1. 1 Managing Hypogonadism in the Primary Care Setting Dr Michael Gillman St Andrews Hospital Specialist Suites, Wickham Terrace Mater Private Clinic, South Brisbane Shore Street West Medical Centre, Cleveland

2. Hypothalamic – Pituitary – Testicular Axis

3. Primary Testicular Failure Klinefelters Bilat Orchidectomy Radiotherapy, Chemotherapy Cryptorchidism Testicular Injury Orchitis Age Co-Morbid conditions particularly Diabetes, Metabolic Syndrome 3

4. Secondary ( Hypogonadotrophic ) Pituitary Tumours Haemachromatosis Thalassaemia Sleep apnoea Other acute or chronic illness affecting hypothalamic-pituitary-testicular axis Substance abuse ( steroids and opiates ) 4

5. Presentation (1) Often picked up incidentally Reduced sense of general wellbeing; Energy Loss; Fatigue; Low mood or depression; Irritability; Poor concentration; Poor memory; 5

6. Presention Continued Decreased Libido Failure to conceive Sexual Dysfunctions Losing strength and muscle mass 6

7. Further History History of onset Past Medical and Surgical History Social and Lifestyle History Family History Sexual History Ask about symptoms of sleep apnoea Ask about LUTS 7

8. Examination Height Weight and Waist Circumference Testicular examination Breast Examination Body Hair distribution Muscle Mass DRE General examination BP Heart chest abdomen etc 8

9. Investigations FBC, E/LFTs, HDL/LDL, serum ferritin, TSH, serum testosterone, PSA ( Total T more reliable than free T ) If Testosterone is low repeat along with LH and PRL Take total T between 8 to 10 a.m.  The patient should be fasting as glycaemic load can distort the results  Avoid prior exhaustive physical exercise (e.g. jogging) as this may influence the testosterone levels ? Sleep Study if suggested by history BMD 9

10. What level of T is hypogonadism? Australia: PBS guidelines - Approved indications for authority: Androgen deficiency in males 40 years and older without pituitary or testicular disorders other than ageing confirmed by x2 early morning total T 1.5 times upper limit of normal for young men) Androgen deficiency in males with established pituitary or testicular disorders Androgen deficiency in males under 18 years of age: Micropenis, pubertal induction, or constitutional delay of growth or puberty Handelsman (2004)

11. What are the correct levels for Diagnosis? Australia <8 nmol/L US <10.4 nmol/L Europe <12 nmol/L

12. Management Diet, exercise and waist loss T levels may be restored by weight loss with a diet and exercise program Attempt weight loss along with TRT and if successful, assess need to decrease or cease TRT (3 to 6 months for function to return) Correct other risk factors and co morbid conditions; 12

13. Management Examine for contraindications for TRT: Prostate or breast cancer Erythrocytosis ( HCT > 55% ) Sleep apnoea Severe LUTS Cardiac failure ( Potential for oedema and raised HCT )

14. If Decide to treat Explain the probability that this will be long term therapy Explain infertility consequences Commence with short acting topical 14

15. TRT – Topical (less likely to have negative effects on lipids, less likely to cause polycythaemia) Androderm patch (testosterone + absorption enhancers) Transdermal patch 2.5 & 5 mg – apply 10 p.m. back, arm, shoulders, abdomen, buttocks, thighs - 1 week between sites Mimics normal circadian rhythms Check T level in a.m. after p.m. patch applied Contact dermatitis 10-60%, visibility, poor adherence, difficulty achieving adequate T concentrations Testogel (testosterone) 50mg testosterone in a 5 g sachet Apply daily in a.m. - 5 to 10 g/day - titrate dose by 2.5 g increments after day 7 (max 10g = 100mg T) Apply to shoulders, arms, abdomen - wash hands Allow to dry 3 - 5 mins Steady state serum T over 24 hours Lack of visibility and less skin irritation Dosage flexibility Take T level 6 to 8 hours after application Skin transfer - cover or bathe (4 - 6 hours after application)

16. Follow up at six weeks Assess total T level and adjust dose Ask about side effects, voiding symptoms Side effects: Male pattern hair loss Worsening of sleep apnoea Acne and oily skin Gynaecomastia Fluid retention and oedema Polycythaemia Testicular shrinkage and decreased sperm count 16

17. TRT - imi injections Reandron 1000 (T undeconoate) 4 ml deep gluteal imi slowly @ 0 and 6 weeks (loading dose) then every 10 to 14 weeks (x4 per year) Check T level @ 30 weeks prior to injection 4 Titrate dose by altering timing of injections - administer more often if T level is below normal Trough levels within normal range More stable levels of energy, mood and libido Less polycythaemia imi not for men with bleeding disorder or on anticoagulants every 3 weeks every 3 months Primosteston depot Reandron 1000

18. @ 3 months, 6 months then annually Assess response to Rx Assess Total T level Hb and HCT (>54%) LFT, lipids, voiding symptoms Sleep apnoea Weight, WC and BMI Breast examination DRE and PSA – assess velocity (BMD each 2 years) 18

19. Axiron Not yet approved for use in Australia or New Zealand This information is provided in response to your request and is intended for your scientific and/or educational purpose and is not intended for promotional use. This material is copyrighted by Lilly USA, LLC with all rights reserved.

20. Background Data on file, Lilly Research Laboratories, AXSEP2010A

21. Delivery System Data on file, Lilly Research Laboratories, AXSEP2010F

22. Delivery System AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

23. Axillary Application

24. Dosing and Administration AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

25. Dosing and Administration AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

26. Dosing and Administration AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

27. Dosing and Administration AXIRON® (testosterone) solution for topical use CIII [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

28. Patient Counseling: How to minimize risk of secondary exposure AXIRON ® (testosterone) topical solution [package insert]). Indianapolis, IN: Eli Lilly and Company; 23 Nov 2010

29. Take-home messages Consider hypogonadism when patients present with typical symptoms and signs Diagnose hypogonadism and either treat or refer Select patients carefully and monitor closely