Medical Information to Support the Decisions of TUECs (Testosterone) US Anti-Doping Agency Philosophical issue is the establishment of minimal criteria for diagnosis of hypogonadism. An athlete may manipulate blood testosterone levels (total and free) by use of anabolic steroids or other medications (narcotics, corticosteroids) . The information requested to support a TUE is intended to eliminate the possibility of this type of manipulation to present as a case of hypogonadism. The athlete must have a confirmed diagnosis and bona fide etiology of hypogonadism, and the onus is on the athlete to provide information necessary to establish the diagnosis and the organic (disease-related) etiology of hypogonadism on the first TUE submission.

1. Medical Condition

a. Male Hypogonadism1

: A clinical syndrome resulting from the failure of the testis to produce sufficient levels of testosterone to maintain normal physiological function. This may result from disruption of the hypothalamic-pituitary-gonadal axis at various levels. Primary hypogonadism failure reflects a disease of testis that impairs normal testicular function resulting in low testosterone production, impairment of spermatogenesis, and a compensatory elevation of gonadotropin levels, e.g. an anorchid male or man with Klinefelter syndrome. Secondary hypogonadism reflects a disease of the pituitary gland or hypothalamus that results in low or inappropriately normal gonadotropin and low testosterone levels, e.g. pituitary adenoma or Kallmann syndrome.

b. Female Hypogonadism2

: Androgen deficiency in women is not recognized as a diagnosis due to the lack of a well-defined clinical syndrome and lack of data on total or free testosterone values that can be used to define the disorder.

2. Diagnosis a. Medical History and Physical Examination (examples):

1. Incomplete sexual development, reduced sexual desire (libido) and activity, decreased spontaneous erections, loss of male-pattern hair pattern, small or shrinking testes size, height loss due to vertebral compression fracture, low bone mineral density (osteopenia or osteoporosis), and reduced muscle bulk and strength.

2. The athlete must not have a short term illness or other condition that would influence testosterone production at the time of evaluation.

b. Diagnostic Criteria (examples):

1. Low serum testosterone levels from multiple measurements in the morning (with results below the low normal value for the reference laboratory), preferably confirmed by low free or bioavailable testosterone levels using an accurate assay method (e.g. calculated free testosterone or free testosterone by equilibrium dialysis).

2. LH values 3. Others as appropriate to establish an organic etiology of hypogonadism.

c. Relevant Medical Information

1. Medical history, laboratory or radiological testing as necessary to support the diagnosis and organic etiology of male hypogonadism.

3. Medical Best Practice Treatment

a. Name of prohibited medication Testosterone

b. Routes of Administration Intramuscular injections, transdermal (scrotal or non-scrotal skin testosterone patch, testosterone gel or cream), oral testosterone (in some countries), testosterone implants, and transbuccal testosterone tablets.

c. Frequency As required for the route of administration to maintain serum testosterone levels within the normal range.

4. Other Non-prohibited Alternative Treatments No known non-prohibited alternatives.

5. Consequences to Health, if Treatment is Withheld Clear adverse consequences in androgen deficiency in cases of organic etiology.

6. Treatment Monitoring a. Require athlete agree to random blood testing and be available. b. Maintain formal record of when treatment is administered and dose. c. Record of number of prescriptions.

7. Duration of TUE and Recommended Review Process

Three years as a maximum, with periodic evaluation of results of treatment on total and free testosterone levels, clinical notes, and prescriptions.

8. Appropriate Cautionary Matters a. The WADA code prohibits a TUE based on low-normal serum testosterone values b. The diagnosis should be made by a qualified endocrinologist or specialist c. The evaluation must include information to document the organic etiology of the

diagnosis of hypogonadism. d. In cases of denial of TUE, decision is up to athlete to use prohibited medication or not

compete. e. Use of testosterone as an anti-aging medication is not recognized, unless an identified

organic etiology for the androgen deficiency exists.

9. References 1 Task Force. Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91: 1995-2010, 2006

2 Task Force. Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91: 3697-3716, 2006