Issues. What is a low testosterone? Who needs testosterone therapy? Benefits/adverse effects of testosterone replacement Treatment options

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1 Male Hypogonadism Jauch Symposium Waterloo, IA May 17, 2013 Janet A. Schlechte, M.D. Disclosure of Financial Relationships Janet A. Schlechte, M.D. has no relationships with any proprietary entity producing health care goods or services consumed by or used on patients. Issues What is a low testosterone? Who needs testosterone therapy? Benefits/adverse effects of testosterone replacement Treatment options Hormonal Control of Testosterone Secretion Cleveland Clinic Journal Medicine Page 720 Oct CNS Stimulation Hypothalamus FSH Anterior pituitary LH + + Sertoli cells Testis Leydig cells Inhibin GnRH Testosterone 24 Hour Testosterone Secretion Testosterone and Advancing Age Testosterone, ng/ml Young men Old men Testosterone (nmol/l) Clock time, hours JCEM 56:1278, 1983 Age, years JCEM 86:724, 2001

2 Total or Free Testosterone Measure total testosterone in most cases Obesity, hypothyroidism, nephrotic syndrome and glucocorticoids affect SHBG Measure free testosterone when SHBG low Normal ranges vary from lab to lab Low or Normal (Hypogonadotropic) Secondary Hypogonadism Low Testosterone Verify (3 AM Samples) Check LH and FSH Elevated (Hypergonadotropic) Primary Hypogonadism Cleveland Clinic Journal Medicine Page 720 Oct Disorders Associated With Primary Hypogonadism Klinefelter s Chemotherapy/radiation Trauma Infection Varicocele Secondary Hypogonadism Alcohol abuse Opiates High dose steroids Sleep apnea Hemochromatosis Hyperprolactinemia Anabolic steroids Diabetes When to Order a Testosterone Level A 60 y.o. man with erectile dysfunction after pituitary surgery A tall 20 y.o. man with atrophic testes and gynecomastia A 40 y.o. with fatigue, depression, weight gain and low energy A 40 y.o. man has noted progressive fatigue, low energy, depression and weight gain. His exam is normal, he has 2 children and his wife is pregnant. He wants you to check a serum testosterone.

3 Specific Symptoms of Androgen Deficiency Delayed sexual development libido Erectile dysfunction Breast enlargement facial hair Hot flashes Infertility, azoospermia Less Specific Symptoms of Androgen Deficiency Low energy Depression Poor concentration/memory muscle mass body fat physical performance Physical Features of Androgen Deficiency Decreased virilization muscle strength body hair Abdominal obesity Gynecomastia Low testicular volume Case Detection Instruments ADAM - androgen deficiency in aging male AMS - aging male symptom scale Both instruments rely on self report Both have low sensitivity and specificity to detect testosterone deficiency when level is <300 Your patient with fatigue and depression has these results Testosterone - 310, 300, 295 LH 3 ( ) FSH 2 ( ) Prolactin 6 (4-23) TSH 1.4 ( ) Does he need testosterone therapy?

4 This 50 y.o. man has fatigue and low libido. His exam is normal. Testosterone - 130, 180, 190 LH 1 ( ) FSH 2 ( ) Prolactin 6 (4-23) Free T4 1.2 ( ) Secondary Hypogonadism Alcohol abuse Opiates High dose steroids Sleep apnea Hemochromatosis Hyperprolactinemia Anabolic steroids Diabetes Endocrine Society Guidelines Regarding Treatment Treat a man who is hypogonadal based on clinical signs of androgen deficiency and who has a distinctly subnormal testosterone level Outcomes of Testosterone Therapy in Hypogonadal Men Virilization muscle strength fat free mass bone density PSA prostate volume No placebo controlled trials looking at effect of testosterone on depression, cognition, fracture, QOL or CV outcome in young hypogonadal men Some trials show improvement in libido but not erectile dysfunction Relationship between low testosterone and increase in overall mortality not established Testosterone Replacement Options Oral Buccal Transdermal Injectable Aim for mid normal range

5 Serum Levels During Chronic Administration of Testosterone Serum testosterone, ng/ml Injection Patch Gel 200 mg 100 mg Time, days 100 mg 200 mg JCEM 51:1335, 1999 Testosterone Gel Androgel, testim, fortesta, axiron Daily administration Levels reach mid normal range in 1 month Levels remain stable for 24 hours Injectable Testosterone Enanthate/cypionate Gradual release mg q 2-3 weeks Less expensive Other Preparations Buccal tablet - twice daily Testosterone pellet - subdermal q 3-6 months Human chorionic gonadotropin - for fertility usually Adverse Effects of Testosterone hematocrit HDL PSA prostate growth Worsen sleep apnea Gynecomastia Heart disease? While on Testosterone Therapy Monitor PSA Prostate size Hematocrit LFT s Lipids

6 Don t Use Testosterone Hematocrit >50% Untreated sleep apnea BPH Congestive heart failure Desire for fertility Breast cancer Prostate cancer A 75 y.o. man complains of fatigue and low libido. He is active and takes no medications. At a recent visit his exam is normal and his testosterone is 210 ( ). Percentage of Men with Hypogonadism Percentage Testosterone Free T index Age Decade JCEM 86:724, 2001 Testosterone Deficiency in Elderly Men With unequivocally low testosterone (<200) do same evaluation as in younger men Target should be ng/dl Digital rectal exam before and after starting testosterone Urology if prostate size increases or nodule develops Durability of androgen effect questionable frail elderly men treated for 6 months. Effect on muscle mass and strength not maintained when treatment stopped. 209 men with low testosterone and limited mobility had increased CV adverse events NEJM 363:109, 2010 Take Home Points Don t screen for testosterone deficiency in the general population Don t use case finding instruments for detection of testosterone deficiency Measure testosterone in appropriate clinical settings Don t test in hospitalized or chronically ill

7 Take Home Points With treatment aim to restore testosterone to normal range Role of testosterone in treating hypogonadism in those >60 is uncertain Testosterone therapy should not replace healthy lifestyle changes References McGill J, Shoskes D, Sabanegh E. Androgen deficiency in older men: Indications, advantages and pitfalls of testosterone replacement therapy. Cleve Clin J Med 79:797, Pantalone K, Faiman C. Male hypogonadism: More than just a low testosterone. Cleve Clin J Med 79:717, Basaria S, Coviello A, Travison T, et al. Adverse events associated with testosterone administration. NEJM 363:109, Endocrine Society Clinical Practice Guideline. Testosterone therapy in adult men with androgen deficiency syndromes. JCEM 95:2536, 2010.