1. Unit II - Reproduction Andropause Dr. Jennifer MacIsaac, MD, CCFP Family Physician and Women’s Health Specialist Faculty of Medicine University of Ottawa

2. Objectives Definitions Definitions Physiological and hormonal changes Physiological and hormonal changes Review signs and symptoms of andropause Review signs and symptoms of andropause Biopsychosocial impact Biopsychosocial impact Appropriate investigations Appropriate investigations Treatment options Treatment options

3. Definitions Andropause Unlike "menopause”, the word "andropause" is not currently recognized by the World Health Organization and its ICD-10 medical classification

4. Definitions Andropause Menopause-like condition in aging men Otherwise known as “male menopause”

5. Physiology of Andropause - A decrease in Leydig cells associated with a slow and steady reduction of the production of the hormones testosterone and DHEA (dehydroepiandrosterone) in middle- aged men, and the consequences of that reduction Mooradian AD, et al. Am J Ther 2006; 13(2): 145–60.

6. Features of Andropause 40-50 years of age 40-50 years of age Not all men experience symptoms Not all men experience symptoms Affects 30% of men in their 50’s Affects 30% of men in their 50’s Very slow decline in testosterone Very slow decline in testosterone Symptom onset may be very gradual Symptom onset may be very gradual 10% of androgen levels by age 70 10% of androgen levels by age 70

7. Physiology Declining Testosterone Declining Testosterone Starting at the age of 30, men experience a drop in testosterone by about 10% every decade Starting at the age of 30, men experience a drop in testosterone by about 10% every decade Increasing SHBG Increasing SHBG Sex Hormone Binding Globulin Testosterone produced is less available to tissues

8. Physiology - Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia in Sertoli cells, which promote differentiation of spermatogoniaSertoli cells spermatogoniaSertoli cells spermatogonia

9. Role of Testosterone Anabolic effects Anabolic effects Muscle mass & strength Muscle mass & strength Bone density & strength Bone density & strength Stimulation of linear growth & bone maturation Stimulation of linear growth & bone maturation Prostate growth Prostate growth Androgenic effects (2ndary sex characteristics) Androgenic effects (2ndary sex characteristics) Sex organ maturation Sex organ maturation Voice deepening Voice deepening Facial and axillary hair Facial and axillary hair

10. Role of Testosterone Libido Libido Clitoral engorgement/ penile erection frequency Clitoral engorgement/ penile erection frequency Mental and physical energy Mental and physical energy Decrease visceral fat mass Decrease visceral fat mass Decrease total cholesterol Decrease total cholesterol Glycemic control Glycemic control Liver function Liver function

11. Symptoms of Andropause low sex drive low sex drive difficulties getting erections or erections that are not as strong as usual difficulties getting erections or erections that are not as strong as usual lack of energy lack of energy depression depression irritability and mood swings irritability and mood swings loss of strength or muscle mass loss of strength or muscle mass increased body fat / weight gain increased body fat / weight gain hot flushes hot flushes

12. Signs of Andropause Decreased muscle mass Decreased muscle mass Increased abdominal circumference Increased abdominal circumference Weight gain Weight gain Loss of axillary or facial hair Loss of axillary or facial hair Depression / Irritability Depression / Irritability Osteoporosis Osteoporosis Memory changes Memory changes Poor glycemic control Poor glycemic control

13. Biopsychosocial Impact Increased risk for osteoporosis and cardiovascular problems such as atherosclerosis Increased risk for osteoporosis and cardiovascular problems such as atherosclerosis Loss of intimacy in relationships Loss of intimacy in relationships Effects on work performance and interpersonal interaction Effects on work performance and interpersonal interaction Negative impact on maintaining healthy lifestyle Negative impact on maintaining healthy lifestyle Only 5% of an estimated 4-5 million men in the U.S. & 400,000-500,000 in Canada are treated Only 5% of an estimated 4-5 million men in the U.S. & 400,000-500,000 in Canada are treated

14. Investigations Testosterone levels Testosterone levels Total Total Free Free Bioavailable Bioavailable SHBG SHBG Other Other Testicular biopsy Testicular biopsy Semen analysis Semen analysis Brain MRI Brain MRI CBC CBC Ferritin Ferritin Vitamin B12, Folate Vitamin B12, Folate TSH + free T4 TSH + free T4 Fasting Blood Glucose Fasting Blood Glucose LFTs LFTs Renal function Renal function PTH / Calcium / PO 4 PTH / Calcium / PO 4

15. Treatment Testosterone replacement therapy Testosterone replacement therapy Shown to improve energy levels, muscle mass, bone density, glycemic control, sleep, and sex drive Shown to improve energy levels, muscle mass, bone density, glycemic control, sleep, and sex drive Shown to reduce osteoporosis & cardiovascular risk, depression, irritability, anxiety, body fat, and cholesterol Shown to reduce osteoporosis & cardiovascular risk, depression, irritability, anxiety, body fat, and cholesterol

16. Testosterone Replacement The American Society of Andrology's position is that: The American Society of Andrology's position is that: "... testosterone replacement therapy in aging men is indicated when both clinical symptoms & signs suggestive of androgen deficiency & decreased testosterone levels are present." "... testosterone replacement therapy in aging men is indicated when both clinical symptoms & signs suggestive of androgen deficiency & decreased testosterone levels are present." J. Androl 2006; 27 (2): 133–4.

17. Testosterone Replacement The American Association of Clinical Endocrinologists says: The American Association of Clinical Endocrinologists says: "Hypogonadism is defined as a free testosterone level that is below the lower limit of normal for young adult control subjects. Previously, age- related decreases in free testosterone were once accepted as normal. Currently, they are not considered normal. Patients with low-normal to subnormal range testosterone levels warrant a clinical trial of testosterone." "Hypogonadism is defined as a free testosterone level that is below the lower limit of normal for young adult control subjects. Previously, age- related decreases in free testosterone were once accepted as normal. Currently, they are not considered normal. Patients with low-normal to subnormal range testosterone levels warrant a clinical trial of testosterone." Guay AT, et al. Endocr Pract 2003; 9 (1): 77–95.

18. Testosterone Replacement Target level may vary depending on the patient’s age Target level may vary depending on the patient’s age Various forms Various forms Gels Gels Injections Injections Patches Patches Pills Pills

19. Testosterone Supplements Patch Patch only delivery method that mimics the natural daily rhythm of testosterone production in healthy young men only delivery method that mimics the natural daily rhythm of testosterone production in healthy young men applied once daily and worn for 24 hours applied once daily and worn for 24 hours can exercise, swim, bathe, and shower like normal can exercise, swim, bathe, and shower like normal

20. Testosterone Supplements Gels Gels Applied once daily to clean, dry skin on the shoulders, upper arm, or abdomen Applied once daily to clean, dry skin on the shoulders, upper arm, or abdomen Must wait several minutes for the gel to dry before dressing Must wait several minutes for the gel to dry before dressing Must wait 5 - 6 hours before showering, bathing, or swimming Must wait 5 - 6 hours before showering, bathing, or swimming Easily absorbed – CAUTION – Do not to allow others to contact medicated skin Easily absorbed – CAUTION – Do not to allow others to contact medicated skin

21. Testosterone Supplements Pills Pills Taken twice daily after meals Taken twice daily after meals Must monitor liver enzymes Must monitor liver enzymes Injections Injections Intramuscular Intramuscular Administered at the doctor's office every 3 - 4 weeks Administered at the doctor's office every 3 - 4 weeks

22. Testosterone Replacement Side effects Side effects Acne or oily skin Acne or oily skin Prostate growth & growth of pre-existing cancers Prostate growth & growth of pre-existing cancers Sleep problems (apnea) Sleep problems (apnea) Increased blood cell production (hematocrit) Increased blood cell production (hematocrit) Infertility Infertility Other effects specific to dosage form Other effects specific to dosage form MUST monitor CBC and PSA levels MUST monitor CBC and PSA levels

23. Treatment Lifestyle changes Lifestyle changes Regular exercise Regular exercise Adequate sleep Adequate sleep Good nutrition Good nutrition Reducing smoking, caffeine and alcohol Reducing smoking, caffeine and alcohol Relaxation via breathing exercise, yoga, meditation Relaxation via breathing exercise, yoga, meditation Psychosocial counseling Psychosocial counseling

24. Case 1 – Mr. Smith 52 year old male 52 year old male 8 month history of night sweats on & off 8 month history of night sweats on & off Lost 30 lbs with aggressive exercise 1y ago Lost 30 lbs with aggressive exercise 1y ago Then gained 10 lbs slowly despite exercise Then gained 10 lbs slowly despite exercise Mostly abdominal weight gain Mostly abdominal weight gain More irritable mood More irritable mood ROS unremarkable ROS unremarkable

25. Case 2 – Mr. Jones 48 year old male 48 year old male 6 months history of fatigue & myalgias 6 months history of fatigue & myalgias Proximal muscle weakness Proximal muscle weakness Osteopenia (T score -2.0) Osteopenia (T score -2.0) Palpitations Palpitations Lack of mental clarity Lack of mental clarity Weight gain Weight gain

26. Question Which gentleman is more likely to suffer from andropause? Which gentleman is more likely to suffer from andropause? A. Mr. Smith B. Mr. Jones

27. Investigations CBC N CBC N TSH N TSH N FBG N FBG N LFTs N LFTs N Renal function N Renal function N Calcium / PO 4 N Calcium / PO 4 N Total & free testosterone both low Total & free testosterone both low CBC N CBC N TSH elevated & free T4 low TSH elevated & free T4 low FBG elevated FBG elevated LFTs N LFTs N Renal function N Renal function N PTH & Ca elevated PTH & Ca elevated Testosterone levels N Testosterone levels N Mr. SmithMr. Jones

28. Question Which gentleman is more likely to suffer from andropause? Which gentleman is more likely to suffer from andropause? A. Mr. Smith B. Mr. Jones

29. Treatment Mr. Smith chose testosterone injections every 3-4 weeks Mr. Smith chose testosterone injections every 3-4 weeks He has had 3 injections over the past 3 months He has had 3 injections over the past 3 months His night sweats have resolved His night sweats have resolved He has lost 10 lbs in the past 3 months He has lost 10 lbs in the past 3 months His mood has stabilized His mood has stabilized

30. THANK YOU!!!