http://www.isitlowt.com

2. http://www.isitlowt.com

3. What is [Low-T]?

6. Definition of Male Hypogonadism • Hypogonadism in men is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and a normal number of spermatozoa due to disruption of one or more levels of the hypothalamic-pituitary testicular axis Endocrine Society clinical practice guideline Wang C et al. Aging Male 2009;12(1):5– 12

7. Clinical Diagnosis – H&P • Symptoms (non-specific) • Fatigue, decreased libido, erectile dysfunction • Androgen Deficiency in Aging Males (ADAM) test

8. http://www.isitlowt.com

10. Screening test for depression?

11. Clinical Diagnosis – H&P • Symptoms (non-specific) • Fatigue, decreased libido, erectile dysfunction • Androgen Deficiency in Aging Males (ADAM) test • Associated disease states e.g. obesity, COPD, metabolic syndrome, diabetes, etc. • Is low-T the cause of these diseases? • Is it a complication of these diseases? • Is it a co-morbidity?

12. Clinical Diagnosis – H&P • Symptoms (non-specific) • Fatigue, decreased libido, erectile dysfunction • Androgen Deficiency in Aging Males (ADAM) test • Associated disease states e.g. obesity, COPD, metabolic syndrome, diabetes, etc. • Is low-T the cause of these diseases? • Is it a complication of these diseases? • Is it a co-morbidity? • Signs • Mostly associated with congenital or developmental hypogonadism (e.g. Klinefelter’s, undescended testes)

14. Definition of Male Hypogonadism Hypogonadismin men is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and a normal number of spermatozoa due to disruption of one or more levels of the hypothalamic-pituitary testicular axis Endocrine Society clinical practice guideline Wang C et al. Aging Male 2009;12(1):5– 12

15. Lab Diagnosis of Hypogonadism Total testosterone <300 ng/dl • Based upon lower limit of total testosterone in young men (usually quoted normal range of 300-1000 ng/dl) • No generally accepted lower limit of normal (lower limit is 220 ng/dl at the Cleveland Clinic) • Does not necessarily reflect free testosterone levels • Should 70-yr old men be judged by norms for 30-yr olds? • 15% of healthy young men will have a testosterone level below the normal range in any 24 hour period • Not necessarily indicative of “physiological levels of testosterone”

17. Hypogonadism defined as Total Testosterone <300ng/dl

19. Definition of Male Hypogonadism Hypogonadismin men is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and a normal number of spermatozoa due to disruption of one or more levels of the hypothalamic-pituitary testicular axis Endocrine Society clinical practice guideline Wang C et al. Aging Male 2009;12(1):5– 12

20. Low-T ≠ T-Deficiency • Low Testosterone levels do NOT necessarily indicate hypogonadism or testosterone deficiency • testosterone levels can be low in normal, healthy young men with normal sperm counts • lots of false positives with low serum testosterone levels alone • Low sperm counts are necessary for the diagnosis of hypogonadism, but seldom done Low-T +Oligospermia =Hypogonadism

21. Work-up of Hypogonadism • LH/FSH  primary vs. secondary • If LH/FSH are inappropriately low, need to get • TSH • am cortisol level • prolactin level to rule out S.O.L. • Consider MRI Diagnosis of Low-T generally made without sperm counts or LH/FSH levels Diagnosis of Low-T is made without ANY blood work in 20% of cases

22. Classification of Hypogonadism Primary Hypogonadism • Testicular etiology • Causes: Undescended testes Klinefleter’s syndrome Hemochromatosis Mumps orchitis Injury to testes (e.g. cancer therapy)

23. Classification of Hypogonadism Secondary Hypogonadism • Extra-testicular etiology • Causes: Hypothalamic disorders (e.g. Kallmann syndrome) Pituitary disorders (e.g. tumor, surgery, radiation) Inflammatory disorders (e.g. TB, sarcoidosis) Medications (especially opioids) Obesity HIV

24. Testosterone Declines Age http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/male-hypogonadism/

25. Late-Onset Male Hypogonadism “Late onset hypogonadism (LOH, also referred to as age-associated testosterone deficiency, TDS) is a clinical and biochemical syndrome associated with advancing age and characterized by symptoms and a deficiency in serum testosterone levels (below the young healthy male reference range)” ISA, ISSAM, EAU, EAA and ASA recommendations (2009) BhasinS et al. J ClinEndocrinolMetab2010;95(6):2536–2559

26. Late-Onset Hypogonadism (LOH)Alternate Terminology • Testosterone-Deficiency Syndrome (TDS) • Age-Related Testosterone Deficiency • Andropause • Androgen Deficiency of the Aging Male (ADAM) • Partial Androgen Deficiency of the Aging Male (PADAM)

27. LOH = Low-T (+ oligospermia)

28. OK, Testosterone declines with age … But is LOH a deficiency syndrome? or a degenerative syndrome?

30. If Low-T were a deficiency … Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html

31. then the syndrome should be completely reversible Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html

32. If Low-T were degenerative … Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html

33. then the syndrome is not so reversible Artwork from: http://www.sci-news.com/medicine/science-low-testosterone-heart-problems-01418.html

34. Reversing Effects of Low-T ? Effects Attributed to Testosterone • Maintains bone density • Supports collagen • Face/body hair • Male-pattern baldness • Aggressiveness • Promotes prostate growth • Red blood cell production • Sex drive • Erectile function • Well-being & energy • Builds muscle mass • Sperm production • Promotes heart health • Anti-obesity/diabetes • Prevents Alzheimer’s

35. Reversing Effects of Low-T ? Effects Attributed to Testosterone • Maintains bone density • Supports collagen • Face/body hair • Male-pattern baldness • Aggressiveness • Promotes prostate growth • Red blood cell production • Sex drive • Erectile function • Well-being & energy • Builds muscle mass • Sperm production • Promotes heart health • Anti-obesity/diabetes • Prevents Alzheimer’s

36. Risks of Treating Low T Possible adverse effects of treatment • BPH / elevation of PSA • Acceleration of prostate CA / breast CA • Mortality, MI and stroke* • DVT • Worsening of OSA • Polycythemia No physiological target range • *Vigenet al. JAMA 2013 Nov 6;310(17):1829-36; Basariaet al. NEJM 2010 Jul 8;363(2):109-22

37. Originator of “Low-T” • Dr. Abraham Morgentaler claims to have coined the term “years ago” • Founder of Men’s Health Boston • Author of “Testosterone for Life” • associate clinical professor of urology at Harvard Medical School • On Speaker Bureaus for Watson, Abbott (Abbvie), Auxillium, Endo (not up to date) • Industry funded research/investigator for GSK (not up to date) Claims testosterone does NOT cause prostate cancer

38. Is it a deficiency syndrome or a triumph of marketing?

40. Excerpt from Abstract: In the absence of any new indications, off-label testosterone prescribing has increased in most countries in 2000–2011, especially over the last half of the period … … By eliminating the fundamental distinction between pathological and functional androgen deficiency, these guidelines tacitly promote increased testosterone prescribing, bypassing the requirement for high-quality clinical evidence of safety and efficacy and creating dramatic increases in prescription of testosterone products. Handelsman DJ. Med J Aust. 2013 Oct 21;199(8):548-51

41. Low “T” as in “Template” How to Sell DiseaseSchwartz and Woloshin, JAMA Intern Med. 2013;173(15):1460-1462 Three strategies: • Lower the bar – broaden the criteria for definition to include more people • Raise the stakes – “It is one thing to tell men that Low T can make them grumpy; it is another to say that it can kill them.” • Spin the evidence – list symptoms/conditions associated with low endogenous testosterone; implication problems reversed with restoration exogenous testosterone

42. For baby-boomers, it’s all about SEX!

43. You know it’s really working when …

44. A man on TV is selling me a miracle cure that will keep me young forever. It’s called Androgel…for treating something called Low T, a pharmaceutical company–recognized condition affecting millions of men with low testosterone, previously known as getting older. The Colbert Report, December 2012

45. Direct to Consumer Advertising from Abbvie (formally Abbott) (makers of Androgel)

47. Are our memories really that short? Remember What?

48. Women are Clearly Smarter than Men Hello …?

49. Women are Clearly Smarter than Men Remember Premarin?

50. Published in 1964 Dr. Robert Wilson “… menopause is a Hormone deficiency and totally preventable” Today, it would be called: [Low-E]