PRISM Bruges June Herman Leliefeld Urologist. The Netherlands

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1 PRISM Bruges June 2015 Herman Leliefeld Urologist The Netherlands

2 Guidelines EAU 2015: a rich source of Knowledge! Epidemiology/ Aetiology / Pathology Diagnostic evaluation Disease management Follow-Up

3 Guidelines EAU 2015: a rich source of Knowledge! Epidemiology/ Aetiology / Pathology : Androgen receptor (AR) Diagnostic evaluation Disease management Follow-Up

4 Definition of LOH: Guidelines EAU 2015 A Clinical Syndrome caused by Androgen Deficiency Most prevalent symptoms: -Reduced sexual desire -Reduced spontaneous erections -Erectile dysfunction -Hot flushes Biochemical condition: -Morning Total T < 12.1 nmol/l -Free T < 243 pmol/l

5 What is the prevalence of LOH in the literature? Numerous observational studies are studies on prevalence of testosterone decline alone with one single blood sample for T Cross-sectional studies Longitudinal studies

6 Serum levels of Testosterone and FT decline with age From the age of 35 years: about 1,2% fall each year So: low Testosteron in men : 20 % in men over 60 years 30 % in men over 70 years 50 % in men over 80 years Harman, 2001 Zitzmann, Nieschlag, 2003

7 Prevalence of Late Onset Hypogonadism Population based survey N=1475 Cut off point for Testosterone:10.4 nmol/l Overall prevalence : 5,6 % Endocrine Society, Bhasin 2010 : 6% Sharp increase with age Araujo, 2007

8 Sharp increase of LOH-prevalence with Metabolic syndrome : 30-50% Diabetes mellitus Type 2 : 40 % COPD Depression Corticosteroid therapy Osteoporosis Sexual disfunction Drug abuse: opiates, marihuana and alcohol HIV infection

9 The pathofysiological concept of LOH 4 factors: functioning of the Hypothalamo-Pituitary-Gonadal Axis Diminishing of the Leydig cell function :T decreases The negative feedback is diminishing : LH doesn t increase SHBG increases with age : bioactive T decreases Diminishing of number and sensitiveness of the Androgen Receptors

10 Androgen Receptor gene is located on the X-chromosome Andrologie, Nieschlag, 3.Auflage 2009

11 Guidelines EAU 2015: a rich source of Knowledge! Epidemiology/ Aetiology / Pathology Diagnostic evaluation: history-taking, questionnaires, hormone testing and physical examination Disease management Follow-Up

12 Definition of LOH: Guidelines EAU 2015 A Clinical Syndrome caused by Androgen Deficiency Most prevalent symptoms: -Reduced sexual desire -Reduced spontaneous erections -Erectile dysfunction -Hot flushes Biochemical condition: -Morning Total T < 12.1 nmol/l -Free T < 243 pmol/l

13 Guidelines EAU 2015 en 2012

14 General history-taking Metabolic syndrome : 30-50% Diabetes mellitus Type 2 : 40 % COPD Depression Corticosteroid therapy Osteoporosis Sexual disfunction Drug abuse: opiates, marihuana and alcohol HIV-infection

15 Are symptom questionnaires of any help? ADAM questionnaire 2000 Good sensitivity AMS-questionnaire 2004 Low specificity NERI Hypogonadism screener 2011 ANDROTEST /70%

16 AMS questionnaire 17 questions 5 points each In total 85 points

17 Physical examination BMI Waist circumference Body hair Male pattern hair loss Gynecomastia Testicular size Penis DRE of the prostate Lumbal fold

18 Age, < 50 y, N=869 Age >50 y, N=606 Araujo et al. J Clin Endocrinol Metabolism 2007,

19 male external & internal genitalia Testosterone Corona et al., J Sex Med 2011;8:3869.

20 Threshold for Total Testosterone 8 nmol/l 8.5 nmol/l 11 nmol/l 13 nmol/l decreased frequency for sexual thoughts erectile dysfunction decreased frequency for morning erections diminished vigour Attention: normal TT and high LH: compensated form of hypogonadism Zitzmann M, J Clin Endocrinol Metab 2006; 91 (11):

21 LOH symptoms in Guidelines EAU 2012 and 2015

22 Four less specific symptoms of LOH Osteoporosis Overweight Mortality! Depression

23 Guidelines EAU 2015: a rich source of Knowledge! Epidemiology/ Aetiology / Pathology Diagnostic evaluation Disease management Follow-Up

24 Guidelines EAU 2015: a rich source of Knowledge!

25 Guidelines EAU 2015: a rich source of Knowledge!

26 Guidelines EAU 2015: a rich source of Knowledge!

27 Influence of Weight change on Testosterone level Longitudinal study in a general population: EMAS n=2736 men; age y FU: 4,4 Y Camacho, Eur J Endocrinol 2013; 168:

28 Guidelines EAU 2015: a rich source of Knowledge!

29 Guidelines EAU 2015: a rich source of Knowledge! Epidemiology/ Aetiology / Pathology Diagnostic evaluation Disease management Follow-Up: Monitoring of TRT

30 Thank you for your attention Herman Leliefeld Urologist The Netherlands

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