Low Testosterone

Testosterone is a hormone made mostly by the testicles in men. It plays an important role in making new red blood cells, increasing muscle mass and strength, enhancing sex drive, maintaining sperm production, and improving bone density

Low testosterone is typically due to one of the following issues:

• The testicles are not making a normal level of testosterone even though the brain is sending the right signals. This is referred to as primary hypogonadism.
• The part of the brain that normally sends a signal to the testicles to make testosterone (the hypothalamus or pituitary gland) is not working correctly. This is referred to as secondary hypogonadism.

It is normal for testosterone levels to decrease with age. By age 60, 20% of men have low testosterone. It is estimated that 4 million American men are living with low testosterone, but only about five percent receive treatment.

Low testosterone is diagnosed by both an abnormal lab value, as well as the presence of at least one of the following symptoms:

• Low sex drive
• Reduced energy level, endurance or physical strength
• Decreased lean muscle mass or physical strength
• Difficulty gaining lean muscle mass or losing body fat
• Erectile dysfunction or impotence
• Male infertility
• Depression
• Mood swings
• Irritability
• Poor memory
• Difficulty concentrating
• Hot flashes

Other physical symptoms of low testosterone that men may notice are increased body fat in the abdominal area, decreased body hair growth, reduced size or firmness of the testicles, breast enlargement, and muscle loss. While testosterone influences voice changes and penis size during puberty, it does not have this affect in adults. Just as estrogen is important for bone health in women, testosterone is important for bone strength in men. Men with low testosterone are at increased risk for osteoporosis and fractures.

Rarely, low testosterone may be caused by one of the following conditions that may be present at birth:

• Klinefelter syndrome. This condition is due to a chromosome abnormality that results in an extra X chromosome leading to abnormal development of the testicles.
• Kallmann syndrome. This condition is the result of abnormal development in the area of the brain that controls the secretion of pituitary hormones. Men with Kallmann syndrome are typically unable to smell (anosmia) and may have red-green color blindness.
• Undescended testicles. The testicles develop inside the abdomen in utero and gradually move down to the scrotum by birth. If there’s a problem in this process, one or both testicles may not function correctly.
• Noonan syndrome. This condition is due to an altered (mutated) gene that results in multiple birth defects including undescended testes.

Most commonly, low testosterone is due to one of the following conditions or exposures:

• Normal aging. Testosterone gradually decreases with age and may be related to aging itself or other medical conditions that come with age.
• Injury to the testicles. If one testicle is injured, the other testicle will typically make enough testosterone and sperm to compensate. Levels may be abnormally low if the other testicle is not functioning normally.
• Chemotherapy or radiation therapy. Various types of cancer treatment can interfere with testosterone and sperm production. The treatment effects may be temporary or can result in permanent changes.
• Pituitary tumors. A tumor located near the pituitary gland in the brain can affect the production of testosterone or other hormones.
• Obesity. Increased body fat affects testosterone production by increasing conversion of testosterone to estrogen.
• Liver disease. Liver disease affects the production of testosterone and the availability of testosterone in its active form.
• Mumps orchitis. A mumps infection during childhood can permanently affect testosterone and sperm production.
• HIV/AIDS. HIV/AIDS can affect the hypothalamus, pituitary, and testis.
• Medications. There are various medications including anabolic steroids, opiates, and glucocorticoids that can affect testosterone production.

Low testosterone should be diagnosed by a healthcare provider with a history, physical exam, and laboratory testing.

History

Questions that your healthcare provider may ask you about your history include:

• Age you went through puberty relative to your peers
• Headaches or vision changes
• Loss of or decreased ability to smell
• History of head trauma
• History of injury or infection of the testicles
• History of mumps
• Current or past use of steroids
• Current or past use of opiates
• Current or past use of glucocorticoids
• History of chemotherapy or radiation
• History of diabetes, stroke, or heart attack
• Alcohol intake
• History of smoking
• Use of illicit drugs including marijuana
• Family history of conditions associated with low testosterone

Physical Examination

Your healthcare provider will examine you for the following:

• Body mass index or waist circumference
• Signs of metabolic syndrome such as high blood pressure, elevated blood sugar, excess body fat around the waist, and elevated cholesterol or triglyceride levels
• Body hair growth
• Enlarged breasts (gynecomastia)
• Testicle size, firmness, and location
• Prostate size and any abnormalities

Laboratory Testing

Your healthcare provider may order the following blood tests:

• Total testosterone level. Normal testosterone levels peak in the morning and decline throughout the rest of the day. To confirm a diagnosis of low testosterone, you should have your levels drawn on two separate occasions, both within several hours after waking. An abnormal level is considered less than 300 ng/dl, although the exact number may vary depending on your symptoms.
• Luteinizing hormone. This test is done to look for causes of low testosterone. An abnormal level can indicate a pituitary problem.
• Prolactin level. An elevated prolactin level can be a sign of a pituitary problem or tumor.
• Hemoglobin level. A decreased hemoglobin level may be seen in men with low testosterone. Your healthcare provider should check you level before starting any treatments for low testosterone, because some treatments can increase the level.

After confirming a low testosterone level, your healthcare provider may order one of the following tests:

• Follicle stimulating hormone. This hormone is important for sperm production, and should be checked if you have abnormal sperm counts.
• Estradiol level. This hormone may be obtained if you have any breast symptoms, are obese, or are considering starting certain medications to treat low testosterone.
• PSA (prostate specific antigen). This is a blood test used for prostate cancer screening. A PSA should be checked in men over age 40 prior to starting testosterone therapy.
• MRI Brain. This test is done to look for abnormalities or tumors of the pituitary gland if you have symptoms of a pituitary problem such as headache or visual changes, if your prolactin level is elevated, or if other pituitary hormones are low (FSH, LH).
• Bone density test (DEXA scan). This is a test to screen for decreased bone mineral density, called osteopenia or osteoporosis, depending on the severity.
• Karyotype analysis. This is a chromosome test to diagnose Klinefelter syndrome.

Benefits of Testosterone Use

Restoring low testosterone levels to a normal level may improve your sex drive, erectile function (your ability to get and maintain an erection), and frequency of spontaneous erections (morning erections). If your decreased sex drive or erectile dysfunction is due to medication that you’re taking or other medical conditions (such as diabetes or high blood pressure), you may not experience a significant improvement in these symptoms even with testosterone therapy.

Testosterone therapy may improve symptoms of erectile dysfunction, libido, anemia, and depressive symptoms. You may also find that it is easier to build muscle mass and/or lose body fat with a diet and exercise program. Testosterone may also be beneficial for increasing bone mineral density, which may be of particular importance in older men.

For men who are concerned about maintaining their fertility, or who are currently trying to get their partner pregnant, discuss this with your healthcare provider prior to starting testosterone therapy. Taking testosterone will lower your sperm counts while you’re on the medication, and it is unknown if long-term treatment may result in permanent effects on fertility.  There are other medications that can be used in this situation to increase your testosterone levels and maintain sperm production.

There are several symptoms which have been reported to improve with testosterone therapy, such as energy, physical endurance, memory, and ability to concentrate.  However, currently available research is often contradictory on these symptoms, and it is not clear if testosterone does or does not improve them in most men.   

Side Effects of Testosterone Use

Testosterone therapy is generally well-tolerated, but it is important that your healthcare provider monitor symptoms and blood work regularly. Potential side effects of testosterone therapy include:

• Skin irritation. Skin rash or itching is more common with the patch, and less common with other forms of testosterone therapy.
• Skin changes. Acne, increased body hair, and facial flushing can occur with any formulation although it is more common at higher testosterone levels.
• Pain. Pain or inflammation at the site of injection with testosterone injections. This may be associated with bruising, bleeding, or redness of the area. Some people may have an allergic reaction to long-acting testosterone injections, which is why you will need to be observed for a period of time in your healthcare provider’s office.
• Enlarged or painful breasts. Breast tenderness or increase in size (gynecomastia) can occur with any formulation of testosterone.
• Decrease in sperm production. Typically this is a temporary effect while on the medication, but it can take up to 12 months for sperm counts to return to normal after stopping testosterone therapy. Although there is little long-term information available, it is possible that sperm counts may not recover in a percentage of men, even after stopping treatment, particularly for men who on long-term testosterone therapy (greater than 12 months).
• Increase in red blood cell count, hematocrit or hemoglobin. The risk is greatest with testosterone injections, particularly when testosterone levels are much higher than what is considered the normal range. This is why it is important for your healthcare provider to check your testosterone levels and blood counts regularly.
• Liver problems. Some patients may have an increase in their liver function numbers. These changes will typically go away when you stop taking testosterone therapy. If you have a history of liver disease, tell your healthcare provider before staring testosterone therapy.
• Abuse. Testosterone can be abused, when taken at higher than prescribed doses and when used with other anabolic androgenic steroids. Abuse can cause serious side effects, including with the heart, red blood cells, brain, and other areas of the body.
• Change in mood. Talk to your healthcare provider if you have changes in mood or behavior.

What about other side effects?

• Prostate cancer. At this time there is no evidence linking testosterone therapy to prostate cancer. Prior to starting testosterone therapy, your healthcare provider should check a blood test called PSA if you are over age 40. In men with a history of prostate cancer, talk to your healthcare provider about the risks of testosterone therapy.
• Blood clots. There is no strong evidence that links testosterone therapy to an increased risk of blood clots that could lead to a deep vein thrombosis or pulmonary embolism. If you have a personal history or family history of blood clots, talk to your healthcare provider before starting testosterone therapy.
• Cardiovascular events. At this time there is no strong evidence that testosterone therapy either increases or decreases the risk of a heart attack or stroke. If you have a history of either, talk to your healthcare provider before starting treatment. If you have symptoms of a heart attack or stroke while on testosterone therapy, seek medical attention immediately.

Treatment Options

There are five general forms of testosterone therapy:  topical (patches and gels), oral (by mouth), intranasal (through the nose), pellets under the skin, and injections. Each method is effective, but some may work better with your lifestyle.

• Topical (patches and gels). Testosterone is available as a topical gel, cream, liquid, or patch.Most topical medications last for about four days, but some may have to be applied daily. You should avoid washing the area until it is time for the next dose, and be sure to wash your hands. Women and children should avoid touching the area and should launder clothing separately because they may absorb the medication through their skin or clothes.
• Oral (by mouth). Testosterone is now available in a pill form in the U.S. It is also available as a patch that you place against your gum just to the side of your front teeth. This patch should not be swallowed. The medication must be applied every 12 hours.
• Intranasal (through the nose). This form of testosterone comes in gel form. It is applied with a pump into each nostril three times a day.
• Pellets (placed under the skin). Your healthcare provider will place testosterone pellets under the skin in your buttock area in the office. You will receive numbing medication in the area, and a small cut (less than 1 inch) will be made in the skin to apply the pellets underneath the fatty tissue. This is a long-acting medication that is released slowly over time, and will need to be reapplied every 3-6 months.
• Injection. There are short and long-acting forms of injectable testosterone. They are injected under the skin or into the muscle. Your healthcare provider will teach you how to perform the short-acting injections at home either weekly, or every two weeks. Some of the long-acting injections must be performed in your healthcare provider’s office so that you can be monitored for a period of time afterward. These injections are performed 4 weeks apart for the first two injections, then every 10 weeks.

Word of Caution about Testosterone Therapy

Men should exercise caution with Men’s Health clinics that advertise testosterone therapy as a cure-all or the fountain of youth. While there are many benefits to testosterone therapy, there are also risks, particularly if you are not being monitored appropriately. Testosterone therapy is not a substitute for diet, exercise, and physical activity, which will have long-lasting benefits without the risks. You should not take testosterone obtained without a healthcare provider’s prescription. Any healthcare provider prescribing testosterone should monitor your testosterone levels and safety labs every 6-12 months. If your testosterone levels are above the normal range, your healthcare provider should lower the dose, reduce the frequency, or change the form of testosterone that you are taking.

Monitoring While on Testosterone

While on testosterone therapy you need regular follow up with your healthcare provider. Once you’ve achieved stable testosterone levels in the normal range, you should have blood tests performed every 6-12 months. This would include at a minimum a total testosterone and hematocrit.  Other labs may also be obtained depending on your specific condition.

• Erectile dysfunction
  • It is common that men with low testosterone may also have erectile dysfunction (trouble getting or maintaining an erection). Restoring a low testosterone level to normal levels may improve the quality of your erections. There are also many other causes of erectile dysfunction. Improving testosterone levels may not be enough to treat erectile problems, and you may benefit from additional medication to address your erections.
• Obesity
  • Men who are obese are more likely to have low testosterone levels. Weight loss, even without testosterone therapy, improves natural testosterone levels. Testosterone therapy may help to jump start a weight loss program, as it is associated with decreasing fat levels and increasing lean muscle mass. Then, as you improve your physical fitness and increase lean muscle mass further, your body will start to naturally produce more testosterone to the point that you may be able to discontinue testosterone therapy.
• Sleep apnea
  • Sleep apnea is associated with low testosterone, obesity, erectile dysfunction, and decreased sex drive.
• Diabetes
  • A third of men with type 2 diabetes also have low testosterone. Obesity is the biggest risk factor for type 2 diabetes. Losing weight will help improve glycemic control and increase natural testosterone production.
• Cardiovascular disease
  • Low testosterone is a risk factor for cardiovascular disease, such as a heart attack or stroke. Currently there is no strong evidence that testosterone therapy increases or decreases the risk of a heart attack or stroke. Men with a history of a heart attack or stroke should consider waiting three to six months before starting testosterone therapy.
• Prostate cancer
  • There is no strong evidence that testosterone therapy causes prostate cancer. The risk of prostate cancer increases with age, just as the incidence of low testosterone increases with age, which is why men over age 40 should have a PSA (blood test for prostate cancer screening) and digital rectal exam checked prior to starting testosterone therapy. If the PSA is elevated, you should discuss this with a urologist who may recommend further testing.
  • Men with a history of prostate cancer and low testosterone may consider testosterone therapy. Discuss this with your healthcare provider prior to starting as the safety of testosterone in this setting is not well studied.

Condition overview written by Sevann Helo, MD