Testosterone Deficiency in Men Ron Rothenberg MD

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1 Testosterone Deficiency in Men Ron Rothenberg MD Relevant financial relationships in the past twelve months by presenter or spouse/partner: NA Equipment: NA Speakers Bureau: NA Stock Shareholder: NA Grant/Research Support: NA Consultant: NA Status of FDA devices used for the material being presented NA Status of off-label use of devices, drugs or other materials that constitute the subject of this presentation NA

2 Testosterone Deficiency in Men Ron Rothenberg MD

3 You can download all slides at CaliforniaHealthSpan.com

4 l We age because our hormones decline, our hormones don t decline because we age Testosterone replacement therapy is safe and can provide dramatic benefits Testosterone decreases inflammation

5 Testosterone Deficiency=Male Menopause=Andropause=Androgen Deficiency Aging Male = Hypogonadism l Less sudden in onset than female menopause l Just as severe in long term consequences l The cause. l Decreased bioavailable TESTOSTERONE +

6 Testosterone Deficiency l Increased aging of heart and circulation Increased MI s and CVA s Decreased hemodynamic function l Increased brain aging Decreased memory Decreased intelligence Increased Dementia, Alzheimer's

7 Testosterone Deficiency l Loss of drive and competitive edge l Stiffness and pain in muscles and joints l Falling level of fitness l Decreased effectiveness of workouts

8 Testosterone Deficiency- Deteriorating body composition l Sarcopenia Less muscle, more fat l Osteoporosis l Anemia Testosterone Deficiency Increased Cancer

9 Testosterone Deficiency l Fatigue, Tiredness l Depression, Mood changes l Irritability l Dysphoria l Reduced libido and potency Decreased desire and fantasies Decreased morning erections Decreased erectile tension Longer recovery time between orgasms Decreased intensity of orgasms

10 Low Testosterone is a deficiency disease l Half of healthy men between the ages of yr will have a BT level below the lowest level seen in healthy men who are yr of age l Korenman SG, Morley JE, Mooradian AD, et al Secondary hypogonadism in older men: its relationship to impotence. J Clin Endocrinol Metab. 71:

11 Testosterone Deficiency l T decline: l Begins early 30 y/o l years old 30% decrease in Total T 50% decrease in bio-available T l Severe T deficiency can start very early in 20 s

12 Testosterone getting lower every year l Travison TG et al. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab Oct 24

13 Phthalates and Decreased T l Plasticizers found in environment, medications, plastic tubing- hormone disruptors l Phthalates significantly reduced T in both sexes. Women and men ages years. Boys 6 12 years old: l 29% reduction in T l Meeker et al. Urinary Phthalate Metabolites Are Associated With decreased Serum Testosterone in Men, Women, and Children From NHANES. J Clin Endocrinol Metab Aug 14

14 Testosterone Deficiency is a lethal disease l Diabetes, Metabolic syndrome l Brain l Heart l Frailty syndrome l Bone l Inflammation l Cancer

15 Testosterone Treatment 56% less mortality l 83,000 VA men > 50 y/o low testosterone l Normalized-TRT treated and test normalized l Non-normalized-TRT treated and test not normalized l No TRT not treated l Sharma, R et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J Aug 6

16 Normalized-TRT vs. No TRT Hazard Ratios l All cause mortality.44 CI p< l Risk of MI.76 CI p< l Risk of Stroke.64 CI p< l Significant but higher hazard ratios Normalized-TRT vs. Non-normalized-TRT l No difference Non-normalized-TRT vs. No TRT l Sharma, R et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J Aug 6

17 Testosterone treatment and Mortality l 1000 male veterans, > 40 years old, 4 years Rx l Total test < 250 l 400 treated with testosterone l Mortality treated 10% vs. 20% controls l p < l Decreased risk of death l Hazard ratio 0.61 l 95% confidence interval , p =.008 l Prostate CA treated 1.6% l untreated 2.0 l Shores MM et al. Testosterone Treatment and Mortality in Men with Low Testosterone Levels. J Clin Endocrinol Metab Apr

18 Ron Rothenberg 2016 Vitamin D Red inhibits Yellow activates Unified Theory of Wellness CRP Resveratrol EPC s Chronic Inflammation Is the Cause and the Effect of the Diseases of Aging Stress Infection Depression High Glucose and Insulin Hormone Decline Lack of Exercise Aging High Homocysteine Trans Fats Nutrition Glucose and Insulin control Inflammatory Cytokines High Homocysteine B vits Control insulin. Less omega 6 Less Diet Arachadonic Acute phase proteins CRP, Fibrinogen EPA, DHA High Glucose Anti-Inflam Diet Anti-Inflammatory Cytokines Adipocytes Adhesion molecules VCAM1, ICAM1, MCP1, MadCAM1 Inflammatory cytokines NF Kappa Beta Inflammatory Enzymes COX, LOX Arachidonic acid Coxibs block vioxx ASA PGI2=prostacyclin good eicosanoids Good Eicosanoids aging GH E2 IBD EPA cancer Diabetic Retinopathy ASCVD P4 ASCVD Pro-oxidants Viral Infections SRIF EPA Anti-oxidants Glutathione DHEA, Testosterone Melatonin EPA Bad Eicosanoids TXA2. ASCVD PGE2, LRC4 - CA Pain PGE2, LTB4 ASCVD cancer Chronic Illness Wellness GH Resveratrol IGF1 Angiotensin II PTH PGE2: Pain Cancer Skin aging p53 Phosphate RANKL Immune Magnesium Catecholamines Pain TXA2 Atherosclerosis

19 Testosterone and CV risk l Significant reduction in risk All cause mortality Cardiovascular mortality Cancer mortality l More information in presentations later today in l Hormones and the heart l Hormone myths

20 Strength and muscle function l T is major predictor of skeletal mass l Synergistic with GH and IGF-1 l Improved strength even without exercise but marked improvement with exercise l Bhasin S. The dose-dependent effects of testosterone on sexual function and on muscle mass and function. Mayo Clin Proc Jan;75 Suppl:S70-5

21 Change in fat free mass Placebo no exer. T no exer. Placebo + exer. T + exer. Change in Quad area Change in squat strength

22 Lower Free T predictive of Frailty in Older Men l Fatigue, stair climbing, walking more than 100 m, > 5 illnesses and weight loss >5 % measured in 3166 community dwelling men aged over 8 years. l Lower free T predicted frailty l Hyde, Zoe et al. Low Free Testosterone Predicts Frailty in Older Men: The Health in Men Study. JCEM 2010 Jul.Vol 95, No 7.p

23 TRT and erectile function l Libido always increased l Nitric Oxide receptors up regulated l Usually improved erectile function l May take up to 6 months l Response to Sildenafil etc improved

24 T and cognitive function l T correlated with cognitive function and TRT improves it l Alexander GM, Swerdloff RS, Wang C, et al. Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities. Hormones and Behavior 1998; 33(2): l Barrett-Connor E et al. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999 Oct;84(10):3681-5

25 Testosterone, LH, AD l Low Testosterone and increased LH Are established AD risk Increase beta amyloid accumulation in humans l Increased Pittsburgh B Imaging (PiB) Low T, Increased LH and positive APOE-4 allele l Verdille G et al. Associations between gonadotropins, testosterone and beta amyloid in men at risk of AD. Mol Psychiatry Jan; 19(1) l Verdille G et al. The impact of LH and testosterone on beta amyloid accumulation: Animal and human clinical studies. Horm Behav Jun 27

26 T Rx Alzheimer s l Treated group improved over 1 year l Control group deteriorated l TRT prevents the production of beta amyloid precursor protein. (in men) l Gouras GK et al. Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Proc Natl Acad Sci U S A 2000 Feb 1;97(3): l Tan RS A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Aging Male Mar;6 (1):13-7.

27 T and mood (and erections) l Effective when psych drugs do not work in pts with low T l Cooper MA. Testosterone Replacement Therapy for Anxiety. Am J Psychiatry 157:1884, November 2000 l TRT increases nocturnal and spontaneous erections and improves mood l Burris A et al. A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men. J Androl 1992 Jul-Aug;13(4):

28 T and cognitive cerebral blood flow l High Free T was associated with better performance on tests of memory, executive function, and spatial ability, and with a reduced risk for Alzheimer's disease. l Improved cerebral blood flow l Moffat SD, Resnick SM. Long-term measures of free testosterone predict regional cerebral blood flow patterns in elderly men.neurobiol Aging May 11

29 Testosterone and Cognition l Conclusion: Verbal memory - aromatization of testosterone to estradiol Spatial memory - absence of increases in estradiol l M.M. Cherrier et al. The role of aromatization in testosterone supplementation.effects on cognition in older men. Neurology. 2005; 64: l M.M. Cherrier et al. Relationship between testosterone supplementation and insulin-like growth factor-ilevels and cognition in healthy older men. Psychoneuroendocrinology 29 (2004) 65 82

30 Testosterone, Diabetes, Depression l All correlated and TRT improves Depression and Diabetes l Tully PJ et al Elucidating the Biological Mechanisms Linking Depressive Symptoms With Type 2 Diabetes in Men: The Longitudinal Effects of Inflammation, Microvascular Dysfunction, and Testosterone. Pychosom Med Feb-Mar; 78(2)

31 Testosterone and BPH/LUTS l Multiple studies: l T does not exacerbate and sometimes improves symptoms l Baas, W et al. Testosterone Replacement Therapy and BPH/ LUTS. What is the Evidence? Curr Urol Rep Jun;17(6):46.

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33 Baas Conclusions: TRT and LUTS l Androgen receptors saturated at near castration and prostate size does not increase with TRT l Prostate size increases with age despite lowered T levels. Young men with high T levels do not have LUTS symptoms l Symptoms of BPH/LUTS do not increase with prostate size l TRT may be beneficial via T mediated nitric oxide synthase up-regulation and smooth muscle relaxation

34 l Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med Jan 29;350(5): l Pearl JA et al. Testosterone supplementation does not worsen lower urinary tract symptoms. J Urol.2013 Nov;190(5): l Kathrins M et al. The Relationship between Testosterone Replacement Therapy and Lower Urinary Tract Symptoms: A Systematic Review. Urology Nov 23.

35 European Study T and PCa l 1023 patients up to 17 years with TRT l Cohort Pca 54.4/10,000 pt years l Cohort Pca 30.7/10,000 pt years l Cohort Pca 0/10,000 pt years l Background prevalence 96.6/10,000 pt yrs l Conclusion- Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer. l Ahmad Haider et al. Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from Five Year-median Follow-up of Three Registries. The Journal of Urology, Volume 193/Issue 1 (January 2015)

36 Prostate CA and Hormones l 3886 men with prostate cancer, 6438 controls l No associations were found between the risk of prostate cancer l Testosterone, calculated free testosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol, estradiol, calculated free estradiol l Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies Endogenous Hormones and Prostate Cancer Collaborative Group. J Natl Cancer Inst :

37 TRT and PC over 20 years l 1365 men with TRT x 20 years l Screened with PSA and DRE q 6 months l Abnormal changes with US prostate and biopsy l Conclusion: No difference in PSA, free PSA and PCa as compared to background All cancer in treatment group localized and curative Testosterone treatment and monitoring may be safer than no treatment l Feneley MR et al. Is testosterone treatment good for the Prostate? Study of safety during long term treatment. Journal of Sex Med 2012; June 6

38 History of T causes PC myth l 1941: Huggins and Hodges reported that marked reductions in T by castration or estrogen treatment caused metastatic PC to regress l Administration of exogenous T caused PC to grow. This was based on only one patient l Based on increased acid phosphatase l Multiple subsequent reports revealed no PC progression with T administration l Some men even experienced subjective improvement, such as resolution of bone pain l Morgantaler A. Testosterone and Prostate Cancer: An Historical Perspective on a Modern Myth. Eur Urol Jul 26

39 1941 l Huggins, C., Hodges, C.V. Studies on prostate cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res.1941;1:293. l

40 l Recent data have shown no apparent increase in PC rates in clinical trials of T supplementation in normal men or men at increased risk for PC l No relationship of PC risk with serum T levels in multiple longitudinal studies l No reduced risk of PC with low T. l The paradox in which castration causes PC to regress yet higher T fails to cause PC to grow l Resolved by a saturation model, in which maximal stimulation of PC is reached at relatively low levels of T

41 Morgentaler conclusion l There is not now-nor has there ever been a scientific basis for the belief that T causes PC to grow

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45 Pomegranate Juice and PC l Rising PSA after surgery or radiotherapy l 8 ounces of pomegranate juice daily until disease progression l Mean PSA doubling time significantly increased with treatment from 15 months to 54 months (P < 0.001). l 12% decrease in cell proliferation l 17% increase in apoptosis l Significant reductions in oxidative state l Pantuck AJ et al. Phase II Study of Pomegranate Juice for Men with Rising Prostate-Specific Antigen following Surgery or Radiation for Prostate Cancer. Clin Cancer Res Jul 1;12(13):

46 Antioxidants and PC l Greater intake of antioxidants (dietary and supplementation) is associated with less aggressive prostate cancer. (P<.001) l Vance TM et al. Dietary total antioxidant capacity is inversely associated with prostate cancer aggressiveness in a population-based study. Nutr Cancer Feb 4:1-11.

47 Treating with T after Radical Prostatectomy for PC l Organ confined PC l Radical Prostatectomy l PSA <0.1 after 1 year l Treated with T l No recurrences or increase in PSA l Agarwal PK et al. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol Feb;173(2):533-6.

48 TRT. Prostate Ca, Brachytherapy l TRT years after brachytherapy l Follow up years l 1 patient with transient rise of PSA <1.0 l No patient stopped TRT due to cancer recurrence or disease progression l Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer Feb 1;109(3):

49 TRT after Radiation TX for PCa l Conclusions: Testosterone therapy in men following radiation therapy for PCa was associated with a minor increase in serum PSA and a low rate of BCR l Pastuszak A et al. Testosterone Therapy after Radiation Therapy for Low, Intermediate, and High Risk Prostate Cancer. The Journal of Urology. 13 May 2015.

50 Active Prostate CA and Testosterone Therapy l 13 testosterone deficient men with untreated prostate CA l Testosterone increased 238 to 664, PSA, prostate volume unchanged l After 2.5 years - No cancer found in 54% of prostate biopsies. l No local progression or metastases l Morgantaler et al.testosterone Therapy in Men with untreated Prostate CA.J Urol 2011 Apr, (185:4)

51 Active Surveillance, Prostate CA, Testosterone Treatment l 28 men on AS with Gleason 3+3, 3+4 x 3 years treated with testosterone, 96 controls untreated l Biopsy progression in men on AS appears unaffected by T therapy over 3 years l Kacker R, Morgantaler A et al. Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results Asian J Androl 2015 Aug 21.

52 l Morgentaler A et al. A New Era of Testosterone and Prostate Cancer: From Physiology to Clinical Implications. Eur Urol Aug 16. l Morgentaler A. Testosterone therapy in men with prostate cancer: scientific and ethical considerations. J Urol Jan;189(1 Suppl):S l Aversa A, Morgentaler A. The practical management of testosterone deficiency in men. Nat Rev Urol Nov;12(11):

53 Testosterone Supplementation Augments Overnight Growth Hormone Secretion l 100 mg T IM q 2 weeks x 26 weeks l Total T increased 33% l E2 increased 31% l SHBG decreased 17% l GH secretion increased 1.9 x l IGF-1 increased 22% l IGFBP-3 no change l Muniyappa R et al. Long-Term Testosterone Supplementation Augments Overnight Growth Hormone Secretion in Healthy Older Men. Am J Physiol Endocrinol Metab. 2007

54 Testosterone Treatment and Diabetes and Metabolic Syndrome l Can have dramatic effect on insulin resistance, visceral fat, blood pressure

55 Bi-directional relationship between visceral fat and testosterone: self-perpetuating cycle promoting insulin resistance.

56 Mechanisms Testosterone vs. Diabetes l Modulator of body composition - promoting myogenesis and inhibiting adipogenesis l Enhances transport of glucose into cells l Improved Endothelial function may be the basis for the reduction of BP and HR and ED l One-year TU is able to improve arterial stiffness and endothelial function l Improved Vitamin D status maybe thru up regulated 1 alpha hydroxylase and decreased adipose

57 Testosterone Induces normal pulsatile GH secretion Regulates lineage of mesenchymal pluripotent cells by promoting the myogenic lineage and inhibiting the adipogenic lineage Mobilizes lipids from the visceral fat depot which improves CV risks Increases motivation, enhancement of mood, and promotion of more energy expenditure

58 Testosterone Treatment with Metabolic Syndrome l Francomano D, Lenzi A, Aversa A. Effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in ageing men with metabolic syndrome. Int J Endocrinol. 2014;2014: l Testosterone = 241 (mean) l Metabolic syndrome l All had nutrition and exercise counseling l T undecanoate 1000 mg q 6 weeks x2 then q 12 weeks x 60 months

59 TRT but not control group BMI 2.9 ± 1.4 P < l BMI Waist circumference 9.6± 3.8cm P < Weight 15 ± 2.8Kg P < HgA1C 1.6±0.5% P < Insulin Sensitivity 2.8 ± 0.6 P < Total/HDL-cholesterol 2.9 ± 1.5 P < Triglycerides 41 ± 25 P < l Francomano D et al.effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in ageing men with metabolic syndrome. Int J Endocrinol. 2014: Feb 12

60 TRT but not control groupcontinued Systolic 23 ± 10mmHg P < Diastolic 16 ± 8mmHg P < Neck/Lumbar T score.5 ± 0.15gr/cm3 P < Serum 25OH Vitamin D ± 1.3ng/mL P < 0.01 TSH 0.9 ± 0.3 mui/ml P < 0.01 IGF ± 11 P < 0.01 Hematocrit +2.8 ± 0.9% P < PSA ± 0.29ng/mL P < 0.01 l Francomano D et al.effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in ageing men with metabolic syndrome. Int J Endocrinol. 2014;2014: Feb 12

61 Lab Testing l Prostate cancer screen PSA < 4.0 PSA similar to baseline if prior values known DRE no suspicious findings of PC PSA Controversy l H and H baseline Keep Hg < 17.5 by donating or discarding blood 1-4 times a year if needed

62 Estradiol - Aromatase - DHT 5-alpha Reductase Sperm Sertoli cell Leydig cell

63 Testosterone Lab Testing Test Sex Reference Optimal Total ng/dl Male Free* ng/dl (Equilibrium dialysis) Female Male Female Bioavailable Male pg/ml Female * Free testosterone results vary with methodology direct analog (RIA) in pg/ml same ref range

64 TOTAL TESTOSTERONE T T T T T T T. T. T ALBUMIN T T T T T T SEX HORMONE BINDING GLOBULIN

65 FREE TESTOSTERONE T T T T T T T T T T T SEX HORMONE BINDING GLOBULIN T T T T ALBUMIN

66 BIOAVAILABLE TESTOSTERONE T T T T T T T T T T ALBUMIN T T T T T T SEX HORMONE BINDING GLOBULIN

67 SHBG binds T > E l nmol/l male l nmol/l female l Low SHBG associated with Insulin Resistance in men and women

68 l Increases SHBG Thyroid Estrogens Progesterone Aging Low Insulin Coffee (not decaf). Green tea, soy l Decreases SHBG Testosterone DHEA Glucocorticoids GH High Insulin

69 Low calculated Free Test - symptoms l Low cft, even in the presence of normal TT, is associated with androgen deficiencyrelated symptoms. l Lab free testosterone inaccurate. l Even the best available measurement procedures have technical and fundamental limitations l Antonio L et al. Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone. J Clin Endocrinol Metab Feb 24

70 Free Free T calculator l freetesto.htm

71 Guys Need Estrogen Too l Higher testosterone, greater muscle size and strength l Higher estrogen, less Fat l Higher testosterone and higher estrogen, better libido and erection function l Finkelstein JS et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med Sep 12;369(11):

72 l Jankowska EA. Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA May 13;301(18):

73 T Metabolites - Estradiol l E2 usually increases with increasing T l Do not let E2 get too low Optimal? pg/ml NEJM 9/2013 Finkelstein study Need E2 for fat control, libido and erectile function l Aromatase Inhibition Chrysin 250 mg BID PO Topical 50 mg/gm Zinc 50 mg per day Progesterone 5-10 mg transdermal

74 Anastrozole Anastrozole 0.5 mg 1-3 x per week l Can precisely control E2 l Do not let levels fall too low, take it easy with E2 control l E2 is necessary for brain, heart, bone, fat control, sexual function l Use with clinical symptoms only?

75 l Schmidt M, Renner C, Loffler G. Progesterone inhibits glucocorticoid-dependent aromatase induction in human adipose fibroblasts. J Endocrinol Sep;158(3): l Leder BZ et al. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrinol Metab Mar;89(3): l Jeong, HJ et al. Inhibition of aromatase activity by flavinoids. Arch Pharm Res Jun;22(3):309-12

76 T Metabolites - DHT l DHT can increase with increasing T, especially with transdermal T l DHT does not aromatize to E2 l Is DHT evil twin of T or good androgen? l DHT needed for erectile function and anabolic effects l Not associated with Prostate CA in serum levels l Possibly associated with BPH and hair loss

77 5-alpha reductase inhibition l 5- alpha reductase and dutasteride and finasteride l PCa risk reduction? l Higher grade Pca? l Major drug intervention

78 5-alpha reductase inhibition l Neuroactive steroids - 5-allo-pregnenolone needed for neuronal repair and memory l Inhibition of 5-alpha-reductase by finasteride inhibits hippocampal neurogenesis l Contributes to the pathophysiology of depression and memory loss l Neurosteroids are potent endogenous modulators of the GABA receptor l Traish AM et al. 5- alpha-reductases in human physiology: an unfolding story. Endocr Pract Nov-Dec;18(6):

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80 Reported side effects of finasteride and dutasteride l Impair sexual function, including sexual desire, erectile and orgasmic function l Impair NO function and can produce ED and this can be long lasting and irreversible l Depression l Do not reduce incidence of aggressive and high grade prostate cancer

81 Mild 5-alpha reductase inhibition l Saw palmetto 320 mg/day l Progesterone transdermal 5-10 mg/ day l Scaglione F et al. Comparison of the potency of 10 different brands of Serenoa repens extracts. Eur Rev Med Pharmacol Sol May16(5)569-74

82 Progesterone men Similar levels present in men and women in follicular phase 0.5 ng/ml GABA receptor binding Improves hot flashes in men treated with leuprolide Oettel M et al. Progesterone: the forgotten hormone in men? Aging Male Sep;7(3):236-57

83 TRT - Potential Adverse effects l Major side effect Increased RBC s - Erythrocytosis l More likely with injections than creams l Phlebotomy if needed every 3 12 months l Donate or discard 1 unit when hemoglobin > 17.5

84 TRT -Potential Adverse effects l Gynecomastia- rare l Acne l Fluid retention (rare) l Does TRT accelerate male pattern hair loss? Possibly. l Possible decrease in testicular size. l Decreased sperm count

85 Subcutaneous Testosterone l CONCLUSION: Weekly subcutaneous testosterone produced serum levels that were within the normal range in 100% of patients for both peak and trough levels. l Al-Fataisi AM et al. Subcutaneous administration of testosterone. A pilot study report. Saudi Med J Dec;27(12):

86 Transdermal l Well absorbed in most men l Saliva levels may reflect intracellular effects l Serum levels usefull for monitoring l More DHT since hair follicles contain 5 alpha reductase l Steady state after 24 hours

87 Pellets l Subcutaneous pellets Minor surgical procedure Last 3 + months 75 mg pellets x 7-14

88 HCG injections l Human chorionic gonadotropin (HCG) l Polypeptide hormone produced by the human placenta l Alpha and beta sub-unit. l Alpha sub-unit is essentially identical to the alpha sub-units of LH and FSH

89 HCG l If there is no Leydig cell failure can use HCG injections units per week sub-q - divided l No decrease in testicular size or sperm count l Can use as TRT (measure free T to confirm success) or cycle with TRT every 6 months l Zitzmann M Hormone substitution in male hypogonadism Mol Cell Endocrinol 2000 Mar 30;161(1-2):73-88

90 HCG l If FSH and LH already relatively high, probably will not work l Avoids the TRT side effects of loss of testicle volume and decreased sperm count l More aromatization?

91 T Dose Men l Cream mg/day l Cypionate mg IM or SQ/ week l Pellets 75 mg x 5-15 q 3 months l HCG units per week Possible dosing: 250 units per day 1000 units twice a week T cypionate 100 mg IM on day 1 l HCG 250 units SC days 5 and 6

92 TRT A clinical specialty l Because of excessive reliance on laboratory measures of androgens and undue safety concerns, many men who could benefit from symptom relief, improvement in related clinical conditions and given preventive medical benefits remain untreated. l Carruthers M et al. Evolution of testosterone treatment over 25 years: symptom responses, endocrine profiles and cardiovascular changes. Aging Male. 2015

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