Health and Testosterone Balance

Sometimes called the "king of hormones", testosterone is certainly the most important hormone when it comes to sexual characteristics in men. The group of hormones that create and support masculinity is known as androgens, but testosterone is the one that is primarily responsible for:

• Determining before birth whether a baby will develop into a boy or a girl
• Influencing sexual preferences
• Forming personalities into poets, athletes, competitors or co-operators
• Regulating the sex drive in men (and in women)
• Starting and maintaining the development of male sexual characteristics including dominance, emotional and physical strength, body shape, hairiness, deep voice, and even odor
• Governing sperm production and quality
• The ability to perform adequately during sexual intercourse

Testosterone plays a role in developing creativity, intellect, thought patterns, assertiveness and drive, as well as the ability to propose new ideas and carry them through to successful conclusions. It also affects general health during childhood, adolescence and adulthood. Adequate levels of testosterone throughout life help males to thrive as children, develop stronger muscles and bones (along with acne) during puberty, cope with stress during peak career years, and age gracefully after retirement.

Production in the BodyThis important hormone is produced mainly in the testes in males (more than 95 percent) and in the ovaries in females; however, small amounts are made in the outer layer of the adrenal glands in both sexes. The process that carefully regulates the amount and timing of testosterone production is complex and begins in the brain. When a man feels aroused or successful, the cerebral cortex, the most sophisticated area of the brain, sends a signal to another part of the brain called the hypothalamus to stimulate the production of testosterone. The hypothalamus is an area at the base of the brain that regulates much of the body's hormonal activity. It does this by sending chemical signals to the pituitary gland, a cherry-sized organ that produces a wide variety of hormones involved in the regulation of growth, thyroid function, blood pressure, pregnancy, birth and other critical body functions. To stimulate testosterone production, the hypothalamus releases a substance to the pituitary gland called gonadotropin-releasing hormone (GnRH). This hormone, in turn, causes the gland to produce two other hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), collectively known as gonadotropins. LH is released into the bloodstream where it travels to the testes and triggers the production of testosterone from cholesterol. If this process continues until the testosterone level becomes too high, the pituitary slows the release of LH so production slows down. FSH is similarly involved in the increase and decrease in sperm production. When LH reaches the testes, it influences activity in the Leydig cells, which are where cholesterol is gradually changed into a series of compounds until it becomes testosterone. When the small but vital amount of testosterone produced is released into the bloodstream, it is mostly bound to a special "carrier" compound called sex hormone binding globulin or SHBG. SHBG, which is produced by the liver, plays an important role in regulating the amount of "free" testosterone circulating in the body at any one time. The more SHBG there is the less unbound, active testosterone is able to move from the blood stream into cells where it is needed. As SHBG levels rise and fall, so do free testosterone levels, except in reverse. With such a complex chain of events leading to a normal testosterone level, many problems or interruptions along the process can lead to sub-normal levels in men at any age. If there are diseases or negative conditions involving the testes, hypothalamus, pituitary gland or genetic material, the resulting state is called hypogonadism. A variety of conditions can cause low testosterone besides aging:

• The testicles may be damaged, especially the Leydig cells, during sports or from other physical trauma.
• A case of mumps after puberty can cause an inflammation of the testes that interferes with testosterone and sperm production.
• Radiation treatment or chemotherapy can have a negative effect on the Leydig cells.
• Testicular or pituitary tumors can also have an impact on the testosterone level.
• HIV/AIDs and other serious viral infections can inflict damage on the pituitary gland, the hypothalamus or the testes.
• Genetic conditions such as Klinefelter's, Kallmann's and Prader-Willi syndromes and myotonic dystrophy all can have a negative impact on testosterone production.
• Vasectomy may damage the Leydig cells and lead to early andropause.

In addition, many lifestyle habits affect the way testosterone is produced. A diet high in meat and poultry may expose a man to hormones used in meat production that act like estrogen in the body. Estrogen is a potent inhibitor of testosterone production as are prolonged periods of high stress. Mild to moderately intense physical stress, as in casual sports and sexual intercourse, may actually boost testosterone production. Alcohol consumption, on the other hand, has been proven to have a strong negative impact on testosterone levels. Beer, which contains plant estrogens, is particularly toxic to the testes. As we all know, the testes are very heat sensitive so switching from jockey shorts and tight jeans to boxers and loose pants may raise the testosterone level.  top of page Age-related changes to testosterone levelIt is helpful to define andropause in terms that relate to lowered testosterone levels in men regardless of age. One doctor in a recent journal defined it as "a decline in serum (blood) testosterone in older men to levels below the normal range for young men, with associated clinical manifestations consistent with androgen deficiency."¹ Aging in men is associated with a one percent decline in total testosterone level each year starting at around age forty. About twenty percent of men in their sixties and fifty percent of men in their eighties have testosterone levels significantly below normal. Men who develop a serious illness, take certain kinds of medications, or who don't eat a healthy variety of foods are even more likely to have low testosterone levels. Furthermore, about one in three men with symptoms of andropause turn out to have a testosterone level lower than normal². Many of these men will simply feel better when their testosterone level is raised through hormone replacement therapy. The relationship between testosterone and SHBG has confused many who question the existence of andropause as a legitimate syndrome. They have argued that the level of total testosterone as measured in blood falls only slightly up to the age of 70. This is true. Yet, the level of SHBG tends to increase with aging. At any time, approximately 98 percent of circulating testosterone is bound to SHBG, which leaves only 1-2 percent available for use by cells. If SHBG levels increase with age while testosterone production decreases, the amount of available testosterone is actually decreasing at a faster rate than total testosterone. The age-related decline in testosterone production is due to many factors that produce a gradual downward spiral:

• The number of Leydig cells declines.
• The existing Leydig cells produce less testosterone.
• Less testosterone is secreted into the bloodstream by the testes in response to LH.
• The hypothalamus secretes less gonadotropin-releasing hormone.
• As a result, production of LH by the pituitary gland decreases and less testosterone production is demanded of the testes.

Aging also may change the daily cycle of testosterone production. In young men, peak testosterone delivery occurs in the morning. As men age, the testosterone level becomes increasingly more constant throughout the day and night. This simplified view of age-related changes to testosterone levels leads to questions about the actual effects the decreasing level has on the body, mind and emotions of the aging male. By no means does the decline in testosterone account for all of these changes but it certainly plays a significant role. Physical symptoms of low testosterone include:

• Poor or no erections
• Decline in sexual activity
• Loss of muscle mass and strength
• Loss of bone mass that can lead to osteoporosis
• Fatigue and loss of energy
• Reduction in body hair and skin thickness
• Development of hair in ears and nose
• Increase in upper and central body fat
• Increase in heart and artery disease
• Problems with circulation
• Sleep disturbances

Mental symptoms include:

• Decreased intellectual ability
• Memory loss

Emotional symptoms include:

• Loss of interest in sex
• Depression
• Irritability
• Loss of sense of well-being

Each individual may experience a different number and type of symptoms. Some symptoms may be clearly related to other physical and mental illnesses or even to such poor habits as smoking, drinking too much alcohol or overeating. Before assuming that testosterone supplementation is necessary to feel better, you and your doctor will want to run through a variety of diagnostic steps to pinpoint specific causes of your symptoms and a full range of behavioral and other changes that might help you feel better.

Diagnosing AndropauseMany of the above symptoms have long been associated with normal aging. Still other symptoms in this list may be attributed to lifestyle problems (excessive alcohol intake, especially beer), poor nutrition, use of certain medications, insufficient exercise or inactivity due to arthritis or injuries, problems with the nervous system, chronic illnesses and even genetic makeup. So, how can you and your doctor decide whether testosterone supplements might help?

The best place to begin the diagnosis is with a questionnaire that you can take by yourself. There are several available but the most commonly used one is called the ADAM (Androgen Deficiency in Aging Males) questionnaire. It consists of ten questions and if a man answers certain questions with a yes or answers any three others with a yes, he can suspect that a low testosterone level may be causing some of his problems. If you would like to answer the questions on the ADAM questionnaire for yourself. You might also want to take the AMS Questionnaire (Aging Male Symptom rating), which allows you to measure symptoms in three different areas, mental, physical and sexual, as well as keep track of changes over time. In fact, if you register at the Andropause Center, you can return once a month or so and retake the AMS questionnaire. This will help you to see how your symptoms are changing as you make changes to your lifestyle or increase your testosterone with supplements. Just because you have a positive score on the ADAM, AMS (or any) questionnaire does not mean that you have low testosterone or Andropause, but it probably indicates that a visit to your doctor is a good idea. Most family physicians or general practitioners should be able to diagnose the syndrome but, certainly, a urologist or an endocrinologist would know the best type of examination to conduct. Regardless of the physician's training, there are certain steps and tests that are standard for diagnosing andropause.

Medical History and Physical ExaminationIn spite of amazing medical advances, one of the most important diagnostic tools is the information a patient provides a doctor in the form of a medical history. Your participation in providing as complete information as you can will be important in this diagnosis. At the first visit, a doctor will ask many questions about general health as well as specific questions about sexual interest and activity that relate to low testosterone. Some of the specific topics asked about may include: Personal History:

• Date of birth
• Blood Type
• Allergies
• All prescription and non-prescription drugs currently being taken
• Dates of immunizations
• Previous and existing conditions and major illnesses
• Names of current and previous doctors
• Dates/reasons for previous medical visits
• Dates and kinds of surgeries
• Copies of past test results
• Lifestyle habits - smoking, alcohol consumption
• Family and relationship problems, including any sexual ones
• Major life events or changes that have occurred

Family History:

• Alcoholism
• Blood diseases (hemophilia or sickle cell)
• Cancer (all types)
• Diabetes
• Heart disease, hypertension or stroke
• Kidney disease
• Mental illness
• Other illnesses and disorders

Before your doctor's appointment, you may find it helpful to make a list of your parents, siblings, aunts, uncles and grandparents, with age at death and its cause, or existing conditions and age if the person is still alive. This information will help the doctor identify potential genetic tendencies in your family. Your doctor will also ask you questions about your sexual history and development. These may include:

• Any genital abnormalities present from birth
• When and how quickly puberty took place
• Current status of sexual function
• Status of secondary sexual characteristics such as beard growth, muscular strength and energy level
• Rate of nocturnal emissions
• Degree of penile rigidity during erections
• Frequency of sexual thoughts, desires and fantasies
• Frequency of masturbation or sexual intercourse

Once the doctor has a general idea about your past and current situation, he will conduct a thorough physical examination. In addition to a typical exam that includes blood pressure, heart rate and other basic measures, the doctor will look at the amount and distribution of body hair, presence and degree of breast enlargement, size and consistency of the testes, abnormalities in the scrotum, and the size of the penis. Once you and your doctor decide that treatment with supplemental testosterone is indicated, the doctor should perform further tests to rule out prostate cancer including a digital rectal exam and prostate specific antigen (PSA) level. These tests should be repeated at 6 weeks, 3 months, 6 months and annually thereafter. Monitoring your health while on treatment is very important and more information about this process will be available at this Andropause Center in the next couple of months.

TestsThe most obvious test required is a measurement of testosterone level in your blood. The test for total testosterone has been widely available for many years but, as discussed earlier, is not a very reliable measure of how much testosterone is actually "free" and available to the cells. There are few reliable and affordable tests currently available for free testosterone. Another test available is for SHBG. By running a test for total testosterone and another for SHBG, your doctor can use these values to calculate the amount of free testosterone in the blood. This is done by dividing the total testosterone value by the value of the SHBG and multiplying by 100 to arrive at a percentage value called the free androgen index. In normal men, this value should stay between 70 to 100 percent, but in andropausal men, it may fall to below 50 percent. In any event, measurement of total testosterone is probably the most widely available and utilized test today. In the United States at present, it also remains the standard for indicating a need for replacement therapy. When to take the blood sample for these tests is important because the level of testosterone normally varies from a high point in the morning to lower points throughout the day. The blood sample should be drawn between 8:00 and 9:00 AM to be sure it will provide the highest level of testosterone during the cycle. The normal range for total testosterone is 300 - 1000 ng/dl. If the testosterone level determined through a blood test is found to be extremely low and your doctor feels that developing an exact clinical diagnosis is important based on the physical exam and patient history, blood tests for FSH, LH and/or prolactin may be ordered. Results of these tests can provide a more complete picture of a man's hormonal status. Other tests may be indicated by the medical history or physical exam. For example, a doctor may order bone density testing if bone loss is suspected, or genetic testing may be useful to confirm an inherited condition. If tests indicate that there might be a problem with the pituitary gland, the doctor may want to examine the gland itself through a computed tomography (CT) scan or magnetic resonance imaging (MRI.) In any case, these tests are chosen to augment an andropause diagnosis. If their results are all normal but a group of symptoms strongly indicates that you have the andropause syndrome, you should be allowed a short trial of at least three months of supplemental testosterone to see if it makes you feel better. Before undertaking such a trial, you and your doctor will want to discuss the potential risks associated with this treatment and measure them against potential improvements in feelings and lifestyle. You may also want to try basic lifestyle changes if your symptoms appear to be directly related to smoking, drinking, overweight or stress. For help and support to make these changes, visit our Wellness Center with Don Ardell.  top of page Feeling better during and after treatmentWhen you and your doctor are comfortable that your symptoms indicate andropause and that testosterone supplementation may be tried, you should decide on your goals for treatment. The goals may differ from man to man and may include improvement in mood, sexual desire, physical stamina and performance, or general quality of life. Alternatively, they may involve improvements in physical condition or the prevention of decline in symptoms discovered during the exam such as osteoporosis, body composition and strength, or mental sharpness. Regardless of the goal, the free testosterone level in the blood will have to be raised until it's comparable to the lower normal limit seen in young men before many changes will occur. This may take several weeks, although certain symptoms may require less testosterone to be affected than others will. For example, improvements in mood and interest in sex may take a smaller increase in testosterone level than significant improvements to muscle strength or bone density. Most studies suggest that a minimum of three months of treatment is necessary to see the complete benefit of supplemental testosterone. By this time, you should expect to feel better in a variety of ways. Supplementing testosterone may produce many benefits, most noticeably an overall feeling of increased energy and vitality. Many men report an increase in drive, ambition or even assertiveness, without becoming aggressive, and they generally say they feel happier and less irritable. Their families say they are easier to get along with and the men often feel they are coping with work stress better. Physical changes that occur soon after treatment begins include an increase in the rate of hair growth, particularly on the chest and in the pubic area, and sometimes improvements in general hair and skin condition. Other men report an increase in penis size and an increase in genital sensitivity, which often corresponds with an increase in sexual activity and improvements in relationships with their partners. Although it's a subtle change, men report improvements in their moods, mostly a decrease in the episodes of depression they experience. In summary, the benefits of supplemental testosterone, in men found to have low levels prior to treatment, include:

• Increased interest in sex and increased frequency of spontaneous erections
• Restored erectile function in some men
• Improved mood with less depression, anger, fatigue, or mental confusion
• Enhanced masculine characteristics such as faster beard growth and an increase in pubic hair
• Increased muscle mass and strength as well as increased bone density

 top of page ReferencesBrawer, Michael K., MD. Androgen Supplementation and Prostate Cancer Risk: Strategies for Pretherapy Assessment and Monitoring. Rev.Urol. 2003;5 (suppl 1):S29-S33. Caruthers, Malcolm, MD. The Testosterone Revolution. London: Thorsons; 2001 Heaton, Jeremy, P.W., MD. Hormone Treatments and Preventive Strategies in the Aging Male: Whom and When to Treat? Rev.Urol. 2003;5(suppl 1):S16-S21. Matsumoto, Alvin M., MD. Fundamental Aspects of Hypogonadism in the Aging Male. Rev.Urol. 2003;5(suppl 1):S3-S10. McCulloch, Andrew, MD. Case Scenarios in Androgen Deficiency. Rev.Urol. 2003;5(suppl 1):S41-S48. Nieschlag, E., Behre, H.M., Nieschlag, S. Testosterone: Action, Deficiency, Substitution. Berlin: 1998. Steidle, Christopher P., MD. New Advances in the Treatment of Hypogonadism in the Aging Male. Rev.Urol. 2003;5(suppl 1):S34-S40. Notes1. Matsumoto, Alvin M. Fundamental Aspects of Hypogonadism in the Aging Male. Urology. Vol. 5, Supplement 1. 2003;S3-10.
2. Morley, JE. J Gend Specif Med. 2001;4:49-53