Shelley Alexander, D.O.
What you must know for optimal health Shelley Alexander, D.O. Board Certified Internist, Geriatrician and Anti-Aging and Regenerative Medicine
Do our hormones decline because we age, Or do we age because our hormones decline?
% Reserve Capacity (% of Maximum Function) 100 75 50 25 0 D e v e l o p m e n t V i t a l i t y D e g e n e r a t i o n 20 40 60 80 100 120 M o r b i d i t y Age (years) Optimum Health Sub-optimum Health Undiagnosed Conditions
Cortisol Progesterone Insulin Vitamin D DHEA Estrogen Testosterone Thyroid
Does It Matter Who? Replace only what leaked out With exactly what leaked out To the optimal levels
Hormones that regulate growth and repair: Growth Hormone Testosterone Estrogen DHEA Insulin
All men are affected. No man will admits it.
Increased aging of heart/cv MI, CVA, hemodynamic fxn Increased brain aging memory, intelligence, dementia/alz Loss of drive/competitive edge Stiff and painful muscles and joints Decrease in body composition sarcopenia, osteoporosis, effective workouts and fitness Increase in all cause Cancer Depression, Fatigue,..
Diabetes Dementia and Alzheimer's Cardiac disease Frailty Syndrome/Sarcopenia Inflammation Osteoporosis Carcinomas Bain. 2010; Testosterone and the aging male: To treat or not to treat? Maturitas. 2010 May;66(1):16 22. European Menopause Jn 2010 Feb 13
Characterized by lower testosterone levels Subtle, insidious loss whereas menopause is abrupt All men lose 2-5% testosterone yearly Severe T deficiency can start in early 20 s By age 50, all men s testosterone levels are approximately half that at their peak
Is a deficiency disease Half of healthy men b/w age of 50-70 yr will have a (Bio) T level below the lowest level seen in healthy men 20-40 yr Korenman SG, Morley JE, Mooradian AD, et al. 1990 Seconary hypogonadism in men: its relationship to impotence J Clin Endocrinol Metab. 71:963-969
Primary Testes lose ability to produce testosterone Secondary Diminished testes stimulation Metabolic andropause Conversion to Estradiol Too much SHBG
Heart muscle has the most testosterone receptors Testosterone Strengthens the heart muscle Lowers LDL and total cholesterol Dilates coronary arteries Reduces angina May prevent blood clots Dilates coronary arteries Improves cardiac stress tests significantly Decreases atherosclerosis or plaques Circulation 2000 Oct 17;102(16):1906 11
Increases Abdominal fat Cholesterol Triglycerides Blood pressure Estrogen Lipoprotein (a) Fibrinogen Insulin levels TT and FT levels of men < 45 yo with CAD were significantly lower than those of controls Turhan S et al. The assoc B/w androgen levels and premature CAD. Coron Artery Dis. 2007 May; 18(3):159-62 Diminishes Coronary artery elasticity Human growth hormone (HGH), weakening the heart muscle
Low testosterone levels common in men with CHF Testosterone Replacement Increases anabolic function Improves arterial dilation Augments cardiac output Has anti-inflammatory activities Improves mood scores
Usually lower in men with low testosterone Men with proven CAD Have about 50% less total & free testosterone Men with the lowest ejection fractions Average 72% lower free testosterone level
Libido always increased Nitric Oxide receptors up regulated Improves ED, can resolve ED with PDES inhibitors when PDES alone do not work Caretta N et al. Erectile dysfunciton in aging men: testosterone role in therapuetic protocols. J. Endocrinol Invest. 2005; 28 (11 Suppl Proceedings) : 108-11
T increases endothelial progenitor cells benefit of T in CV disease and ED Forresta C et al. Reduced number of circ EPC. Journal of Clinical Endocrinol Metab. 91 (11) Older men tx T: dose dep. increase in muscle fiber and (satellite cell) stem cell # Sinha-Hikim I et al. Effects of t supplement J Clin Endocrinol Metab. 2006 Aug; 91 (8)
T correlated with cognitive fxn and TRT improves it Barrett-Conner E et al. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999 Oct; 84 (10) High free T assoc w/ high performance, executive fxn, spatial ability and improved blood flow Moffat SD, Resnick SM. Longterm measures of free T. Neurobiol Aging. 2006 May 11 TRT prevents the production of beta amyloid (in men) & improves Alz pts Gouras GK et al. T reduces neuronal secr Alz beta amyloid, Proc Natl Acad Sci 2000 Feb 1; 97(3) Tan RS A pilot study on the effects Aging Male. 2003 Mar; 6(1) : 13-7
Low Testosterone Correlates with symptoms of depression Testosterone Replacement improves Depression scores Fatigue Libido Prescription antidepressants frequently diminish libido Testosterone replacement enhances libido
Reported Effects of Low Testosterone Levels Loss of ability to concentrate Moodiness and emotionality Touchiness and irritability Great timidity Feeling weak Inner unrest Memory failure Reduced intellectual agility Passive attitudes General tiredness Reduced interest in surroundings Hypochondria T effective when psych drugs do not work in pts with low T Cooper MA. TRT for Anxiety Am J Psychiatry 157:1884, Nov 2000
Prostate Cancer Affects 1 out of 8 1 in 20 will die Second most fatal cancer in men No correlation between testosterone & PSA Endogenous Sex Hormones and Prostate Cancer: A collab analysis of 18 Prospective Studies. J Natl Cancer Inst 2008 100:170-183 Gould DC, Kirby RS. Testosterone replacement therapy for late onset hypogonadism: what is the risk of inducing prostate cancer? Prostate Cancer Prostatic Dis. 2006;9(1):14-8 Feneley MR et al. Is T tx good for prostate? Study of safety during long term tx. Journal of Sex Med 2012; June 6 Highest free testosterone associated with lower risk (18-26%) in most studies
Obese men have Lower testosterone Higher estrogen Fat cells convert testosterone to estrogen
Testosterone plays a regulatory role in counteracting visceral fat accumulation Boosting testosterone levels can Decrease abdominal fat Reverse glucose intolerance Reduce lipoprotein abnormalities
Men with elevated Hemoglobin A1c Tend to have lower testosterone levels Associations are independent of obesity and body fat distribution T improves glucose homeostasis and body comp, decreases HgA1C
T is major predictor of skeletal mass vs Sarcopenia: From the Greek meaning poverty of flesh Synergistic with GH and IGF-1 T supplementation augments overnight GH Muniyappa R et al. Long-term T. AM J Physiol Endocrinol Metab 2007
Muscle mass and strength improve with testosterone
Perception Reality Possibility
10 year prospective study, 11,606 men ; 40-79 years old Higher Testosterone = Lower Mortality from both CV disease and cancer Low Testosterone predicts cardiovascular diseases High Testosterone = Less Cancer Khaw KT. et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men. Circulation. 2007;116:2694-2701
4 major studies Low T assoc with increased all cause mortality Shores MM, Moceri VM, Gruenewald DA, et al. Low T is assoc with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehab unit. J Am Geriatr Soc 2004; 52:2077 Khaw KT, Dowsett M, Folkerd E, et al. Endogenous T and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (Epic Norfolk) Prospective Population Study. Circ 2007; 116: 2694e701 Shores MM, Matsumoto AM, Sloan KL, et al> Low serum T and mortality in male veterans. Arch Intern Med 2006; 166:1660e5 Laughlin GA, Barrett-Conner E, Bergstrom J. Low serum T and mortality in older men. J Clin Endocrinol Metab 2008; 93:68e75
Without proper testosterone levels, no amount of exercise will appreciably increase muscle mass. Testosterone and exercise are necessary for the best results, in both men and women. 80 year old Bob Delmontique 75 year old Nancy Kelly
Reduce excess body fat Exercise Nutrition Stress management Avoid Rx/drugs that increase estrogen Nutritional Supplementation
Contraindications: Active prostate Ca Breast Ca Unexplained PSA Erythrocytosis Unstable CHF Severe untreated sleep apnea R/O prolactinoma
1. P.E. w/ DRE 2. Essential Lab: Free and total T, PSA, prolactin, SHBG, FSH/LH, E2, DHT, CBC, CMP, Vit D 3. Possible add on labs: Thyroid panel, fasting insulin (goal <6), A1C, Lipids, homocysteine, AM cortisol, DHEA-s
39 yo healthy, athletic male with increased fatigue, decreased endurance and libido, loss of muscle mass and developing love handles. Decreased mental acuity and more moody. Had been to see PCP and was told level at 350 was normal.
Delivery Method and Dosing: consider age and goals of each patient HCG +/- T (1,000u sq twice per week) Polypeptide alpha subunit essentially identical to LH and FSH If no Leydig failure can treat hypogonadism while maintaining testicular size and sperm count
Started HCG injections. Patient very satisfied and reports all symptoms have markedly improved and/or resolved. A separate patient with HCG treatment at age 24 (strong h/o multiple concussions) improved, but not at optimal.. Why?
45 year old with treatment of Rx Androgel at average dose for greater than one year. Presents with low T symptoms What is the problem???
Saw Palmetto 320mg/d Arimidex ¼ tab twice / week
Replacement dosing: 5-10mg/day Delivery Method and Dosing: Rx/compound cream/gels at 50 200mg/d Rx/compound injections at 100-200mg/wk Troche (as needed enhancement) Pellets 75mg x 7-14 pellets Lab: TT: 500+ (790-1100), FT: 20-35 (LabCorp) 150-210 (Quest), BioT: 400-640, DHT: 50-165 Estradiol 25-35, DHEAs 400-600, SHBG 25-50
Increased RBC s erythocystosis Phlebotomy at Hct 50-55% No T assoc thrombotic events have been reported to date Rhoden NEJM Gynecomastia watch for elevated E2 Decreased sperm count/testicular size
Monitoring Regularly Blood levels Maintain within optimal physiologic range Free and total testosterone Estradiol, DHT, liver function, CBC PSA Symptoms Physical changes Prostate
Increased Energy Muscle strength Sexual desire HDL cholesterol Bone density Decreased Body fat Blood pressure LDL cholesterol Heart disease Improved Sexual function Mood Blood glucose levels
Summary
Hormones protect men from nearly all diseases studied Cancer Heart Disease Dementia BHRT is safe BHRT makes you look and feel good
Think about where you want your patient to be
Shelley Alexander, D.O. Anti-Aging & Regenerative Medicine