Testosterone

Testosterone Deficiency

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:

  • Improved sense of well-being
  • Increased strength, especially in the upper body
  • Increased repair mechanisms (protein synthesis)
  • Increased libido
  • Increased nipple and clitoral sensitivity
  • Increased bone mineral density
  • Maintenance of skin collagen level

Low testosterone levels are associated with:

  • Loss of lean muscle mass
  • Increased fat especially in the trunk
  • Increased risk of cardiovascular disease
  • Loss of libido (sex drive and interest)
  • Hopelessness, helplessness, depression
  • Erectile dysfunction
  • Decreased enthusiasm
  • Fatigue
  • Muscle & joint pain
  • Impaired healing
  • Premature aging of the skin

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
Total Testosterone

  • Men – target = 750-1100
  • Women – target = 40-85

Free Testosterone

  • Men – target = 160-220 or 30-40 depending on the lab reference value
  • Women – target = 6-8 or 3-4 depending on the lab reference value

SHBG – target < 60 nmol/ml
Estradiol – target < 60 pg/ml

Testosterone Replacement
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.

Controversy
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.