Human Health Solutions

Men & Testosterone

I would like to know what causes men below the age of 45 to have very low testosterone (i.e. free testosterone under 7(pg/ml) or total testosterone under 240(ng/dl); and what cures are available. Also, I would like to find out what role low testosterone plays in causing arthritis and depression?

Low testosterone, also called hypogonadism, occurs when the testes produce smaller amounts of testosterone than is considered a normal range. Not as well known a term as female menopause, andropause, is the term for the naturally occurring drop in testosterone. A ballpark normal range for total testosterone in males is 300-1100ng/dl, with 700ng/dl being the mean. This site however quotes 437 to 707 ng/dl as a normal range. You should base your results on the lab who performed your test’s range, not these. Regardless of the performing lab, your results appear to be low, particularly for the free testosterone value.

http://health.allrefer.com/health/testosterone-values.html

Another site quotes these normal ranges: 15.0 – 40.0 pg/ml as a normal range for free testosterone, and 300ng/dl – 1,000ng/dl for total testosterone. http://www.keratin.com/ab/ab018.shtml

Yet another site; Free testosterone 50–210 picograms per milliliter (pg/mL) and total testosterone 300ng/dl -1,000ng/dl http://my.webmd.com/hw/mens_conditions/hw27307.asp “Dr. Malcolm Carruthers, a British specialist in men's health, says that clinicians need to look at the level of free active testosterone (FAT) rather than total testosterone to get an accurate reading. Dr. Quigley agrees that measuring FAT is much more accurate. Additionally, along with measuring total testosterone, Dr. Quigley measures the man's serum estrogen level. He explains that high serum estrogen could produce the symptoms of reduced testosterone. If the serum estrogen level is high, he gives the patient medication that turns off the estrogen production.” http://www.scrippshealth.org/scrippsnews_1218.asp

“Starting at the age of 30, men experience a drop in testosterone by about 10% every decade, while amounts of the hormone that are still being manufactured may not be as effective because of increased production of another hormone called SBHG. For some men, this decrease in testosterone results in a condition called andropause, which has a range of symptoms, including: •low sex drive •difficulties getting erections or erections that are not as strong as usual •lack of energy •depression •irritability and mood swings •loss of strength or muscle mass •increased body fat •hot flashes http://www.medbroadcast.com/channel_health_features_details.asp?channel_id=1002&relation_id=145&health_feature_id=148&article_id=449

As you will see on the following site, as many as 50% of all men may have low levers of testosterone. According to the Great Smokies Diagnostic Lab, these are the causes of hypogonadism:

chronic/systemic illness
surgery
chemotherapy
infections
premature aging
testicular trauma
stress
Kleinfelter's syndrome
autoimmune damage
tobacco and alcohol sleep apnea
excessive heat
obesity
hypercortisolism
medications
hyperthyroidism
malnutrition

“Subtle clinical signs of hypogonadism may include slight gynecomastia and soft small testes. However, researchers have noted that "the findings of physical examination in men with adult-onset hypogonadism are often normal.”

Secondary hypogonadism can develop as a result of hypothalamic or pituitary disease, obesity, hypothyroidism or other causes. Some conditions, such as hypercortisolemia, AIDS and severe systemic illnesses, can trigger hypogonadism through a combination of both primary and secondary mechanisms.” http://www.gsdl.com/home/assessments/malehormone/appguide/index3.html

One cause was omitted from the list above, and that is diabetes. Are you diabetic? Have you been tested recently? “About one third of men with type 2 diabetes show low levels of testosterone, and this is seems to be related to abnormal function of the pituitary gland -- the master regulator of hormone production -- according to a new study.

Although lower total testosterone levels have been reported in type 2 diabetics, the underlying cause has not been known, Dr. Paresh Dandona of the State University of New York at Buffalo and colleagues note in the Journal of Clinical Endocrinology and Metabolism.” http://www.dental.am/more.php?id=4834_0_1_0_M16

“Testosterone helps men reduce body fat and improves the way their bodies handle insulin. So low testosterone levels may have serious consequences for men with diabetes, suggests Sandeep Dhindsa, MD, of State University of New York at Buffalo. "We are describing a new complication of type 2 diabetes. We are saying that the largest group of people who have [low testosterone] are diabetics," http://my.webmd.com/content/article/97/104303.htm

=========================== Testosterone and Depression ===========================

“There is increasing evidence of an association between testosterone levels and male depression. Two epidemiological studies examined this relationship, with inconclusive results. Observational studies comparing the mean testosterone levels of groups of depressed men with those of non-depressed controls have also yielded discrepant findings. In both types of studies diurnal, seasonal situational and age-related variability in testosterone secretion may have contributed to the inconsistent results.

One relevant study measured afternoon testosterone in 12 men with major depression and in 12 age-matched controls. Although no difference in testosterone levels between the two groups was found, there was a significant negative correlation between hormone level and age in the depressed patients, but not in the controls. This suggests that depressed men may be more sensitive to the normal age-related decline in testosterone levels. Other studies summarized in the review corroborate this suggestion. However, the significance of a low testosterone level in the setting of depressive illness remains unclear.”

http://www.healthandage.com/PHome/gid2=344

“Leading experts in the field of brain research have observed that "sex steroids exert profound effects on mood and mental state."6 Many studies have established a direct relationship between decreased testosterone levels and negative mood factors such as depression, anger, confusion, anxiety, and fatigue.32,33 Wang et al. found that testosterone replacement used to restore androgen balance in hypogonadal men improved many emotional parameters, including friendliness, energy levels, and sense of well-being.34 Significantly, these benefits were maintained over the course of a six-month period of therapy, precluding the possibility of a short-term placebo effect.”

http://www.gsdl.com/home/assessments/malehormone/appguide/index4.html

“Men who have low testosterone levels are more likely to suffer depression, says an article in the February issue of the Archives of General Psychiatry. Researchers examined the clinical records of 278 men, 45 years or older. Over a two-year period, 21.7 percent of the men with testosterone deficiency (hypogonadism) were diagnosed with depression, compared with 7.1 percent of men with normal testosterone levels.

When they adjusted for age, alcohol use and other factors, the researchers concluded that men with hypogonadism were 4.2 times more likely to be diagnosed with depression. "Hypgonadal men showed an increased incidence of depressive illness and a shorter time to diagnosis of depression. Further prospective studies are needed to confirm these preliminary findings and to clarify the role of testosterone in the treatment of depressive illness in older men," the study authors write.
http://www.medicinenet.com/script/main/art.asp?articlekey=26638

“While an estimated 4-5 million men in the U.S. and 400,000-500,000 in Canada suffer from symptoms related to testosterone deficiency, only about 5% are treated. Aside from the fact that that leaves a lot of men who simply aren't feeling as good as they should, it also puts a high number at risk for osteoporosis, or a weakening of the bones, and cardiovascular problems such as atherosclerosis, hardening of the arteries - both of which are conditions associated with low testosterone.

But there's no reason for this condition to get so many men down! Doctors can easily diagnose low testosterone with a simple blood test. If levels come back low, further testing, including more blood tests, taking a sample of tissue from the testicles (called a biopsy), semen analysis, or brain imaging may be required. Once low testosterone is diagnosed, there are a number of different treatment options.”

http://www.medbroadcast.com/channel_health_features_details.asp?channel_id=1002&relation_id=145&health_feature_id=148&article_id=449

“It's normal for men to lose testosterone gradually, beginning in their 20s. By age 75, half a man's testosterone is gone, Lites said. But Michael's testosterone had switched off prematurely. "The real issue is that if they get into their 60s and 70s and it falls even below that, based upon where they started, or if they see a more accelerated drop, they may be at risk for the problems associated with low testosterone," said Dr. Laurence Levine, a urologist at Rush Presbyterian Hospital.

Levine calls the condition hypogonadism. Others call it male menopause or irritable male syndrome, Lites reported. Symptoms can include depression, weight gain, loss of energy, and less sex drive. And for some, including Levine's patient, David Mohl, fatigue is also part of it.

"Right after dinner, I was feeling tired," Mohl said. "I didn't seem to have much energy." Mohl's testosterone level was just half of what it should have been, Levine told him. So Levine prescribed a new testosterone gel. It's less obvious than a testosterone patch and does not involve the ups and downs of periodic injections, Levine said. The gel is spread on -- to an arm, for instance -- once a day.” More on treatments near the end of my answer. After using the gel, Mohl said his testosterone returned to normal, and so did he.” http://www.nbc5.com/health/2002074/detail.html

“Loss of testosterone, which happens normally as men age, seems to be at the root of some memory loss.” “Previous studies have shown memory loss to be common in men with prostate cancer who have had treatment with testosterone deprivation therapy. The therapy involves reducing the body's production of testosterone and is a common treatment for prostate cancer. However, it wipes out most of the male hormones in the body. Receptors for testosterone are located in the brain's memory centers.”

http://my.webmd.com/content/article/96/103557.htm

=====================================
Testosterone and Rheumatoid Arthritis
=====================================

There does seem to be a link between low testosterone and rheumatoid arthritis (RA), but it is not well documented or researched. It appears that some men with RA do have lower levels of testosterone, but why remains to be seen. There is a proven link however, between testosterone and osteoporosis in males.

“…there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels.”

http://arthritis-research.com/content/3/6/362/abstract

“…the male sex hormone testosterone exerts a powerful, far-ranging influence over emotional well-being, sexual function, muscle mass and strength, energy, cardiovascular health, bone integrity, and cognitive ability throughout a man's entire life.”

“This profile also provides clear insight into testosterone's synergistic impact on immune, metabolic, and inflammatory functions, allowing more effective prevention and treatment for a diverse array of health disorders, ranging from rheumatoid arthritis, heart disease, and AIDS to obesity, osteoporosis, and prostate cancer.” http://www.gsdl.com/home/assessments/malehormone/appguide/ A Finish study found no correlation between RA and testosterone levels. “The findings are not in line with the contention that low concentrations of testosterone and DHEAS play a part in the aetiology of RA.”

http://ard.bmjjournals.com/cgi/content/abstract/57/5/281

“Other researchers have conducted studies looking at how sex hormones influence RA. There also have been a limited number of investigations into the hormonal status of children with arthritis. However, the past work has looked mostly at the serum levels, and not the amount of hormone in the synovial fluid, Hendrix noted. Synovial fluid is lubricating joint oil. Serum is the fluid portion of the blood.

Zhila Ellis, Ph.D., an assistant research scientist in anatomy and cell biology who works in Hendrix's lab, led the UI investigation. In collaboration with St. Louis University's Terry L. Moore, M.D., the UI researchers examined the synovial fluid and serum from 21 JRA patients -- half of whom were between ages five and 12, the other half of whom were between 15 and 18 years old. Specifically, the researchers wanted to analyse the serum and synovial fluid for levels of testosterone, as well as the hormones dehydroepiandresterone (DHEA) and its sulphated conjugate DHEA-S, progesterone and 17 beta-estradiol.

The investigators then compared the hormone levels in the synovial fluid and serum to the levels found in the serum of a control group of subjects. The researchers did not look at the synovial fluid from the control group because it would be almost impossible to sample the small amount found in non-inflamed joints.

The UI data showed reduced levels of DHEA-S and testosterone in the synovial fluid and serum of JRA patients. In addition, the ratio of DHEA/DHEA-S in both synovial fluid and serum was much higher than that of the corresponding control serum, thus indicating the potential importance of hormonal imbalances in the JRA disease process.” http://www.docguide.com/dg.nsf/PrintPrint/2AFA02D33489C136852566D40050AEEA

“As with women, most men with osteoporosis only become aware they have it when they suffer a fracture. While both sexes run the risk of developing brittle bones as a result of smoking or drinking too much, or from taking high dose steroids over a long period, in men almost half of all diagnosed cases are idiopathic, which means there is no known cause. Twenty per cent of cases are due to a low level of the male hormone testosterone, a condition known as hypergonadism. Other causes can be hypothyroidism (under activity of the thyroid gland) hyperparathyroidism (in which too much of the parathyroid hormone is secreted, leading to calcium being drained from the bones). A new drug to counter this action could be available within a couple of years. Gastrointestinal problems such as coeliac disease, which reduces the body' ability to absorb food properly is also a known risk factor. Dr Francis has spent the past 20 years researching into osteoporosis in men, helping to establish that genetic factors play a major role in the development of the disease, and that oestrogen (the predominantly female hormone) may also play a role. He is currently running a clinical trial comparing calcium and Vitamin C plus testosterone with testosterone alone.”

http://www.arc.org.uk/newsviews/arctdy/121/manthing.htm

“…the decline of testosterone production due to aging often begins in a man's forties. At age 50, it is estimated that at least half of all males have bioavailable testosterone levels that are lower than that found in healthy young men.4 The primary cause of this decline is chronic deterioration of Leydig cells in the testes; a 20-old man has approximately 700 million Leydig cells, by age 80 that number will be reduced to about 200 million.5 This age-related drop in testosterone is more pronounced in patients with chronic illnesses such as rheumatoid arthritis or those at risk of frailty or wasting conditions. In men of advanced age (over 70), dramatic drops in testosterone levels often occur in conjunction with a decline in circulating IGF-1 levels.” http://www.gsdl.com/home/assessments/malehormone/appguide/index2.html

A low serum testosterone level is a risk factor for osteoporosis, at any age. “By age 75, one third of all men will be affected by osteoporosis. Though osteoporosis is thought of as an old person's disease, it actually can strike at any age.” http://arthritis.about.com/cs/osteopor/a/boneup.htm

“Basal serum testosterone concentrations were significantly lower in male RA patients than in the osteoarthritis control subjects (P less than 0.01). After human chorionic gonadotropin stimulation, serum concentrations of testosterone were also lower in the RA patients than in normal healthy controls (P less than 0.05). These findings suggest that diminished testicular steroid biosynthesis might contribute to the serum testosterone deficiency observed in male RA patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3140823&dopt=Citation

The study in this except shows taking testosterone injections was of no help “There was no suggestion of a positive effect of testosterone on disease activity in men with RA.”

http://rheumatology.oupjournals.org/cgi/content/abstract/35/6/568 http://ard.bmjjournals.com/cgi/content/abstract/47/1/65

The following study found men with with rheumatoid arthritis and low testosterone, who take prednisone, may be predisposed to other diseases. “Male patients with RA taking low doses of prednisone have lower testosterone and gonadotropin levels, suggesting that prednisone may suppress the hypothalmic-pituitary-testicular axis. Since testosterone affects immune function as well as bone and muscle metabolism, androgen deficiency in some men with RA may predispose these patients to more severe disease and to increased complications of steroid therapy such as myopathy and osteoporosis.”

========== Treatment: ==========

First, you should get a complete physical, especially a rectal exam (DRE) for prostate problems. Get checked for diabetes and prostate cancer with blood tests for glucose and PSA, respectively. Another blood test for testosterone would be a good idea, along with estrogen, TSH and prolactin. Ideally, have the blood drawn as early in the morning as possible. Have a second sample drawn a week or so later, for testosterone, at the same time, and be sure it is sent to the same lab. Many different testing methods are available, and you do not want to compare results from Lab A to results from Lab B, as their methodology and normal ranges will be different.

“Having confirmed the presence of testosterone deficiency, the next step is to determine the general location of the problem. If most cases of adult hypogonadism resulted from a defect in the testis, pituitary luteinizing hormone levels would be a sensitive indicator of early hypotestosteronemia. Certainly this type of response is true of hypothyroid cases in which thyrotropin values rise long before thyroxine levels drop below normal. However, the decreases in testosterone observed in most hypogonadal men are the result of inadequate pituitary luteinizing hormone secretion. Because current serum assays are unable to consistently distinguish between normal and subnormal pituitary secretion, luteinizing hormone values even in severely hypogonadal men may be reported to be within the normal laboratory range.”

http://www.postgradmed.com/issues/2003/10_03/macindoe.htm

“If I have a low testosterone level, will taking supplemental testosterone help? Maybe. Testosterone supplements, either with patches or injections, can raise testosterone levels. They may help to relieve some symptoms and to prevent muscle and bone loss that occurs with aging in men. However, this has not been definitively proven, and there is concern that testosterone replacement therapy may increase the risk of developing prostate cancer. This is because cancers grow in response to androgens, such as testosterone. In addition, although men with erectile dysfunction may have low testosterone, in many cases testosterone administration does not improve the symptoms. Therefore, consult your doctor for a medical evaluation and consultation to determine if this is the right therapy for you.”

http://www.labtestsonline.org/understanding/analytes/testosterone/faq.html

“Circulating testosterone levels have a diurnal variation in normal young men, usually reaching a mean maximum level of 25 nmol/L (710 ng/dL) at approximately 8 AM and declining to a mean minimum level of 15 nmol/L (426 ng/dL) at approximately 10 PM.This circadian variation in testosterone level appears to be a result of temporal modulation of hormone secretion by the testes rather than of a diurnal change in testosterone clearance, although the precise mechanism is unknown. Circulating testosterone is metabolized to DHT in the skin, liver, prostate, and other organs that contain the enzyme 5 -reductase.Testosterone is also metabolized to estradiol (E2) by the aromatase enzyme complex in the brain, fat, and testes.”

http://archfami.ama-assn.org/cgi/content/full/8/3/257

“A high serum prolactin level may indicate pituitary dysfunction and may require consultation with an endocrinologist. Serum LH levels are measured when serum prolactin levels are normal or low to help differentiate intrinsic testicular failure from a pituitary or hypothalamic abnormality. LH is usually high in patients with primary testicular disease. When the serum testosterone level is low and LH is elevated, testosterone replacement therapy is warranted.”

http://www.duj.com/Article/Hellstrom2/Hellstrom2.html

Rationale for prescribing testosterone replacement therapy: -stabilizing or increasing bone density -enhancing body composition by increasing muscle strength and reducing adipose -improving energy and mood -maintaining or restoring secondary sexual characteristics, libido and erectile function

http://www.duj.com/Article/Hellstrom2/Hellstrom2.html

“Testosterone Replacement Therapy is also known as androgen replacement therapy, and its goal is to eliminate symptoms in men experiencing male menopause. As testosterone deficiency is a normally a permanent condition and lifelong treatment is usually required.”

http://www.familydoctor.co.nz/conditions.asp?A=32750&category_name=&

Studies were done, comparing 3 forms of testosterone therapy; implants, injections, and oral tablets. The study concluded the testosterone implant was more effective.”… implantation remains overall the most physiological form of androgen replacement therapy, is generally well accepted and attended by few side effects; TU may have a useful role in the initial phases of therapy.”

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6467640&dopt=Citation

“In addition to its relatively uncommon congenital causes, testosterone deficiency in men occurs in a diverse range of clinical conditions. Even healthy men are now known to begin experiencing progressive yet subtle declines in testosterone secretion after age 30. Diagnosis can be challenging, and testosterone replacement therapy does not alleviate all symptoms in all men. Nevertheless, some men can get relief with intramuscular long-acting testosterone esters, transdermal testosterone patches, or transdermal testosterone” And “The most common symptoms of testosterone deficiency in men (eg, loss of libido, sexual dysfunction, fatigue, loss of stamina, depressed mood) are vague and not specific for hypogonadism. Furthermore, men as a group interact with the healthcare system far less often than women, and when they do visit the physician's office, they often do not volunteer such complaints unless directly questioned about them. Physicians can minimize the chance of missing these complaints by routinely asking about libido, sexual function, and stamina in their systems assessment. An alternative is to use a simple questionnaire that patients can fill out in the waiting room.”

http://www.postgradmed.com/issues/2003/10_03/macindoe.htm

“Patients with normal or slightly low levels of testosterone most likely will derive no benefit from replacement therapy and as such it is not recommended.”

http://www.urosoc.org.au/info/hormonereplacement.html

Testosterone therapy can be administered in several ways, such as gels, injections, patches, injections and implants. “Testosterone replacement has also been linked to improvement in men's mental functioning, night sweats, bone density and muscle mass.”

http://www.familydoctor.co.nz/conditions.asp?A=32750&category_name=&

--------------------------------------------------------
Transdermal Delivery: Gels, Creams, Patches, and Pellets
--------------------------------------------------------

Human skin is able to absorb hormones into the bloodstream rather effectively. Controlled transdermal delivery of testosterone, at a contstant rate is possible, maintaining a steady blood level. Injections can cause very high and very low levels. About 50% of men who participated in clinical trials had a skin reaction to the patch, ranging from mild to blisters. It was found that applying a 0.1% triamcinolone acetonide cream before applying the patch eliminated most skin reactions.

“Because scrotal skin is at least 5 times more permeable to testosterone than are other skin sites, the first available testosterone transdermal delivery system (Testoderm; Alza Pharmaceuticals, Palo Alto, Calif) was designed as a scrotal patch. Patients using the scrotal testosterone system have reported substantially improved sexual function, including the achievement of potency, and an improvement in sense of well-being, mood, and energy.”

http://archfami.ama-assn.org/cgi/content/full/8/3/257

“Currently, three testosterone transdermal systems are marketed: a system applied to the scrotum that has no permeation enhancers [Testoderm, 6 mg, ALZA Corporation, Palo Alto, CA] and two systems that contain permeation enhancers for application to appendage or torso skin [Androderm 2.5 mg and 5 mg, SmithKline Beecham Pharmaceuticals, Philadelphia, PA; Testoderm TTS, 5 mg, ALZA Corporation, Palo Alto, CA]. Scrotal patches produce high levels of circulating dihydrotestosterone (DHT) due to the high 5-alpha-reductase enzyme activity of scrotal skin. Clinical studies of transdermal systems demonstrate their efficacy in providing adequate testosterone replacement therapy.Skin irritation may be associated with the use of transdermal systems; however, Testoderm and Testoderm TTS caused significantly less topical skin irritation than Androderm in two separate clinical studies.”

http://www.duj.com/Article/Hellstrom2/Hellstrom2.html

Testosterone gel may increase muscle mass in men, but it is not without potential side effects. Testosterone may lower HDL, known as the “Good Cholesterol”, and some studies show it may cause liver problems in some men. Although testosterone has not been shown to cause prostate cancer, it can accelerate cancer growth in men that may have unknown prostate cancer.

“Nonscrotal transdermal testosterone patches (Androderm, Testoderm TTS) are applied daily and are available in a 2.5-mg (Androderm) and a 5-mg (Androderm and Testoderm TTS) dose. Blood testosterone levels rise to peak values within 4 to 6 hours after application, then decrease slightly to remain within the physiologic range over the next 18 to 20 hours. Applying a patch after showering at night can reproduce diurnal testosterone levels similar to those seen in younger men, in whom morning values are somewhat higher than evening ones. The most common side effect reported is skin irritation. Its frequency seems to increase with age in men over age 50. It often can be prevented or reduced by rubbing triamcinolone cream (Aristocort, Atolone, Kenacort) into the skin before application of the patch.” http://www.postgradmed.com/issues/2003/10_03/macindoe.htm ”AndroGel is a clear gel that is rubbed into the shoulders, upper arms or abdomen every day to maintain more even levels of testosterone in the body. It's available only by prescription, and men who take it must be evaluated and monitored by a doctor.

AndroGel has caught the attention of men like Poltz because it is easier to use than previous testosterone medications. Until AndroGel hit the market, men needing a testosterone boost had to give themselves injections or wear a patch on their skin. Injections can't mimic the body's fine control of the hormone, so men often experience emotional and physical ups and downs, including irritability right after the injection and fatigue as it wears off. The patches maintain testosterone at a more even level but can cause skin irritation and may fall off in hot weather.”

“For years, doctors have used testosterone as a medical treatment for some men who have abnormally low levels of the hormone because of the aging process, chronic disease or exposure to alcohol or chemicals. Symptoms of low testosterone include fatigue, decreased sex drive, depression and low energy. Between 4 million to 5 million men have this medical condition, according to Unimed Pharmaceuticals, the company that makes AndroGel. Some experts say that about 25 percent of men go through andropause, the male version of menopause, in which levels of testosterone drop significantly with age. However, in most men, testosterone levels don't change much with age.”

http://www.intelihealth.com/IH/ihtIH/WSIHW000/23414/24788.html

“Recent research from Harvard Medial School shows that rubbing testosterone gel on the skin can help relieve depression in middle-aged men with low blood testosterone levels. In the 1940s, experiments showed that major depression can be relieved by injecting testosterone into men with low levels. The treatment never caught on because effective antidepressant drugs started coming to market. More recently, however, testosterone patches and gels became available. In June 2000, the United States Food and Drug Administration approved a new form of gel for treating muscle loss, decreased sex drive, lack of energy, and other symptoms of so-called hypogonadism, or underactivity of the testes.

Harrison Pope, A professor of psychiatry are Harvard Medical School wondered if the gel might also help males with the combination of low testosterone and depression not treated successfully with drugs. He received a grant from Unimed Pharmaceuticals Corp., which makes a topical skin testosterone gel called AndroGel. Of the first 56 men screened, Pope and his colleagues found 24 who were both depressed and had low levels of that hormone. More than 40 percent of the men who applied to be admitted to the study suffered from both low testosterone and depression.

Twelve men rubbed 2.5 grams of AndroGel on their skins each night. Another 10 subjects received identical packets containing a placebo. By the end of the experiment, Pope found a significant improvement in mood among those taking testosterone compared with those using the dummy rub. Ten men on the active gel completed the full eight-week study. Three showed almost no improvement, and four experienced only modest relief. However, three enjoyed "striking, dramatic gains."” http://www.drmirkin.com/men/1732.html

•Scrotal patch (Testoderm). Thin scrotal skin is much more permeable to testosterone absorption than other skin sites. You apply this patch in the morning and remove it before bathing or sexual intercourse. Itching and skin irritation can occur, but they're usually mild and diminish with continued use.

•Nonscrotal patch (Androderm). This patch is applied each night to your back, abdomen, upper arm or thigh. The site of the application is rotated to maintain 7-day intervals between applications to the same site. Up to 50 percent of men experience some skin reaction to this product, with approximately 7 percent having a severe reaction.

http://www.cnn.com/HEALTH/library/DS/00300.html

To use testosterone topical scrotal patches: • Testoderm patches should be applied to clean, dry scrotal skin. The scrotal hair should be dry-shaved before a patch is applied. Do not use chemical hair removers to remove scrotal hair.

• Each patch should be worn for 22 to 24 hours.

• Apply a new patch every 24 hours.

• Scrotal patches should be removed during bathing, showering, or swimming and may be reapplied following these activities. Patch removal is optional during intercourse.

• If a Testoderm patch falls off, try to reapply it. If it comes off after being worn for more than 12 hours and it cannot be reapplied, wait until the next scheduled application time to apply a new system.

http://www.drugs.com/MTM/testosterone_topical.html You rub testosterone gel (AndroGel, Testim) into your skin on your lower abdomen, upper arm or shoulder. As the gel dries, your body absorbs testosterone through your skin. Avoid showering or bathing for several hours after an application to ensure adequate absorption. A potential side effect of the gel is the possibility of transferring the medication to your partner. You can avoid this by waiting approximately 5 hours after an application or covering the area before having skin-to-skin contact.

--------------------------------------- Gum and cheek (buccal cavity) delivery ---------------------------------------

Striant, a small putty-like substance, delivers testosterone through the natural depression above your top teeth where your gum meets your upper lip (buccal cavity). This product rapidly adheres to your gumline and, as exposed to saliva, softens into a gel-like form, allowing testosterone to be absorbed directly into your bloodstream.

http://www.cnn.com/HEALTH/library/DS/00300.html

From the makers of Striant, “STRIANT is a unique system for providing testosterone to your body. It is a very small tablet-like product that you put in a comfortable position between your cheek and gum. Once there, STRIANT gradually releases testosterone that is absorbed into your bloodstream through your cheek and gum. This type of medication delivery is called “buccal” (BUCK-al) delivery. STRIANT should not be swallowed because testosterone is broken down by the digestive system and would not be useful to the body.

STRIANT is applied twice daily. This twice-a-day dosing allows it to keep your body’s testosterone at normal levels throughout the day.

STRIANT delivers amounts of testosterone to your body that approximate amounts seen in healthy young men.

Placed properly, the buccal system will soften, producing a gel-like form that remains in place over each 12-hour dosing period. STRIANT is designed to stick to the tissue of your gum or cheek as it absorbs moisture. It will stay in place, gradually releasing testosterone that is absorbed through your gum and cheek directly into your bloodstream.”

http://www.columbialabs.com/Striant/StriantPatientBooklet.htm http://striant.drugs.com/

----------- Injections: -----------

“In men 20-50 years of age, an intramuscular injection of 200 to 300 mg testosterone enanthate is generally sufficient to produce serum testosterone levels that are supranormal initially and fall into the normal ranges over the next 14 days. Fluctuations in testosterone levels may yield variations in libido, sexual function, energy, and mood. Some patients may be inconvenienced by the need for frequent testosterone injections.11 Increasing the dose to 300 to 400 mg may allow for maintenance of eugonadal levels of serum testosterone for up to three weeks, but higher doses will not lengthen the eugonadal period.” http://www.duj.com/Article/Hellstrom2/Hellstrom2.html

A German study of testosterone undecanoate showed good results in participants. “The i.m. injections of 1000 mg TU into either one or both gluteal regions were well tolerated by all 21 hypogonadal patients included in the studies. No serious adverse effects were observed. In study II, detailed weekly diaries of 4 out of 14 patients revealed some discomfort at the injection site persisting not longer than 1 week after injection; one patient reported some pain at the injection site on day 14. No patient reported the injections to be more painful or inconvenient than former i.m. injections. One patient reported transient testicular pain at day 28. Clinical examinations revealed no new occurrence of gynecomastia nor any enlargement or soreness of the liver; one patient showed sporadic signs of acne 2 and 5 weeks after TU injection. No patient discontinued treatment because of side-effects.

http://www.eje.org/eje/140/0414/1400414.pdf

Testosterone injections should NOT be used in the following circumstances: • Breast cancer in men

Breastfeeding
Cancer of the prostate
Pregnancy

“This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.”

Possible Side Effects of Testosterone Injections:

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

• Persistent painful erection of the penis (priapism)

• Reduced volume of ejaculation

• Premature closure of the ends of bones in prepubescent males causing stunted growth

• Decreased sperm count (oligospermia)

• Hoarse voice

• Sodium and water retention

• Increased frequency of erections in prepubescent boys

• Premature sexual development in prepubescent boys

• Enlargement of the penis in prepubescent boys

http://www.tiscali.co.uk/lifestyle/healthfitness/health_advice/netdoctor/archive/100004308.html

------------------ Oral Testosterone: ------------------

“Although testosterone supplements are manufactured in capsule or pill form, they are not generally recommended for use in the United States. They are quickly broken down by the liver and do not achieve high enough blood levels to be useful. They also may cause adverse changes in blood lipids (fats) and liver damage. [AACE Clinical Practice Guidelines]”

http://www.androgel.com/diagnosis/treating.htm

“Several alkylated derivatives of testosterone are available for oral or sublingual use, including methyltestosterone and fluoxymesterone. Alkylated androgens are more slowly metabolized by the liver than is natural testosterone, but, like testosterone, these androgens interact directly with androgen receptors. Although their oral route of administration is advantageous, clinical response is variable and plasma levels cannot be determined, because alkylated androgens are not recognized by most testosterone assays. Moreover, in our clinical experience, alkylated androgens may increase levels of low-density lipoprotein cholesterol and profoundly suppress high-density lipoprotein cholesterol levels because of their route of absorption and metabolism. Prolonged use of high doses of androgens (principally the 17 -alkylated androgens) has been associated with development of the following potentially life-threatening conditions: hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis. Cholestatic hepatitis and jaundice may occur at relatively low doses of 17 -alkylated androgens.”

http://archfami.ama-assn.org/cgi/content/full/8/3/257

One man from the UK says, of oral testosterone: “'He put me on testosterone tablets immediately,' said Reg. 'Within two days I began to feel better and after a week I was back to normal. It was like turning the clock back to when I was in my 20s or 30s,' he said.

'I have now been having testosterone treatment for five years and I can honestly say I couldn't live without it. When I have stopped taking it, all the symptoms return. I don't get it on the NHS and it costs me about £1000 a year which to me is money well spent,' explained Reg.”

http://www.netdoctor.co.uk/menshealth/feature/malemenopause.htm

---------------- Pellet Implants ----------------

Pellets are a newer, testosterone delivery system.

“The pellet is loaded in the pellet inserter and placed into the buttock once every 2-5 months. The pellets slowly release the hormone, usually preventing a 'crash' in hormones until the end of treatment. Most insurance companies, including Blue Cross, reimburse the placement of pellets. The pellets may or may not be reimbursable by individual policies. Medicare does not cover pellets.” http://www.usdoctor.com/pellets.htm

Many years ago, the Food and Drug Administration approved the use of testosterone pellets for male hormone deficencies. They are manufactured in our office by a compounding pharmacist. We place 6-8 testosterone pellets under the skin. These pellets dissolve slowly over a period of approximately three to four months. This provides a normal and very stable serum testosterone level. I feel that the addition of androgens in this form causes less lowering of HDL cholesterol, as this does not pass through the liver.

The implant procedure consists of a small incision through which a trocar and cannula are inserted. The pellets are inserted through the cannula, and then the cannula is withdrawn. The incision is then closed with a Steri-Strip, and pressure is applied until bleeding stops, and the area is then covered with a dressing. We have not had any major problems in terms of side effects from this procedure. Some expertise is required in terms of placing the pellets so that underlying structures are not traumatized.

The average cost per visit (approximately every 3 months) is in the range of $400. Insertion Fee is $160.00 and Pellets cost $33.00 apiece.The requirement for the use of subdermal pellets include

Good General Health

No evidence for heart disease

Normal Cholesterol levels

Normal PSA levels

Normal prostate examination, no history of prostate disease http://www.midlife-passages.com/hormone.htm

One health insurance company’s take: “Aetna considers implantable testosterone pellets (Testopel Pellets) medically necessary subject to the following selection criteria: A. As second-line testosterone replacement therapy in males with congenital or acquired endogenous androgen absence or deficiency associated with primary or secondary hypogonadism when neither oral nor intra-muscular testosterone replacement therapy is effective or appropriate. Primary hypogonadism includes conditions such as testicular failure due to cryptorchidism, bilateral torsion, orchitis, or vanishing testis syndrome; inborn errors in testosterone biosynthesis, or bilateral orchiectomy. Hypogonadotropic hypogonadism (secondary hypogonadism) conditions include gonadotropin-releasing hormone (GnRH) deficiency or pituitary-hypothalamic injury as a result of surgery, tumors, trauma, or radiation, and are the most common forms of hypogonadism seen in older adults.

B. For treatment of delayed male puberty. A 6-month-or-shorter course of androgen may be indicated for induction of puberty in members with familial delayed puberty, a condition characterized by spontaneous, non-pathological, late-onset puberty.”

http://www.aetna.com/cpb/data/CPBA0345.html

An Australian study concluded “We conclude that fused pellets of crystalline testosterone provides very satisfactory depot androgen replacement exhibiting many desirable features for androgen replacement.”

http://jcem.endojournals.org/cgi/content/abstract/71/1/216 “Testosterone pellets are currently in use in the United Kingdom and in Australia; 3 to 6 testosterone pellets, 200 mg each, are implanted subcutaneously every 4 to 6 months. Testosterone buciclate, an experimental formulation, is a long-acting 17 -hydroxyl ester of testosterone administered intramuscularly at a dosage of 600 mg every 12 weeks.”

http://archfami.ama-assn.org/cgi/content/full/8/3/257 Side Effects of Testosterone:

“Androgen therapy does lead to recovery of a normal prostate size (the prostate shrinks when testosterone levels are low). It does not affect prostate specific antigen (PSA) levels. Androgen therapy is not thought to increase the risk of prostate cancer above that of men with naturally higher testosterone levels of the same age.

However, the safety of androgen therapy on the cardiovascular system, prostate and mental functioning still needs to be properly studied. Further well conducted investigations into whether androgen therapy benefits bone and muscle are also needed.

Androgen therapy is believed to be a risk factor for heart disease but the existing studies are inconclusive. In fact, low testosterone levels have been recorded prior to heart attacks which may indicate that hormone therapy could help protect against cardiovascular disease.

The use of androgens should also be used with caution in older men who may have undiagnosed prostate cancer. Sleep apnoea is also an occasional risk factor with androgen therapy.

http://www.familydoctor.co.nz/conditions.asp?A=32750&category_name=& “With any testosterone delivery system, prolonged use may cause liver damage, breast enlargement, or increase the risk of prostate enlargement. Geriatric patients who could be at risk of prostate cancer should be evaluated prior to initiation of treatment. In addition, fluid accumulation may be a serious complication in patients with preexisting heart, kidney or liver disease, with or without heart failure. Men with breast cancer or known or suspected prostate cancer should not receive testosterone therapy. The patch, gel and injections are not indicated for use in women and should not be used in women. Testosterone may cause fetal harm.

Patients taking testosterone should be instructed to report any of the following to their physician:

• Too frequent or persistent erections

• Any nausea, vomiting, changes in skin color, or ankle swelling

• Breathing disturbances, including those associated with sleep.”

http://www.androgel.com/diagnosis/treating.htm

======================= Additional Information: =======================

“What is bioavailable testosterone? Testosterone is present in the blood as "free" testosterone (2-3%) or bound testosterone. The latter may be bound to either albumin (a serum protein) or to a specific binding protein called Sex Steroid Binding Globulin (SSBG) or Sex Hormone Binding Globulin (SHBG). The binding of testosterone to albumin is not very tight and is easily reversed; so the term bioavailable testosterone (BAT) refers to the sum of free testosterone plus albumin-bound testosterone. Alternatively, it is the fraction of circulating testosterone that is not bound to SSBG. It is suggested that BAT represents the fraction of circulating testosterone that readily enters cells and better reflects the bioactivity of testosterone than does the simple measurement of serum total testosterone. Also, varying levels of SSBG can result in inaccurate measurements of BAT. Decreased SSBG levels can be seen in obesity, hypothyroidism, androgen use, and nephritic syndrome. Increased levels are seen in cirrhosis, hyperthyroidism, and estrogen use. In these situations, measurement of free testosterone may be more useful.”

http://www.labtestsonline.org/understanding/analytes/testosterone/faq.html

Testosterone and the Brain

http://my.webmd.com/content/article/25/2952_1502 Here’s a short quiz that may be useful to you:

http://www.seekwellness.com/andropause/adam_quiz.htm More on testosterone injections

http://www.healthdigest.org/TESTOSTERONE-(Injection)-(Injectable)_6762_PRO.php Other Google Answer Questions you may find useful:

http://answers.google.com/answers/threadview?id=321268 http://answers.google.com/answers/threadview?id=355536 http://answers.google.com/answers/threadview?id=402073

Let me point out that this answer is for informational purposes only, and is not intended to diagnose or treat any medical condition, or to replace sound medical advice from a licensed physician. Please discuss your concerns with your physician. Now that you are informed as to what treatment exists, you and your doctor can determine if testosterone replacement therapy is for you, and if so, which form would be best.

If any part of my answer is unclear, please request an Answer Clarification, before rating. By doing so, I can assist you further, if possible. I wish you the best!

Regards, crabcakes

Search Terms Androgen replacement therapy Transdermal delivery testosterone Hypogonadism + arthritis Testosterone injections Testosterone + arthritis + men Testosterone + depression

Comments Log in to add a comment Subject: Re: Low testosterone in Men From: thedon1-ga on 09 Jun 2005 10:44 PDT I too have low testosterone for a young man (29)...no chronic illness and/or diseases. I'm eat healthy and workout regularly (5'10"; 78lb; 14%body fat). The one thing is I have been taking Propecia for the last 9 years...with success. Never had any of the symptoms described as the side effects. However, I just noticed symptoms that concerned me (erections weren't as strong; rarely any morning erections and if so they were more 'chubbies'; also desire was lowered (quit masturbating and was only having sex 5x a week w/fiance...as opposed to daily masturbating and daily sex). This was ongoing for 2 months before I saw my physician (didn't know if it was physcological...until i realized the loss of morning erections) Initial Dr response was that I'm probably fine and blood tests showed no issues with Thyroid. Requested Hormone test to be done and also a referral to urologist. Tests came back and sure enough my Total Testosterone measured 276 ng/dL and Free Testosterone is 9.4 pg/mL (ranges i was given are 260-1000 ng/dL for TT and 10.3-28.8 pg/mL for FT). Urologist was somewhat surprised by my low level of Free Testosterone...figuring the Propecia would make it go higher. Also, the fact that my Total Testosterone was so low. Were in process of measuring my Prolactin levels to see if there is any Pituitary tumor and if so go from there. Otherwise it may be in my testicles...which is odd cuz I've never had this before...nor has anyone in my family (both sides of my family have tons of kids and healthy lives). I'll fill you in on what comes out of my tests and experience. I hope I don't have to take Testosterone replacement therapy...but if that's the case oh well. I do want to have children! I hope there will be no issues there. Good luck!

Article from http://answers.google.com/answers/threadview?id=450553