HEALTH SUPERVISION OF THE DOPING ATHLETE

Andy Peterson MD MSPH University of Iowa DISCLOSURES

• Grants: • UI Injury Prevention Research Center • NIH sub-contract • B1G conference • American Academy of Pediatrics • Royalties from McGraw-Hill • Intellectual property with Team Safesport • Wife (Vanessa Curtis) receives consulting fees from Rhythm Pharmaceuticals GOALS AND OBJECTIVES

1. Ethical Basis of Caring for Doping Athletes 2. Monitoring of Common Drugs (mainly anabolics) 3. Pitfalls and Red Flags A FEW KEY ADDITIONAL POINTS • There is almost no data to guide us here • Don’t break the law • No one up here is advocating for use of PEDs in sports • All of the example cases are real PRINCIPLES OF MEDICAL ETHICS

1.Principle of respect for autonomy 2.Principle of nonmaleficence 3.Principle of beneficence 4.Principle of justice

Beauchamp and Childress (2008) DON’T LIE TO PATIENTS

HOW DO PEOPLE TAKE THEM?

• Injectable • Oral • Topical

• Single • Stacked • Pyramid • Cycled

CASE 1

28 year old male graduate student Recreational weight lifter – body image / appearance

Creatine (oral) Dianabol (metandienone) (oral) Anadrol (oxymetholone) (oral) Testosterone (injection) Trenbolone (injection) Levothyroxine (oral) Methylphenidate (oral) CASE 1 – MORE INFORMATION

Interested in ”backing off”

Has noticed elevated BP when checked at pharmacy (150s systolic)

Concerned about acne

No other side effects noted

Tried to quit once before – went very poorly CASE 1 – EXAM

Pertinent abnormal findings: BP 142/74 Highly virilized Diffuse acne Severe folliculitis from body hair grooming Testes 2cm and firm

Pertinent normal findings: Normal heart exam No hepatosplenomegaly Normal affect CASE 1 – LABS

• WBC 5.9; nl diff • Normal: • Hgb 19, Hct 58 • Liver tests • Plt 222 • ECG • Total Testosterone 994 • Echo • FSH 0.1 • Electrolytes • LH < 0.1 • TSH 0 • Total Cholesterol 134 • HDL 12 • TG 155 • LDL 91 CASE 1 – REVISIT PEDS

• WBC 5.9; nl diff Creatine (oral) • Hgb 19, Hct 58 Dianabol (metandienone) (oral) • Plt 222 Anadrol (oxymetholone) (oral) • Total Testosterone 994 Testosterone (injection) • FSH 0.1 Trenbolone (injection) • LH < 0.1 Levothyroxine (oral) • TSH 0 Methylphenidate (oral) • Total Cholesterol 134 • HDL 12 • TG 155 • LDL 91 • Elevated BP CASE 1 -- PLAN

PLAN RESULT (6 WEEKS)

• Continue Creatine, Methylphenidate • BP 122/68 • NL CBC • TSH 1.1 • Stop all anabolics except Testosterone

• HDL 10 • Wean off synthroid over 4 weeks

• Total Test 990

• Not interested in stopping ORAL ANABOLICS ORAL ANABOLICS ORAL ANABOLICS 17-ALPHA-ALKYLATED STEROIDS

1. By far most commonly used oral anabolics 2. More anabolic effect = more hepatotoxicity

3. 3 categories: • Testosterone based (high estrogen effect) • DHT based • Nandrolone based A FEW EXAMPLES – WHAT OUR PATIENT WAS ON

Dianabol (metandienone) (oral) Anadrol (oxymetholone) (oral) • Testosterone derivative • DHT derivative • Highly hepatotoxic • Weak anabolic • Weakly hepatotoxic • Previously used clinically to treat anemia A FEW EXAMPLES – MOST COMMON

Stanozolol Oxandrolone • DHT derivative • DHT derivative • Highly anabolic • Weak anabolic • Highly hepatotoxic • Weakly hepatotoxic CASE 2 (EMAIL FROM HOSP EXECUTIVE RE HIS SON)

I’ve been through three cycles, first starting with the following: 250 mg/ml Trenbolone ethanoate, 250mg/ ml Testosterone ethanoate and 1mg of Arimidex oral tablets. The second and third cycle consisted of 100mg/ml Trenbolone Acetate (stronger concentration), 250mg/ml Testosterone ethanoate, 1mg Arimidex and for the last two weeks of the cycle lasting for an additional four more weeks 25mg Winstrol oral tablets. For proximal results, a 10-week cycle is recommended. Although, I did not want to endure high dosages of these supplements. My cycle originally consisted of 1ml total between tren and test, then a half tablet of Arimidex every two days. The dosage of test was then depreciated to .2ml (~1/2) its original dose for the reason that I started to retain water. During my second cycle, I did 1.2ml of tren acetate and test combined—1ml of tren and .2ml of test. The dose of Arimidex remained the same, as for Winstrol, a half of a tablet was orally consumed (the last two weeks continuing for four additional weeks) every day. The process was first to obtain the oily substance (Trenbolone) then testosterone. Reason I did it this way was because the oil would sit at the back of the syringe and you’d notice the separation between liquids. CASE 2 (EMAIL FROM HOSP EXECUTIVE RE HIS SON)

I’ve been through three cycles, first starting with the following: 250 mg/ml Trenbolone ethanoate, 250mg/ ml Testosterone ethanoate and 1mg of Arimidex oral tablets. The second and third cycle consisted of 100mg/ml Trenbolone Acetate (stronger concentration), 250mg/ml Testosterone ethanoate, 1mg Arimidex and for the last two weeks of the cycle lasting for an additional four more weeks 25mg Winstrol oral tablets. For proximal results, a 10-week cycle is recommended. Although, I did not want to endure high dosages of these supplements. My cycle originally consisted of 1ml total between tren and test, then a half tablet of Arimidex every two days. The dosage of test was then depreciated to .2ml (~1/2) its original dose for the reason that I started to retain water. During my second cycle, I did 1.2ml of tren acetate and test combined—1ml of tren and .2ml of test. The dose of Arimidex remained the same, as for Winstrol, a half of a tablet was orally consumed (the last two weeks continuing for four additional weeks) every day. The process was first to obtain the oily substance (Trenbolone) then testosterone. Reason I did it this way was because the oil would sit at the back of the syringe and you’d notice the separation between liquids. “DO YOU BELIEVE WHAT HE IS DOING IS SAFE?” GENERAL RESPONSE

1. This is illegal 2. A lot of the sources where people get it aren’t reliable, so strength and purity are often questionable 3. Long-term, there are real effects on cardiovascular health.

• But, over the short to medium-term, not super high risk. SPECIFIC RESPONSE

• The trenbolone and testosterone are both strong anabolics that are commonly taken together. There is some risk of withdrawl if he comes off quickly.

• Tren metabolites are highly aromatized, so the arimidex he takes when on that should limit some of the edema and estrogen-like side effects.

• Biggest risk is probably from the Winstrol (which is stanozolol, probably the most commonly abused anabolic steroid). It is a 17-alpha-methylated steroid, which is why it can be taken orally, but also increases risk of liver injury. And, big-picture, it is a pretty weak anabolic. So, with the doses he is taking of Test and Tren, it is unlikely to be adding much other than increased risk.

• If he were my patient, I would probably counsel him on 1,2,3 above, check his heart, liver, RBC count, and lipid panel. And encourage him to stop the stanozolol. MONITOR ANABOLICS

• Thyroid: Thyroid levels-Decreased TBG, decreased T4 • Liver: INR-increased, Other liver tests-Neoplasms, Peliosis hepatitis (blood filled cysts) • CNS: Depression, excitation, insomnia • GI: Nausea, vomiting, diarrhea • Breast: Gynecomastia • Larynx: Voice deepening • Hair: Hirsutism and male pattern baldness • Skin: Acne • Skeletal: Premature closure of epiphysis in children • Fluid and Electrolytes: Edema, fluid retention-Na, Cl, K, Phos, Ca • Metabolic/Endocrine: Decrease glucose tolerance, Increased LDL, decreased HDL, Elevated creatinine, Increased CK, insulin levels for exogenous use • Heart: Monitor HTN, cholesterol • GU: Prostate enlargement, prostate CA, bladder irritability • Heme: CBC for polycythemia MONITOR ANABOLICS (BRIEF TAKE HOME)

• Oral steroids are more hepatotoxic • Higher doses have more side effects • Hypertension • Polycythemia

• Suppress HPG axis • Androgen effects • Including mood / aggression? WEANING ANABOLICS

• Encourage transition to testosterone If oral 17-alpha-alkylated testosterone • If HPG axis suppressed, plan 30-90 • Consider Tamoxifen day taper • ??LH/FSH recovery?? • Consider clomiphene • Decrease peripheral estrogen • ??LH/FSH recovery?? effects?? • Consider psychologist • Consider ED meds. CASE 3

• Fitness competitor

• 2014: • Synthroid 100µg/d • Caffeine 800mg pre workout • DHEA • Testosterone (patch)

• Rare palpitations CASE 3 – AFTERMATH

Edema (30 lbs) 1 month after competition • TSH: 0.1 (L) Sleep disturbance • Free T4: 0.15 (L) Hair loss • Reverse T3: 3 (L) Brittle nails • TBG: 22 (NL) Dry skin Normal • LH, FSH, Estradiol • CMP • Cholesterol Panel • ECG Rubinoff and Fireman. J Clin Epidemiol. 1989.

Vagenakis. NEJM. 1975. CASE 3 – PLAN

• Restart synthroid 25µg/d 1 month • Dx: central hypothyroidism • TSH: 0.2 • Free T4: 6.22 • 1 month follow up • Felt normal 3 month • Weight still up • TSH 0.26 • Started wean over next 8 weeks • Free T4: 4.15

• 3 month follow up • Felt normal • Weight back to normal CASE 3 – 2 YEARS LATER Returned to competition • Testosterone patch • Creatine • Caffeine

• No side effects • Normal labs • Weaned off quickly after competition THYROID HORMONE

Monitoring Weaning off • TSH, FT4 • Should be quick and easy • Vital signs • Lots of anecdotes of long recovery • Cardiac testing to symptoms • No real down-side to weaning dose • Palpitations • Fatigue • Exercise intolerance STIMULANTS

Most common Side effects • Caffeine • Cardiovascular • Methylphenidate • Sleep • Amphetamine salts • Mental Health • Benzadrine • Increased heat illness risk • Nicotine • Tremor • Sexual dysfunction • Clenbuterol (also anabolic) STIMULANTS

Monitoring Weaning off • ??ECG?? • Nothing to do. • Counseling re titration and heat illness Monitoring: None Weaning: Non Issue CASE 4 • 26 yo elite MTB racer • History of anemia in college – treated with IV iron • Started using EPO to “prevent anemia”

• Now • Caffeine • EPO: 3000 IU / week CASE 4

”Can you refill it for me?” NL CBC, iron, TIBC, ferritin, transferrin

• Counseled regarding legal / ethics Planed to recheck every 6 months or after change in dose → never saw him again. • Discussed risk of polycythemia • Ensured no other polypharmacy issues

EPO: MONITORING / WEANING

Monitoring: No one knows “case reports”

Weaning: Nothing to do TAKE HOME POINTS

• Take care of the patient • Don’t break the law or violate medical ethics standards • Know the drugs