Testosterone is a steroid hormone from the androgen group. Although most people associate testosterone with men (and with body builders!), women make it also, though in much smaller amounts. Testosterone is secreted in the testes of men and the ovaries of women. It is the principal male sex hormone and the "original" anabolic steroid. In both males and females, it plays key roles in health and well-being. Examples include enhanced libido (sex drive), energy, immune function, and protection against osteoporosis, prostate cancer and cardiovascular disease.
In our practice, we check testosterone levels in patients complaining of persistent fatigue, symptoms of Fibromyalgia, chronic muscle aches or sense of muscular weakness, or who demonstrate evidence of poor or slow healing.
Sources of Testosterone
Like other steroid hormones, testosterone is derived from cholesterol. The largest amounts of testosterone are produced by the testes in men, but it is also synthesized in smaller quantities in women by the ovaries, by the placenta, as well as by the adrenal gland in both sexes. Like most hormones, testosterone is supplied to target tissues by the blood where much of it is transported bound to a specific plasma protein, sex hormone binding globulin (SHBG).
Effects of Testosterone
In general, androgens promote protein synthesis and growth of tissues that have androgen receptors. Testosterone effects can be classified as virilizing and anabolic effects, although the distinction is somewhat artificial, as many of the effects can be considered both. Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of height growth and bone maturation. Therefore, testosterone is important as part of the body’s normal maintenance and repair processes. Virilizing effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in fetuses, a deepening of the voice in both sexes at puberty, and growth of facial and body hair. Testosterone analogs are also often used (illegally) by bodybuilders, gym enthusiasts, to enhance muscle building, and by athletes to enhance power and strength performance. Interestingly testosterone does not help athletes perform in a pure endurance sports like marathon racing.
In addition, in the brain and bones, testosterone gets metabolized (converted) through a process called aromitization to estradiol (a form of estrogen). In the bones, estradiol accelerates maturation of cartilage into bone, leading to closure of the growth plates and conclusion of normal growth. In the central nervous system, estradiol, rather than testosterone, serves as the most important feedback signal to the hypothalamus, a portion of the brain that links the nervous system to the endocrine system, which helps control the release of many hormones in the body.
As mentioned above, testosterone is typically associated with men. But testosterone is essential in women as well. In women, testosterone contributes to:
Low testosterone levels are associated with:
Measuring Testosterone Levels
Testosterone should be measured by serum blood levels. While most labs have established “normal” ranges, optimum testosterone blood levels are listed below. In addition, PSA (prostate-specific antigen) levels should be measured in men, and sex hormone binding globulin (SHBG) and estradiol levels should also be measured (estrogen blocks the receptor sites for testosterone, especially in men). The PSA test can change when a man is started on Testosterone Replacement. If the PSA goes up by a point there is a small chance that the patient has hidden or an occult prostate tumor and the hormone should be stopped and a diagnostic work up should be initiated to rule out prostate cancer. There is an unfounded fear that if testosterone is added to a patient with prostate cancer, it would be like adding gasoline to a fire. Dr. Morgantaler, a Harvard trained urologist who did his research on the effects of testosterone on prostate cancer, all but proved this theory to be false. However, if starting someone on testosterone causes a significant bump in their PSA, and it leads to an earlier diagnosis of prostate cancer in our patients this is viewed as a good thing. Once the prostate is treated and cleared of any cancer, our patients are cleared to restart testosterone in most cases as long as their PSA stays at zero.
PSA should be <2.0 ideally, 2-4.0 is a level of possible concern and >4 is too high- to start treatment
SHBG – target < 60 nmol/ml
Estradiol – target < 60 pg/ml
Although testosterone supplementation is available in commercially-prepared forms, bio-identical hormone replacement—replacing exactly what your body makes—is preferred. We give patients a prescription for a custom-formulated cream that is prepared by a compounding pharmacy. (Your local CVS or Walgreen’s does not have compounding capabilities. They only dispense medications.) The cream is applied to the skin where it gets absorbed directly into the blood stream.
For men, testosterone supplementation usually starts at 100-400 mg a day, depending on initial lab test results. For women, we usually start at 5 mg a day. Dosing is adjusted based on subsequent lab testing and patient symptoms. The advantages of using a custom compounded cream include the ability to fine-tune the dose and the ability to mix other hormones in the cream.
Some patients (about 15%) do not absorb medications well through the skin or don’t like putting the cream on twice a day for men. In those cases injectable testosterone, as Depotestosterone cypionate, is available as an intramuscular (IM) injection. It most commonly comes in vials containing 200 mg per (1 cc) of the drug. Injections are best given once weekly. However, a daily subcutaneous dose is best for men who have a worsening of their cholesterol profile with IM testosterone treatment. It is common practice for urologists and endocrinologists to prescribe testosterone injections every 2 weeks. The problem with this practice is the drug only lasts, at a maximum, for 7 days in a patient’s blood stream. After day 7 the blood levels go to near 0 and the patient will suffer from dramatic lowering of their blood or serum testosterone levels. Side effects of no testosterone in ones blood stream can be severe. It takes up to 2 months for a patient’s testes to return to normal testosterone production. This is why it is so important to dose testosterone weekly and patients should not stop their medication abruptly.
Labs should be rechecked in a month after starting therapy or after changing doses. It’s very important that labs are checked approximately 24 hours prior to the next weekly dose to check for adequate lab levels.
Potential Side Effects of Testosterone Replacement Therapy
When used under careful medical supervision, testosterone replacement is safe and effective, especially if it used to replace low or suboptimal Testosterone levels. However, it important to keep an eye open for potential side effects. If side effects do occur, they are almost always mild and reversible.
Testosterone can exert a negative feedback on the Hypothalamic-Pituitary-Testicular axis. This can affect other hormone levels. Women can experience acne or the development of facial hair (especially in women who have a history of polycystic ovarian syndrome- or who have never been diagnosed with PCOS). Men can experience testicular atrophy (shrinking testicles). Male pattern baldness and benign prostatic hypertrophy can occur especially with the use topically applied creams as they increase the DHT (dihydrotestosterone) in the hair follicle more directly than injectable forms do. In addition, reflective of potential increased estrogen, there is a risk of increased fat deposition around the trunk, and the development of enlarged breast tissue in men. Men who already are over weight or who aromatize testosterone to estrogen more strongly than others do are at increased risk. This side effect can be reversed by changing to an injectable dose and/ or adding an aromatase inhibitor drug (it will decrease the estrogen level) for two months and it usually does not come back. Some doctors are trained to automatically put a man on an aromatase inhibitor to keep the estrogen levels as low as possible. New evidence is showing this is probably not the right treatment approach. When a young man’s testosterone is at their highest in their 20s to 30s, men aromatize some of their testosterone to estrogen and end up with fairly high levels of estradiol in their blood stream. This higher estradiol level is important to help protect men’s bone mass, cardiovascular system, etc. Therefore the literature supports not lowering estrogen levels automatically in men on Testosterone replacement. We only do so if levels go too high or men get side effects of too much estrogen in their system. Some men who have risk factors for heart disease may see swelling of their ankles or changes in their cholesterol profile. With proper management and regular check ups all of the cardiac risk factors can be improved upon with the addition of testosterone to a patient’s medication regimen.
Recently a couple of studies were published on the cardiovascular effects of testosterone supplementation. One of them was published in the prestigious JAMA journal. The study focused on older veterans from a hospital. The study was poorly done and many question why it ever reached a widely read journal like JAMA. The conclusion of the study was that testosterone supplementation caused more heart attacks than those that were not on supplementation. Since that publication came out, a group of researchers headed by Abraham Morgantaler as well as several cardiology associations and cardiologists came out and said the study was poorly conducted and the results reported could not be validated. Further they concluded that 1 negative study on the cardiovascular risk of taking testosterone does not negate over 100 articles in the literature that have supported and prove not only that testosterone supplementation is safe but that it is an important drug to help lower the risk of developing cardiac disease. The other controversy that is commonly touted in the lay press and doctor’s offices is that testosterone supplementation can cause prostate cancer. As I said under the section on PSA testing, there is no evidence in the literature that testosterone supplementation causes or increases the risk of developing prostate cancer. As a matter of fact the reverse is true. In study after study, the higher the level of testosterone supports a lower risk of developing prostate cancer. Conversely the risk of developing prostate cancer rises as the level of testosterone falls. Some doctors even say it is negligent to not treat a man’s testosterone deficiency, as we know low levels of testosterone increase their risk of developing not only prostate cancer but cardiovascular disease among other disease states.