Noridian has noted a rapid increase in the use of testosterone supplements
that exceed the expected use in the Medicare population based on current
published data. According to a Health Technology Assessment on Testosterone
Testing from the Washington State Health Care Authority, the presence of low
serum testosterone is 9.0% in men aged 45 to 54 years, 16.5% in men aged 55 to
64 years, and 18.3% in men aged 65 to 74 years. These estimates were derived
from the National Health and Nutrition Examination Survey III (NHANESIII),
which defined low testosterone levels as < 300 nanogram per deciliter (ng/dL)
(10.4 nanomoles per liter [nmol/L]). The diagnosis of hypogonadism depends on
measuring the total, free and/or biologically active testosterone; sex hormone
binding globulin (SHBG) and the pituitary axis. Male hormone is bound to SHBG,
and SHBG tends to rise with age, lowering the free testosterone level.
Testosterone level accuracy varies among labs with different assays, and can
be affected by chronic diseases, age, levels of binding, measurement
variables, testing accuracy, etc. Estimates of the low end of testosterone
depend on the method and accuracy of testing and can be as low as 160 ng/dl.
Decisions on hypogonadism depend on both repeated hormone testing and a group
of clinical symptoms. Neither alone is adequate for defining hypogonadism.  
  
Testosterone levels are controlled by interaction of the testicular-pituitary-
hypothalamic axis. Primary hypogonadism is failure of the testes to produce
testosterone (for a number of reasons) and is usually accompanied by elevated
LH and/or FSH. Secondary hypogonadism is disruption of the testicular-
pituitary-hypothalamic pathway and may be due to pituitary or hypothalamic
axis damage including systemic illness and genetic aberration. Age related
hypogonadism (e.g. lower testosterone in the older male population) _is not
necessarily a disease and may be asymptomatic_ and / or may be related or
associated with many chronic illnesses. "Low T Syndrome" or "Low T" is not a
syndrome and may be an incidental finding or lab error. Low serum testosterone
alone does not constitute a diagnosis of androgen deficiency or clinical
hypogonadism. Diagnosis of a clinical condition requires the presence of
certain characteristic symptoms as well as an abnormally low serum
testosterone.  
  
Many of the symptoms are not specific to, and not directly correlated to
specific levels of testosterone. Guidelines from the Endocrine Society suggest
some of the following symptoms may be related to low serum testosterone but
**may** also have many other causes in the elderly population:  
  
More Specific Signs / Symptoms  
  

    * Incomplete or delayed sexual development; eunuchoidism



    * Reduced sexual desire (libido) and activity



    * Breast discomfort, gynecomastia



    * Loss of body (axillary and pubic) hair, reduced shaving



    * Very small (Especially < mL) or shrinking testes



    * Inability to father children



    * Low or zero sperm count



    * Height loss, low-trauma fracture, low bone mineral density



    * Hot flushes, sweats

  
Less Specific Signs/Symptoms  
  

    * Decreased energy, motivation, initiative and self confidence



    * Feeling sad or blue, depressed mood, dysthymia



    * Poor concentration and memory



    * Sleep disturbance, increased sleepiness



    * Mild anemia



    * Reduced muscle bulk and strength



    * Increased fat or increased body mass index



    * Diminished physical or work performance

  
Noridian expects that the evaluation of primary hypogonadism be undertaken
with at least 2 separate serum testosterone levels taken on two different days
in the morning (when testosterone secretion is highest) , and / or two morning
levels of "free" or bioavailable testosterone) **and** LH or FSH levels.
Elevated LH /FSH confirms primary hypogonadism and the potential need for
replacement hormone. If the two testosterone determinations are low AND the
LH/FSH levels are also low, pituitary disease (including a serum prolactin) or
chronic diseases should be assessed before making a diagnosis of age related
low testosterone. Only patients with low testosterone associated significant
symptoms should be considered for treatment. A comprehensive examination is
required to evaluate for medications or chronic diseases known to cause
decreased energy, memory problems, impotence and mental health problems.  
  
Noridian would consider the low testosterone related symptoms from the
nonspecific and specific groups described above to be documented in the chart
**along with two low testosterone levels drawn on two mornings and a single LH
or FSH** to demonstrate the need for testosterone therapy in the age related
group of symptomatic androgen deficiency. Documentation of the symptoms,
signs, physical examination and lab tests must be available in the chart if
requested.  
  
Treatment of symptoms associated with low testosterone is controversial. It is
not certain if low testosterone is the cause of the symptoms, a marker for
underlying chronic diseases, or the effect of the symptoms-and there is a
considerable placebo effect. Long term effects of testosterone on the
geriatric population are mixed but are being studied by the NIH. Long term use
of testosterone can damage the hypothalamic-pituitary-testicular axis and lead
to permanent testicular failure.  
  
Testosterone replacement therapy is **contraindicated** in patients with
breast cancer and untreated prostate cancer. There are recent FDA listed
warnings about thromboembolic disease, increase in erythrocythemia, and
hypertension. The clinical records shall reflect that these issues were
discussed with the patient before initiating therapy. Some physicians
recommend obtaining baseline PSA testing and ongoing monitoring to test for
prostate cancer.  
  
Long term testosterone therapy will shrink testicular tissue and can lead to
infertility, and therefore would be contraindicated in those interested in
reproduction.  
  
Where replacement is indicated, the dose of replacement therapy should be the
least amount necessary to obtain a serum testosterone in the low normal range.
Testosterone replacement can be administered by many routes. The current
preferred routes are by transdermal preparations. Since topical or transdermal
agents are administered daily in low dose, the risk of supraphysiological or
subtherapeutic levels is minimized. The use of topical agents is thought to
minimize adverse events. Indeed, in series examining the toxicity of topical
agents, adverse events are nearly nonexistent when administered by these
routes (Steidle et al., 2003). The main disadvantage of the topical agents are
their high cost ($100 to $150 per month), substantially higher than self-
administered injection therapy, and the potential risk of inadvertent transfer
of hormone to women or children through skin contact. There is no evidence
that unusually high doses-or higher than published frequencies of
administration-are any more effective than doses established by the FDA and
could lead to increased side effects. Ongoing monitoring of hormone levels and
side effects are necessary.