Hormones and Mental Health - Thyroid and Testosterone ptx

This is the second of two presentations given by Dr. Cady on June 22, 2024, to a nationwide audience on the virtual seminar meeting of Psychiatry Redefined.

In this presentation, Dr. Cady carefully reviews the rationale for being appropriately concerned about thyroid and testosterone levels. Those are the only two hormones covered in this presentation.

Appropriate lab testing and dosing is reviewed. Clinical cases are presented.

1. Hormones and Mental Health – Focus on Thyroid and Testosterone Louis B. Cady, MD, FAPA CEO, Founder – Cady Wellness Institute Presented for Psychiatry Redefined – June 22 – 23, 2024

2. THYROID & Depression c. 30 million people in US suffer from thyroid disease. Roughly 15 million diagnosed, and 15 million undiagnosed. Chiovato L et.al. Hypothyroidism in context. . Adv. Ther. 2019;36(Suppl 2):47-58.

3. “Sit down before fact as a little child; be prepared to give up every preconceived notion; follow humbly wherever nature leads … or you shall learn nothing.” - Thomas H. Huxley Words of advice for this presentation

4. Early 20’s depressed college student Weight gain, fatigue, brain fog Saw “numerous” MD’s asking for help Told “nothing is wrong with your thyroid; your labs are fine.” (Permission granted to use photos & data)

5. (Permission granted to use photos & data)

6. A physician’s wife. “Fatigued” “No sex drive.” Permission granted to use image.

7. Hypothyroidism and goiter close to home Used with permission

8. SHOULD WE BE LOOKING??? 30 million in US. (½ dx; ½ un-dx} 99% - primary hypothyroidism Iodine deficiency the most common cause With adequate iodine in environment, HASHIMOTO’S disease is most common cause. Chiovato L et.al. Hypothyroidism in context. . Adv. Ther. 2019;36(Suppl 2):47-58 (Unfortunately, this article cites “check TSH and treat with T4”)

9. Suboptimal thyroid hormone replacement is assoc. with worse hospital outcomes. Retrospective cohort study From 1/1/2008 to 12/1/2015 Patients aged 64 years or younger. 4 groups studied TSH </- 0.40 MIU/L NORMAL TSH {0.40 – 4.5} Intermediate TSH {4.51 – 10.0 HIGH TSH group {>10 mIU let Outcomes: measured length of stay; in hospital mortality, and 90 day readmission. Ettleson MD, et al. Suboptimal Thyroid Hormone Replacement Is Associated With Worse Hospital Outcomes. J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3411-e3419. 

10. RESULTS OF THE STUDY: Those with high TSH level: Had average LOS that was 1.2 days longer. 49% higher risk for 30 day readmission 43% risk of 90-day readmission. Patients with NORMAL TSH: Decreased risk of in-hospital mortality (RR = 0.46) 90-day readmission rate (RR = 0.92 ) Ettleson MD, et al. Suboptimal Thyroid Hormone Replacement Is Associated With Worse Hospital Outcomes. J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3411-e3419. 

11. Depressed mood 100% Reduced energy : 97% 3 Fatigue or loss of energy: 94% 2 Impaired concentration: 84% 3 Tiredness : 73% 1 Hypersomnia : 10%–16% 4 (Insomnia) Useful Target Symptoms in Major Depression 1. Tylee et al. Int Clin Psychopharmacol 1999;14:139-151. 2. Maurice-Tison et al. Br J Gen Pract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath et al. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215.

12. Hypothyroidism and Depression “Multiple studies concluded that undiagnosed, untreated, undertreated patients with hypothyroidism are at increased risk of developing depression. Hypothyroidism is known to be one of the leading causes of treatment resistant depression. Elevated TSH, antithyroglobulin (TgAb) and a thyroid peroxidase (TPO Ab) level have a been linked to depression and an increased risk of suicide.” NNuguru SP, Rachakonda S, Sripathi S, Khan MI, Patel N, Meda RT. Hypothyroidism and Depression: A Narrative Review. Cureus. 2022 Aug 20;14(8):e28201.

13. Prevalence of Depression in Patients Affected by Subclinical Hypothyroidism 63 patients with “subclinical hypothyroidism” HAM-D and MADRS scales with serum TSH Free T4, free T3 TPO AB and Tg-AB levels Prevalence of depressive symptoms in this population was 63.5% “This study suggests the importance of a psychiatric evaluation in patients affected by subclinical hypothyroidism .” (Huh?) Demartini B et al. Panminerva Med. 2010 Dec;52(4):277-82

14. A Typical Conventional View “Thus, any abnormal thyroid function tests in psychiatric patients should be viewed with skepticism. Given the fact that thyroid function test abnormalities seen in non-thyroidal illness usually resolve spontaneously, treatment is generally unnecessary, and may even be potentially harmful.” Dicerman AL, Barnhill JW. Abnormal thyroid function tests in psychiatric patients: a red herring? Am J Psychiatry . 2012 Feb;169(2):127-33

15. Subclinical Hypothyroidism & Depression 103, 375 subjects 21 studies – 7 were pooled for meta-analysis. Primary outcome: odds ratio (OR) depression. OR = 1.78 for the risk of depression in presence of subclinical hypothyroidism. SCH found to be associated with depression, especially in patients >/= 50 yoa. Tang R. Front Endocrinol (Lausanne). 2019 Jun 4:13:340.

16. Subclinical hypothyroidism and cognitive dysfunction in the elderly 337 outpatients selected (177 men & 160 women). Mean age 74.3 years Subjects with thyroid dysfunction and treatment with thyroid drugs were excluded. “The score of Mini Mental State examination was significantly lower in the group of patients with subclinical hypothyroidism than in euthyroid subjects (p<0.03).” RR of cognitive dysfunction = 2.028 Resta F et al. Metab immune Disorder Drug Targets. 2012 Sep; 12(3):260-7.

17. Factors for production of thyroid hormones: Iron , iodine, tyrosine, Zn, Se, E, B2, B3, B6, C, D Factors affecting T4 to REVERSE T3 (RT3): STRESS, trauma, low calorie diet , inflammation , toxins, infections, liver/kidney dysfxn, certain Rx Factors that INHIBIT proper T4 production: STRESS Infection, trauma, radiation, Rx Fluoride Toxins: pesticides, Hb, Cd, Pb Celiac disease T4 to T3 requires Se and Zinc! T4 And these are the factors that improve cellular sensitivity to thyroid hormones: Vitamin A Exercise Zinc Adapted by Louis B. Cady, MD (2018) from Institute For Functional Medicine graphic, 2011 Factors that Affect Thyroid Function THYROID GLAND T3 Nucleus, mitochondria Rev T3

18. “Pending strong evidence …from randomized trials, it appears prudent for all adults to take vitamin supplements.” Fletcher & Fairfield, JAMA 2002

19. SELENIUM DEFICIENCY in FASEB: “Adaptive dysfunction of selenoproteins from the perspective of the ‘triage’ theory: why modest selenium deficiency may increase risk of diseases of aging.” Foundation of American Societies for Experimental Biology McCann, J, Ames BM. FASEB J. 2011 Jun;25(6):1793-814.

20. “the foot soldier” “the evil twin ” Selenium required! FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the liver Iodine required (65% of T4)

21. Conventional medical practice: Only TSH is typically considered. You get T4 if you’re lucky. Ill-considered: “T7”, Total T4, Total T3, %T3 uptake You DON’T get Free T3 or Rev T3 ? ?

22. So what does the American Association of Clinical Endocrinologists (ACEE) say? “The upper limit of TSH should remain at 4.5 mIU/L , rather than 3.0-3.5 as some other organizations have suggested.” https://www.aace.com/files/po “Routine T4 treatment for patients with TSH between 4.5 and 10mIU/L is not warranted.” https://www.aace.com/files/position-statements/subclinical.pdf retrieved August 25, 2014

23. What are the TYPES of Hypothyroidism (from a dysfunctional Hypothalamic-Pituitary-Thyroid axis)? Tertiary hypothyroidism – deficiency in hypothalamus – not enough TRH Secondary hypothyroidism – pituitary isn’t kicking out enough TSH, and therefore…. “your thyroid labs are just fine.” PRIMARY hypothyroidism – where thyroid gland can’t make thyroid hormone This is the only one that high TSH is good for diagnosing!! Low TSH  Low TSH  Your doc is happy!!  HIGH TSH (finally!) https://medical-dictionary.thefreedictionary.com/tertiary+hypothyroidism

24. Thyroid Deficiency: Three Other Causes – Version 2; Thyroid down… Over time the amount of thyroid hormone decreases secondary to a decreased production by the gland (primary) Decreased conversion of T4 to T3 (“ secondary” ) https://restorativemedicine.org/journal/peripheral-thyroid-hormone-conversion-and-its-impact-on-tsh-and-metabolic-activity/ Less effectiveness at the receptor sites causing low thyroid symptoms despite “normal” blood levels (“ tertiary” ) Rivas & Lado-Abeal. Thyroid hormone resistance and its management. Proc (Bayl Univ Med Cent). 2016 Apr; 29(2):209-11.

25. What Causes Elevation in Rev T3? High Cortisol (STRESS, TRAUMA) or high copper Nutritional starvation Heavy metal toxicity – mercury, lead, cadmium * Selenium or Zinc deficiency* And high dose of thyroxine (T4) – a “pro-hormone” (for T3) iatrogenic !) “My doctor put me on Synthroid® and I felt worse.” [direct patient quote] NOTE: REV T3 will feed back on pituitary and produce a “normal” TSH. *Integrative tip: Hair analysis, RBC-Selenium and RBC Zinc.

26. Per HDRS – 17, remission in: 15.9% on Li 24.7% on T3 Per QIDS-SR16, remission in: 13.2% on Li 24.7% for T3 * LEVEL III RESULTS: * Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry * Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry

27. 1963 case where hyperthyroid patient became toxic when imipramine was introduced. Preclinical theories: thyroid hormone enhances noradrenergic receptor sensitivity Perhaps modest amounts of T3 might accelerate imipramine’s antidepressant activity without producing toxicity. Prange AJ. Paroxysmal auricular tachycardia apparently resulting from combined thyroid-imipramine treatment. Am J Psychiatry 119:994-995, 1963.

28. “Hypothyroidism depression” 9/10/2022 1,594 citations

29. “Hypothyroidism depression” 6/6/2024 1,715 citations

30. Quick detour and clinical pearl “ADRENALS BEFORE THYROID.”

31. Reduction of cholesterol biosynthesis in frontal cortex as function of hypothyroidism Glombik K et a. Pharmacol Rep. 2022 Aug 11. online ahead of print. Subclinical hypothyroidism not found correlated with depression – [but only TSH and free T4 used. What about Free T3?? And Rev T3??] Hirtz R et al. Thyroid. 2022 Aug 9. online ahead of print “The presence of subclinical hypothyroidism and of thyroid autoimmunity in depressed adolescents is increased.” Hirtz R et al. J Clin Psychiatry. 2021 Feb 23;82(2):20m13511. Anxiety with MDD patients had higher serum TSH level. Yang R et al. Front Psychiatry. 2022 Jun 24;13:920723

32. A solid review in one slide “Levothyroxine has long been the main tool to treating hypothyroidism.” “Nearly 1/3 rd of treated patients still exhibit symptoms.” Hypothyroidism is a chronic disease assoc. with deficiency in …T4 and T3.” Chiovato L et.al. Hypothyroidism in context. Adv. Ther. 2019;36(Suppl 2):47-58.

33. New ideas – that you haven’t heard of Need for T4 AND T3 Kraut E et al. Clin Invest Med. 2015;38:E305-E313. Perros P. European Thyroid Assn. guidelines on L-T4 and L-T3 combination of hypothyroidism: a weary step in the right direction. Eur Thyroid J. 2012;1:51-564. [https://bit.ly/3d0yLVN ] Wiersinga WM et al. ETA Guidelines: the use of L-T4 and L-T3 in the treatment of hypothyroidism. Eur Thyroid J. 2012;1:55-71. LT4 + L T23 combo tx “should be considered solely as an experimental treatment modality.” (2012 ETA Guidelines) Wiersinga WM et al. ibid.

34. Yes, T-3 DOES Get into the Brain (Transthyretin = carrier protein ) (Previous notion was that T3 “couldn’t get into the brain”, and therefore, you had to use T4. Terasaki, T. and Pardridge, W.M.: Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport. Endocrinology , 121(3):1185-1191, 1987 . Mooradian, A.D.: Blood-brain transport of triiodothyronine is reduced in aged rats. Mech. Ageing Dev ., 52(2-3):141-147, 1990. Cheng, L.Y., Outterbridge, L.V., Covatta, N.D., et al.: Film autoradiography identifies unique features of [125I]3,3'5'-(reverse) triiodothyronine transport from blood to brain . J. Neurophysiol ., 72(1):380-391, 1994. Rudas, P. and Bartha, T.: Thyroxine and triiodothyronine uptake by the brain of chickens. Acta Vet. Hung , 41(3-4):395-408, 1993. Or: The idiocy of T4 only thyroid treatment

35. A Mini-review of Conventional Group Think Regarding Thyroid with New Studies Offered

36. Dr. Imre Zs-Nagy, MD Archives of Gerontology and Geriatrics, Volume 48, Issue 3, May-June 2009, 271-275 "[The] gerontological elite has instead sought to obfuscate the facts ... the reason for this is nothing less than an abject fear ... to avert their loss of control, power, prestige, and position in the multi-billion dollar industry of gerontological medicine . ” Prof. Dr. Imre Zs.-Nagy, MD - part of the gerontology movement for four decades; founder and Editor-in-Chief of the Archives of Gerontology and Geriatrics

37. Thyroid Treatment Riffs “Compounded slow-release T3 has been suggested for use in combination with T4, which proponents argue will mitigate many of the symptoms of functional hypothyroidism and improve quality of life. This is still controversial and is rejected by the conventional medical establishment.” Todd, C H (2010). "Management of thyroid disorders in primary care: challenges and controversies". Postgraduate Medical Journal 85 (2010): 655–9.

38. T3 Therapy Called Not Ready for Prime Time Triiodothyronine therapy is most definitely not a treatment whose time has come, a panel of experts agreed… American Thyroid Association . in the case of Euthyroid sick syndrome, there is a “distinct potential for harm,” the panelists said. [ WHERE?? WHAT??] Elaine M Kaptein, MD, added that there is no role for T3 in the treatment of the Euthyroid sick syndrome, either. The low serum total T3… does not appear to be maladaptive. Jancin B. T3 therapy called not ready for prime time. Family Practice News. 2005 January 1. TRANSLATION: FORGET ABOUT T3

39. Rx Controversies “ As of 2012 , there are no controlled trials supporting the preferred use of desiccated thyroid hormone over synthetic L-thyroxine in the treatment of hypothyroidism or any other thyroid disease . ” American Thyroid Association Garber, Jeffrey R., et al. “Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.” Endocrine Practice 18.6 ( 2012 ): 988-1028.

40. Combined Therapy With Levothyroxine and Liothyronine in Two Ratios, Compared with Levothyroxine Of the patients who preferred combined T4/T3 therapy, 44% had serum TSH less than 0.11. Patients preferred combined LT(4)/LT(3) therapy to usual LT(4) therapy Decrease in body weight was associated with satisfaction with study medication Appelhof BC, Fliers E, Wekking EM, et al. Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. J Clin Endocrinol Metab . 2005 [7 years earlier!!] May;90(5):2666-2674.

41. 70 patients- ages 18-65 years of age. w/ primary hypothyroidism on stable T4 for 6 months. Randomized to either desiccated thyroid extract (DTE) or T4 for 16 months, then crossed over for another 16 months. RESULTS: - “No differences in symptoms” and neurocognitive measures BUT: DTE patients lost 3 lbs ! 48.6% of patients (n=34) PREFERRED DTE. Those patients preferring DTE lost 4 lbs during the DTE treatment and subjective symptoms were all significantly better while taking DTE as per general health questionnaire-12 and thyroid symptom questionnaire. Hoang, TD et al. J Clin Endocrinol Metab . 2013 May;98(5):1982-90.

42. Conclusions: DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (46.8%) of the study patients expressed preference for DTE over L-T4. “DTE therapy may be relevant for some hypothyroid patients.” Hoang, TD et al. J Clin Endocrinol Metab . 2013 May;98(5):1982-90.e

43. Adding Triiodothyronine to Thyroxine May Benefit Hypothyroid Patients Combined therapy with thyroxine and triiodothyronine may be an improvement over standard thyroxine treatment for patients with hypothyroidism Although generally effective, not all patients benefit from thyroxine therapy alone. Combination therapy group scored their mood as significantly improved. These patients reported having more energy, better concentration, and an improved sense of well being. No test scores for patients on thyroxine alone showed any improvement. Bunevicius R, Kazanavicius G, Zalinkevicius R, et al. Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism. N Engl J Med. 1999; 340:424-429. Andersen LF, Gram J, Skouby SO, Jespersen J. Effects of hormone replacement therapy on homeostatic cardiovascular risk factors. Am J Obstet Gynecol. 1999;180:283-289.

44. If T4 by itself doesn’t work…TREAT WITH T4 and T3. Or just T3! Raising T3 levels to optimal will improve symptoms Raising T3 level by itself cannot be accomplished with just T4 alone A combination of T4 & T3 is frequently required in order to optimize T3 Sometimes, in presence of stress, T3 Rx is the only safe option!

45. RX Options Levothyroxine (T4) – classic. MAY work. May not. Liothyronine (T3) – per Star*D (and previous psychiatric treatment ideas) - but short ½ life T4 + T3 – individually selected doses Compounded T4 + T3 – at any dose desired. Porcine thyroid (4:1 T4:T3. Also includes T1 and T2)

46. Porcine Thyroid= Armour Thyroid = NP Thyroid T4 and T3 and T1 and T2 Porcine not bovine Doses in tablets: ¼ ½ 1 2 3 grain 15 30 60 120 180 mg = 25ug 50ug 100ug 200 300 ug of T4 (But T4 component ONLY)

47. The grain – legal foundation of traditional English weight systems. One grain of Barley = “1 grain” = 60 mg.

48. Kelly, T. An examination of myth: a favorable cardiovascular risk-benefit analysis of high-dose thyroid for affective disorders. J Affect Disord. 2015 May 15;177:49-58 CONCLUSION: The cardiovascular risks of HDT appear to be low. HDT is at least as safe as or safer than many psychiatric medications. It is effective and well tolerated. CONCLUSION: High circulating levels of thyroid hormone is not the cause of the sequelae of hyperthyroidism. The reluctance to using high dose thyroid is unwarranted. Kelly, T et al. Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jun 11;71:1-6.

49. TESTOSTERONE

50. Testosterone and women 06/07/2024 “ Testosterone women mood” (1,202!) “Testosterone women heart disease” (495) “Testosterone women cognition” (480) “Testosterone women depression” (647) “Testosterone women libido” (504) https://www.ncbi.nlm.nih.gov/ - accessed 6/7/2024

51. Come – let us reason together… THIS IS WHAT THE OLD LAB REPORTS USED TO SAY : “Male and female reference ranges used for flagging are based on statistics for all male or female subjects tested . The age-specific guidelines in some cases show normal values for a given age to lie outside the collective normal distribution for all ages combined.”

52. Age Female – Free Test. level Male – Free Test 20-29 = premenopausal “up to 3.8 pg/ml” 13 – 40 PG/ML 30-39 = premenopausal The same 13 – 40 PG/ML 40-49 = premenopausal The same 13 – 40 PG/ML Post-menop POST-MENOPAUSAL – UP TO 1.8 PG/ML “>age 50” = 10.8 – 24.6 pg/mL Where would you like YOUR oil quality to be? Age Female – DHEA levels Male – DHEA levels 20-29 65-380 280-640 30-39 45-270 120-520 40-49 32-240 95-530 50-59 26-200 70-310 60-69 13-130 42-290 70-79 17-90 28-175

53. TESTOSTERONE THERAPY: HAS OVER USE UNDERMINED USE? www.thelancet.com /diabetes-endocrinology . Vol 6, March 2018 DTC’S in US until 2014: “low T”, imagery of cars and speedboats, “suggesting that youthful vigour is achievable with testosterone products.” “The issue of the cardiovascular safety of testosterone therapy is of particular relevance in this context, although the evidence from both trials and observational studies in conflicting and inconclusive.” “In the large population of healthier off-label users, the possibility of an increased risk of cardiovascular events is a major cause for concern.” “Inappropriate and overuse of testosterone therapy remains widespread.”

54. 9 Unanimous Resolutions TD is well established, clinically significant, and affects male sexuality. S/Sxs of TD occur as a result of low levels of T and may benefit from treatment regardless of whether there is an identified underlying etiology. TD is a global health concern. T therapy for men is effective, rational, and evidence-based. Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.

55. 9 Unanimous Resolutions 5. There is no T threshold that reliably distinguishes those who will reliably respond to tx from those who will not. 6. There is no scientific basis for any age-specific recommendations against the use of T therapy in men 7. The evidence does not support increased risks of cardiac event with T therapy. Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.

56. 9 Unanimous Resolutions The evidence does not support increased risk of prostate cancer with T therapy. The evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes. “These resolutions may be considered points of agreement by a broad range of experts based on the best available science." Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.

57. Testosterone Deficiency (in younger men) is typically secondary hypothalamic failure, not primary testicular failure FSH and LH low is commonly low in men with low T; rarely elevated as it is in women R/O hyperprolactinemia due to pituitary tumor (normal level ≤ 20) https://www.mayoclinic.org/diseases-conditions/male-hypogonadism/symptoms-causes/syc-20354881

58. Role of testosterone in the elderly Several therapeutic effects and good safety profile: Restores normal levels of serum testosterone Increases libido and energy level Beneficial effects on bone density, strength, and muscle Cardioprotective effects. Barone B et al. The Role of Testosterone in the elderly: what do we know? Int. J Mol Sci. 2022 Mar 24;2397):3535.

59. T vs. Mood in Men Study: 278 men, > 45yo, followed 2 years Compared to eugonadal patients, hypogonadal men w/TT < 200ng/dL had : 4-fold increase risk of depression Significantly shorter time to depression diagnosis Depression risk inversely related to TT w/statistical significance < 280ng/dL Shores MM, Arch Gen Psychiatry . 61(2004):162-7

60. T vs. Mood in Men (June 2019) “Recent publications support the finding that  testosterone replacement therapy in men with low testosterone  may improve  depression , and that androgen deprivation therapy in men with prostate cancer may contribute to  depression .” Need KT. Androgens and depression: a review and update. Curr Opin Endocrinology Diabetes Obes. 2019 Jun;26(3):175-179.

61. Testosterone tx of depressive sxs – JAMA Psychiatry Review of 27 randomized placebo controlled 1,890 men “Testosterone treatment appears to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples .” Walther A et al. JAMA Psychiatry. 2019;76(1):31-40.

62. T vs. Cognitive Function 400 independently living men, 40-80yo 100 in each age decade MMSE 21-30, average 28 TT: 208-1141ng/dL; Bio-avail T 78-470ng/dL HIGHER T = Better cognitive performance in OLDEST AGE category Men in lowest quintile of T = worse than men in highest quintile of T Highest Bio-available T more significant than TT, age, intelligence level , mood, smoking , and alcohol . Muller M, et al. Neurology . 2005 Mar;64(5): 866-71. [NB – more recent studies show no correlation.]

63. How to become the ”testicle whisperer” Two ways to increase testosterone in MEN Endogenous (preserves testicles) - and off-label Clomiphene - $30 - $60 /month HCG (injectable) - $400 – $800 /month EXOGENOUS ( deteriorates testicles) Big pharma testosterone gels, cremes and pumps. NOT RECOMMENDED. WEAK. “FDA approved” Injections “FDA approved” – but typically poorly prescribed. Pellets - FDA approved. Cremes – compounded (2 – 5-6 x more potent than big pharma) – not FDA approved (but very effective). Troches – fussy and not recommended in men and not FDA approved.

64. The Case of the Mismanaged Executive – Summary 42 year old male ADHD CEO, Background in psychology, Now EXTREMELY stressed “So tired I feel like I’m dying.” “Depressed.” Lab findings – Low testosterone, despite multiple pumps daily of low potency FDA-approved “Big Pharma” transdermal testosterone gel managed by endocrinologist Low thyroid, Low DHEA RX: Testosterone cypionate IM (started prior to clomiphene review) 60 mg twice weekly. DHEA – 50 mg SR. Porcine thyroid – ½ grain Clinical status: Total resolution of symptoms in 3 - 4 weeks. No antidepressant used

65. Another Literature Review Men with low T have higher all cause mortality, mainly due to increase in CV disease Shores MM et al. Arch Intern Med . 2006;166:1660-5. Khaw KT et al. Circulation . 2007;116:2694-7091 Haring R et al. Low serum testosterone levels are associated with increased risk of mortality in a population cohort of men aged 20 – 790 (!!) Heart J . 2010;31:1494-501 T Rx assoc with inc LBM, fat reduction, inc in muscle strength Svartberg J et al. In J Impo Res . 2008;20:378-87. Page ST et al. J Clin Endocrinol Metab . 2005;90:1502-10. Sih R et al. J Clin Endocrinol . Metab. 19978; 82:1661-7. Srinivas-Shankar U et al. J Clin Endocrinol . 2010;95:639-50. (NB – randomized, double-blind, placebo controlled study.)

66. What You Can Do with an Integrated Approach in 15 Months RX: dairy free diet (+IgG test); D3 5000 IU/d; porcine thyroid, Testosterone cypionate 100 mg IM q wk ., MVI, Zinc, DHEA 50 mg SR, CoQ10 400mg (permission granted to use photos & data)

67. Long-term T Treatment… Reduction in fat mass, increase in muscle strength with significant changes in FUNCTIONAL ABILITY in older men. Svartber J et al. Int J Impot Res . 2008;20:378-87. Page ST et al. J Clin Endocrinol Metab . 2005;90:1502-10 Sih R et al. J Clin Endocrinol Metab . 1997;82:166-7. Srinivas-Shankar U et al. (randomized double blind, placebo controlled study in elder men) J Clin Endocrinol Metab . 2010;95:639-50.

68. Long-term T Treatment… Reduces body fat mass, regional fat distribution and waist circumference in hypogonadal men w/ and w/o obesity. Page ST et al. J Clin Endocrinol Metab. 2005;90:1502-10. Does not increase risk of voiding symptoms but may increase prostate size to that of eugonadal men. McVary KT et al. J Urol . 2011; 185:1793-803. Behre HM et al . Clin Endocrinol (Oxf). 1994;40:341-9.

69. Testosterone in women (Transdermal) testosterone improves: Sexual desire, arousal, orgasm frequency, and sexual satisfaction in premenopausal and post-menopausal women. Also associated with favorable effects on body composition, bone, cardiovascular fxn, and COGNITION Davis SR. Androgen therapy in women, beyond libido. Climacteric. 2013 Aug;16 Suppl 1:18-24. doi: 10.3109/13697137.2013.801736. Epub 2013 May 27.

70. Testosterone: The “sexist” bias against women (e.g., “your loss of sex drive is just natural for your age.”) Fall in the circulating testosterone and the adrenal preandrogens most closely parallel increasing age. Accelerated decrease occurs in the years preceding menopause (like estrogen). Their loss affects: libido, vasomotor symptoms (hot flashes) , mood, well-being, bone structure, and muscle mass. Burd, Bachmann. Androgen replacement in menopause. Curr Womens Health Rep. 2001 Dec; 1(3):202-5.

71. Testosterone Enhances Estradiol’s Effect on Postmenopausal Bone Density and Sexuality Study of effects of E2 and T implants on BMD and sexuality 2 year, single-blind, randomized trial N= 34 50 mg of E2 , or 50 mg of E2 + 50 mg T Cyclic oral “progestins” used in cases of intact uterus Results: DEXA scans improved in both groups BMD increased more rapidly in T treated group at all sites All sexual parameters improved in both groups Davis DR. Maturitas . 1995 Apr;21(3):277-36.

72. The Glamorous Grandmother – Post Tune-up: DHEA, Thyroid, Testosterone, Progesterone 9/28/2011 (Permission granted to use photos & data) 01/26/2012

73. CONCLUSIONS:

74. “Aim high in hope and work.” (REMISSION) “Why settle for the silver when you can go for the gold?” Start LOW and get comfortable with it. Daniel Burnham (1846-1912) Stephen M. Stahl, MD, Ph.D.

75. Louis B. Cady, MD Cady Wellness Institute 4727 Rosebud Lane – Suite F Newburgh, IN 47630 USA Office [phone] www.cadywellness.com www.facebook.com/cadywellness Instagram:cadywellnessinstitute Follow us on social media: Link to slides: