Testosterone in Old(er) Men Disclosure Information J. Bruce Redmon, M.D. Associate Professor Division of Endocrinology I have no financial relationships to disclose. I will not discuss off label use and/or investigational use in my presentation. A Case 43 YO man with one year or so of not feeling as well as I should fatigue, moodiness, decreased libido. PMH unremarkable. Meds PRN allergy meds. Nl virilized, P 55 BP 126/72. Testes 15 ml bilaterally. T = 174 ng/dl, repeat 175 ng/dl (241-827) Free T = 4.2 ng/dl (8-30) What to Do? Another Case 52 YO man with low libido, erectile dysfunction. Previous eval, T = 44 ng/dl ;T therapy with patch recommended. PMH: Hypothyroidism, borderline diabetes. Exam notable for decreased axillary, pubic hair, small testes (4-6 ml). What to Do? 1
Testosterone Prescriptions in the US 2000-2008 Testosterone Physiology GnRH H P LH -- Free T SHBG-T T T Alb-T Total Testosterone Hypogonadism Signs and Symptoms Decreased libido Decreased frequency of erections and sexual events Female body habitus Decrease/absence of androgen dependent hair Decreased bone density Smaller testes Increased breast tissue www.rejuvalife.md Andropause ADAM What is a Normal Testosterone Level? 2
24 hr Testosterone Profile in a Healthy Young Man Spratt, AJP, 1988. Testosterone Levels in Healthy Young and Older Men What About Testosterone Levels with Aging? Testosterone and Aging Total T SHBG Free T DHT How Common is Androgen Deficiency Syndrome in Older Men Low normal/mildly low 20 60%? Pathologically low T levels 2 5%? Symptoms 40%? 3
Prevalence of Androgen Deficiency MMAS (JCEM, 2004) Operational definition of androgen deficiency in men age 40 70 yr 3+/8 signs/symptoms Total T < 200 ng/dl or free T < 8.91 ng/dl ( T 200 400). Overall prevalence: 6% Age dependent: 4% - age 40-49, 9% - age 60-70 Predicting Androgen Deficiency 1,691 men studied 685 (40%) 3 symptoms 504 (74%) had T > 400 ng/dl 18 (3%) had T < 200 ng/dl 84 (12%) had FT < 8.91 ng/dl European Male Aging Study Proposed Definition of Late-Onset Hypogonadism Presence of 3 sexual symptoms: Decr freq of AM erections Low libido/decr sexual thoughts Erectile dysfunction Total testosterone < 320 ng/dl Free testosterone < 6.4 ng/dl June 16, 2010 Randomized Trials of Testosterone Therapy in Older Men Does Treatment Make A Difference? Study N Age (yrs) Snyder (1999) 108 73 Sih (1997) 32 66 Nair (2006) 58 66 Amory (2004) 48 71 Duration 3 yr 1 yr 2 yr 3 yr T (ng/dl) Pre/Post 367/625 294/370 358/483 295/744 4
What is the most likely clinically significant effect of testosterone supplementation? Increased muscle mass leading to improved functional status. Increased bone density. Improved sexual function. Improved cognitive function. Polycythemia. Testosterone Rx in Aging Males Summary Small increase in muscle mass, decrease in fat mass (2-3 kg); inconsistent effects on muscle strength and minimal effects on functional status. Some increase in bone density (if lower testosterone at baseline or higher testosterone dose). No clear benefit in erectile function, mood, cognitive function. Small increases in PSA, hemoglobin; no clear evidence of increase in clinically significant prostate events. No adverse effects on lipid profiles. Where to Go From Here? 2002 NIH asked IOM to review and make recommendations regarding future directions for clinical trials of T therapy in older men. IOM recommendations: Establish the nature of benefits in populations of aging men most likely to see benefit. Initial short term efficacy trials in older men ( 65) with clinically low T levels and at least one symptom that may be related to T deficiency. Establish clear benefit before assessing long term risk. NEJM, 2010 What to Do Until the Evidence Comes? Men with good libido, nonspecific symptoms, normal exam would not look for a diagnosis of low testosterone (i.e., I would not order a testosterone level). Men with clinical evidence of low testosterone or symptoms of low libido, +/- other sexual or nonspecific symptoms measure total testosterone in the AM. Total T > 300 ng/dl would not pursue. Total T < 300 ng/dl repeat AM total T with SHBG Total T < 200 ng/dl evaluate. Total T 200 300 ng/dl Apply the art of medicine Free T assessment (calculation or direct measurement) How low is the T, how significant are the symptoms. Risk/benefit discussion with patient. Do nothing and repeat in 3-6 months. Empiric trial of T therapy. Enroll in a clinical trial (The T Trial - www.ttrial.org) A Case 43 YO man with one year or so of not feeling as well as he should fatigue, moodiness, decreased libido. PMH unremarkable. Meds PRN allergy meds. Nl virilized, P 55 BP 126/72. Testes 15 ml bilaterally. T = 174 ng/dl, repeat 175 ng/dl (241-827) Free T = 4.2 ng/dl (8-30) 5
What to Do? Labs drawn in am: Evaluation T = 327 ng/dl SHBG = 30 nm (11 80) Another Case 52 YO man with low libido, erectile dysfunction. Previous eval, T = 44 ng/dl ;T therapy with patch recommended. PMH: Hypothyroidism, borderline diabetes. Exam notable for decreased axillary, pubic hair, small testes (4-6 ml). What to Do? Evaluation T = 23 ng/dl. LH = 0.8 IU/l. Prolactin = 5 MRI: No pituitary mass. Ferritin = 1073 ng/ml; % iron sat = 88%. Hemochromatosis 6