-Testosterone-
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.