MI Androgen Deficiency Hypogonadism

Transcription

1 MI Androgen Deficiency Hypogonadism WADA TUE Expert Group John A Lombardo, MD October 2014, Columbus, Ohio USA

2 Hypothalamic-Pituitary-Gonadal Axis / 2

3 Hypogonadism/Androgen Deficiency Clinical syndrome: failure of testes to produce physiological levels of testosterone and/or normal # spermatazoa due to disruption of hypothalamicpituitary-testicular axis. Primary: testicular problem Secondary: hypothalamic-pituitary-testicular axis Combined: both primary and secondary / 3

4 Organic Etiology Pathologic physical change in structure of an organ or within the hypothalamic-pituitary-testicular axis usually long lasting or permanent Examples: Primary Genetic abnormalities Developmental abnormalities Trauma/surgery/testicular torsion Orchitis Radiation / 4

5 Organic Etiology Pathologic physical change in structure of an organ or within the hypothalamic-pituitary-testicular axis usually long lasting or permanent Examples: Secondary Genetic abnormalities Pituitary disorders Structural and infiltrative effects of systemic diseases Anatomic problems / 5

6 Functional Etiology No observable pathological physical change in structure of an organ or within the hypothalamic-pituitary-testicular axis; functional defects are potentially reversible. Examples: Severe emotional stress Morbid obesity Overtraining Medication/Alcohol excess Chronic systemic illness Aging Late Onset Hypogonadism (LOH) Alcohol excess / 6

7 Hypogonadism/Androgen Deficiency TUE should only be approved for androgen deficiency that has an organic etiology. TUE should not be approved for androgen deficiency due to functional disorder. TUE for androgen deficiency should not be approved for females. / 7

8 Medical Evaluation Physician preferably endocrinologist History: pubertal progression, libido/sexual activity, erections, hot flushes, sweats, decreased energy, depressed mood, dysthmia, sleep disturbance, decreased muscle, increased body fat/bmi, diminished work performance Low or zero sperm count, low bone density, history of cryptorchidism, torsion or significant testicular injuries, significant head injuries, orchitis, family history of delayed puberty / 8

9 Physical Exam Physical findings Gynecomastia Changes in hair patterns-axillary & pubic absence of temporal recession Decreased testicular volume (< 15cc by orchidometry or ultrasound) / 9

10 Testing imaging/laboratory Blood testing (drawn in the morning) a) Total testosterone (assay using an accurate and reliable method) b) Free testosterone (e.g. calculated free testosterone from total testosterone and SHBG measurements or free testosterone by equilibrium dialysis) c) LH and FSH d) SHBG e) Semen analysis (if? Fertility) f) DEXA scan (if? Bone density) g) Urine drug screen a, b, c drawn on two occasions at least a week apart / 10

11 Secondary Hypogonadism Additional testing required: MRI of brain with pituitary (sella) cuts with and without contrast Pituitary function tests (LHRH stimulation test, LH or hcg stimulation test) Other appropriate dx ic tests (e.g. prolactin, iron studies, genetic testing) / 11

12 Treatment Testosterone IM injection Transdermal patch or gel Oral preparation hcg IM injection IU 2-3 times per week / 12

13 Monitoring Treatment Dosage determined by prescribing endocrinologist Monitored with trough serum testosterone for IM Monitored with testosterone any time for Gels hcg monitored with trough testosterone levels Record of dosage, timing and blood tests must be submitted for annual review / 13

14 Duration of TUE Duration of approval limited to 4 years at a maximum Annual review process demonstrating Symptom control Copies of medical records Testosterone levels Record of product dosage and dates of treatment Record of names of administering medical personnel for IM Proposed changes in dosage or medication should be provided with report to ADO or national body granting TUE for permission for proposed change / 14

15 Washout Table Product with route of administration Washout period Urine test (anti-doping) Blood tests LH, FSH, Test Transdermal testosterone (testosterone patch, gel or cream) 2 weeks At beginning of wash-out (week 0) End of wash-out (week 2) and again between week 3-4 Oral (testosterone undecanoate) or buccal testosterone 2 weeks At beginning of washout period (week 0) End of wash-out (week 2) and again between week 3-4 Intermediate acting testosterone by IM injection (testosterone, enanthate, cypionate or mixed esters) 8 weeks At week 0 plus 1 random between weeks test at week 8 and then another within the next 4 weeks, at least one week apart. Long acting testosterone by IM injection (testosterone undecanoate) 26 weeks At week 0 plus 2 random tests between weeks test at week 26 and then another within the next 4 weeks, at least one week apart. Subcutaneous testosterone pellets 40 weeks Week 0 plus 2 or 3 random tests during weeks test at week 40 and then another within the next 4 weeks, at least one week apart. / 15