In this presentation for the Psychiatry Redefined program, Dr. Cady breaks down and deconstructs the accepted, unthinking, "practice guideline based" notions of thyroid and tesotsterone, with there seemingly "normal" levels and dosing, versus what the actual peer reviewed medical literature says. In this presentation, do use of all forms of thyroid, and all forms of testosterone are reviewed. The idiocy of "T4 only treatment" is covered. The use of T4, T3, a combination of T4 and T3, and all of the porcine and compounded products is review. In terms of testosterone, dr. Katie reviews the concept of "do you want to be optimal or do you want to be normal." He notes that it is "normal" for oil in cars to deteriorate and break down with age. It's also "normal" for men's and women's testosterone (as well as thyroid) to go down with age. The question is, "do we want to do anything about it?" Logical ways of intervening in both the thyroid and female and male gonadal axes are covered. There is scrupulous attention paid to the thyroid hormone pathways, and the relevance of reverse T3 versus free T3. Similarly, in terms of women, the downstream effect of estradiol coming from testosterone is also reviewed.

1. Hormones and Mental Health – Focus on
Thyroid and Testosterone
Louis B. Cady, MD, FAPA
CEO, Founder – Cady Wellness Institute
Presented for Psychiatry Redefined – September 10, 2022

2. “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. 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.

5. Key concept
“ADRENALS
BEFORE
THYROID.”

7. DHEA(S) – The Critical Hormone Most
Conventional Doctors Never Check
• Produced in the adrenal cortex
– Humans and primates are unique in secreting large amounts –
“the most abundant steroid hormone in the human body.”
(Maninger et al. Front. Neuroendocrinol. 2009 Jan; 30(1):65-91.)
• Immune system booster, Insulin regulator
• Energy increase* – remarkable
• Boosts growth hormone
– 20% in men; 30% in women in one study
• [Yen, Morales Khorram – one year double-blind placebo controlled crossover
experiment – with 100mg DHEA]
• Antidepressant effects
DHEA(S) – The Critical Hormone Most
Conventional Doctors Never Check
• Produced in the adrenal cortex
– Humans and primates are unique in secreting large amounts –
“the most abundant steroid hormone in the human body.”
(Maninger et al. Front. Neuroendocrinol. 2009 Jan; 30(1):65-91.)
• Immune system booster, Insulin regulator
• Energy increase* – remarkable
• Boosts growth hormone
– 20% in men; 30% in women in one study
• [Yen, Morales Khorram – one year double-blind placebo controlled crossover
experiment – with 100mg DHEA]
• Antidepressant effects

8. DHEA appears remarkably effective
for reducing chronic fatigue
• CFS patients frequently associate their disease onset with a
period of high physical &/or emotional stress
• Of initially screened patients with CF
– 76% (116/of 153) were 35-55 yoa
– 89% (103/116) of all those screened had decreased production of
DHEA
• Supplementation with DHEA to CFS patients led to multiple
benefits…
Himmel PB, Seligman TMN. A pilot study employing Dehydroepiandrosterone
(DHEA) in the treatment of chronic fatigue syndrome. J Clin Rheumatol. 1999
Apr;5(2):56-9,

9. Here were the benefits:
• Significant reduction in symptoms of CFS
• Pain: improved by 18%
• Fatigue – decreased by 21%
• ADL’s – improved by 8.5%
• Helplessness – decreased by 11%
• Anxiety – decreased by 35% (!! p<0.01)
• Thinking – improved by 22%
• Memory – improved by 17%
• Sexual problems – improved by 22%
Himmel PB, Seligman TMN. A pilot study employing Dehydroepiandrosterone (DHEA) in the
treatment of chronic fatigue syndrome. J Clin Rheumatol. 1999 Apr;5(2):56-9,

10. THYROID AND DEPRESSION

11. 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)

12. (Permission granted to use photos & data)

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

14. Hypothryoidism and goiter close to
home
Used with permission

15. 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”)

17.  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.

18. 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

19. 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

20. 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

21. Subclinical Hypothyroidism and Cognitive
Dysfunction in the Elderly
• Aim: Evaluate relationship of subclinical hypothyroidism and
cognition in the elderly
– 337 outpatients; {177 = men; 160 = women}
• MMSE scores were SIGNIFICANTLY lower in subclinical
hypothyroid patients compared to euthyroid (p<0.03)
• “Patients with subclinical hypothyroidism had a probability
about 2 times greater (RR = 2.028, p<0.05) of developing
cognitive impairment.”
Resta F, et al. Endocr Metab Immune Disord Drug Targets. 2012 Sep;12(3):260-7

22. 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

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

24. North America 85%
South America 76%
Asia 76%
Africa 74%
Europe 72%
Australia 55%
% Mineral depletion from the soil
during the past 100 years, by continent
Source: UN Earth Summit Report 1992

25. 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.

26. • “Iron deficiency impairs thyroid hormone synthesis by
reducing activity of heme-dependent thyroid
peroxidase.”
– Zimmermann MB, Kohle J. Thyroid. 2002 Oct;12
(10):867-78
– Subclinical hypothyroidism assoc. with
Fe deficiency.
– Nekrasova TSA, 2013 Kloin Med (Mosk).2013; 91
(9):29-33.
– Fe deficiency assoc with Thyroid microsomal
antibody levels.
– Wang YP et al. J Formos Med Assoc. 2014
Mar;113(3):155-60.
– Fe salts + T4 worked best.
– Ravanbod M et al. Am J Med. 2013 May;126(5):420-4.
• Association between iron deficiency and thyroid
disease (and RLS)
– Geng C et al. Front Neurol. 2022 Aug 12;13:974229
Consider IRON deficiency
204 citations - search on “iron deficiency
hypothyroidism” as of 9/10/2022

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

28. 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
? ?

29. What are the TYPES of Hypothyroidism
(from a dysfunctional Hyptothalamic-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

30. 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 in spite of “normal” blood levels
(“tertiary”)
– Rivas & Lado-Abeal. Thyroid hormone resistance and its management. Proc (Bayl Univ
Med Cent). 2016 Apr; 29(2):209-11.

32. What Causes Elevation in Rev T3?
• High Cortisol (emotional stress) 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.

33. • 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.

34. 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 *
* Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry
LEVEL III RESULTS:

35. “Hypothyroidism depression” 7/31/2017
965 citations
Louis B. Cady, MD

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

37. • 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

38. A solid review in one slide
• “Levothyroxine has long been the main tool to treating
hypothyroidism.”
• “Nearly 1/3rd 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.

39. 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 Thryoid 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.

40. 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…

41. 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

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

43. 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.

44. 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

45. 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.

46. 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 May;90(5):2666-2674.

47. 70 patients- ages 18-65 years of age. w/ primary hypothyroidism on stable T4 for 6 months.
Randomized to either dessicated 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.

48. “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.

49. 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.

50. If T4 by itsef 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!

51. RX Options
Levothyroxine (T4) – classic. MAY work. May not.
Liothyronine (T3) – per Star*D (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)

52. Porcine Thyroid= Armour Thyroid = Westhroid
= “Natural 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)

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

54. 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 sequela
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.

56. TESTOSTERONE

57. Do you really want to try 100,000
miles without changing the oil?
Personal photo, Louis B. Cady, MD © 2003
Do you really want to try 100,000
miles without changing the oil?
Personal photo, Louis B. Cady, MD © 2003

58. 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.”

59. 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 “>50” 10.8 – 24.6
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

60. 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.”

61. 9 Unanimous Resolutions
1. TD is well established, clinically significant, and affects
male sexuality.
2. 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.
3. TD is a global health concern.
4. T therapy for men is effective, rational, and evidence-
based.
Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.

62. 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.

63. 9 Unanimous Resolutions
8. The evidence does not support increased risk of
prostate cancer with T therapy.
9. 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.

64. 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

65. 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.

66. 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

67. 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.

68. 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.

69. 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.]

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

71. 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 – 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

72. 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.)

73. 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
(photo shot 15
months after tx)
(permission granted to use photos & data)

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

75. 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 Clinc 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.

76. 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.

77. 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.

78. Testosterone and women 09 10 2022
• “Testosterone women heart disease” (455)
• “Testosterone women cognition” (440)
• “Testosterone women mood” (1,112)
• “Testosterone women depression” (594)
• “Testosterone women libido” (488)
https://www.ncbi.nlm.nih.gov/ - accessed 9/10/2022

79. 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.

80. 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.

82. Estrogen as MAOI (& testosterone gives you more of it.)
• Estrogen & Testosterone (!) decrease MAO
– Luin, VN. Effect of gonadal steroids on activities of MAO
and choline acetylase in rat brain. Brain Res. 1975;86:273-306
• Platelet MAO levels inversely
correlated to estradiol levels
– Klaiber EL et al. Psychoneuroendocrinology.
1997 Oct;22(7):549-58.
• Estrogen decreases MAO-A & MAO-B
– Holschneider DP et al. Life Sci. 1998;63(3):155-60

84. Estrogen: Good For Your Brain
• Estradiol influences performances of learning and memory
tasks as well as increase working memory
– Sub-point – women are living three decades longer; hence they are
spending more time hypoestrogenic
• Pompilli A et al. Estrogens and memory in physiological and neuropathological conditions.
Psychoneuroendocrinology. 2012 Sept; 37 (9):1379-96
• Estradiol = protective against schizophrenia.
• Kulkarni J, et al. Hormones and Schizophrenia. Curr Opin Psychiatry. 2012 Mar;25(2):89-
95

85. Three thoughts to leave you with.
Make no little plans. Make BIG plans.
“Aim high in hope and work.”
(REMISSION)
And remember the fundamental
biological platform of HORMONES.
Daniel Burnham (1846-1912)

86. Louis B. Cady, MD
Cady Wellness Institute
4727 Rosebud Lane – Suite F
Newburgh, IN 47630 USA
Office (812) 429-0772
www.cadywellness.com
info@cadywellness.com
www.facebook.com/cadywellness
Twitter: @LouisCadyMD
www.cadywellness.com
See all of the slides, in color, NOW, at
www.slideshare.net/lcadymd