March 11, 2008
By Robert H. Shmerling, M.D.
Beth Israel Deaconess Medical Center
When you think of testosterone, what comes to mind? Macho men? Aggressive, impatient, type A behavior? Road rage? Violence?
Testosterone's role in bad behavior is largely a myth. What's more, testosterone plays other important roles in health and disease that may surprise you. For example, did you know that testosterone is a key player in prostate cancer? Or, that women need testosterone, too? There's more to testosterone than guys behaving badly.
Testosterone's Role
Testosterone is the major sex hormone in males and plays a number of important roles, such as:
The development of the penis and testes
The deepening of the voice during puberty
The appearance of facial and pubic hair starting at puberty; later in life, it may play a role in balding
Muscle size and strength
Bone growth and strength
Sex drive (libido)
Sperm production
Adolescent boys with too little testosterone may not experience normal masculinization. For example, the genitals may not enlarge, facial and body hair may be scant and the voice may not deepen normally.
Testosterone may also help maintain normal mood. There may be other important functions of this hormone that have not yet been discovered.
Signals sent from the brain to the pituitary gland at the base of the brain control the production of testosterone in men. The pituitary gland then relays signals to the testes to produce testosterone. A "feedback loop" closely regulates the amount of hormone in the blood. When testosterone levels rise too high, the brain sends signals to the pituitary to reduce production.
Did You Know?
Testosterone is synthesized in the body from cholesterol. But having high cholesterol doesn't mean your testosterone will be high. Testosterone levels are too carefully controlled by the brain for that to occur.
If you thought testosterone was only important in men, you'd be mistaken. Testosterone is produced in the ovaries and adrenal gland. It's one of several androgens (male sex hormones) in females. These hormones are thought to have important effects on:
Ovarian function
Bone strength
Sexual behavior, including normal libido (although evidence is not conclusive)
The proper balance between testosterone (along with other androgens) and estrogen is important for the ovaries to work normally. While the specifics are uncertain, it's possible that androgens also play an important role in normal brain function (including mood, sex drive and cognitive function).
The Perils of Too Much Testosterone
Having too much naturally-occurring testosterone is not a common problem among men. That may surprise you given what people might consider obvious evidence of testosterone excess: road rage, fighting among fathers at Little League games and sexual promiscuity.
Part of this may be due to the difficulty defining "normal" testosterone levels and "normal" behavior. Blood levels of testosterone vary dramatically over time and even during the course of a day. In addition, what may seem like a symptom of testosterone excess (see below) may actually be unrelated to this hormone.
In fact, most of what we know about too much testosterone in men comes from athletes who use anabolic steroids, testosterone or related hormones to increase muscle mass and athletic performance.
Problems associated with excessive testosterone in men include:
Low sperm counts, shrinking of the testicles and impotence (seems odd, doesn't it?)
Heart muscle damage and increased risk of heart attack
Prostate enlargement with difficulty urinating
Liver disease
Acne
Fluid retention with swelling of the legs and feet
Weight gain, perhaps related in part to increased appetite
High blood pressure and cholesterol
Insomnia
Headaches
Increased muscle mass
Increased risk of blood clots
Stunted growth in adolescents
Uncharacteristically aggressive behavior (although not well studied or clearly proven)
Among women, perhaps the most common cause of high testosterone is polycystic ovary syndrome (PCOS). This disease is common. It affects 6% to 10% of premenopausal women.
The ovaries of women with PCOS contain multiple cysts. Symptoms include irregular periods, reduced fertility, excess or coarse hair on the face, extremities, trunk and pubic area, male-pattern baldness, darkened, thick skin, weight gain, depression and anxiety. One treatment available for many of these problems is spironolactone, a diuretic (water pill) that blocks the action of male sex hormones.
Women with excess testosterone, due to either disease or drug use, may experience a decrease in breast size and deepening of the voice, in addition to many of the problems men may have.
Too Little Testosterone
Despite the notion that too much testosterone is responsible for impulsiveness, violence, rage and stereotypical machismo, too little testosterone is probably a much bigger problem.
Recently, more attention has been paid to the effects of testosterone deficiency, especially among men. In fact, as men age, testosterone levels drop very gradually, about 1% to 2% each year — unlike the relatively rapid drop in estrogen that causes menopause. The testes produces less testosterone, there are fewer signals from the pituitary telling the testes to make testosterone, and a protein (called sex hormone binding globulin (SHBG) increases with age. All of this reduces the active (free) form of testosterone in the body. More than a third of men over age 45 may have "testosterone deficiency." That's about 13 million men in the U.S. alone. At some point, testosterone levels in the blood may become very low.
Symptoms of testosterone deficiency in adult men include:
Reduced body and facial hair
Loss of muscle mass
Low libido, impotence, small testicles, reduced sperm count and infertility
Increased breast size
Hot flashes
Irritability, poor concentration and depression
Loss of body hair
Brittle bones and an increased risk of fracture
If a man's symptoms of deficiency go away when he's given testosterone replacement, he's said to be experiencing "andropause." This term is not yet well-accepted, but it is true that aging men gradually make less and less testosterone and some men experience symptoms as a result. Some of the symptoms experienced by men when testosterone levels are low are remarkably similar to those experienced by women during menopause. That's one reason why the concept of andropause has appeal.
Some men who have a testosterone deficiency have symptoms or conditions related to their low testosterone that will improve when they take testosterone replacement. For example, a man with osteoporosis and low testosterone can increase bone strength and reduce his fracture risk with testosterone injections or a patch.
Did You Know?
There are times when low testosterone is not such a bad thing. The most common example is probably prostate cancer. Testosterone may stimulate the prostate gland and prostate cancer to grow. That's why medications that lower testosterone levels (for example, leuprolide) and castration are common treatments for men with prostate cancer. Men taking testosterone replacement must be carefully monitored for prostate cancer. Although testosterone may make prostate cancer grow, it is not clear that testosterone treatment actually causes cancer.
As surprising as it may be, women can also be bothered by symptoms of testosterone deficiency. For example, disease in the pituitary gland may lead to reduced testosterone production from the adrenal glands disease. They may experience low libido, reduced bone strength, poor concentration or depression. Some studies find that testosterone treatment does not eliminate these problems. As a result, the link between these problems and testosterone levels in women remains uncertain.
A recent study found that lower testosterone levels in men may be associated with an increased risk of cardiovascular disease and some cancers. We’ll need additional research to know for sure and to find out whether testosterone treatment might have significant and previously unrecognized benefits.
Diseases and Conditions That Affect Testosterone
Men can experience a drop in testosterone due to conditions or diseases affecting the:
Testes – direct injury, castration, infection, radiation treatment, chemotherapy, tumors
Pituitary and hypothalamus glands – tumors, medications (especially steroids, morphine or related drugs and major tranquilizers, such as haloperidol), HIV/AIDS, certain infections and autoimmune. conditions
Genetic diseases, such as Klinefelter's syndrome (in which a man has an extra x-chromosome) and hemochromatosis (in which an abnormal gene causes excessive iron to accumulate throughout the body, including the pituitary gland) can also affect testosterone.
Women may have a testosterone deficiency due to diseases of the pituitary, hypothalamus or adrenal glands, in addition to removal of the ovaries. Estrogen therapy increases sex hormone binding globulin and, like aging men, this reduces the amount of free, active testosterone in the body.
Testosterone Therapy
Currently, testosterone therapy is approved primarily for the treatment of delayed male puberty, low production of testosterone (whether due to failure of the testes, pituitary or hypothalamus function) and certain inoperable female breast cancers.
However, it is quite possible that testosterone treatment can improve symptoms in men with low levels of active (free) testosterone, such as:
Generalized weakness
Low energy
Disabling frailty
Depression
Problems with sexual function
Problems with cognition.
However, so far the research doesn't prove that the benefits outweigh the risks. One study, published in October 2006, found that men over age 64 who fell tended to have the lowest testosterone levels. This study did not treat these men to see if testosterone reduced their risk of falling.
Similarly, testosterone therapy may make sense for women who have low testosterone levels and symptoms that might be due to testosterone deficiency. (It's not clear if low levels without symptoms are meaningful; treatment risks may outweight benefits.) However, the wisdom and effectiveness of testosterone treatment to improve sexual function or cognitive function among postmenopausal women is unclear. Side effects, lack of FDA-approval and a large amount of uncertainty limit the use of testosterone or other androgens in women. Well-designed research studies should be able to provide guidance in this regard.
People with normal testosterone levels are sometimes treated with testosterone at the recommendation of their doctors or they obtain the medication on their own. Some have recommended it as a "remedy" for aging. For example, a study from Harvard Medical School in 2003 found that even among men who started out with normal testosterone results noted loss of fat, increased muscle mass, better mood, and less anxiety when receiving testosterone therapy. Similar observations have been noted among women. However, the risks and side effects of taking testosterone when the body is already making enough still discourages widespread use.
The Bottom Line
Testosterone is so much more than its reputation would suggest. Men and women need the proper amount of testosterone to develop and function normally. And most badly behaved men have normal amounts. Too little, rather than too much, tesosterone is probably a much bigger problem.
Checking testosterone levels is as easy as having a blood test. The difficult part is interpreting the result. Levels vary over the course of the day. A single low level may be meaningless in the absence of symptoms, especially if it was normal at another time. We need more research to know when to measure testosterone, how best to respond to the results and when it's worthwhile to accept the risks of treatment. In the meantime, don't blame testosterone for everything male. More often than not, a man behaving badly is the fault of the man, not his hormones.
Robert H. Shmerling, M.D. is associate physician at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School. He has been a practicing rheumatologist for over 20 years at Beth Israel Deaconess Medical Center. He is an active teacher in the Internal Medicine Residency Program, serving as the Robinson Firm Chief. He is also a teacher in the Rheumatology Fellowship Program.
When you think of testosterone, what comes to mind? Macho men? Aggressive, impatient, type A behavior? Road rage? Violence?