testosterone decline and produce predictable and reproducible optimal levels of testosterone without increasing levels of other potentially harmful hormones. The fact that testosterone can be converted to estradiol by an aromatase enzyme is a serious concern for men because, in some, any intervention that raises testosterone levels will raise estradiol levels. With proper laboratory follow up, this is easily identified and corrected. The raising of serum levels of dihydrotestosterone (DHT) can also be clinically important in men. DHT, as discussed earlier, is the agent associated with male-pattern baldness and prostate enlargement. These do not become a problem if DHT levels are closely monitored and controlled.

Testosterone is available directly in oral, injectable, topical, and implantable formulations, and may also be supplemented indirectly by the administration of human chorionic gonadotropin (hCG). Oral testosterone and androgens such as fluoxymesterone, methyltestosterone, oxandrolone, or danazol are available for clinical use, but are not appropriate for long-term testosterone replacement therapy. Their use is specific for certain clinical disorders and must be used with great caution as they can cause liver damage, and even malignant liver tumors. They also dramatically raise serum LDL cholesterol, decrease HDL cholesterol, and have been associated with increased risk of heart attacks and stroke. Testosterone undecanoate is an oral testosterone compound that is taken up by the lymph ducts in the intestines and able to bypass the liver, thus minimizing side effects. However, it has a very short half-life (or length of effect), has low and frequently variable bioavailability from dose to dose, and is not approved by the FDA. At present, there are no recommended oral testosterone formulations in the United States for men.

One oral preparation that is useful for helping normalize testosterone levels in women is DHEA. Men do not convert DHEA into meaningful levels of testosterone, but many women do. A good first step in improving testosterone levels in women is to optimize DHEA levels and re-check testosterone levels after 5-7 weeks. If testosterone levels have not increased, testosterone therapy can be started at that time. Testosterone pellets have also been developed that can provide augmented serum testosterone levels up to six months. Pellets, however, require a surgical procedure for implantation and removal, and once they are placed they do not allow for altering dosages based on an individual's testosterone blood levels.

Testosterone cypionate for use in men comes in a low cost, easily self-injectable form. It is not associated with the undesirable effects of oral androgen administration and is available in a formulation that provides a long biological effect time. A dosage interval of once a week works very well. Delivering testosterone in this way has a 100% success rate in providing every cell with usable hormone. It is also easy to precisely control the dosage of testosterone and manage the results by following levels over time at regular intervals. This is the supplementation of choice for men whose testicles are no longer able to produce testosterone in adequate amounts.

Testosterone formulations are also available for topical placement, which allows testosterone to be absorbed through the skin. Testosterone cream is the therapy of choice for raising testosterone levels in women. There is only limited application for this delivery system for men because this method can produce elevated serum levels of DHT. Testosterone that is absorbed through the skin is exposed to high levels of 5-alpha-reductase, which converts much of the testosterone to DHT, thereby, increasing exposure of the prostate and hair follicles to excessive amounts of this hormone. The very small amounts of testosterone cream required to raise testosterone levels in women have not been associated with any problems. Testosterone patches (available by prescription for men) have been associated with problems including, inability to achieve adequate serum testosterone levels and local reactions from the adhesive. Mild to moderate reactions occur in as many as 50% of men using some formulations of the skin patch, which have also been shown in studies to produce a 30-50% failure rate in clinical applications.

An interesting new way of increasing testosterone levels in men with deficiencies has been achieved through the use of human chorionic gonadotropin (hCG). hCG is a hormone that is able to bind to lutenizing hormone (LH) receptors with the same binding affinity as LH. Administration of hCG can, therefore, mimic the same effect as LH and increase testosterone production by stimulating Leydig cells in the testicles. In men who still have a functional LH/testosterone control loop, testosterone production with hCG is the most physiologic method, and is not associated with the testicular atrophy that can occasionally happen with direct testosterone administration. The preferred method of administering hCG is to give subcutaneous doses with a tiny insulin syringe twice weekly. While direct injection of testosterone has a 100% success rate, there is an approximately 10-15% failure rate seen in individuals using hCG. With normal aging, the testicles will at some point stop responding to the LH and hCG signals. If testosterone levels do not rise in a patient receiving hCG after 6 weeks, we know the "disconnect" between the testicles and the pituitary gland has occurred and direct testosterone supplementation is the preferred route.

Once a hormonal augmentation program is initiated, laboratory markers, which include hormone blood levels, should be followed at regularly scheduled intervals and therapy must be adjusted accordingly if an endocrine supplementation program is to be safe and effective. Physicians specifically trained and certified in Age Management Medicine are best suited to oversee such programs.

Conclusion

Hormonal health plays a large role in determining the overall health and wellbeing of both men and women (Tenover JL. Mayo Clin Proc. 2000 Jan; 75 Suppl: S77-81, Raisz et al. J Clin Endocrinol Metab. 1996; 81: 37-43). Today age-related hormone deficiencies and imbalances are correctable and optimal hormone balances, that place individuals in the upper percentiles of their normal hormone range, can be safely achieved. Men, women, and their loved ones need not suffer the consequences of a mid-life crisis. There is definitely hope. It is now within our power to make the rest of our lives the best of our lives!



Jeffry S. Life, M.D., Ph.D. - Institute Physician
Dr. Life is a Diplomate of both the American Board of Family Practice and the American Board of Anti-Aging Medicine. He is also a Fellow of the American Academy of Family Physicians and is certified in Age Management Medicine. After receiving his medical degree from the University of Iowa, Dr. Life completed his Residency in Family Medicine and Internal Medicine at West Virginia University. In 1998, after reaching a lifetime high body weight, percentage of body fat, and level of deconditioning, he decided to enter EAS’ National Body-for-LIFE Challenge at the age of 60. He won the contest after losing 35 pounds of body fat and gaining 15 pounds of muscle as a direct result of improving his nutrition and starting an exercise program. Today he continues to live a lifestyle that promotes health and fitness and writes a column on Performance Nutrition for Muscle Media Magazine. He has also written a chapter on “Exercise, Fitness, and Lifestyle” for a popular medical textbook that was published in 2002. Prior to joining Cenegenics, Dr. Life was a full-time Family Physician and a part-time Assistant Professor at Marywood University in Scranton, Pennsylvania where he taught graduate courses in the nutritional sciences and exercise physiology. He is currently completing a Masters of Science program in Sports Nutrition and Exercise Science and working on his book. Dr. Life joins the Cenegenics team with an intense desire and enthusiasm to share with our patients the lifestyle changes and knowledge that have had such a positive impact on his life.



About Cenegenics

Cenegenics Medical Institute is the largest and most experienced Age Management Medicine Practice in the world with patients from every state in the United States and several countries, 25% of whom are physicians and their families. Cenegenics consistently receives regional, national, and international media exposure and has been the featured expert in the media, including USA Today, Wall Street Journal, ABC’s 20/20, and CBS’s 48 Hours.

Alan P. Mintz, M.D., is the Chief Medical Officer, Chief Executive Officer, and Co-Founder, of Cenegenics Medical Institute. He is a Diplomate for the American Board of Radiology, including Nuclear Medicine and Radiation Therapy and is certified in Age Management Medicine. For further information contact Dr. Mintz or Dr. Life at 1-866-953-1530 or email at doctor@cenegenics.com.

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