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

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

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

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

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

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

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

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 350-400 ng/dl is borderline, treat based on severity of symptoms

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

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

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.

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

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 89 2016, pg 27 *Kavoussi, Clinical Urologic Endocrinology, Ch 5

Risks/Side Effects of TRT Acne Erythrocytosis Peripheral edema Atrophy of testicles Lowering of sperm count Gynecomastia * Morgantaler, Urology 89 2016, pg 27

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

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

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

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

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)

Implants/Pellets BioTE Testopel Both are bioidentical testosterone

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Discussion Any questions?