Male Aging Hypogonadism

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1 Male Aging Hypogonadism Dr. Fahim Ebrahimi Endocrinology, Diabetes and Metabolism Endokrinologie und Diabetologie - SGED

2 Testosterone Lab Testing and Initiation of Replacement Layton et al., Endokrinologie J Clin Endocrinol und Diabetologie Metab. - SGED 2014;99:835 42

3 Serum Testosterone Levels of Tested Men Layton et al., Endokrinologie J Clin Endocrinol und Diabetologie Metab. - SGED 2014;99:835 42

4 Largest Group of Prescribers: Primary Care Physicians SHA Integrated Endokrinologie Database, und Diabetologie nonprojected - SGED claims counts

5 Testosterone Replacement Therapy: Usage by Age SHA Integrated Endokrinologie Database, und Diabetologie nonprojected - SGED claims counts

6 Testosterone Replacement Therapy: Usage by Age over Time SHA Integrated Endokrinologie Database, und Diabetologie nonprojected - SGED claims counts

7 Agenda! Physiology of Testosterone! Whom to test?! How and when to measure?! Primary and secondary Hypogonadism! Male aging Hypogonadism! Testosterone replacement therapy Endokrinologie und Diabetologie - SGED

8 Physiology of Testosterone GnR H LH FS H Testosterone Sperm s modified from Rao et al., Nat Rev Endocrinol 2013;9:479 93

9 Testosterone in Plasma SHBG bound T Albumin bound T 80% 15-20% 2% Free T Bioavailable T Travison TG et al. Schweizerische J Clin Endocrinol Gesellschaft Metab für 2017;102: Endokrinologie und Diabetologie - SGED Bhasin et al., J Clin Endocrinol Metab 2018.

10 When to measure T levels? Testosterone (nmol/l) Young Men (mean 25 y) Older Men (mean 70 y) Time Bremner Endokrinologie et al, J Clin Endocrinol und Diabetologie Metab - SGED 1983; 56: 1278

11 Signs and symptoms of Hypogonadism Suggestive Symptoms: Diminished libido & spontaneous erections Gynecomastia Reduced body hair & shave interval Testes volume <5ml, Infertility Osteopenia / Osteoporosis, Fractures Less specific symptoms Decrease of energy and vitality Depressive mood, diminished concentration & memory Sleep disturbances, Fatigue Mild anemia Reduced muscle mass and -strength, increased fat visceral mass Endokrinologie und Diabetologie - SGED

12 Conditions with high prevalence of «Low T»! Low libido or erectile dysfunction! Infertility! Medications that affect T production: opioids, glucocorticoids! Osteoporosis or low trauma fracture! HIV-associated weight loss! Pituitary mass! Metabolic syndrome (+signs & symptoms) Endokrinologie und Diabetologie - SGED

13 How to measure T levels? Screening: Total morning T, fasting, 2x How? Ideally LCMS/MS When to measure Free T? - SHBH (i.e. obesity), (i.e. Aging) - Total T borderline at lower limit How? - Gold standard: equilibrium dialysis (not available in CH). - Direct Immunoassays not recommended. - Calculation of FT more accurate than immunoassays. - i.e. Vermeulen formula (TT, SHBG, Albumin) ( - LH & FSH: Primary vs. Secondary Hypogonadism Travison TG et al. Schweizerische J Clin Endocrinol Gesellschaft Metab für 2017;102: Endokrinologie und Diabetologie - SGED Bhasin et al., J Clin Endocrinol Metab 2018.

14 What are «normal» T levels? Harmonized Reference Ranges 9.2 nmol/l 33 nmol/l Harmonized Reference Range: nmol/l Endokrinologie und Diabetologie - SGED Travison TG et al. J Clin Endocrinol Metab 2017;102:

15 Classification of Hypogonadism! Primary Hypogonadism - e.g. Klinefelter-Syndrome (1:500), Testicular trauma, Mumps orchitis, Maldescensus testis! Secondary Hypogonadism - e.g. Kallmann-Syndrome, Pituitary tumor, idiopathic hypogonadotropic hypogonadism, iron overload syndromes! Age-related decline - combination: primary & secondary hypogonadism - decline in FT greater than in TT Endokrinologie und Diabetologie - SGED

16 Prevalence of Symptomatic Hypogonadism EMAS: Wu et al., NEJM 2010; 363: BACH: Araujo et al., J Clin Endocrinol Metab. 2007;92(11): MMAS: Araujo et al., J Clin Endocrinol Metab. 2004;89(12): Endokrinologie und Diabetologie - SGED

17 Symtoms and signs of testosterone deficiency Exclude other factors (e.g. systemic illness, drugs, sleep disorders) Measure morning fasting total T and free T if borderline total T or altered SHBG <9.2nmol/L <9.2nmol/L Bhasin et al., J Clin Endocrinol Metab 2018.

18 Consider potentially reversible functional causes (Hyperprolactinemia, Opioids, Drug abuse, Systemic illness) Measure Prolactin and Transferrin saturation Evaluate karyotype to diagnose Klinefelter syndrome (XXY) If TT< 5nmol/L perform pituitary MRI Bhasin et al., J Clin Endocrinol Metab 2018.

19 Testosterone Therapy Testosterone Patches Testoviron ( mg i.m. 3-4 weekly) Nebido (1000mg i.m. 12 weekly) Androgel / Testogel / Tostran (e.g. Testogel 5g daily) Endokrinologie und Diabetologie - SGED

20 Testosterone Replacement Sexual Function Snyder Endokrinologie PJ et al. und N Diabetologie Engl J Med - SGED 2016;374:

21 Testosterone Replacement Erectile Dysfunction Endokrinologie Corona et und al., Diabetologie J Sex Med - SGED 2014;11:

22 Testosterone Replacement Muscle mass and force Srinivas-Shankar Endokrinologie et al., und Diabetologie J Clin Endocrinol - SGED Metab 2010

23 Testosterone Replacement Bone Mineral Density Endokrinologie Snyder und PJ Diabetologie al., JAMA - SGED Intern Med 2017

24 Testosterone Replacement Vitality? Snyder Endokrinologie PJ et al. und N Diabetologie Engl J Med - SGED 2016;374:

25 Testosterone Replacement Anemia Roy Endokrinologie et al., JAMA und Diabetologie Intern Med - SGED 2017;177:480 90

26 Risks & Adverse Events of Testosterone Replacement Erythrocytosis the most frequent AE No significant change in LUTS Trials not large or long enough to evaluate effects on: - cardiovascular risk? - prostate cancer risk? Snyder et al., NEJM 2016; 374: Ponce et al., J Clin Endocrinol Metab Endokrinologie und Diabetologie - SGED Bhasin et al., J Clin Endocrinol Metab 2018.

27 Monitoring of Testosterone Therapy Symptoms Monitor T levels When? Goal: Check hematocrit Osteoporosis Prostate Evaluation 3-12 months after initiation of T therapy, then annually. 3-6 months after initiation of T therapy i.m.: at nadir; gel: 2hrs after application Serum TT in mid-normal range At baseline, 3-6 months after initiation of T therapy, and then annually. DXA approx. 2 years after initiation of T therapy Discuss potential benefits & risks of prostate cancer screening in patients 55-69y & >10y life expectancy If prostate monitoring: PSA (and DRE) 3-12 months after initiation of T therapy, then annually Refer to urologist, if increase in PSA>1.4 ng/ml or PSA >4.0 ng/ml Bhasin et al., J Clin Endocrinol Metab 2018.

28 Summary Whom to screen Men with clear symptoms, case detection in diseases with high prevalence (i.e. T2DM) Measure what and when? Total morning Testosterone, fasting, 2x Free T if SHBG alteration, LH & FSH Whom to treat? Patients with primary and secondary hypogonadism;tt<9.2 Male aging hypogonadism with clear symptoms on individual basis How to treat? Testosterone i.m. or gel Monitoring: After 3 & 6 months, then yearly: Symptoms, Testosterone, hematocrit, Bone, prostate, cardiovascular? Endokrinologie und Diabetologie - SGED