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Metabolic Syndrome and Erectile Dysfunction

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Case discussion at UMED conference 2009

Case discussion at UMED conference 2009


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  • 1. Erectile Dysfunction and Metabolic Syndrome Iris Thiele Isip Tan MD (PhiSSAM) Dennis Serrano MD (PUA)
  • 2. The Case •46/M on follow-up at Diabetes Clinic •Known diabetic x 5 years •Glimepiride 2 mg od and Metformin 500 mg bid •Currently smoking ‣ 60-pack year smoking history
  • 3. The Case •RUQ pain unrelated to food or movement 3 months PTC ‣ Fatty liver changes on ultrasound •Screened for erectile dysfunction for a study ‣ IIEF-5 score: 11
  • 4. The Case Pink conjunctivae, anicteric sclerae No thyromegaly. No neck vein BP 130/80 engorgement. No carotid bruit. HR 80 Equal chest expansion. Clear breath sounds. No gynecomastia. RR 16 Wt 88 kg No heaves or thrills. Apex beat and PMI 5th ICS LMCL. Good S1 and S2. Ht 1.77 cm No murmurs. BMI 28 kg/m2 Abdomen flabby, soft. No tenderness, Waist circ 103 cm masses or organomegaly. Hip circ 100 cm No edema or varicosities. Full pulses. Waist-hip ratio 1.03 Pubic hair and genitalia Tanner Stage V.
  • 5. The Case FBS 181 mg/dL HbA1c 6.6% AST 192 (NV <47 u/L) Uric acid 295 mmol/L BUN 5.1 mmol/L Crea 76 Total cholesterol 208 mg/dL HDL 48 mg/dL LDL 124 mg/dL Triglyceride 179 mg/dL
  • 6. The Case Lab work from study LH 6.8 (NV 1.9-9.4 uIU/dL) FSH 2.5 (NV 1.0-10.5 uIU/L) Prolactin 526 (NV 90-500 nmol/L) SHBG 51.8 (NV 7-81 nmol/L) Total testosterone 2 (NV 2.8-5 nmol/L) Free testosterone 0.00373 (NV 0.225 nmol/L) Bioavailable testosterone 0.138 (NV 5.2 nmol/L)
  • 7. What is the diagnosis? Metabolic syndrome (Type 2 diabetes mellitus, hypertension, obesity, dyslipidemia) Fatty liver Erectile dysfunction Hypogonadotrophic hypogonadism
  • 8. Question 1 1. The patient fulfills the NCEP-ATP III criteria for Metabolic Syndrome as he has a. elevated total cholesterol, low HDL, diabetes and hypertension b. elevated triglycerides, BP >130/85 mm Hg, diabetes and abdominal obesity c. elevated total cholesterol, elevated LDL, diabetes and abdominal obesity d. elevated total cholesterol, low HDL, hypertension and abdominal obesity
  • 9. NCEP-ATP III (2001) definition Metabolic Syndrome Three or more of • Central obesity (waist circ) ‣ >102 cm ( ) & >88 cm ( ) • TG >150 mg/dL • HDL <40 ( ) & <50 ( ) mg/dL • BP >130/>85 mm Hg • FPG >110 mg/dL
  • 10. The Case BP 130/80 Wt 88 kg Ht 1.77 cm BMI 28 kg/m2 Waist circ 103 cm Hip circ 100 cm Waist-hip ratio 1.03 FBS 181 mg/dL HbA1c 6.6% Total cholesterol 208 mg/dL HDL 48 mg/dL LDL 124 mg/dL Triglyceride 179 mg/dL
  • 11. IDF definition Metabolic Syndrome Central obesity (waist circ) ‣ >90 cm ( ) & >80 cm ( ) PLUS any two of • TG >150 mg/dL • HDL <40 ( ) & <50 ( ) mg/dL • SBP >130 mm Hg or DBP >85 mm Hg or on treatment • FPG >100 mg/dL or pre-existing IFG or IGT
  • 12. Metabolic Syndrome predicts CV mortality
  • 13. Question 1 1. The patient fulfills the NCEP-ATP III criteria for Metabolic Syndrome as he has a. elevated total cholesterol, low HDL, diabetes and hypertension b. elevated triglycerides, BP >130/85 mm Hg, diabetes and abdominal obesity c. elevated total cholesterol, elevated LDL, diabetes and abdominal obesity d. elevated total cholesterol, low HDL, hypertension and abdominal obesity
  • 14. Question 1 1. The patient fulfills the NCEP-ATP III criteria for Metabolic Syndrome as he has a. elevated total cholesterol, low HDL, diabetes and hypertension b. elevated triglycerides, BP >130/85 mm Hg, diabetes and abdominal obesity c. elevated total cholesterol, elevated LDL, diabetes and abdominal obesity d. elevated total cholesterol, low HDL, hypertension and abdominal obesity
  • 15. Question 2 2. All of the following are signs and/or symptoms of androgen deficiency EXCEPT a. depression b. lethargy c. weight loss d. sleep disturbance
  • 16. Signs/Symptoms of Androgen Deficiency ‣ Loss of libido ‣ Depression (current use of antidepressants) ‣ Erectile dysfunction ‣ Lethargy ‣ Inability to concentrate ‣ Sleep disturbance ‣ Irritability ‣ Depressed mood Kupelian et al JCEM 2006;91:843-50
  • 17. Late-onset Hypogonadism (LOH) ‣ Age-associated testosterone deficiency syndrome (TDS) ‣ Clinical and biochemical syndrome associated with advancing age ‣ Characterized by symptoms and a deficiency in serum T levels (below young healthy adult male reference range) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 18. Suggestive of T deficiency ‣ Low libido ‣ Erectile dysfunction ‣ Decreased muscle mass and strength ‣ Increased body fat ‣ Decreased bone mineral density and osteoporosis ‣ Decreased vitality and depressed mood ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 19. Use of Questionnaires •Not recommended for the diagnosis of hypogonadism because of low specificity ‣ Aging Male Symptom Score ‣ Androgen Deficiency in Aging Men ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 20. Question 2 2. All of the following are signs and/or symptoms of androgen deficiency EXCEPT a. depression b. lethargy c. weight loss d. sleep disturbance
  • 21. Question 2 2. All of the following are signs and/or symptoms of androgen deficiency EXCEPT a. depression b. lethargy c. weight loss d. sleep disturbance
  • 22. Question 3 3. The patient should have been screened for erectile dysfunction regardless of enrollment in the study a. Yes b. No
  • 23. International Index of Erectile Function Erectile Function Domain 0 1 2 3 4 5 How often were you able to get an X erection during sexual activity? When you had erections after stimulation, X how often were your erections hard enough for penetration? When you attempted sexual intercourse, X how often were you able to penetrate 0 = No sexual activity (enter) your partner? 1 = Almost never/never X During sexual intercourse, how often 2 = A few times (much less than half the time) were you able to maintain erection after 3 = Sometimes (about half the time) you had penetrated (entered) your 4 = Most times (much more than half the time) partner? 5 = Almost always/always During sexual intercourse, how difficult is X it to maintain your erection to completion of intercourse? How do you rate your confidence that X you could get and keep an erection? Total score 11 = moderate EF score
  • 24. ED in Diabetes •35-75% of men with diabetes have ED •Compared to age-matched control subjects, men with diabetes develop ED ~5-10 years earlier Romeo et al J Urol 2000;163:788-91
  • 25. Prevalence of ED in diabetes increases with age Cross-sectional survey in a ~ 50 pop %i community-based clinic n an ulat 541 men with diabetes Agin ion unsele gM (Ma cted ale ssa Sur chu vey sett 6% 52% 55-95% ) s 20-24 y 55-59 y >60 y Feldiabetesan et al J Urol 1994;151:54-61 Kaiser FE. Med Clin North Am 1999;83:1267-78
  • 26. ED in Diabetes •Correlated with HbA1c •Presence of peripheral neuropathy increases risk of ED ‣ Underlying autonomic neuropathy ‣ Almost 100% of patients with diabetic neuropathy have ED Romeo et al J Urol 2000;163:788-91
  • 27. Question 3 3. The patient should have been screened for erectile dysfunction regardless of enrollment in the study a. Yes b. No
  • 28. Question 3 3. The patient should have been screened for erectile dysfunction regardless of enrollment in the study a. Yes b. No
  • 29. Evaluation of ED ? •Medication history ‣ Antihypertensives: B-blockers and thiazide diuretics ‣ Acting on CNS: TCA, SSRI, phenothiazines, butyrophenones, atypical antidepressants ‣ Affecting endocrine: anti-androgens, GnRH agonists and antagonists, estrogens, cimetidine, metoclopramide, fibric acid derivatives, alcohol, marijuana Theti et al Clinical Diabetes 2005;23(3):105-13
  • 30. Evaluation of ED •Vascular disease ‣ Doppler studies of penile blood flow ‣ Pharmacodynamic testing using vasoactive compounds ‣ Pudendal angiography and cavernosometry •Psychosocial Assessment ‣ Combine with nocturnal penile tumescence test ‣ Marital counseling Theti et al Clinical Diabetes 2005;23(3):105-13
  • 31. Evaluation of ED •Hormonal status ‣ LH, FSH, prolactin ‣ Testosterone level ‣ Ferritin (to evaluate for hemochromatosis) •Autonomic neuropathy ‣ ECG (R-R variability), heart rate variability ‣ Orthostatic blood pressure readings ‣ Tilt table testing Theti et al Clinical Diabetes 2005;23(3):105-13
  • 32. Gradual Decline of T in Aging Males Free T index = serum total T / SHBG Lamberts et al. Science 1997;278:419-24
  • 33. Prevalence of Metabolic Syndrome Increases with Age in Males Prevalence Prevalence Study N in males by age 8814 adults 6.7% (20-29 y) NHANES III (US) 24% >20 y 43.5% (60-69 y) N. Trondelag 10206 adults 13% (20-29 y) 26.8% Study (Norway) 20-89 y 46% (80-89 y) Urban Chinese 2359 adults 35.3% (40-64 y) 36.8% (China) >40 y 43.2% (>65 y) Ford et al JAMA 2002:287:356-9 Hildrum et al BMC Public Health 2007 Lin et al BMC Public Health 2007
  • 34. Declining androgen levels associated with components of the Metabolic Syndrome Inverse correlation between plasma T levels and Obesity BMI, WC, WHR and amount of visceral fat Positive correlation between plasma T levels Dyslipidemia and HDL-C; inverse correlation with triglycerides, total cholesterol and LDL-C Inverse correlation between T levels and Hypertension SBP/DBP; ↑hypogonadal men with history of hypertension in HIM study Impaired glucose Low T is associated with insulin tolerance resistance; diabetic men have low T levels Wu & von Eckardstein. Endocr Rev 2003;24(2):183-217 Lunenfeld B. The Aging Male 2007;10(2):53-6
  • 35. Low T: A Marker of Metabolic Syndrome? •Low total T and symptomatic androgen deficiency increased risk for metabolic syndrome in non-obese men (BMI<25) over time Early warning • For every 1 SD decrease in total T: sign for CV risk adj RR 1.41 (95%CI, 1.06-1.87) and opportunity • Symptomatic androgen deficiency: for early RR 2.51 (95% CI 1.12-5.65) intervention in non-obese men Kupelian et al JCEM 2006:91:843-850
  • 36. No recommendation to screen men with symptoms of T deficiency for metabolic syndrome No recommendation to screen men with metabolic syndrome for T deficiency
  • 37. 2009 Unified ISA, ISSAM, EAU, EAA and ASA Recommendations for Late-onset Hypogonadism Recommendation 8 •Serum T should be measured in men with type 2 diabetes mellitus with symptoms suggestive of T deficiency (Level 2b, Grade A) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 38. The Case Lab work from study SHBG 51.8 (NV 7-81 nmol/L) Total testosterone 2 (NV 2.8-5 nmol/L) Free testosterone 0.00373 (NV 0.225 nmol/L) Bioavailable testosterone 0.138 (NV 5.2 nmol/L)
  • 39. Laboratory diagnosis of LOH in males Obtain serum sample for total T between 0700 and 1100 h Total T >12 Total T <8 nmol/L Total T 8-12 nmol/L: nmol/L (350 (230 ng/dL): repeat total T with ng/dL) does usually benefit SHBG to calculate not require from T treatment free T substitution Consider treatment if free T below 225 pmol/L (65 pg/mL) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 40. Algorithm for suspected hypogonadism Lunenfeld & Nieschlag,The Aging Male 2007;10(3):139-153
  • 41. The Case Lab work from study LH 6.8 (NV 1.9-9.4 uIU/dL) FSH 2.5 (NV 1.0-10.5 uIU/L) Prolactin 526 (NV 90-500 nmol/L) SHBG 51.8 (NV 7-81 nmol/L) Total testosterone 2 (NV 2.8-5 nmol/L) Free testosterone 0.00373 (NV 0.225 nmol/L) Bioavailable testosterone 0.138 (NV 5.2 nmol/L)
  • 42. Hypogonatrophic hypogonadism •Common in obese men and those with type 2 diabetes ‣ Attributed to ↑ levels of estrone and estradiol produced by aromatase enzyme in adipose tissue from adrenal (androstenedione) and testicular (testosterone) androgen ‣ Aging also associated with progressive decline in androgens Theti et al Clinical Diabetes 2005;23(3):105-13
  • 43. Nitric oxide (NO) and erection Theti et al Clinical Diabetes 2005;23(3):105-13
  • 44. Pathophysiology and factors complicating diabetic ED •Reduced nitric oxide (NO) ‣ Advanced glycation end products → increase in reactive oxidizing substances and reduced NO production ‣ Failed neural signal transmission to and from the spinal cord due to diabetic neuropathy and reduced production of neuronal NO synthase → reduced levels of neuronal NO release to cavernosal smooth muscle ‣ Endothelial dysfunction of the sinusoidal endothelial cells → decrease in NO release and impaired vasodilatation Theti et al Clinical Diabetes 2005;23(3):105-13
  • 45. Pathophysiology and factors complicating diabetic ED • Increasing age and hyperglycemia → glycation of elastic fibers → failure of relaxation of the corpora cavernosa • Peripheral vascular disease → reduced arterial and arteriolar inflow •Hypogonadotrophic hypogonadism •Multiple drug regimens •Dyslipidemia Theti et al Clinical Diabetes 2005;23(3):105-13
  • 46. Modifiable risk factors for ED Risk Factor Strategy Sedentary lifestyle Increase physical activity Depression Treatment of depression Diabetes Improved control Alcohol Abstinence from alcohol Tobacco Quit smoking/use of patch Hypogonadism Testosterone replacement Overweight or obesity Weight loss Theti et al Clinical Diabetes 2005;23(3):105-13
  • 47. Question 4 4. The patient has low testosterone levels. Will you start testosterone replacement for this patient? a. Yes b. No Total testosterone c. It depends 2 (NV 2.8-5 nmol/L) Free testosterone 0.00373 (NV 0.225 nmol/L) Bioavailable testosterone 0.138 (NV 5.2 nmol/L)
  • 48. Who should receive T replacement? •Reserved for those who are androgen deficient, especially if use of a PDE-5 inhibitor is contemplated ‣ Neuronal NO production is androgen dependent ‣ PDE-5 inhibitors require the presence of NO to be effective Theti et al Clinical Diabetes 2005;23(3):105-13
  • 49. Who should receive T replacement? •Men with erectile dysfunction and/or diminished libido and documented T deficiency are candidates for T therapy (Level 2a, grade A) ‣ An inadequate response to T treatment requires reassessment of the causal mechanisms responsible for the ED ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 50. Who should receive T replacement? •Evidence suggesting therapeutic synergism with combined use of T and PDE-5 inhibitors in hypogonadal or borderline eugonadal men (Level 1b, grade B) ‣ Consider combination treatment in hypogonadal patients with ED failing to respond to either treatment alone ‣ Unclear whether men with hypogonadism and ED should be treated initially with PDE-5-I, T or both ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 51. Who should receive T replacement? •Premature to recommend T treatment for metabolic syndrome or type 2 diabetes mellitus in the absence of laboratory and other clinical evidence of hypogonadism ‣ T treatment for traditional hypogonadal symptoms may have other unproven benefits on their metabolic status (Level 2a, grade B) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 52. Testosterone treatment and CV events Wide confidence interval: consistent with 1-fold decrease and a 4-fold increase in odds of CV events in patients using testosterone Haddad et al Mayo Clin Proc 2007;82(1):29-39
  • 53. Who should NOT receive T replacement? •Contraindicated in men with breast or prostate CA (Level 3, grade A) •Relatively contraindicated in men at high risk of developing prostate CA ‣ Unclear whether localized low-grade (Gleason score <7) prostate cancer represents a relative or absolute contraindication for treatment (Level 4, grade C) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 54. Who should NOT receive T replacement? •Men with significant erythrocytosis (Hct >52%) (Level 3, grade A) •Untreated significant obstructive sleep apnea (Level 3, grade B) •Untreated severe congestive heart failure (Level 3, grade B) •Resolve co-morbid conditions prior to T treatment ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 55. Who should NOT receive T replacement? •Aging is NOT a contraindication to initiate T treatment (Level 2a, grade A) ‣ Individual assessment of co- morbidities (as possible causes of symptoms) and potential risks vs benefits of T treatment ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 56. Question 4 4. The patient has low testosterone levels. Will you start testosterone replacement for this patient? a. Yes b. No Total testosterone c. It depends 2 (NV 2.8-5 nmol/L) Free testosterone 0.00373 (NV 0.225 nmol/L) Bioavailable testosterone 0.138 (NV 5.2 nmol/L)
  • 57. Question 4 4. The patient has low testosterone levels. Will you start testosterone replacement for this patient? a. Yes b. No Total testosterone c. It depends 2 (NV 2.8-5 nmol/L) Free testosterone 0.00373 (NV 0.225 nmol/L) Bioavailable testosterone 0.138 (NV 5.2 nmol/L)
  • 58. Recommendations for androgen therapy •Preparations of natural testosterone should be used ‣ 17-α-alkylated androgen preparations i.e. 17α- methyltestosterone are obsolete because of potential liver toxicity (Level 2a, grade A) ‣ Non-testosterone androgen precursor preparations (i.e. DHEA, DHEA-S, androstenediol, androstenedione) are not recommended (Level 1b, grade A) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 59. Recommendations for androgen therapy •Not enough evidence to recommend anti-estrogens and aromatase inhibitors which ↑ endogenous T levels (Level 2b, grade B) •Selective androgen receptor modulators are under development but not yet clinically available ‣ Non-aromatizable and risks of long-term use unclear ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 60. Testosterone delivery systems •Currently available preparations of T are safe and effective (Level 1b, grade A) ‣ Intramuscular, subdermal, transdermal, oral and buccal Route Generic name Trade name Dosage Implants Testosterone 200 mg Testosterone implants 200 mg 3-6 implants every 6 months Testosterone enanthate 250 mg Testosterone depot 250 1 ampule every 2-3 weeks Intramuscular Testosterone undecanoate Nebido 1 ampule every 10-14 weeks Oral Testosterone undecanoate Andriol Testocaps 2-4 capsules at 40 mg/day Testosterone patch Androderm 2x5 mg/day TTS scrotal Testoderm 1 membrane/day Transdermal Testosterone gel 25 or 50 mg Testogel Androptop gel 50-100 mg/day Testosterone gel 50 mg Testim 50-100 mg/day Buccal Testosterone 30 mg Striant 1 tablet twice daily ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Lunenfeld and Nieschlag The Aging Male 2007 10(3):139-53 The Aging Male March 2009;12(1):5-12
  • 61. not die from this disease (Ruijter et al., three and six pellets of 200 mg unmo Historical overview of T preparations available for clinical use 1940 subdermal T pellet implants, 1954 IM T enanthate, 1977 oral T undecanoate, one preparations and the years they became available for clinical use: 1940 ¼ subdermal testostero 1992 scrotal T patch, 1995 and 1998 transdermal T patches, 2002 transdermal T gels, nanthate, 1977 ¼ oral testosterone undecanoate, 1992 ¼ scrotal testosterone patch, 1995 and 1998 2004 buccal T and IM T undecanoate testosterone gels, 2004 ¼ buccal testosterone and intramuscular testosterone undecanoate. Nieschlag et al Hormone Reprod Update 2004, 10(5):409-19
  • 62. Oral testosterone undecanoate •Safe and effective, free of liver toxicity ‣ Circumvents the first passage through the liver •Brings serum T within the physiological range •Liposoluble ‣ 120-200 mg daily taken with meals ‣ Extremely variable absorption and bioavailability; influenced by amount of simultaneously ingested fat Morales and Lunenfeld The Aging Male 2002;5:74-86
  • 63. IM testosterone undecanoate •Single injection of 1000 mg T undecanoate normalize serum T levels for about 3 months •Free from supra- physiological peaks ‣ Maintains very stable serum testosterone levels within normal range for an extended period of time Jockenhovel F. The Aging Male 2003;6:200-206
  • 64. Testosterone delivery systems •Sufficient knowledge and adequate understanding of pharmacokinetics and advantages/drawbacks of each preparation ‣ Selection of preparation should be a joint decision of an informed physician and patient ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 65. Testosterone delivery systems •Short-acting preparations may be preferred over long- acting depot preparations in the initial treatment of patients with LOH (Level 4, Grade C) ‣ Possible development of an adverse event during treatment (especially elevated hematocrit or prostate carcinoma) requires rapid discontinuation of T substitution ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 66. Goals of treatment for T replacement •Restore normal serum testosterone levels into the physiologic range •Restore metabolic parameters to the eugonadal state •Increase muscle mass, strength,and function •Maintain BMD and reduce fracture risk •Improve neuropsychological function (cognition and mood) •Improve libido and sexual functioning •Enhance quality of life Lunenfeld and Nieschlang The Aging Male 2007 10(3):139-53
  • 67. Recommended standard (initial regimen) for i.m. testosterone undecanoate therapy Total serum testosterone (nmol/L) Injection interval before 30-wk injection 10-15 12 weeks <10 10 weeks >15 14 weeks Morales et al The Aging Male 2006, 9(4):221-7
  • 68. Monitoring efficacy of T replacement Parameter Reference range Frequencya Comments Serum testosterone Total 300-1050 ng/dL At baseline, For i.m. T injection, Free 5-21 ng/dL steady state, and measure serum T at the % free 2.0-4.8% as warranted midpoint between clinically injections Bioavailable T 92-420 ng/dL As warranted DHT 30-85 ng/dL clinically Indicated for hypergonadotropic hypogonadism. Failure to LH 1.29-1.8 IU/l At 3-6 months suppress to normal range indicates inadequate replacement a Monitor clinical response and side effects at 3- to 4- month intervals during the first year of therapy unless otherwise designated. A Seftel. Int J Impot Res 2007;19(1):2-24
  • 69. For how long? •Discontinue T replacement if clinical manifestations do not improve within a reasonable time interval ‣ 3-6 months: for libido and sexual function, muscle function, and improved body fat ‣ Longer interval for bone mineral density •Further investigation for other causes of symptoms is then mandatory (Level 1b, Grade A). ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. The Aging Male March 2009;12(1):5-12
  • 70. Question 5 5. If testosterone replacement is given for this patient, all the following should be done at baseline EXCEPT a. Hemoglobin/hematocrit b. ALT/AST c. Breast examination d. Creatinine
  • 71. Potential risks of androgen therapy Potential risk Comments Existing evidence suggests a neutral or possibly Cardiovascular disease beneficial effect Most studies show no change with physiologic Lipid alterations replacement doses Wide range of risk, depending on mode of Erythrocytosis administration (up to 44% with i.m.); requires monitoring Fluid retention Rarely of clinical significance BPH Rarely of clinical significance Controversial; unknown level of risk; requires long-term Prostate cancer monitoring A Seftel. Int J Impot Res 2007;19(1):2-24
  • 72. Potential risks of androgen therapy Potential risk Comments Acne or oily skin Infrequent Testicular atrophy or Common especially in young men, usually reversible infertility with cessation of treatment Wide range of risk, depending on mode of Erythrocytosis administration (up to 44% with i.m.); requires monitoring Sleep apnea Infrequent Gynecomastia Rare, usually reversible Skin reactions Rare with injections A Seftel. Int J Impot Res 2007;19(1):2-24
  • 73. Monitoring for safety Parameter Reference range Frequency Hemoglobin 13-18 g/dL Every 6 months x first 18 months then Hematocrit 42-52% yearly if stable and normal TC <200 mg/dL Serum lipid panel LDL-C <70-160 mg/dL Baseline, 6-12 mo of first year, then (ATP III) HDL-C >40 mg/dL annually TG <350 mg/dL ALT 13-40 U/L At baseline, 6-12 months, and as AST 19-48 U/L warranted clinically Breast Baseline examination Sleep apnea Baseline and as needed clinically a Monitor clinical response and side effects at 3- to 4- month intervals during the first year of therapy unless otherwise designated. A Seftel. Int J Impot Res 2007;19(1):2-24
  • 74. Question 5 5. If testosterone replacement is given for this patient, all the following should be done at baseline EXCEPT a. Hemoglobin/hematocrit b. ALT/AST c. Breast examination d. Creatinine
  • 75. Question 5 5. If testosterone replacement is given for this patient, all the following should be done at baseline EXCEPT a. Hemoglobin/hematocrit b. ALT/AST c. Breast examination d. Creatinine
  • 76. Thank You http://www.endocrine-witch.info