1. TESTOSTERONE REPLACEMENT THERAPY
C. Sloan Teeple M.D.
Board Certified Urologist and Testosterone Specialist

2. Testosterone Deficiency
A medical condition caused by low serum testosterone levels which results in typical symptoms
Otherwise known as: “Low Testosterone” – “Low T” – “Hypogonadism”

3. Testosterone Defined Naturally occurring steroid hormone (an androgen)
Produced in testicles of males, ovaries of females and adrenal glands of both sexes
95% of male testosterone is secreted by Leydig cells in the testicles
* Kavoussi, Clinical Urologic Endocrinology, pg 26

4. Why is this important to my practice?
FDA reports over 15 million men in America have Low T but only 5% of those men are diagnosed
40% of men over the age of 45 have Low T
30% of Diabetics have Low T
2012 American Urology Association World Conference concluded that “the single best indicator of a man’s health is his testosterone level”
* Urology Times, August 2012, pg 28

5. Industry Facts
2012 T-related advertising skyrocketed from $14 billion to $107 billion
2013 FDA reports 2.3 million men prescribed Testosterone
2014 One year later it tripled to 6.5 million

6. Natural Decline Testosterone peaks at the age range of 20-25
Normal decline of 1% a year after the age of 30
Faster decline leads to Testosterone Deficiency

7. Primary and Secondary Hypogonadism
Primary due to testicular failure. Causes: injury, infection, systemic diseases, any acute illness or stress, chromosomal abnormality, drug use and idiopathic
Secondary due to Hypothalamus or Pituitary failure
Insufficient GnRH production from hypothalamus
Insufficient LH/FSH production from pituitary
Causes: trauma, neoplasm, genetic mutations and idiopathic
* Kavoussi, Clinical Urologic Endocrinology

8. Testosterone Deficiency: How to diagnose
Diagnosis has 2 requirements: combination of subjective symptoms with objective low serum testosterone levels
Need two blood levels on two separate days drawn in the morning (7-11AM)
Men over 40 have less diurnal variation so timing is less important
Total testosterone <350 ng/dl is low
ng/dl is borderline, treat based on severity of symptoms

9. How to diagnose continued
> 400 ng/dl is considered normal
Free Testosterone <6 ng/dl is low (range 6-31 ng/dl)
If either the total testosterone OR free testosterone is low then Hypogonadism is confirmed
Do not check testosterone levels the same day as an acute illness, major stressful event (surgery, death of loved one), or extreme endurance exercise. All of these can temporarily lower testosterone
* Morgantaler, Testosterone For Life, Ch. 4

10. More on Free and Total Testosterone
In bloodstream, Testosterone is either unbound (free) or bound to proteins
Testosterone is bound to either albumin or sex hormone binding globulin (SHBG)
Total testosterone measures the total amount, free & bound
Free testosterone is the active testosterone because it is unbound
Some men have higher concentrations of SHBG where total T will be completely normal but free T is low
If either total T or free T is low then consider Hypogonadism
* Morgantaler, Testosterone for Life, Ch 4

11. Signs and Symptoms of Low T
Occur for many months prior to presentation
Sexual: low libido, erectile dysfunction, lack of sensation to genitals, loss of morning or spontaneous erections, and delayed ejaculation or climax
Physical: muscle loss and weakness, weight gain, hot flashes, night sweats, loss of body hair, loss of height, decreased bone density
Mental: fatigue, irritability, depression, moodiness, lack of motivation, poor memory, lack of concentration/focus, poor sleep.

12. Signs and Symptoms continued
Urinary: similar symptoms to BPH, urgency/frequency, weak stream and sensation of incomplete emptying
* Morgantaler, Testosterone for Life, Ch 3

13. Benefits of TRT Reversal of low T symptoms within 3 months
Improvement in energy, strength, sexual function, bone mineral density, mood, cognition, lipid parameters, glycemic control, and reduces fat mass
Reduces risk of diabetes, osteoporosis, depression, obesity, and metabolic syndrome
Current research into lowered risk of heart disease, Alzheimer’s and prostate cancer. * Morgantaler, Urology , pg 27 *Kavoussi, Clinical Urologic Endocrinology, Ch 5

14. Risks/Side Effects of TRT
Acne
Erythrocytosis
Peripheral edema
Atrophy of testicles
Lowering of sperm count
Gynecomastia
* Morgantaler, Urology , pg 27

15. Prostate Cancer and Cardiovascular Disease
Prostate cancer is no longer a risk with TRT
Low testosterone levels are associated with worse prognosis for prostate cancer
Dozens of studies show CV benefits of TRT
VA retrospective study 2015: 83,010 men with Low T followed for 5 years concluded: 47% reduced mortality, 30% less stroke and 18% less risk for heart attack. Large scale study from Mayo Clinic 2015 showed no increased rate of venous thromboembolism.
* Morgantaler, Urology 89, 2016

16. Contraindications for TRT
Congestive heart failure
Pitting edema
Breast cancer
Uncontrolled erythrocytosis
Exacerbation of sleep apnea

17. Treatment: TRT
Goal is to get testosterone consistently in the normal therapeutic range of 400 ng/dl to 1000 ng/dl
Average testosterone level for men is 550 ng/dl
Once diagnosis is established then obtain baseline levels of: Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin, Prostate Specific Antigen (PSA) and Hemoglobin and Hematocrit (H/H)
Physical exam including digital rectal exam (DRE) for men over 50 or men over 40 with family history of prostate cancer

18. Treatment: TRT continued
Elevated prolactin: obtain MRI of pituitary gland
Very low FSH or LH: obtain MRI of pituitary gland
Expect normal levels of FSH and/or LH or elevated levels of FSH and/or LH in men with hypogonadism
Obtain baseline bone mineral density scan
Most common therapies: intramuscular injections, topical gels, implantable pellets, patches, buccal delivery, nasal spray and a pill to indirectly raise testosterone

19. Normal Ways to boost Testosterone
Weight lifting with free weights
8 hours of sleep
Routine competitions
Increasing frequency of sexual relations
Stress relief
Consuming healthy fats: avocados, pistachios, almonds, fish
Consuming cruciferous vegetables: broccoli, cauliflower, brussels sprouts, and cabbage – they have diindolylmethane (DIM)

20. Implants/Pellets
BioTE
Testopel
Both are bioidentical testosterone

21. BioTE Compounded pellets, proprietary
Implanted subcutaneously in office
Effective for average of 5 months
Testosterone released by cardiac output
100% effective
Not FDA approved
Not covered by insurance $600 direct patient cost per treatment

22. Testopel Endo Pharmaceuticals Implanted subcutaneously in office
Effective for 3 months
20% success rate in my practice
FDA approved
Covered on most insurance plans

23. Injectables Testosterone Cypionate Testosterone Enanthate Aveed
Human Chorionic Gonadotropin (HCG)

24. Testosterone Cypionate/Enanthate
Generic, inexpensive
Intramuscular injection weekly
200 mg/ml, starting dose 0.5 ml Q 7 days
Oil based, time release
Synthetic testosterone, not bioidentical
100% effective

25. Aveed 3 ml IM injection every 10 weeks Requires safety training
In office injection only
Monitor for 30 minutes due to pulmonary oil microembolism or anaphylaxis

26. Transdermal Gels/Topicals
Androgel 1/62% (avoid the 1%)
Axiron
Fortesta (generic available)
Testim (generic available)
All are bioidentical testosterone
Expensive, but covered on insurance plans

27. Androgel 1.62% 4 pumps applied to shoulders/upper arms
Rub in until dry, once daily
Alcohol based gel, odorless
80% effective
Wash hands, avoid skin contact to area for 6 hours

28. Axiron 2 pumps to underarm (1 for each) daily
Use applicator, use deoderant after dry
Alcohol based liquid, odorless
80% effective
Don’t share deoderant

29. Fortesta 4 pumps to inner thigh daily (2 to each leg) Rub in until dry
Alcohol based gel, odorless
80% effective
Wash hands, avoid skin contact for 6 hours

30. Testim 1 tube to shoulders/upper arms daily Rub in until dry
Petroleum based, fragrance
80% effective
Wash hands, avoid skin contact for 6 hours

31. Fertility Safe Options
Preserve healthy sperm count
Prevent testicle atrophy
Clomiphene (Clomid) oral pill form
Human Chorionic Gonadotropin (HCG) injectable

32. Clomiphene Selective Estrogen Receptor Modulator (SERM)
Raises FSH and LH
Increases testosterone production
50 mg PO daily
Side effects of visual disturbances and headaches
Will only work if testicles will respond to high LH

33. Clomiphene continued Will not work if baseline LH is already high
50% effective
Not covered by insurance
Not FDA approved
Typical cost $75/month

34. HCG 1500 units once a week IM or Sub Q 500 units 3 days a week
Hormone that acts similar to LH
Not covered by insurance
Cost $150/month

35. Other Treatment Options
Natesto Nasal Gel applied 3 times daily
Androderm Patch applied once nightly
Striant buccal system applied to gum twice daily
None are used in my clinical practice due to poor effectiveness or inconvenience

36. Evaluation and Follow Up
Evaluate for compliance and correct usage
Assess symptom improvement
Discuss side effects
Draw appropriate lab work

37. Transdermal Gel Follow Up
1 month, 3 months, Q6 months
Draw free and total testosterone at every visit
Draw H/H at 3 months and 6 months
Draw PSA Q6 months
After 2 years of stability then may see patient Q12 months

38. Testosterone Cypionate/Enanthate F/U
1 week after initial injection, 3 months, Q6 months
Draw free and total testosterone at 1 week and give second injection
Draw free and total T and H/H at 3 months
Draw free and total T, H/H and PSA at 6 months
After 2 years of stability then may see patient Q12 months

39. Aveed Follow Up 4 weeks after initial injection then Q10 weeks
Draw free and total T and H/H at every 10 week injection
Draw PSA at Q6 months

40. Clomiphene Follow Up 1 month, 3 months, and Q6 months
Draw free and total T, FSH/LH at every visit
Draw H/H at 3 months and 6 months
Draw PSA at Q6 months
After 2 years of stability then may see patient Q12 months

41. HCG Follow Up 1 month, 3 months and Q6 months
Draw free and total T at every visit
Draw H/H at 3 months and 6 months
Draw PSA Q6 months
After two years of stability then may see patient Q12 months

42. Discussion
Any questions?