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Male Androgen Deficiency

Male Androgen Deficiency. A/Prof Usman Malabu MBBS, MSC (Chem Path), FWACP, MRCP, FACP, FRACP Staff Endocrinologist & Year 6 JCU Academic Coordinator Department of Diabetes & Endocrinology TTH. MALE ANDROGEN DEFICIENCY. A 70 year-old Caucasian male Low testosterone 7 nmol/l

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Male Androgen Deficiency

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  1. Male Androgen Deficiency A/Prof Usman Malabu MBBS, MSC (Chem Path), FWACP, MRCP, FACP, FRACP Staff Endocrinologist & Year 6 JCU Academic Coordinator Department of Diabetes & Endocrinology TTH

  2. MALE ANDROGEN DEFICIENCY • A 70 year-old Caucasian male Low testosterone 7 nmol/l • PMH: Type 2 DM, obesity, dyslipidemia, hypertension, low back pain, osteoarthritis and depression • Meds: • Metformin XR 2g, Atorvastatin 40 mg OD, Perindopril 4 mg OD, Fentanyl patch daily Prednisolone 10 mg OD • O/E: BP 130/80, Wt 110 KG, Ht 1.60, BMI 43 kg/m2. • Invs: A1c 7%, Total cholesterol 3 mmol/l, Total Testosterone 7 nmol/l

  3. Group A • Q1. What further history would you inquire? • Q2. What further examination would you do? • Q3. How would you evaluate this patient? • Q4. What is the next step in work up?

  4. Group D • 26 year-old male married 6 months with poor erection • Was sexually abstinent & Libido is “fair to poor” • Puberty 15-17 yrs & Exercise tolerance was “good.” • Testes have always been “small” • Negative head trauma, loss of smell, testicular trauma, testicular surgery, or treatment for cancer • The patient denied chronic illness or taking medication • Family history was unremarkable • Exam: Wt 76 Kg, Height 181 cm

  5. Group D • Q13. What further examination would you do? • Q14. How would you evaluate this patient? • Q15. What is the next step in confirming the diagnosis? • Q16. What would be your long-term plan for this patient?

  6. Group B • Q5. List risk factors for hypogonadism in this subject • Q6. What would you do before starting testosterone Rx? • Q7. What are the side effects of testosterone Rx? • Q8. List absolute/relative contraindications to testosterone Rx

  7. Group C • Q9. What conditions require measuring serum T in males? • Q10. What are pros/cons of mode of T Rx of your choice? • Q11. How are you going to monitor the patient on T Rx? • Q12. When would you consider stopping T Rx?

  8. Androgen Deficiency • Androgen deficiency is a condition in which tissues do not have enough exposure to androgens for normal function • One in 200 men under 60 years of age suffer from androgen deficiency • Testosterone levels fall with age • At age 65 years, 10% of men have androgen deficiency and this increases to 20% by 70 years

  9. Testosterone and Ageing Range from about 7% between 40-60 years rising to 25% between 60-80 years Androgen deficiency 1 in 10

  10. Androgen deficiency: symptoms • Decreased libido • Decreased energy • Loss of muscle mass, sex hair – chronic • Bone loss – chronic • Reduced testicular size & sperm count • Gynaecomastia

  11. Diminished muscle mass Loss of body hair Abdominal obesity Gynaecomastia Testes frequently normal, occasionally small Physical Signs

  12. Male hypogonadism Primary hypogonadism Testes Serum Testosterone↓, FSH & LH ↑ Secondary hypogonadism Pituitary gland or Hypothalamus Serum Testosterone↓, FSH & LH ↔ , ↓

  13. Primary testicular failure Hypothalamus LH FSH Pituitary Insult Testosterone Testis • Testosterone  LH ( FSH)

  14. Causes – testicular disease • Klinefelter’s syndrome • Toxin exposure (cancer chemotherapy or radiotherapy, environmental, toxins) • Idiopathic • Defects of testis development • Orchitis • Orchidectomy (advanced prostate cancer)

  15. Evaluation of Men with Androgen Deficiency Confirmed low testosterone Check LH+FSH (SA if infertility) High gonadotropins – 1o Low/low nl gonadotropins – 2o Prolactin, other pituitary hormones, iron studies, sella MRI Karyotype

  16. Patient 2 How would you evaluate this patient? Total testosterone: 2 nmol/l (9-35) Luteinizing hormone (LH): 66 U/L (1.0-9.0) What is the initial diagnosis? Primary hypogonadism What is the next step in work up? Karyotype: 47 XXY

  17. Klinefelter’s Syndrome Incidence ~ 1/1,000 live male births Extra X chromosome, usually 47 XXY Manifestations Hypogonadism Gynecomastia Behavioral disorders Bronchiectasis/emphysema/bronchitis Mediastinal germ cell tumors Non-Hodgkin’s lymphoma Diabetes mellitus Lower extremity varicosities

  18. Patient 2 How would you manage this patient? Androgel 5 g topically QD Counseling regarding infertility and extragonadal manifestations of Klinefelter’s syndrome Make patient aware of Klinefelter’s support groups

  19. Secondary testicular failure Insult Hypothalamus LH FSH Pituitary Testosterone Testis • Testosterone LH ( FSH)

  20. Hypothalamic-pituitary Diseases • Pituitary tumour/therapy (surgery, radiation) • Haemochromatosis • Craniopharyngioma • Idiopathic hypogonadotropic hypogonadism, Kallmann’s syndrome • Hyperprolactinemia

  21. Causes of “Male Menopause” Pituitary/testes decline Excessive alcohol consumption Obesity Smoking Hypertension Medications Poor diet Lack of exercise Poor circulation Psychological problems - depression These issues are seen in metabolic syndrome & other medical problems

  22. Look for co-morbidities in non-responders to PDE-5 inhibitors Depending on co-morbidities: Hypogonadism 50% Diabetes mellitus 35% LUTS / BPS 22% Hypertension 23% Hyperlipidaemia Obesity Yassin et al. IJIR Vol. 14, Suppl. 3, 9/2002

  23. Diagnostic Testing for Androgen Deficiency Who to test? Only men with consistent symptoms and signs of unequivocally low serum testosterone levels Screening in the general population is not recommended

  24. Screening Questionnaires Androgen Deficiency in the Aging Male Questionnaire Massachusetts Male Aging Study questionnaire Both have fair sensitivity (80-90%) but poor specificity (50-60%) Not generally recommended Bhasin, S. et al. J Clin Endocrinol Metab 2006;91:1995-2010

  25. Laboratory evaluation • Testosterone and LH levels • >2 early morning samples • Free testosterone – requires validation • Protein binding – • Sex hormone binding globulin (SHBG) • Free androgen index • T / SHBG • Poor empirical validation

  26. Circulating Testosterone Total T Bioavailable T

  27. Common Alterations in SHBGAffect Total and Free T Levels • SHBG  Total T  SHBG  Total T • Moderate obesity • Aging • Low protein (nephrotic) • Hepatitis, cirrhosis • Hyperthyroidism • Hypothyroidism • Anticonvulsants • Glucocorticoids • Anabolic steroids • Acromegaly • Estrogens • HIV

  28. St Louis ADAM questionnaireAndrogen Deficiency in Ageing Males Decrease in sex drive Lack of energy Decrease in strength &/or endurance Lost height Decreased enjoyment of life Sad &/or grumpy Erections less strong Deterioration in sports ability Falling asleep after dinner Decreased work performance Beware that depression may result in a high score Answering yes to questions 1 or 7, or any other 3 questions indicates a high likelihood of having a low testosterone level.

  29. Equilibrium dialysis (gold standard) is very expensive and not readily obtainable Analog free testosterone is inaccurate and should NOT be used Calculate bioavailable testosterone using derived formula Diagnostic Testing for Androgen Deficiency

  30. www.issam.ch/freetesto.htm

  31. Variation in serum total testosterone concentrations Bremner, WJ, Vitiello, V, Prinz, PN, J Clin Endocrinol Metab 1983; 56:1278

  32. PBS criteria for testosterone therapy • Established pituitary/testicular disorder • Male  40y, no established disorder • Not due to aging •  2 early am samples, different mornings • Testosterone level • < 8 nmol/l • 8-15 nmol/l plus LH > 1.5 x upper limit • Micropenis, delayed puberty < 18y

  33. Testosterone Formulations Intramuscular T Extensive experience, inexpensive High-normal T, mood swings or libido, pain T Patch Low-normal T, skin irritation, expensive T Gel Low- to high-normal T, flexibility, no irritation Contact transfer, expensive Buccal T Twice daily, altered taste, gum irritation Choice often left up to patient

  34. Monitoring: When to refer to Urologist PSA > 4 ng/ml Increase in PSA > 1.4 ng/dl within 12 months Rx Abnormal DRE Increase in IPSS prostate symptom score > 19 Bhasin, S. et al. J Clin Endocrinol Metab 2006;91:1995-2010

  35. Summary: Diagnosis of Male Hypogonadism Symptoms/signs of androgen deficiency Sex (erections) Brain (libido, mood, memory, hot flush/sweats) Body (muscle, bone, breast and hair) Consistently low T level x 2 Free or bioavailable T, if suspect  SHBG R/o reversible illness, drugs, nutritional deficiency LH and FSH  1O vs 2O hypogonadism 46

  36. Conclusions: Hypogonadism in Older Men Common disorder Nonspecific clinical findings affected by age, severity and duration of  T and co-morbidities Diagnosis confirmed by repeated  T Accurate free T, if  SHBG suspected R/O reversible causes LH and FSH  1o vs 2o hypogonadism T treatment if benefits > risks Injectable, patch, gels, buccal T available 47

  37. Thank You

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