Thyroid Dysfunction

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Thyroid Dysfunction

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Pathologies

• Hypothyroidism

• Hyperthyroidism

• Autoimmune thyroid (Hashimoto’s and Grave’s)

• Thyroid cancer Advanced Clinical Focus: Hormones and Endocrinology Thyroid Deﬁnitions

• Thyrotropin releasing hormone (TRH): hormone made by hypothalamus

• Thyroid Stimulating Hormone (TSH): hormone made by pituitary

• Thyroxine (T4): hormone made by thyroid

• Triiodothyronine (T3): active thyroid hormone

• Thyroid peroxidase (TPO): enzyme that makes thyroid hormone

• Thyroglobulin: protein that joins iodine to make T4

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH

Pituitary releases TSH

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH 93% is T4

Pituitary releases TSH

TSH stims TPO

7% is T3 ✓

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH 93% is T4

Pituitary releases TSH 60% converted to T3 in liver TSH stims TPO

7% is T3 ✓ Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH 93% is T4

Pituitary releases TSH 60% converted to T3 in liver TSH stims TPO

20% goes to reverse T3 (inactive) 7% is T3 ✓

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH 93% is T4

Pituitary releases TSH 60% converted to T3 in liver TSH stims TPO

20% goes to reverse T3 (inactive) 7% is T3 ✓ 20% converted to active T3 in GI ✓

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Metabolism

Hypothalamus sends TRH 93% is T4

Pituitary releases TSH 60% converted to T3 in liver TSH stims TPO

20% goes to reverse T3 (inactive) 7% is T3 ✓ 20% converted to active T3 in GI ✓ Remaining T4 to T3 in tissues ✓ Advanced Clinical Focus: Hormones and Endocrinology Thyroid Statistics (US)

• 27 million with thyroid disease

• 13 million undiagnosed

• 14 million Hashimotos

• 80% are women

American Association of Clinical Endocrinologists (AACE)

Advanced Clinical Focus: Hormones and Endocrinology

The thyroid is the ‘sentinel’ gland for the environment.

Dr. Jeffrey Bland

Advanced Clinical Focus: Hormones and Endocrinology Loss of Thyroid Function

• No thyroid gland • Nutritional deﬁciencies or excesses • Autoimmune • Thyroid hormone • Postpartum thyroiditis resistance

• Medications

• Toxins

• Stress Advanced Clinical Focus: Hormones and Endocrinology Thyroid Symptoms (Most Common)

• Fatigue • Excessive sleep

• Weight gain • Hypochlorhydria

• Depression • Itchy, dry skin

• Constipation • Dry, brittle hair

• Hypersensitivity to cold water • Hair loss

• Poor circulation • ↓ Body temp

• Muscle cramps • Edema (esp. face)

• ↓ Immunity • Lost of outer 1/3 of eye brow

• Slow wound healing

Advanced Clinical Focus: Hormones and Endocrinology

Others Signs Indicating Thyroid Issues

• Heart palpitations • Difﬁculty gaining weight

• Inward trembling

• Increased pulse rate

• Feeling nervous

• Insomnia

• Night sweats

Advanced Clinical Focus: Hormones and Endocrinology Top 10 Symptoms: Hypothyroidism

1. Fatigue 7. Edema

2. Weight gain 8. Muscle aches and joint pain 3. Feeling cold 9. Constipation 4. Dry hair and skin 10. Depression 5. Hair loss

6. Menstrual irregularities Advanced Clinical Focus: Hormones and Endocrinology Hypothyroid

Hypothyroidism can aﬀect all organ systems. These manifestations are largely independent of the underlying disorder but are a function of the degree of hormone deﬁciency.

Shilomo, Melmed, Kenneth S. Polonsky, et .al. Williams Textbook of Endocrinology, 12th Ed. Elsevier Saunders: Philadelphia, PA. 2011.

Advanced Clinical Focus: Hormones and Endocrinology Assessing Thyroid Function

• Symptomatology (questionnaire)

• Basal temperature test

• Blood work

• Ultrasound

• Biopsy

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Questionnaire Advanced Clinical Focus: Hormones and Endocrinology Simple Test

• Basal Temperature Test

• Easy, non-invasive

• Monitor progress

• Not well validated

• Not diagnostic

Advanced Clinical Focus: Hormones and Endocrinology Hypothyroidism

• Primary: ↑TSH, ↓FT4

• Secondary: ↓TSH, ↓ FT4

• Subclinical: ↑TSH, normal FT4

• Hashimoto’s thyroiditis: antibodies Dx present

Advanced Clinical Focus: Hormones and Endocrinology Hyperthyroidism

• ↓TSH, ↑FT4

• Subclinical: ↓TSH, normal FT4, high FT3

• Grave’s disease: antibodies present Dx Advanced Clinical Focus: Hormones and Endocrinology Thyroid: Lab Testing

• Standard of care = TSH

• Is this enough?

Advanced Clinical Focus: Hormones and Endocrinology Example of TSH Unreliability

• Patient with Hashimoto's getting no treatment

TSH January 4.5 February 0.08 March 2.3 April 3.8 May 8.7 June 7.4 July 1.6

Advanced Clinical Focus: Hormones and Endocrinology TSH Considerations…

• Can TSH reﬂect variations in target cell sensitivity?

• Can TSH reﬂect peripheral T4 to T3 conversion?

• Can TSH reﬂect cellular transport problems where there is faulty transport into the mitochondria?

• Can TSH reﬂect displacement of thyroid hormones from cellular receptors by RT3? Advanced Clinical Focus: Hormones and Endocrinology What Does TSH Test?

• TSH indicates pituitary production

• Genetic and environmental factors can effect TSH secretion

• Pituitary hormone levels alone are not sufﬁcient to measure the function of the gland they regulate

Advanced Clinical Focus: Hormones and Endocrinology European Thyroid Association

• “…pituitary TSH secretion may not reﬂect what happens in other target tissues, and therefore serum TSH alone may not be a good marker for the adequacy of thyroid hormone replacement.”

Wiersinga W.M., L. Duntas. V. Fadeyev. et al. ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism.. European Thyroid Journal 2012 . Vol 1 No. 12 2012

Advanced Clinical Focus: Hormones and Endocrinology TSH Range

• Standard of care for thyroid monitoring

1-2 mU/L Symptoms Symptoms

0.0-0.39 mU/L 0.4-5.5 mU/L 5.5+ mU/L

Hyperthyroid/ Normal Hypothyroid/ Grave’s Hashimotos Advanced Clinical Focus: Hormones and Endocrinology National Academy of Clinical Biochemistry (NACB)

• New guideline suggested in 2002

• TSH may be too wide

• People in this range = borderline thyroid disease

1-2 mU/L Symptoms Symptoms

0.0-0.39 mU/L 0.4-5.5 mU/L 5.5+ mU/L

Hyperthyroid/ Normal Hypothyroid/ Grave’s Hashimotos

Advanced Clinical Focus: Hormones and Endocrinology

American College of Clinical Endocrinologists

• Clinicians should consider treatment for patients who “test outside the boundaries of a narrower margin based on a target TSH level of 0.3-3.04 mU/L.”

• “ The AACE believes the new range will result in proper diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated until now.” TSH is normal but my patient is not well.

ACCE Press release January 2003

Advanced Clinical Focus: Hormones and Endocrinology TSH Conclusion

• “Normal” is too wide

• Optimal should be 0.4-2.0 mU/L

Following an optimal range, is probably a much better approach.

Vanderpump M.P.J., W.M.G. Tunbridge, J.M. French, et al. The incidence of thyroid disorders in the community; a twenty year follow up of the Whickham survey. Clinical Endocrinology 1995; 43(1):55-68 Advanced Clinical Focus: Hormones and Endocrinology What to Measure

• TSH

• Free-T4

• Free-T3

• Thyroid antibodies

Advanced Clinical Focus: Hormones and Endocrinology “Bound” is Unavailable

Thyroid Hormone

99% Bound 1% Free

Free T3 Free T4

Advanced Clinical Focus: Hormones and Endocrinology Why Test for T3?

All had normal TSH

Medication No Meds

15.2% below normal 29.6% below normal for Free-T3 FT3/FT4

Gullo D, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One. 2011; 6(8):e22552. Advanced Clinical Focus: Hormones and Endocrinology Why Test for T3?

“…a subset of patients…do not reach a serum FT3/FT4 ratio within the reference range…These patients, therefore, live in chronic condition of abnormal thyroid hormone availability for the peripheral tissues, even if the administered levothyroxine dose is able to maintain the serum TSH within the normal range.”

Gullo D, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One. 2011; 6(8):e22552.

Advanced Clinical Focus: Hormones and Endocrinology Why Test for T3?

The insuﬃcient T3 peripheral production cannot be appropriately corrected by increasing levothyroxine because T4 inhibits the conversion, and furthers the problem.

Gullo D, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One. 2011; 6(8):e22552.

Advanced Clinical Focus: Hormones and Endocrinology European Thyroid Association

• “Theoretically, thyroid hormone replacement therapy should aim not only at normalization of serum TSH but also at normalization of serum free T4, free T3 and FT4:FT3.”

Wiersinga W.M., L. Duntas, V. Fadeyev , et. al. ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. European Thyroid Journal 2012. Vol 1 No. 12 2012 Advanced Clinical Focus: Hormones and Endocrinology Reverse T3

Hypothalamus send TRH 93% is T4

Pituitary releases TSH 60% converted to T3 in liver TSH stims TPO

20% goes to reverse T3 (inactive) 7% is T3 ✓ 20% converted to active T3 in GI ✓ Remaining T4 to T3 in tissues ✓

Advanced Clinical Focus: Hormones and Endocrinology Reverse T3

20% goes to reverse T3 (inactive)

✓ ✗

Advanced Clinical Focus: Hormones and Endocrinology Reverse T3

• Converting T4 to T3 is optional

• The body determines whether it will convert T4 to T3 or RT3 Advanced Clinical Focus: Hormones and Endocrinology Reverse T3: Contributing Factors

• Stress • Liver/Kidney dysfunction • Trauma • Certain medications • Low-calorie diet

• Inﬂammation

• Toxins

• Infections

Kelly GS. Peripheral metabolism of thyroid hormones: a review. Altern Med Rev. Aug 2000; 5(4):306-33.

Advanced Clinical Focus: Hormones and Endocrinology Function of RT3

• Discovered in 1975 and found incapable of increasing metabolism

• RT3 considered “functionless”

• RT3 useful when a slower metabolism is advantageous: life-threatening illness, injury, or starvation

• Example: RT3 lets a person live longer without food and water

Advanced Clinical Focus: Hormones and Endocrinology What Slows T4 to T3 Conversion

• Certain medications • Cd, Hg, Pb, herbicides, pesticides • Se deﬁciency • Stress (cortisol) • Protein deﬁciency, high carb diet • Excess estrogen

• Chronic illness • RT3

• Compromised liver/ kidney T4 - T3 Advanced Clinical Focus: Hormones and Endocrinology Autoimmune Thyroid

• Most common AI disease

• It is not a metabolic issue

• This is an immune issue

Advanced Clinical Focus: Hormones and Endocrinology

Autoimmune Thyroid Known to Follow

• Radiation exposure

• Bacterial and viral infection

• Toxic exposure

• Other AI diseases

• Pregnancy

Advanced Clinical Focus: Hormones and Endocrinology Thyroid Antibodies

• TPO antibodies

• Anti-TG antibodies

• Should be negative Advanced Clinical Focus: Hormones and Endocrinology Autoimmune Disease

Genetics Environmental Trigger Gut Permeability

Nat Clin Prac Gastro & Hep, Sept 2005, Vol2;No.9

Advanced Clinical Focus: Hormones and Endocrinology Leaky Gut Syndrome

“The autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re- establishing intestinal barrier function.”

Genes Environment

You

“Phenotype”

Nat Clin Prac Gastro & Hep, Sept 2005, Vol2;No.9

Advanced Clinical Focus: Hormones and Endocrinology Estrogen and Thyroid

• Estrogen can trigger Hashimoto’s

• Can cause Hashimoto’s after pregnancy

• Perimenopause also common due to ﬂuctuations

• Thyroid symptoms can mimic PM symptoms

Amino N, Hidaka Y, Takano T, et al. Possible Induction of Graves disease in painless thyroiditis by gonasotropin- releasing hormone analogues. Thyroid 2003;13(8):815-8 Risk of subclinical hypothyroidism in pregnancy women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metal 1994;79(1):197-204 Massoudi MS, Milan EN, Orchard TJ, et al. Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women. Ann Epidemiol 1995:5(3):229-33 Advanced Clinical Focus: Hormones and Endocrinology Reference Ranges

Source: The Gitalis System

Advanced Clinical Focus: Hormones and Endocrinology Other Nutrients to Consider

• Selenium

• Zinc

• Iron

• Iodine

• Vitamin D and A

• Celiac screen

Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Factors that contribute to Factors that inhibit proper proper production of T4/T3: production of T4/T3: • Iron • Stress • Iodine • Trauma • Zinc + - • Toxins • Selenium T4/T3 • Infections • Vitamin E, B2, B3, B6, C, D • Certain medications • Tyrosine • Radiation • Fluoride • Hg, Cd, Pb + • Pesticides + • Autoimmune (celiac)

Factors that increase conversion RT3 T3 Factors that increase conversion of T4 to RT3: of T4 to T3: • Stress • Selenium • Trauma • Zinc • Toxins • Infections Factors that improve cellular • Certain medications + sensitivity to thyroid hormones: • Low calories • Vitamin A • Inﬂammation • Zinc • Liver/Kidney dysfunction • Exercise

JoshGitalis.com Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Selenium

• Two enzymes involved in thyroid hormone synthesis are selenoproteins

• Thyroid contains one of the highest Se concentrations of any tissue

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Selenium

• Selenium inversely correlated with TSH

• Selenium inversely correlated with TPO antibodies

↑TSH, Ab ↓Selenium

Tong YJ et al. An epidemiological study on the relationship between selenium and thyroid function in areas with different iodine intake. Zhonghua Yi Xue Za Zhi. 2003 Dec 10;83(23):2036-9.

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Selenium Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Factors that contribute to proper Factors that inhibit proper production of T4/T3: production of T4/T3: • Iron • Stress • Iodine • Trauma • Zinc + • Toxins • Selenium T4/T3 - • Infections • Iron • Certain medications • Vitamin E, B2, B3, B6, C, D • Radiation • Tyrosine • Fluoride • Hg, Cd, Pb + • Pesticides + • Autoimmune (celiac)

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Zinc

• Zn deﬁciency lowered thyroid hormones by 30%

• Zn supplements normalized thyroid hormones

Kralik A, et al. Influence of zinc and selenium deficiency on parameters relating to thyroid hormone metabolism. Horm Metab Res. May 1996; 28(5):223-6. Nishiyama S, et al. Zinc supplementation alters thyroid hormone metabolism in disabled patients with zinc deficiency. J Am Coll Nutr. Feb 1994;13(1):62-7. Taneja SK & R. Mandal. Beneficial effect of modified egg on serum T3, T4 and dyslipidaemia following dietary Zn-supplementation in Wistar rat. Indian J Exp Biol. March 2008;46(3):171-9.

Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

• 15.7% of women with subclinical hypothyroidism were iron deﬁcient compared to only 9.8% in the control group

Duntas LH, et al. Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism. Exp Clin Endocrinol Diabetes. 1999;107(6):356-60. Cinemre H, et al. Hematologic effects of levothyroxine in iron-deﬁcient subclinical hypothyroid patients: a randomized, double-blind, controlled study. J Clin Endocrinol Metab. Jan 2009; 94(1):151-6.

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Iron

• Iron deﬁciency imparts thyroid hormone synthesis by reducing activity of thyroid peroxidase

• Iron supplementation normalizes thyroid hormones

Zimmermann MB, Köhrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid. Oct 2002; 12(10):867-78. Eftekhari MH, Eshraghian MR, Mozaffari-Khosravi H et al, Effect of iron repletion and correction of iron deficiency on thyroid function in iron-deficient Iranian adolescent girls. Pak J Biol Sci. 2007 Jan 5;10(2):255-60.

Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

• Diets both low and high in iodine associated with hypothyroidism

• High intake of iodine increases risk of Hashimoto’s

• “For the person with Hashimoto’s, supplementing with iodine is like throwing gasoline onto a ﬁre.” - Datis Kharrazian

• Iodine supplementation prevents and treats Hashimoto’s and other thyroid disorder. - David Brownstein

Laurberg P, et al. Environmental iodine intake affects the type of nonmalignant thyroid disease. Thyroid. May 2001; 11(5):457-69. Duarte GC, et al. Excessive iodine intake and ultrasonographic thyroid abnormalities in schoolchildren. J Pediatr Endocrinol Metab. April 2009; 22(4):327-34.

Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Vitamin A

• Vitamin A deﬁciency results in poor thyroid hormone signalling

Feart C, et al. Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells. Eur J Endocrinol. Mar 2005; 152(3):449-58. Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Vitamin D

• Vitamin D deﬁciency signiﬁcantly higher in those with autoimmune thyroid disease (72%) versus healthy individuals (30.6%)

Kivity S, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. May 2011; 8(3):243-7.

Advanced Clinical Focus: Hormones and Endocrinology Vitamin D Deﬁciency Causes

• Indoor/sedentary lifestyle

• Skin pigment

• Aging

• Sunscreen

• Latitude Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Advanced Clinical Focus: Hormones and Endocrinology Basic Supplementation

• Selenium: 200-400 mcg

• Zinc: 15-30 mg

• Iron: 15-20 mg (conﬁrm deﬁciency)

• Iodine: 150 mcg

• Vitamin D: 2000 iu

• Vitamin A: 2000 iu

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Toxins

• 150 industrial chemicals have been shown to result in reduction of TSH and/ or T4

Howdeshell KL. A model of the development of the brain as a construct of the thyroid system. Environ Health Perspect. Jun 2002;110 Suppl 3:337-48. Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Toxins

Alternative Medicine Review. Thorne Research, Inc. 4 November 2009; Volume 14.

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Toxins

Alternative Medicine Review. Thorne Research, Inc. 4 November 2009; Volume 14.

Advanced Clinical Focus: Hormones and Endocrinology Halogens Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Advanced Clinical Focus: Hormones and Endocrinology Iodine Forms

Iodine Iodide Both

Kidneys Spleen Breasts Thyroid Liver Prostate Skin Blood Stomach Salivary glands Intestines

Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Gluten

• Studies conﬁrm link between gluten and Hashimoto’s

• “Cellular mimicry” =

Eur J endocrinol 1994 Feb; 103(2):137-40 Hepatogastroenterology 2003 Dec;50 Eur J Gasteroenterol Hepatol 1999 Aug;11(8):939-40 Clin Endocrinol (Oxf) 2003 Sep;59(3):396-401 Dig Dis Sci. 2001 Dec;46(12):2631-5 Physical Res 2003;52(1):79-88 Advanced Clinical Focus: Hormones and Endocrinology Thyroid and Gluten

• Removing gluten is a critical step in any thyroid protocol

Advanced Clinical Focus: Hormones and Endocrinology Non-Celiac Gluten Sensitivity (NCGS)

“Increased intestinal permeability after gliadin exposure occurs in all individuals.”

Nutrients 2015, 7, 1565-1576.

Advanced Clinical Focus: Hormones and Endocrinology Factors that Affect Thyroid Function

Factors that increase conversion RT3 T3 Factors that increase conversion of T4 to RT3: of T4 to T3: • Stress • Selenium • Trauma • Zinc • Low calories • Inﬂammation Factors that improve cellular • Toxins + sensitivity to thyroid hormones: • Infections • Vitamin A • Liver/Kidney dysfunction • Zinc • Certain medications • Exercise Advanced Clinical Focus: Hormones and Endocrinology Thyroid Summary

• Assess function • Address infection

• Support proper • Decrease hormone production: inﬂammation

• Essential nutrients • Heal the gut

• Stress management • Remove gluten

• Decrease toxins

Female Speciﬁc

Advanced Clinical Focus: Hormones and Endocrinology Female Concerns

• PMS

• Low libido

• Fibroids

• Endometriosis

• PCOS

• Menopause Advanced Clinical Focus: Hormones and Endocrinology Healthy Menstrual Cycle

Advanced Clinical Focus: Hormones and Endocrinology Healthy Menstrual Cycle

• Flow 3-6 days • Post-ovulatory 12-16 days • Raspberry, wine, or currant red in colour • Cycle 26-35 days

• Flow is like a jellied ﬂuid • Premenstrual symptoms mild or non- • 30-125 ml existent

• None to mild cramping not requiring meds

Source: Justisse Method

Advanced Clinical Focus: Hormones and Endocrinology Menstrual Cycle Advanced Clinical Focus: Hormones and Endocrinology PMS: What is it?

• Recurrent signs and symptoms that develop during the 7-14 days prior to menstruation

Advanced Clinical Focus: Hormones and Endocrinology PMS: What is it?

• Diagnostic criteria: • Social withdrawal

• Emotional: • Physical:

• Depression • Breast tenderness

• Angry outbursts • Bloating

• Irritability • Headache

• Anxiety • Swelling of extremities • Confusion

Advanced Clinical Focus: Hormones and Endocrinology PMS Causes

• Stress

• Hormone imbalance

• Poor diet

• Nutrient deﬁciency Advanced Clinical Focus: Hormones and Endocrinology PMS and Hormones

• No consistent pattern in all women

• Often associated with estrogen dominance

• May also result from:

• Hypothyroidism

• ↑ prolactin

• ↑ FSH

• ↑ Aldosterone

• Lower levels of neurotransmitters (i.e. serotonin)

Advanced Clinical Focus: Hormones and Endocrinology Helpful Treatments for PMS

• Exercise • Calcium: 800-1200 mg

• Stress management • Zinc: 30-50 mg

• Whole foods diet • Vitamin B6: 50-200 mg

• Detox support • Vitex: 20-40 mg

• Magnesium: 400-800 mg

Advanced Clinical Focus: Hormones and Endocrinology Chaste Tree Berry (Vitex)

• One of the top remedies for PMS

• Effective in moderate to severe PMS after 3 cycles

Dante et al., J Psychosom Obstet Gynaecol. 2011Mar;32(1):42-51 Freeman, Expert Opin Pharmacother. 2010 Dec;11(17):2879-89 Ma et al., Gynecol Endocrinol. 2010 Aug;26(8):612-6 Advanced Clinical Focus: Hormones and Endocrinology Chaste Tree Berry (Vitex)

• Reduces prolactin

• Improves Est:Proges

Advanced Clinical Focus: Hormones and Endocrinology Chaste Tree Berry (Vitex)

• Can mimic estrogen

• Proceed with caution:

• Fibroids

• Endometriosis

• Breast cancer (or high risk)

J trig. Food Chem. 2001, 49, 2472-2479

Advanced Clinical Focus: Hormones and Endocrinology Chaste Tree Berry (Vitex)

• 1-5 ml/day (1:5 tincture)

• 1-4 ml/day (1:2 extract)

• 500 mg BID

Mills Simon, Bone Kerry. Principles and Practice of Phytotherapy. Churchill Livingstone. 2009 Advanced Clinical Focus: Hormones and Endocrinology Cimicifuga Racemosa Black cohosh

• Used since the 1950s

• Does not activate estrogen receptors

• Anti-estrogenic effects

• Can treat hot ﬂashes

• Activity against breast cancer

Menopause: The Journal of the North American Menopause Society. Vol 9, No. 2, pp. 145-150

Advanced Clinical Focus: Hormones and Endocrinology Cimicifuga Racemosa Black cohosh

• 3.5-7 ml/day (1:5 tincture)

• 1.5-3 ml/day (1:2 extract)

• 40-200 mg/day

Mills Simon, Bone Kerry. Principles and Practice of Phytotherapy. Churchill Livingstone. 2009

Advanced Clinical Focus: Hormones and Endocrinology Birth Control Pill

Before age 20 = 3x Risk of Breast Cancer More than 5 yrs before age 35 Advanced Clinical Focus: Hormones and Endocrinology Birth Control Pill

• ↑ed risk cervical • Nutrient depletions: cancer B2, B6, B12, F.A., Vitamin C, Zn, Mg • ↑ed risk heart attack • Immature reproductive • Yeast overgrowth system

• Mask underlying issues • Increased risk of DVT (PCOS, endometriosis, ﬁbroids) • Possible contributor to autism1,2

1. Medical Hypothesis. December 2014 Volume 83, Issue 6, Pages 718–725 2. Medical Hypothesis. December 2015 Volume 85, Issue 6, Pages 1006–1011

Advanced Clinical Focus: Hormones and Endocrinology Birth Control Pill Discontinuation

• 3-6 months for body to heal

• Length of time it takes depends on:

1. Type of hormonal contraceptive used

2. Length of time on drug

3. Age of drug introduction

4. How healthy cycle was before drug

5. Basic health and nutritional status

Source: Justisse Method

Advanced Clinical Focus: Hormones and Endocrinology Endocrine Disrupting Chemicals

• Bisphenol A

• Phthalates

• Pesticides

• Persistent organic pollutants

Gore AC, et.al. Executive Summary to EDC-2: The Endocrine Society’s Second Scientiﬁc Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews 36: 09, 2015 doi: 10.1210/er.2015-1093 Advanced Clinical Focus: Hormones and Endocrinology Endocrine Disrupting Chemicals

REVIEW

• Obesity Executive Summary to EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals

A. C. Gore, V. A. Chappell, S. E. Fenton, J. A. Flaws, A. Nadal, G. S. Prins, J. Toppari, and R. T. Zoeller • Diabetes Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003

This Executive Summary to the Endocrine Society’s second Scientific Statement on environmental endocrine- • Female reproduction disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the • Male reproduction probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health. (Endocrine Reviews 36: 593–602, 2015)

Introduction conducted in rodent models, but with some notable ex- ceptions in sheep and nonhuman primates); 2) reports in- n 2008, The Endocrine Society convened a group of ex- • Cancers vestigating the mechanistic underpinnings of these disor- perts to review the state of the science on endocrino- I ders (gene expression and epigenetic changes induced in logical effects of environmental endocrine-disrupting cell and tissue culture, together with molecular and cellu- chemicals (EDCs), leading to the landmark Scientific Statement on EDCs published in 2009, called hereafter lar work conducted in endocrine tissues of EDC-exposed “EDC-1” (1). EDCs are the hundreds or more “exogenous animals); 3) work documenting associations between chemical(s), or mixtures of chemicals, that interfere with body burdens of certain EDCs with disease propensity in any aspect of hormone action” (2). In the subsequent 5 humans (mainly epidemiological work); and 4) investiga- • Thyroid disease years, the field has moved forward substantially. Four tions of humans with known occupational or acute expo- lines of research have particularly influenced our knowl- sures to a particular chemical or group of chemicals with edge about EDCs: 1) studies describing the consequences EDC activity. In 2015, there is far more conclusive evi- of EDC exposure on development and physiology (mainly dence about whether, when, and how EDCs perturb en-

ISSN Print 0163-769X ISSN Online 1945-7189 Abbreviations: BPA, bisphenol A; DOHaD, developmental origins of health and disease; Printed in USA EDC, endocrine-disrupting chemical; ER, estrogen receptor; PBDE, polybrominated diethyl Copyright © 2015 by the Endocrine Society ether; PCB, polychlorinated biphenyl; PPAR, peroxisome proliferative-activated receptor. Received August 27, 2015. Accepted September 2, 2015. • Neurodevelopment First Published Online September 28, 2015

doi: 10.1210/er.2015-1093 Endocrine Reviews, December 2015, 36(6):593–602 press.endocrine.org/journal/edrv 593

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 11 December 2015. at 09:58 For personal use only. No other uses without permission. . All rights reserved.

Gore AC, et.al. Executive Summary to EDC-2: The Endocrine Society’s Second Scientiﬁc Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews 36: 09, 2015 doi: 10.1210/er.2015-1093

Advanced Clinical Focus: Hormones and Endocrinology Endocrine Disrupting Chemicals

• Common in household products: food storage, water bottles, health and beauty products, household products

• The BPA substitute BPS also an endocrine-disruptor

• Long-lived chemicals have life-time body burden

• Short-lived may induce permanent changes

• Transgenerational effects now observed

Gore AC, et.al. Executive Summary to EDC-2: The Endocrine Society’s Second Scientiﬁc Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews 36: 09, 2015 doi: 10.1210/er.2015-1093

Advanced Clinical Focus: Hormones and Endocrinology Chemicals

• By the time a women leaves her home, she has applied 126 different chemicals in 12 different products to her face and hair

ewg.org Advanced Clinical Focus: Hormones and Endocrinology Libido

• Always a downstream • Relationship effect of other factors: • Mind • Adrenals

• Thyroid

• Sex hormones

• Stress

• Sleep

Advanced Clinical Focus: Hormones and Endocrinology Female Hormonal Pathologies

• Fibroids

• Endometriosis

• PCOS

Advanced Clinical Focus: Hormones and Endocrinology Fibroids and Endometriosis

• Similar etiology

• It’s more than estrogen dominance

Evans, JM. Fibroids and endometriosis. In Textbook of Functional Medicine (Ch. 32, Clinical Approaches to Hormonal and Neuroendocrine Imbalances). Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005. pp. 635-638. Advanced Clinical Focus: Hormones and Endocrinology Estrogen Inﬂuence

• Not seen prior to puberty

• Enlarge during pregnancy

• Regress at menopause

✗ ↑ ↓

Advanced Clinical Focus: Hormones and Endocrinology Inﬂammation Increases Estrogen

• PG2 stimulates aromatase

Bulun SE, et al., Regulation of aromatase expression in breast cancer tissue. Ann N Y Acad Sci. 2009 Feb;1155:121-31

Advanced Clinical Focus: Hormones and Endocrinology Aromatization

Aromatase Advanced Clinical Focus: Hormones and Endocrinology Decrease Estrogen Formation

• Aromatase inhibitors:

• Dietary ﬁber and lignins (i.e. ﬂax seed)

• Soy (genistein daidzein)

• Resveratrol (grapes)

• Grape seed extract (proanthocyanidins)

• White button mushrooms

Wang et al., J Steroid Biochem Molec Biol Eng et al., Cancer Res. 2003; 63:8516. 1994;50:205-12. Grube et al., J. Nutr. 2001; 131:3288. Eng et al., Ann N Y Acad Sci. 2002 Jun;963:239-46. Balunas et al., Phytochem. Lett. 2008. Kijima et al., Cancer Res. 2006; 66:5960.

Advanced Clinical Focus: Hormones and Endocrinology Estrogen Dominance

• Relatively small amounts (nanograms) of estrogen compared to larger amounts (micrograms) of other steroid hormones have powerful effects

• Regulation of estrogen is potentially much more important

Textbook of Functional Medicine. Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005.

Advanced Clinical Focus: Hormones and Endocrinology Estrogen Dominance Symptoms

• Breast tenderness • Anxiety/Depression

• Fibrocystic changes • Fibroid growth

• Heavy periods • Endometriosis

• Fat distribution on hips • Dysmenorrhea and thighs • Cervical dysplasia

↑Estrogen ↓Progest.

Textbook of Functional Medicine (Ch. 32, Clinical Approaches to Hormonal and Neuroendocrine Imbalances). Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005. pp. 623-6248. Advanced Clinical Focus: Hormones and Endocrinology Lack or Progesterone

• Spotting

• Anxiety

• Infrequent ovulation

• Peri-menopause

• Hormone replacement

↑Estrogen ↓Progest.

Textbook of Functional Medicine (Ch. 32, Clinical Approaches to Hormonal and Neuroendocrine Imbalances). Jones DS (Ed), Institute for Functional Medicine; Gig Harbor, WA: 2005. pp. 623-6248.

Advanced Clinical Focus: Hormones and Endocrinology

Estrogen Detoxiﬁcation and Elimination

• Support liver detoxiﬁcation

• Promote elimination

• Prevent recirculation

Advanced Clinical Focus: Hormones and Endocrinology Food and Hormones

• Chemicals can have a hormonal effect

• Full fat dairy from pregnant cows contain lots of estrogen

• Inﬂammatory foods can increase estrogen Advanced Clinical Focus: Hormones and Endocrinology Therapeutic Foods

• Raspberries

• Pomegranate

• Mung beans

• Cruciferous veg.

• Fermented Soy

• Flax

Advanced Clinical Focus: Hormones and Endocrinology Nutrients Supporting Detoxiﬁcation

• Indole-3-Carbinol (I3C): 200mg BID

• Calcium D-Glucarate: 500 mg BID

• Sulforaphane: 1.1-5.5 mg/day

• Curcumin: 500 mg TID (depends on form)

• Rosemary extract: 200-300 mg/day

• Green tea extract: 50mg TID

• Milk thistle extract: 70-210 mg TID

• N-Acetyl-Cysteine: 1 gram TID

Advanced Clinical Focus: Hormones and Endocrinology Vitamin D

Lower vitamin D levels resulted in higher risk of ﬁbroids. Check vitamin D! Advanced Clinical Focus: Hormones and Endocrinology Fibroids and Endometriosis

Estrogen + + + + + Inﬂammation Fat +

Insulin

Advanced Clinical Focus: Hormones and Endocrinology Stress and Endometriosis

“Endometriosis is an inﬂammatory disease, and stress and poor quality of life may cause inﬂammation…”

Advanced Clinical Focus: Hormones and Endocrinology PCOS

• Affects 5-10% of women of • Acne childbearing age • Male pattern baldness (in • Symptoms: women)

• Irregular menstrual cycles • Lack of ovulation

• Hirsutism Advanced Clinical Focus: Hormones and Endocrinology Polycystic Ovarian Syndrome (PCOS)

↑ Stress

↑ Cortisol

Insulin Metabolic ↑ Blood Sugar Obesity Resistance Syndrome

↑ Insulin

↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen

Advanced Clinical Focus: Hormones and Endocrinology Polycystic Ovarian Syndrome (PCOS)

↑ Stress Stress management

↑ Cortisol

Insulin Metabolic ↑ Blood Sugar Obesity Resistance Syndrome

↑ Insulin

↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen

Advanced Clinical Focus: Hormones and Endocrinology Polycystic Ovarian Syndrome (PCOS)

↑ Stress Blood sugar regulation

↑ Cortisol

Insulin Metabolic ↑ Blood Sugar Obesity Resistance Syndrome

↑ Insulin

↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen

Basin S, Fisher CE, Swerdcloff RS. Follicle stimulating hormone and luteinizing Virilization Amenorrhea hormone. In: Memed S (ed). The pituitary. 2nd ed. Malden, MASS: Blackwell Publishing 2002; 216-278 Advanced Clinical Focus: Hormones and Endocrinology Polycystic Ovarian Syndrome (PCOS)

↑ Stress Decrease androgen production

↑ Cortisol

Insulin Metabolic ↑ Blood Sugar Obesity Resistance Syndrome

↑ Insulin

↑ Androgens ↑ Estrone ↑ LH ↓ FSH More Androgen

Advanced Clinical Focus: Hormones and Endocrinology Multi-Factorial Treatment

• Decrease inﬂammation

• Improve estrogen metabolism Functional • Production Diet Foods • Detoxiﬁcation and elimination

• Check vitamin D Lifestyle Supplements • Decrease BMI

• Improve insulin sensitivity

• Stress management

Menopause Advanced Clinical Focus: Hormones and Endocrinology Menopause

• Permanent cessation of menstruation

• Avg age: 51

• Ovaries stop making hormones

• Adrenals and adipose tissue take over

Advanced Clinical Focus: Hormones and Endocrinology Menopause Symptoms

• Hot ﬂashes

• Headaches

• Atrophic vaginitis

• Freq. UTIs

• Cold hands/feet

• Forgetfulness

• Inability to concentrate

Advanced Clinical Focus: Hormones and Endocrinology Menopause and Exercise

• Women who spent 3.5 hours per week exercising had no hot ﬂashes

Hammar M, Berg G, Lingren R. Does physical exercise inﬂuence the frequency of post-menopausal hot ﬂushes? Acta Obstetrica et Gynecologica Scandinavica 1990;69:409-412 Advanced Clinical Focus: Hormones and Endocrinology Menopause and Soy

• ↓s hot ﬂashes

• Slow bone loss

• ↓s cholesterol

• ↓s blood pressure

• ↓s risk of breast cancer Dose = 2/3 cup

Dalais FS, Rice GE, Dahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1998;1(2):124-129

Advanced Clinical Focus: Hormones and Endocrinology Menopause and Soy

• Key factor: ability to convert isoﬂavones into equol

• Healthy microbiome essential

Advanced Clinical Focus: Hormones and Endocrinology Microbiome and Hormones

Effect of Antibiotic Treatment on the Intestinal Metabolomeᰔ L. Caetano M. Antunes,1 Jun Han,2 Rosana B. R. Ferreira,1 Petra Lolic´,1,3 Christoph H. Borchers,2 and B. Brett Finlay1,3* Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada1; University of Victoria Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia V8Z 7X8, Canada2; and Department of Microbiology and Immunology, The University of British Columbia, Of theVancouver, many Britishmetabolic Columbia V6T pathways 1Z3, Canada3 Receiveda 1 Decemberffected 2010/Returned by antibiotic for modification treatment, 8 January 2011/Accepted 21 January 2011 The importance ofthe the mammalian metabolism intestinal microbiota of steroid to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial Downloaded from communities need tohormones be characterized inwas molecular the detail most if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complexprofoundly systems to maintain impacted. or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and http://aac.asm.org/ its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.

The human body is colonized by a complex community of dispensable to our understanding of the effects of antibiotics in microbes termed microbiota or microbiome (9, 17, 18, 24). the human body and the importance of the intestinal microbi- Virtually every surface of the human body that is exposed to ota for human health, the mechanisms involved in these inter-

the environment has its own microbial assemblage, with dif- actions remain mostly unknown. on October 26, 2015 by guest ferent microbial species and distinct functions associated with Much of what we have learned about the intestinal micro- them. The intestinal tract is by far the most heavily colonized biota comes from high-throughput sequencing studies of the body site; it has been estimated that the human gut harbors intestinal metagenome, which address only the microbial com- 14 some 10 microbial cells (14, 22, 32). This microbial consor- position of the samples but do not define the metabolic func- tium is critical for human health and has been implicated in the tions involved (3, 34). Recently, metabolomics has been estab- development of the immune system, energy homeostasis, and lished as a new technology whose aim is to study the complex protection against pathogens, among other processes (18, 24). lexicon of small molecules present in any given biological sam- Conversely, imbalances in the intestinal microbiota have also ple, or the metabolome (6, 8, 19, 31). In order to expand our been associated with many pathological processes, including understanding of the importance of the intestinal microbiota inflammatory bowel disease, diabetes, asthma, obesity, autism, as well as the disturbances elicited by antibiotic treatment, we and others (18, 24). have used metabolomics to obtain a snapshot of the chemical The use of antibiotics is known to have significant effects on composition of the intestinal environment before and after the intestinal microbiota. The acquisition and spread of anti- antibiotic treatment. By using Fourier transform ion cyclotron biotic resistance genes between and within bacterial commu- resonance mass spectrometry with direct infusion (DI-FT- nities due to antibiotic use have also been studied thoroughly ICR-MS) (6), we determined that a single, high dose of the (12). This has caused an increased awareness of the impor- antibiotic streptomycin can have a profound impact on the tance of a more responsible use of antibiotics. However, it is only recently that studies began to reveal details of the impact levels of the majority of the compounds detected. Predictive of these drugs on intestinal microbial communities. For in- mapping of these compounds to corresponding metabolic stance, it is now well established that antibiotic treatment in- pathways showed that many crucial host metabolic functions creases susceptibility to enteric infections (10, 23, 25); some of are disturbed. Among some of the pathways affected are those the members of the microbiota involved in this process are involved in sugar, amino acid, fatty acid, bile acid, steroid, and currently under investigation. Although these studies are in- eicosanoid metabolism. Additionally, we show that clinically relevant antibiotic doses can also disrupt host eicosanoid metabolism. Our results show that the microbiota has effects on * Corresponding author. Mailing address: The University of British previously unidentified host functions. Additionally, the critical Columbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada. functions of all pathways affected suggest that the impact of Phone: (604) 822-2210. Fax: (604) 822-9830. E-mail: bfinlay @interchange.ubc.ca. antibiotics on mammalian physiology extends far beyond the ᰔ Published ahead of print on 31 January 2011. development of microbial drug resistance.

1494 Advanced Clinical Focus: Hormones and Endocrinology Menopause and Flax Seeds

• Contain lignans: matairesinol, secoisolariciresinol

• Estrogen-modulating effect

• 2 tbsp BID decreases hot ﬂashes by 50% within 6 weeks

Haggans CJ, Hutshins AM, Olson BA, et al. Effect of flax-seed consumption on urinary estrogen metabolites in post-menopausal women. Nutrition and Cancer 1999;33(2):188-195 Pruthi SL et al. Pilot evaluation of flaxseed for the management of hot flashes. Journal of the Society for Integrative Oncology 2007;5(3):106-112

Advanced Clinical Focus: Hormones and Endocrinology Cimicifuga Racemosa Black cohosh

• Selective estrogen receptor- modifying activity

• Most prescribed natural treatment

• As good as estrogen replacement without the risks

Wattle W. Seilova-Wuttke D, Gorkow C. The Cimifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind study: effects on menopause symptoms and bone markers. Maturitas 2003;44:S67-S77

Advanced Clinical Focus: Hormones and Endocrinology Other Nutrients That Can be Helpful

• Fish oil: 1000 mg/day • Maca: 3.5 grams/day

• Vitamin C: 500-1000 • Red Clover: 40-80 mg/ mg/day day

• Vitamin E: 200-400 iu/ • Dong Quai: 1-2 g TID day • Estrovera: 1 tablet/day • Black Cohosh: see above Male Speciﬁc

Advanced Clinical Focus: Hormones and Endocrinology Male Concerns

• Andropause

• Erectile dysfunction

• Prostate enlargement (benign prostate hyperplasia)

• Prostate cancer

Advanced Clinical Focus: Hormones and Endocrinology Does Andropause Exist? Advanced Clinical Focus: Hormones and Endocrinology Testosterone Decline

http://www.londonendocrinecentre.co.uk/Androgen-Deﬁciency.html

Advanced Clinical Focus: Hormones and Endocrinology

Prevalence of Low T In Other Conditions

• Obesity 52%

• Diabetes 50%

• AIDS/HIV 30%

• Hypertension 42%

• Hyperlipidemia 40%

• Erectile dysfunction 19%

Daniel HW. J Pain. 2002: 3:377-384 Mulligan T, et al., Int J Clin Pract. 2006; 60: 762-769 Grinspoon S, et al., Ann Intern Med. 1998; 129:18-26 Dobs AS. Bailliere Clini Endocrin Metabol. 1998

Advanced Clinical Focus: Hormones and Endocrinology Catch 22

Low testosterone

Obesity

Chen RY, et al., Diabetes Obes Metab. 2006 Jul;8(4):429-35. Advanced Clinical Focus: Hormones and Endocrinology Obese Teens and Testosterone

• Obese males 14-20 = 50% less testosterone

• Increases risk of impotence and infertility

Testosterone

Advanced Clinical Focus: Hormones and Endocrinology Testosterone and Longevity

• Mortality levels 88% higher in men with low testosterone

Shores MM, et al., Arch Intern Med. 2006 Aug 14; 166(15):1660-5.

Advanced Clinical Focus: Hormones and Endocrinology Inﬂuence of Testosterone

Brain Skin •Libido • Growth of facial •Positive feelings and body hair •Cognition and • Supports memory collagen Muscle Male sex organs •Muscle mass and •Sperm production strength •Prostate growth Bone marrow •Erectile •RBC production dysfunction Bone •Bone density Advanced Clinical Focus: Hormones and Endocrinology Erectile Dysfunction

• Inability to maintain erection

• Prevalence:

• <59 = 12%

• 60-69 = 22%

• >69 = 30%

• Atherosclerosis cause of ED in 50% over 50

Hatzimouratidis K. Epidemiology of male sexual dysfunction. American Journal of Men’s Helath 2007 Jun;1(2):103-125

Advanced Clinical Focus: Hormones and Endocrinology Erectile Dysfunction Causes

• 90% Organic

• Vascular insufﬁciency

• Drugs

• Alcohol/tobacco

• Endocrine disorders

• 10% Psychological

Advanced Clinical Focus: Hormones and Endocrinology Nitric Oxide

• Plays a critical role in erections

• Causes vasodilation

• Nutrients that increase:

• L-arginine

• L-citrulline Advanced Clinical Focus: Hormones and Endocrinology Selenium and Prostate

• Selenium decreases PSA

• 200 mg/day

Zhang W, et al., Nutr Res. 2011 Feb 12.

Advanced Clinical Focus: Hormones and Endocrinology Maca and Prostate

• Red maca reduces prostate size in rats

• Increase sperm production, motility, and semen volume

• 4:1 extract 525 mg TID

Forsch Komplementmed. 2009 Dec;16(6):373-80. Epub 2009 Dec 16.

Advanced Clinical Focus: Hormones and Endocrinology Pygeum Africanum and Prostate

• “Pygeum Africanum extract administration improved all the urinary parameters we investigated; prostatic echography relieved reduction of peri-urethral edema.”

• 300 mg BID-TID

Arch Ital Urol Nefrol Androl. 1991 Sep;63(3):341-5. Advanced Clinical Focus: Hormones and Endocrinology Urtica Dioica (Nettle) and Prostate

• Decreases prostate size

• Beneﬁcial for benign prostate hyperplasia

• 1000 mg BID-QID

J Herb Pharmacother. 2005;5(4):1-11.

Advanced Clinical Focus: Hormones and Endocrinology Saw Palmetto and Prostate

• “The evidence suggests that serenoa repens provides mild to moderate improvement in urinary symptoms and flow measures. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events.”

• 300-600 mg BID

Cochrane Database Syst Rev. 2002;(3):CD001423. Cochrane Database Syst Rev. 2009;(2):CD001423.

Advanced Clinical Focus: Hormones and Endocrinology Zinc for Sexual Health

• Multiple studies on Zn for infertility and low testosterone

• 37 infertile men given 60 mg of Zn for 45-50 days

• Testosterone in 22 patients signiﬁcantly increase and sperm count went from 8 to 20 million

Tikkiwal M, et al. Ind J Phys Pharm 1987 Jan-Mar; 31(1):30-34. Takihara H, et al. Urology 1987 Jun; 29(6): 638-641. Netter A, et al. Arch Androl 1981; 7(11): 69-73. Advanced Clinical Focus: Hormones and Endocrinology Exercise and Testosterone

• Strength training, high-intensity cycling increase testosterone

Izquierdo M, et al. J App Physiol 2001; 90(4): 1497-1507. J Strength Cond Res. 2011 Jan;25(1):23-31. Kraemer WJ, et al. J App Physiol 1999 Sep; 87(3): 982-92.

Advanced Clinical Focus: Hormones and Endocrinology

Addressing Male Hormone Imbalance

• Decrease aromatase activity

• Prevent the cortisol steal Functional • Improve BMI, and muscle Diet Foods • Eliminate xenoestrogens

• Avoid toxins Lifestyle Supplements • Low GI/GL diet

• Exercise

• Supplements

Advanced Clinical Focus: Hormones and Endocrinology Summary

• The endocrine system autocorrects when the root cause is addressed

• Address blood sugar ﬁrst, then adrenals, then thyroid, then sex hormones

• Give at least 2-3 months to begin to see changes Advanced Clinical Focus: Hormones and Endocrinology Summary

Functional Diet Foods

Lifestyle Supplements

Advanced Clinical Focus: Hormones and Endocrinology

Current Patient’s Evidence Story

Advanced Clinical Focus: Hormones and Endocrinology

Personalized Advanced Clinical Focus: Hormones and Endocrinology

“Knowledge is not power, until it’s applied.”

Dale Carnegie

Advanced Clinical Focus: Hormones and Endocrinology

Thank you!

evidence-based clinical nutrition and integrative healthcare