1. The face of Androgen deficiency

2. Between 2.1% and 21% of men with ED have low testosterone, depending on the test used to measure testosterone Korenman et al. J Clin Endocrinol Metab. 1990;71:963-969. Buvat and Lemaire. J Urol. 1997;158:1764-1767. Nehra A. Mayo Clin Proc. 2000;75 Suppl:S40-S45. Shabsigh R. Int J Impot Res. 2003;15 Suppl 4:S9-S13. AndrogenDeficiencyErectileDysfunction

3. Issues covered: Hormonal Diagnosis of Androgen deficiency Etiological approach to Low T Therapeutic aspects

4. Hormonal Diagnosis Testosterone Measurement Total T Free TAlbumin bound T Bound to SHBG Which one to measure? Bio available Testosterone

5. Testosterone Measurements Need to be measured close to 8 am Assays at a reputable reference lab Total T and calculated free T usually correlate Free T is more accurate when SHBG is altered ObesityDMRenal/HepaticThyroid ds

6. What defines a low Testosterone? Normal range 300-900 ng/dl (age relevant) Total T less than 200-250 = low Total T between 250 -300 = Borderline Free T (n=> 65 pg/ml) helps when total T is borderline or a Affected by changes in SHBG Opioids Anabolic steroidsGluco corticoids T levels affected by drugs

7. Issues covered: Hormonal Diagnosis of Androgen deficiency Etiological approach to Low T Therapeutic aspects

8. The Hypothalamic Pituitary Gonadal Axis GnRH LHFSH Testosterone Spermatogenesis - Inhibin - T -

9. Low TESTOSTERONEHigh LH HYPER GONADOTROPHIC HYPOGONADISM Klinefelters syndrome Adult testicular failure Orchitis Testicular trauma Chemo/Radiation Ketoconazole Primary Gonadal Failure High LH

10. Low LH Low TESTOSTERONE HYPOGONADOTROPHIC HYPOGONADISM Kallman Syndrome Pituitary failure Pituitary tumor Prolactinoma Hemochromatosis HIV Primary Hypothyroid Anorexia Nervosa Low LH Steroids Alcohol Opioids Secondry Gonadal Failure

11. Normal LH Low TESTOSTERONE Seen in clinical practice in association with Several common conditions Metabolic syndrome Type 2 Diabetes Aging Obstructive Sleep Apnea

12. Androgen Deficiency in the Aging Male

13. *Hypogonadal: at least 1 free testosterone value <11.3 nmol/L (325 ng/dL). Harman et al. J Clin Endocrinol Metab. 2001;86:724-731. % Hypogonadal * 50-5960-6970-79>80 Age (years) 12% 22% 42% 68% Hypogonadism defined as serum T <300 ng/dL

14. Issues covered: Hormonal Diagnosis of Androgen deficiency Etiological approach to Low T Therapeutic aspects

15. Androgen Deficiency Poor Concentration Ability Decreased Hematopoiesis Decreased Body Hair Muscle Wasting Sexual Dysfunction Increased Fat Osteoporosis Increased Fractures AACE Guidelines. Endocr Pract. 2002;8:439-456. Harman et al. J Clin Endocrinol Metab. 2001;86:724-731.

16. Androgen deficiency in aging male: ADAM Total, free T dramatically decline after age 60 Symptoms and T levels may not correlate ED can be multifactorial in males > 60 Age, depression, atherosclerosis, co morbidities and meds contribute to ED Issues:

17. SEP consists of 5 questions rate from 1-5 for each 1.Were you able to achieve at least some erection? 2.Were you able to insert your penis into your partners vagina? 3.Did your erection last long enough to have successful intercourse? 4.Were you satisfied with the hardness of your erection? 5.Were you satisfied with the overall sexual experience? Mulhall JP et al. J Urol. 2003;170:353-358.

18. Depression Burn out Stress Hostility Bored with partner Loss of attraction Hostility Guilt ?Testosterone Deficiency

19. Androgen Therapy NOT recommended unless the Testosterone level is low!!

20. Examination/laboratory tests Digital rectal examination, PSA, breast evaluation Eliminate absolute contraindications Prostate cancer Breast cancer Consider relative contraindications Sleep apnea, Polycythemia Rhoden EL, Morgentaler A. N Engl J Med 2004;350:482-492; accessed January 29, 2004. Endocr Pract. 2002;8:439-456.

21. Parenteral Testosterone Cypionate Enanthate 200 q 2 weeks Dermal patch: (Androderm) 5 mg patches Gel: Androgel1% or 1.62% Testim Fortesta 2% Liquid Axiron Buccal Gum (Striant) Pellets

22. N=54; P<.01; PSA=prostate-specific antigen. *Testosterone replacement in hypogonadal men defined as testosterone <300 ng/dL. Gerstenbluth et al. J Androl. 2002;23:922-929. Mean follow-up=30.2 months Mean age= 60.4 years 652 Hypogonadal men (T<300ng/dL) Dose=200-300 mg, q 2-4 Weeks 6 Biopsies, 1 prostate cancer 0.96 Serum PSA (ng/mL) PretreatmentPosttreatment

23. Aging is associated with In prevalence of androgen deficiency Testosterone replacement in hypogonadal men Strength, lean body mass Bone mass Libido Sense of well-being May augment the treatment of ED with PD5 inhibitors

24. Erectile dysfunction and low testosterone frequently occur together Study to evaluate whether the addition of testosterone to sildenafil improves erectile function in men with low T (total T <330 ng/dl or free T < 50 pg/ml) 140 Men 40 -70 y/o with EFD of IIEF scores of <25 randomized to 10-g daily of transdermal testosterone gel or placebo after sildenafil dose was optimized EFD score improvement analyzed after 14 weeks Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691

25. CharacteristicsTestosterone (n=70)Placebo (n=70) Age, y55.154.6 BMI, kg/m231.532.7 Diabetes, n1314 Hypertension, n3532 Cardiovascular disease, n3532 Total Testosterone, ng/dl248254 Free Testosterone, pg/ml4547 EFD of IIEF score12 Baseline Characteristics at Randomization Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691

26. CharacteristicsTestosterone (n=70)Placebo (n=70) Increase in EFD Score (after Sildenafil optimized) 7.7 [95% CI, 6.5 to 8.8] (Compared to baseline EFD Scores) Total Testosterone, ng/dl (after Sildenafil optimized) 364347 Total Testosterone, ng/dl (after 14 weeks of Tx.) 649No Change Increase in EFD Score (after Testosterone Tx) 2.2 [CI, -0.8 to 5.1] (Compared to placebo) Results There was no effect of age, BMI, disease state, initial T level, EFD score, or response to sildenafil alone on the results Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691

27. There was no additional benefit of adding testosterone therapy to optimized sildenafil treatment on ED (though there was also no increase in adverse events) However, this should not preclude use of testosterone for its other beneficial effects A confounder may be the 100 ng/ml increase in testosterone seen in the sildenafil run-in period Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691