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TESTOSTERONE –
GETTING THE FACTS FROM “FAQS”

Q:  What is “Testosterone”?

A:  Testosterone is the primary male sex hormone (otherwise known as androgen) found in all men, women and children. Testosterone is made in the testicles, ovaries and adrenal glands, and it is also also found in brain tissue.

2-Dimensional Drawing of a Testosterone Molecule

Q:  Why is Testosterone Important?

A: Testosterone is the most important sex hormone produced in the male body. It is the hormone that is primarily responsible for producing and maintaining the typical adult male qualities. At the onset of puberty, testosterone stimulates the physical changes that characterize an adult male, such as enlargement of the penis and testes, growth of facial and pubic hair, deepening of the voice, an dramatic increase in muscle mass and strength, and growth in height. Throughout adult life, testosterone helps stimulate and maintain libido (in both men and women), is needed for the production of sperm cells, for the maintenance of muscle mass as well as bone mass. Mood is also affected by testosterone, and low levels of the hormone can cause severe and prolonged depression as well as fatigue.

Q:  When does Testosterone Start to Become Important?

A:  Almost from the very moments of conception!   While it is commonly perceived that testosterone is not a major factor in prepubescent male development, testosterone is active long before puberty begins! For example, while a fetus is still in utero, testosterone and a product of its metabolism, dihydrotestosterone, cause the male genitalia to form.  Without it, there would be no physical differentiation between men and women.

Q:  How is Testosterone Produced and Regulated?

A:  The body keeps a very tight control around the production of testosterone. Hormonal signals from two locations — the pituitary gland at the base of the brain, and a part of the brain called the hypothalamus — signals other areas in the body (in men, primarily the testes) how much testosterone to produce.  The hypothalamus controls hormone production in the pituitary gland by means of gonadotropin-releasing hormone (GnRH). This hormone tells the pituitary gland to make follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH signals the testes to produce testosterone. If the testes begin producing too much testosterone, this is sensed by the brain which sends signals to the pituitary to make less LH. This, in turn, reduces the production of testosterone. If the testes begin producing too little testosterone, the brain senses this and sends signals to the pituitary gland telling it to make more LH, which causes the testes to make more testosterone.

Q:  Can Testosterone Levels Be Detected Using Laboratory Testing?

A:  Yes!  Medical Professionals and Laboratory Scientists have established what are considered “normal ranges” for blood/plasma testosterone levels in men.  Testosterone is released in a pulsatile manner so levels vary from hour to hour, causing “circadian changes” which can be detected in men with no apparent problems. As a rule, the highest testosterone levels occur in the early morning hours, so measurements should be taken at this time. Testosterone levels also can vary substantially by age.  Normal ranges are determined in normal, healthy men between the ages of 20 and 40 or 45.  If a physician believes that someone is not producing enough testosterone, the physician will check if the total blood/plasma testosterone level falls into the acceptable range. The physician also may ask the laboratory to measure the amount of “free or bioavailable” testosterone (about 40 percent of the total testosterone is strongly bound to a protein called sex hormone binding globulin, known as SHBG; about 58 percent is weakly bound to another protein called albumin) and the amount of “free” testosterone (only about two percent circulates freely in the blood). Blood levels of SHBG increase with age, so older men may have a higher percentage of bound testosterone and a lower percentage of free testosterone. Bioavailable testosterone includes the non-SHBG bound testosterone or the sum of the testosterone, which is bound to albumin and free (unbound) testosterone.

Q:  What are the Symptoms of “Low Testosterone?”

A: Symptoms of low blood/plasma testosterone in men can include decreased libido, poor erections by the penis (erectile dysfunction or “ED”), decreased sperm production and count and reduced fertility, or increased breast size (gynecomastia). Men also can also experience symptoms very similar to those seen during menopause in women — hot flashes, increased irritability, inability to concentrate, and depression. Some men may have a prolonged and severe decrease in testosterone production. This may result in loss of body hair and reduced muscle mass, brittle bones that may break easily and their testes may become smaller and softer. In younger men, low testosterone production may reduce the development of body and facial hair, muscle mass, and penile size. Additionally, their voices also may fail to deepen.

Q:  If I think I am suffering from “low testosterone” what should I do?

A:  The very first (and most important thing) to do is to speak with your primary care physician.  A simple blood test can determine whether or not your suspicions are correct.  If they are correct, your primary care physician may opt to refer you out to a hormone specialist physician called an “endocrinologist”.  For more information about endocrinologists and how they relate to testosterone based problems, please contact the following:

American Association of Clinical Endocrinologists (AACE)
1000 Riverside Avenue, Suite 205
Jacksonville, FL 32204
(904) 353.7878
www.aace.com

American Society of Andrology (ASA)
11 North Plaza Drive, Suite 550
Schaumburg, IL 60173
(847) 619.4909
www.andrologysociety.com

Q:  How is “low testosterone treated” in Men?

A:  Men with “low testosterone” are often treated with prescription testosterone products.  All of these products are “controlled substances” in the United States of America and some physicians are very hesitant to prescribe any of them for this very reason.  Currently, there are only four delivery methods of testosterone supplementing products that have been approved by the U.S. Food and Drug Administration (FDA). Supplemental testosterone is typically used in one of the following forms:

*Available in Canada, Mexico, and Europe only – not available in the United States of America.
Although methyl testosterone is manufactured in capsule or pill form (and available in the United States of America), it is not recommended for testosterone replacement in men because it is a weak androgen and not as effective as other preparations, and it has potentially serious adverse effects on the liver and lipids. When capsules/pills are swallowed and absorbed into the bloodstream, they are quickly broken down by the liver and do not achieve high enough blood levels to be useful unless given in large doses (40-50 mg/day). At these doses, they may cause adverse changes in blood lipids (fats) and liver damage. Testosterone undecanoate is moderately effective, but it must be given in capsular form three times daily. It has unique properties that reduce rapid metabolism by the liver and has not been associated with serious adverse effects on the liver.

Once your physician has diagnosed low testosterone the physician should determine if the low testosterone levels are due to testicular, pituitary, or hypothalamic problems. Men with low testosterone and normal or low serum LH levels may require further evaluation and treatment. After resolving these issues, treatment with supplemental testosterone may start.

Q: Many of The Treatments Sound Inconvenient or Messy – Are There Any Other Potential Options?

A:  Yes, there are other potential options although they are not “approved” currently by the United States Food and Drug Administration (FDA).  These options include various herbal supplements such as Tribulus Terrestis and Tongkat Ali – but none of the “herbal remedies” have ever been conclusively proven to work well, if at all.  Other methods of potentially raising blood/plasma testosterone levels include the use of a class of compounds called ‘anti-aromatases’ which can literally ‘trick’ the body into dramatically increasing testosterone output.  There is substantial in-vitro and in-vivo (in human) studies to demonstrate that the use of anti-aromatase type products does increase blood/plasma testosterone levels.  Some examples of anti-aromatases are (by prescription) anastrazole, letrozole, vorozole, 4-hydroxyandrostenedione, and exemestane and (foot supplement/over the counter) androstatrienedione (ATD), 3-hydroxy-androstene-dione (3-OHAT) and androstenetrione.

Q:  Wow!  Is There Any Other
Important Information About Testosterone
I Should Know About?

A:  Yes!  However, the very first place you should start is with your primary care physician.  Below, we have listed many abstracts from various research studies that you may find to be of interest.

Testosterone and Its Effects on Sexual Function

1. A long-term prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men — A.S. Burris et al. Journal of Andrology 1992; 13(4):297-304.

Men with low levels of testosterone who had not yet been treated with supplemental hormone showed significantly higher levels of depression, anger, fatigue and confusion than did men with acceptable testosterone levels. During testosterone replacement therapy, scores improved. Also during treatment, these men reported increased sexual interest and greater numbers of spontaneous erections. (Design of Study: Hypogonadal men before and during testosterone treatment compared to untreated normal men and untreated infertile men; no placebo treated controls.)

2. Effects of androgen on sexual behavior in hypogonadal men — J.M. Davidson et al. Journal of Clinical Endocrinology and Metabolism 1979; 48(6):955-958.

The study found that the effect of testosterone replacement on sexual activity in hypogonadal men is rapid, reliable, and not due to placebo effect. To maintain testosterone levels and adequate sexual function, testosterone replacement should be administered on an ongoing basis. (Design of Study: Hypogonadal men during double blind, randomized, cross-over treatment with sub-replacement and replacement doses of testosterone; no placebo treated controls.)

3. Improvement of sexual function in testosterone deficient men treated for one year with a permeation enhanced testosterone transdermal system — S. Arver et al. Journal of Urology, 1996; 155(5): 1604-1608.

This study observed that nocturnal erections occurred more frequently with longer duration and greater rigidity, and patient assessments of sexual desire and weekly number of erections were higher in hypogonadal men when testosterone levels were normalized, as compared with measurements occurring during testosterone withdrawal. (Design of Study: Hypogonadal men during open-label testosterone treatment; not a controlled study.)
Testosterone and Its Effects on Mood and Thinking

1. A long-term prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men — A.S. Burris et al. Journal of Andrology 1992; 13(4):297-304.

Men with low levels of testosterone who had not yet been treated with supplemental hormone showed significantly higher levels of depression, anger, fatigue, and confusion than did men with acceptable testosterone levels. During testosterone replacement therapy, scores for the previously untreated hypogonadal men improved indicative of less depression, anger, fatigue, and confusion. (Design of Study: Hypogonadal men before and during testosterone treatment compared to untreated normal men and untreated infertile men; no placebo treated controls.)

2. Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities — G.M. Alexander et al. Hormones and Behavior 1998; 33(2):85-94.

Reasoning abilities were assessed in 33 men with low levels of testosterone who were receiving supplemental testosterone, 10 men with normal levels of testosterone who were given the hormone as part of a male contraceptive clinical trial, and 19 men with normal testosterone levels who did not receive supplemental testosterone. Prior to and after being given testosterone the men completed tests that measured visual-spatial ability, verbal fluency, perceptual speed, and verbal memory. Men with low testosterone seemed to have lower levels of verbal fluency; these improved following treatment with testosterone. These data suggest that testosterone may play some role in influencing some aspects of reasoning and thinking. (Design of Study: Hypogonadal men before and during testosterone replacement treatment compared to normal men before and during high dose testosterone and untreated normal men; no placebo-treated controls.)

3. Testosterone replacement therapy improves mood in hypogonadal men — a clinical research center study - C. Wang et al. Journal of Clinical Endocrinology and Metabolism 1996; 81(10):3578-3583.

The study evaluated changes in mood for 60 days in 51 hypogonadal men. Researchers found that testosterone replacement therapy in hypogonadal men improved their positive mood parameters including energy, well/good feelings, and friendliness. Testosterone replacement also decreased negative mood parameters including anger, nervousness, and irritability. (Design of Study: Hypogonadal men before and during testosterone treatment with a variety of testosterone formulations; not a controlled study.)
Testosterone and Its Effects on Body Composition and Bone Density

1. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research center study — I.G. Brodsky et al. Journal of Clinical Endocrinology and Metabolism 1996; 81(10):3469-3475.

Researchers measured body composition and muscle protein synthesis in five men with low testosterone before and six months after beginning testosterone replacement therapy. After testosterone therapy, all five men showed an increase in fat-free mass, a decrease in fat mass and an increase in muscle mass (65 percent of the increase in fat-free mass could be attributed to increased muscle mass). The scientists also found that the increased muscle mass was caused by the ability of testosterone to stimulate muscle protein synthesis. (Design of Study: Hypogonadal men before and during testosterone treatment; not a controlled study.)

2. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men — C. Wang et al. Journal of Clinical Endocrinology and Metabolism 2000; 85(8): 2839-2853.

This study evaluated the effects of 180 days of treatment with testosterone patch and testosterone gel on sexual function, muscle strength, lean body, and fat mass in 227 hypogonadal men aged 19-68. The study found that sexual function and mood improved in all treatment groups; mean muscle strength in the leg press increased in all treatment groups; lean body mass increased greater in the highest dose of testosterone gel compared to lower dose gel and patch. An increase in lean body mass and reduction in fat mass were correlated with the mean testosterone levels after treatment. (Design of Study: Hypogonadal men before and during testosterone treatment with either testosterone gel or testosterone patch; no placebo treated controls.)

3. Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men — C. Wang et al. Clinical Endocrinology 2001; 54(6): 739-750.

This study found that transdermal testosterone gel application in doses of 5-10 grams/day (delivering 50-100 mg of testosterone) for 6 months decreased bone resorption markers and increased bone formation activity markers (transiently) in 227 men aged 19-68 years. The highest dose gel resulted in increased bone mineral density in the spine and hip only in the higher treatment group. At the time of the articles the authors indicated that longer term data would determine if the positive effects on bone would persist. The same authors reported at the 2002 Endocrine Meetings that positive effects on bone continued to increase with continued treatment up to 42 months. (Design of Study: Hypogonadal men before and during testosterone treatment with either testosterone gel or testosterone patch; no placebo treated controls.)

4. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism — L. Katznelson et al. Journal of Clinical Endocrinology and Metabolism 1996; 81(12):4358-4365.

Scientists assessed the muscle and bone effects of testosterone replacement therapy in 29 men aged 22 to 69 with low blood levels of the hormone. The men were evaluated at six-month intervals for 18 months. The researchers found that body fat and subcutaneous fat significantly decreased while lean mass and bone density significantly increased. The scientists concluded that the beneficial effects of testosterone administration on body composition and bone density may provide additional indications for testosterone therapy in such men. (Design of Study: Randomized, placebo controlled study of older hypogonadal men before and during testosterone injections compared to before and during placebo injections.)

5. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial — R. Sih et al. Journal of Clinical Endocrinology and Metabolism 1997; 82(6):1661-1667.

Researchers examined the year-long effects of testosterone replacement therapy in 32 men in their 60s (15 men received a placebo and 17 received biweekly injections of testosterone). They found that the men who received testosterone showed improved grip strength in both hands and increased levels of hemoglobin, the blood component that carries oxygen. The investigators concluded that testosterone may have a role in treating frailty in older men. (Design of Study: Hypogonadal men before and during testosterone treatment; no placebo treated controls.)

6. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men — H.M. Behre et al. Journal of Clinical Endocrinology and Metabolism 1997; 82(8):2386-2390.

The researchers studied bone mineral density in 72 men who received testosterone replacement therapy for up to 16 years. Bone mineral density was measured annually. The most significant increase in bone mineral density was seen during the first year of testosterone replacement therapy. Long-term treatment maintained bone mineral density at levels consistent for age in all men. (Design of Study: Randomized, placebo controlled study of older hypogonadal men treated with testosterone patches or placebo patches.)

7. Effect of testosterone treatment on bone mineral density in men over 65 years of age — P.J. Snyder, et al. Journal of Clinical Endocrinology and Metabolism 1999;84:1966-1972.

Researchers examined changes in bone mineral density in 108 men over 65 years of age who received testosterone for 36 months. The study found that increasing testosterone to the midnormal range for young men did not increase lumbar spine bone density overall, but did increase it in those men with low pretreatment testosterone levels. (Design of Study: Randomized, placebo controlled study of older hypogonadal men treated with testosterone patches and placebo patches.)

8. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age — P.J. Snyder, et al. Journal of Clinical Endocrinology and Metabolism 1999;84:2647-2653.

Researchers examined changes in body composition and muscle strength in 108 men over 65 years of age who received testosterone for 36 months. The study found that increasing testosterone concentrations in men over 65 years of age to the midnormal range decreased fat mass and increased lean mass, but did not necessarily increase muscle strength. (Design of Study: Randomized, placebo controlled study of men over age 65 treated with testosterone patches and placebo patches.)
Testosterone and Its Effects on HIV Positive Men With Low Testosterone

1. Testosterone replacement in HIV illness — J.G. Rabkin et al. Archives of General Psychiatry 2000; 57(2):141-147.

A total of 70 HIV-positive men with low testosterone levels completed a six-week trial of biweekly testosterone or placebo treatments. Seventy four percent of men who received testosterone reported much or very much improved libido, compared to 19 percent of placebo-treated men. Of men with fatigue at baseline, 59 percent of testosterone-treated men had improved energy, compared to 25 percent of placebo-treated men. Of men with Axis 1 depression at baseline, 58 percent of men who received testosterone versus 14 percent of men treated with placebo reported improved mood. Testosterone improved muscle mass by 1.6 kg over 12 weeks in the entire group of men treated with testosterone, and 2.2 kg in those with wasting at baseline. (Design of Study: HIV-positive men with low testosterone levels before and during testosterone treatment; no placebo treated controls.)

2. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial — S. Grinspoon et al. Annals of Internal Medicine 1998; 129(1):18-26.

Fifty-one HIV-positive men with a mean age of 42 who had wasting and low testosterone were randomly assigned to receive testosterone or placebo every three weeks for six months. Testosterone-treated men gained fat-free mass, lean body mass and muscle mass. These men also reported they felt better, had an improved quality of life and improved appearance. (Design of Study: Double-blind, randomized, placebo-controlled trial of testosterone versus placebo therapy in HIV-infected men with AIDS wasting syndrome.)

3. Testosterone supplementation therapy for older men: Potential benefits and risks — D.A. Gruenewalk and A.M. Matsumoto. Journal of the American Geriatric Society 2003; 51(1):101-115.

This study of men age 60 years evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. In general, these studies found increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone treatment. Testosterone improved exercise-induced coronary ischemia in men with coronary heart disease, but angina was improved or unchanged. Compared to men with less marked testosterone deficiency, men with low testosterone levels were more likely to demonstrate improvements in bone mineral density, self-perceived functional status, libido and sexual function, and exercise-induced ischemia. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen often increased. (Qualitative review of placebo-controlled trials.)