The Steroidogenic Pathways

THE KEY TO UNDERSTANDING HORMONES BY WILLIAM CLEARFIELD D.O. Objectives

01

Provide an Overview of the Steroidogenic Pathway 02

Review the Enzymes Involved in the Genesis of Active Hormones 03

Case Histories No Relevant Relationships with a Commercial Interest to Disclose In Memorium:

The Johnny Castle Memorial Lecture

Johnny Castle (1952-2009) Our Prime Directive What Issues Do We Deal With?

20’s ▶ Teen Years ▶ PCOS Acne ▶ ▶ Worsening PMS ▶ PCOS ▶ Infertility ▶ Endometriosis ▶ Hypothyroid

▶ Weight gain ▶ Endometriosis ▶ Fibroids ▶ Irregular periods ▶ Heavy periods ▶ Menstrual cramps ▶ Painful periods ▶ PMS ▶ Weight gain Common Hormonal Complaints

30s and 40s

Acne Weight gain Infertility Hair loss PMS Facial hair PCOS Hypothyroid Fibroids Perimenopause Endometriosis Common Complaints Hormonal Etiology

50’s 60+ Hot flashes Osteoporosis Night sweats Decreased libido Weight gain Sexual dysfunction Depression Insomnia Insomnia Migraine headaches Vaginal dryness Mood swings/anxiety Low libido Hair loss/Hair in places it shouldn’t be Hypothyroid Erectile dysfunction What You Need to Know What You Need to Ask

Estrogen Excess

1.Hot Flashes 1. Cysts 1. Agitation 2.Night Sweats 2. Breast Tenderness 2. Irritability a. Ovarian, Breast 3. Sleep Disturbance 3.Brain Fog b. Uterine (Fibroids) 4. Panic Attacks 4. Belly Fat c. Gallstones 5. Poor Libido 3. Anxiety 6. Headaches 5. Memory Loss 4. Spotting, Irreg menses 7. Short Tempered 6. Bone Loss Cramping 5. Infertility 7. Heart S/S DOE 6. Joint pain 7. Wt. Gain 8. PMS What You Need to Ask

Testosterone Excess Thyroid

1. Anxiety 1. Oily Skin 1. Dry Skin 2. Depression 2. Oily Hair 2. Dry Hair 3. Poor Sense of Well 3. Acne 3. Hair loss evenly on scalp Being 4. Skin Breakout 4. Fingernails 4. Muscle Tone neck and shoulder a. Crack/Break 5. Urinary 5. Road rage 5. Constipation Incontinence 6. Higher BPs 6. Weight Gain 6. Vaginal 7. ASVD (Long term) 7. Tired All Day Dryness/ED 8. Acne 8. Eyebrows Thin At outer 7. Poor Libido edge 8. Poor Sexual 9. Oral Temp <97.6 Performance What You Need to Ask

Cortisol Growth Hormone Insulin

1. Tired Upon Rising 1. Strength/Energy 1. Excess 2. Need Stimulant in 2. Memory a. Thirst mid morning 3. Task Initiation b. Excess Urination 3. Nap in afternoon 4. Planning and Prioritizing c. Abdominal Pain 4. Exhausted by 5. Organization d. Visual Disturbance Dinner time 6. Ability to Switch Between 5. Second Wind after Tasks 2. Deficiency 8 PM 7. Completing Tasks a. Sweating 6. Sugar/Salt 8. Paranoia b. Tired Cravings 9. Dark Moods c. Hunger 7. Nods off easily 10. OCD d. Easily Irritable e. Feels Shaky

1. Deficiency a. Lightheaded b. Needs to Eat Every 2 hours c. Irritable d. Moodiness What You Need to Ask

DHEA Low Prolactin

1. Flabby Muscles 1. Memory loss 1. Treatment Resistant: 2. Aging Faster than 2. Stress intolerant a. Anxiety Peers 3. Crave Salty Food b. Depression 3. Prone to Infections 4. Thing are dim vs. 2. Poor Immune Responses 4. Feels less well the past

5. Noise intolerant 5. Less hair High Prolactin 1. Unexplained headaches. 2. Visual impairment. 3. Reduced sex drive or fertility problems. 4. Erectile dysfunction 5. Abnormal lack of body and facial hair. 6. Irreg or no menses 7. Galactorrhea 8. Menopausal S/s Types of Steroid Hormones Understanding Steroid Hormones

All Steroid Hormones:

▶ Are derived from ▶ Differ in the ring structure and attached side chains ▶ Are lipid soluble ▶ Are not stored in cells

Holst, Jennifer P et al. “Steroid hormones: relevance and measurement in the clinical laboratory.” Clinics in laboratory medicine vol. 24,1 (2004): 105-18. doi:10.1016/j.cll.2004.01.004 Functions

★ “In Health” ○ -Carbohydrate Regulation, Anti-inflammatory, Energy Production ○ Gonadal -Reproduction ○ Mineral Balance-, Maintains BP and Blood Volume, Reabsorbs Sodium ○ ★ “In Sickness” ○ Inflammation ○ Stress Response ○ Bone Deterioration ○ ASVD ○ Behavioral Issues ■ Cognition ■ Agitation/Irritability ■ Mood

Hu, J., Zhang, Z., Shen, WJ. et al. Cellular cholesterol delivery, intracellular processing and utilization for of steroid hormones. Nutr Metab (Lond) 7, 47 (2010). https://doi.org/10.1186/1743-7075-7-47 Lipid Based Steroid Hormones Travel in Bloodstream Linked to Binding Globulins ❖ Binding Globulin carries Testosterone and Estrogen

❖ Binding Globulin carries

Hammond, Geoffrey L. “Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action.” The Journal of endocrinology vol. 230,1 (2016): R13-25. doi:10.1530/JOE-16-0070 The FIrst Step in Steroid Hormone Production

The “Mom and Pop” of the Steroidal Hormones

Cholesterol

▶ Healthy fats and an adequate cholesterol levels to make hormones

▶ Very low cholesterol levels contribute to poor hormone production

▶ Statins, Red Yeast Rice, Binders, and genetically low cholesterol

▶ Associated with increased risk for cancer, suicide, cancer, memory concerns

Conversion of Cholesterol Modulated by To Pregnenolone Cytochrome P450 Let’s Go Back to “The Way It Was”

DeBose-Boyd, Russell A. “Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase.” Cell research vol. 18,6 (2008): 609-21. doi:10.1038/cr.2008.61 Added “Off Topic Bonus” Statins Effect on the Steroidogenic Pathway

Statins inhibit HMG CoA reductase, the rate-limiting enzyme in the synthesis of cholesterol

Sniderman, A.D., Thanassoulis, G. Do statins lower testosterone and does it matter?. BMC Med 11, 58 (2013). https://doi.org/10.1186/1741-7015-11-58

Statins Effect on Cholesterol

https://www.intechopen.com/books/cholesterol-lowering-therapies-and-drugs/cholesterol -lowering-drugs-and-therapies-in-cardiovascular-disease

Cholesterol to Pregnenolone

Transfer of Chol. from Outer to Inner Membrane of Steroid Cells

Steroidogenic Acute Regulatory Protein STaR: The Rate Limiting Step

Organs: Adrenal cortex, Gonads, Brain, Nonhuman placenta

Inhibited by Endocrine Disruptors: ETOH, DES, Arsenic, BPA

Kallen CB, Billheimer JT, Summers SA, Stayrook SE, Lewis M, Strauss III JF (October 1998). "Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein". J. Biol. Chem. 273 (41): 26285–8. doi:10.1074/jbc.273.41.26285. PMID 9756854. Cholesterol to Pregnenolone

STaR: The Rate Limiting Step Steroidogenic Acute Regulatory Protein 1. Cytochrome P450

2. Co-Factors- NADPH + 3 H + 3 O 2

Hanukoglu I (December 1992). "Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis". The Journal of Steroid Biochemistry and Molecular Biology. 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824

Old Enzymes-New Names Pregnenolone

MOA: Inhibits tonic (NMDA) receptor-mediated neurotransmission Provides neuroprotection Preferentially metabolizes to . ALLO levels triple two hours post oral administration of 400 mg pregnenolone Pregnenolone protects the brain from cannabis intoxication

1. Marx CE, Keefe RS, Buchanan RW, Hamer RM, Kilts JD, Bradford DW, et al. Proof-of-Concept Trial with the Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia. Neuropsychopharmacology 2009 2. Marx CE. 2007 unpublished data. 3. Vallee, M., et al., “Pregnenolone can protect the brain from cannabis intoxication,” Science 2014; 343(6166):94-8. Pregnenolone

Indications Dose Memory 1. Maintenance-25-50 mg/25-50 mg/d Neuroprotection 2. Memory Enhancement- 150 mg/d Anti-stress, anti-anxiety, anti-depressive 3. Fatigue-150-200 mg 2x/d) x 4 mo. Anti-arthritic 4. Depression/Anxiety 400 mg/d Lowers Lipids Improves mental alertness Improves psychomotor performance Anti-fatigue

https://selfhacked.com/blog/top-11-scientific-health-benefits-pregnenolone-including-drawbacks/accessed January 29, 2021 Tai, P., 8 Powerful Secrets to Anti-Aging, Health Secrets USA, Tucker, GA; 2007:89. https://www.grc.com/health/research/Pregnenolone/The_Promise_of_Pregnenolone.pdf, accessed January 29, 2021

1. https://selfhacked.com/blog/top-11-scientific-health-benefits-pregnenolone-including-drawbacks/accessed January 29, 2021 2. Tai, P., 8 Powerful Secrets to Anti-Aging, Health Secrets USA, Tucker, GA; 2007:89. 3.https://www.grc.com/health/research/Pregnenolone/The_Promise_of_Pregnenolone.pdf, accessed January 29, 2021 To Progesterone and Testosterone and Beyond!

3β- Dehydrogenase (3β-HSD)

Converts Pregnenolone to Progesterone Converts 17-OH Pregnenolone to 17-OH Progesterone Converts DHEA to to testosterone Androstadienol to androstadienone

To Progesterone and Testosterone and Beyond!

3β-Hydroxysteroid Dehydrogenase (3β-HSD)

Decreased by: Progestins, ETOH, Metformin, Isoflavonoids, PCB’s Increased by: PCOS, Hyperinsulinemia, IL-4 and IL-13 (allergies), Hyperthyroidism, Forskolin, SSRIs, SNRIs, Congenital Deficiency=Virilism, Adrenal Hyperplasia

Santín-Márquez, Roberto et al. “Sulforaphane - role in aging and neurodegeneration.” GeroScience vol. 41,5 (2019): 655-670. doi:10.1007/s11357-019-00061-7

Progesterone

MOA: Calming/Improves Sleep Lowers High Blood Pressure Helps Body Use and Eliminate Fats-Lowers Cholesterol Balances Estrogen- Bioidentical-Not Progestins) Stimulates new bone production Enhances thyroid function Improves libido Restores cell oxygen levels Induces conversion of E1 to inactive E1S form Promotes Th2 immunity

Deficiency S/S Agitation Poor Libido Headache Short Temper Irritability Insomnia Progesterone

▶ Increase in Progesterone: ▶ Pregnancy ▶ Pregnenolone administration ▶ Chaste Tree Berry (Vitex) ▶ Decreased Progesterone: ▶ Progesterone based Birth control pills ▶ Stress Luteal phase defect/anovulation ▶ Increased insulin High prolactin ▶ Underweight Hypothyroidism ▶ Opioids – Underweight ▶ Progestin releasing IUD (Mirena – releases low levels of progestins) ▶ Dose ▶ Cream 2-7. 5 % (20-75 mg)/night ▶ Oral 50-200 mg (Micronized) @ bedtime ▶ Cycle Night's 14-25 x 3 cycles if menstruating 17α-HYDROXYLASE

▶ Converts Pregnenolone to 17-OH Pregnenolone

▶ Converts Progesterone to 17-OH Progesterone

▶ Downregulated activity:

▶ Spironolactone

▶ Azole antifungals

▶ Congenital adrenal hyperplasia

▶ Upregulated activity:

▶ High insulin Smoking: Yeh J, et al. J Steroid Biochem. ▶ PCOS 1989 Oct;33(4A):627-30 ▶ Hyperglycemia -Antifungals: Weber MM, et al. Clin ▶ Stress Investig. 1993 Nov;71(11):933-8.

▶ Alcohol -Spironolactone: Kossor DC, et al. Mol Pharmacol. 1991 Aug;40(2):321-5. The “Hidden Pathway” Revisited 3 alpha HSD Enhancement Increases ALLO

SSRIs, SNRIs,Sulforaphane Increase activity

21 Hydroxylase and 11 Hydroxylase Progesterone to 17 OH Progesterone to 11-Deoxycortisol

▶ Cortisol Production

▶ • Made in the adrenal glands

▶ • Two enzyme reactions to convert from 17-OH-Progesterone

▶ • Increased conversion to cortisol seen in:

▶ Sodium depletion

▶ High prolactin

▶ Stress

▶ Inflammation

▶ Cushing’s

▶ Obesity

▶ • Decreased cortisol:

▶ use Antifungals

▶ Addison’s Disease DHEA

▶ Opioid use Soy Hanukoglu I, Privalle CT, Jefcoate CR (May 1981). ▶ Chronic marijuana use "Mechanisms of ionic activation of adrenal mitochondrial ▶ Accutane cytochromes P450scc and P-45011 beta" (PDF). J. Biol. ▶ Resveratrol Chem. 256 (9): 4329–35. PMID 6783659. 11β – Hydroxysteroid Dehydrogenase 1 & 2 ▶ Cortisol (active stress hormone ) vs (inactive form)

▶ Via 11β hydroxysteroid dehydrogenase 1&2

▶ MORE CORTISOL

▶ Stress, inflammation Cushing’s disease, obesity, hypothyroidism, licorice, grapefruit, high insulin, excess sodium, hypoxia, , forskolin

▶ MORE CORTISONE

▶ Hyperthyroidism, , quality sleep, hGH (via IGF-1), good insulin sensitivity, reduced inflammation, Na restriction ▶ Cortisol is metabolized by: 5α-Reductase and 5β-Reductase (and 3α-HSD) to a/b-THF & THE (cortisone metabolite) for excretion

▶ Increased in:

▶ Obesity -Metabolic syndrome: Seckle

▶ High insulin JR, et al. Recent Prog Horm Res. 2004;59:359-93. ▶ Hyperthyroid -Inflammation: Cai TQ, et al. J ▶ Decreased in: Steroid Biochem Mol Biol. 2001

▶ Hypothyroidism May;77(2-3):117- 22. -Hypothyroid: Hoshiro M, et al. Anorexia ▶ Clin Endocrinol (Oxf). 2006 ▶ Poor liver function Jan;64(1):37-45 . -Licorice: Ferrari P, et al. Hypertension. 2001 Dec 1;38(6):1330-6

Aromatase

▶ Enzyme responsible for biosynthesis of ▶ A CYP19A1, a member of the cytochrome P450 superfamily ▶ Conversion of androstenedione to (E1) ▶ Conversion of testosterone to estradiol (E2) ▶ Induces cytokines IL-6, Il-1 Beta ▶ ▶ Increased aromatase activity: ▶ Inflammation ▶ TBI-Neuroprotection ▶ Excess adipose ▶ High insulin ▶ Alcohol ▶ Mold/biotoxin illness (CIRS) ▶ 5 alpha reductase inhibitors ▶ Prolactin ▶ Glyphosate Aromatase References

▶ http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=co re;g=ENSG00000137869;r=15:51208057-51338610 ▶ Raven G, de Jong FH, Kaufman JM, de Ronde W: In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion. J Clin Endocrinol Metab. 2006, 91: 3324-3328. 10.1210/jc.2006-0462. ▶ Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM: Testosterone therapy in adult men with deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006, 91: 1995-2010. 10.1210/jc.2005-2847. ▶ Nelly Mauras, John Lima, Deval Patel, Annie Rini, Enrico di Salle, Ambrose Kwok, Barbara Lippe, Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males, The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 12, 1 December 2003, Pages 5951–5956, https://doi.org/10.1210/jc.2003-03127 ▶ Duncan KA, Saldanha CJ (July 2011). "Neuroinflammation induces glial aromatase expression in the uninjured songbird brain". Journal of Neuroinflammation. 8 (81): 81. doi:10.1186/1742-2094-8-81

▶ Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Séralini GE (August 2009). "Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines". Toxicology. 262 (3): 184–91. doi:10.1016/j.tox.2009.06.006. PMID 1953968 Aromatase Inhibitors

▶ MOA: Binds w heme iron of enzyme (Anastrozole) ▶ Mimics androstenedione (Exemestane) ▶ Decreases mean plasma mean plasma estradiol/testosterone ratio by 77% ▶ Lowers estrogen, LH, FSH, Testosterone ▶

▶ Side effects: Decrease in bone mineral density ▶ Typical Estrogen Deficiency Symptoms ▶

▶ Inflammatory Action: Aromatase Inhibitors down-regulate IL-6, TNF-alpha

Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C (2004). "Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels". J. Clin. Endocrinol. Metab. 89 (3): 1174–80. doi:10.1210/jc.2003-031467.

Simpson ER (2003). "Sources of estrogen and their importance". J. Steroid Biochem. Mol. Biol. 86 (3–5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515. S2CID 11210435 Aromatase Inhibitors

Aromatase Inhibitors 1. Anastrozole-1 mg 1-7x/week (usual dose 1 mg 2x/wk) 2. Exemestane-25-50 mg/d 3. Letrozole-2.5 mg 1/week Off Label Aromatase Inhibitors 1. Spironolactone-25-100 mg/d 2. Metformin-500-2000 mg/d ▶ OTC Aromatase Inhibitors

– Resveratrol 250 mg 2x/d – Chasteberry 120 mg 2x/d – Spearmint Tea-100 mg/d – Deglycerinated Licorice (DGL) 150 mg/d

– Omega 3 Fatty Acids 2-4 gm/d Balunas, M. J., Su, B., Brueggemeier, R. W., & Kinghorn, A. D. (2008). Natural products as – N-acetyl cysteine 600 mg 3x/d aromatase inhibitors. Anti-cancer agents in medicinal chemistry, – Chrysin 140 mg/d 8(6), 646–682.

– Zinc 30 mg 2x/d https://www.ifm.org/wp-content/upl oads/Aromatase-Inhibitors-1.pdf – Flaxseed 2 gm 1-2 x/d – Nettles 500 mg/d 5 Alpha Reductase

▶ Makes (testosterone) more potent •

▶ Activity:

▶ Metabolizes progesterone into a-

▶ Metabolizes cortisol into a-THF (b-metabolites of both through 5β activity

▶ Upregulated leads to high androgen symptoms:

▶ Men (thinning hair, prostate issues)

▶ Women (PCOS, thinning hair, acne, facial hair growth)

▶ Increased enzyme activity:

▶ High insulin and obesity

▶ Decreased enzyme activity:

▶ Saw palmetto, nettles, EGCG, progesterone, zinc, finasteride

Goldman, R., Hodgson, A., Enlarged Prostate, 9 OTC Medications, Healthline, December 16, 2016. https://www.healthline.com/health/over-the-counter-enlarged-prostate

Estrogens

E1 (Estrone) Main estrogen body makes postmenopausally. Increased levels may inc. breast ca. risk

E2 (Estradiol) Over 400 functions in body Most potent estrogen

E3 () Least powerful, most beneficial Efficient metabolism results in predominance of 2-OH-E1 and 2-MeOE1 Inefficient estrogen metabolism results in predominance of 16-OH-E1 and 4-OH-E1 Acts negatively to allow oxidation Damages DNA (4-OH-E1)

Estrogen

Healthy metabolism: Unhealthy metabolism: Exercise Pesticides Cruciferous vegetables Smoking Pesticide free diet Caffeine (conversion to 16OHE1) Weight loss Hypothyroidism DIM/I3C Less/no ETOH Soy High protein-anti-inflammatory diet Flaxseed, Omega-3 fats

COMT – Catechol-O-Methyltransferase

▶ One of several enzymes that degrade catecholamines:

▶ Dopamine, Epinephrine, Norepinephrine

▶ Principal enzyme in the conjugation pathway for hydroxylated estrogens

▶ Carcinogenic 4-hydroxy estrogens

▶ Methylation of 2-OH/4-OH estrogens is slowed in:

▶ Genetic variants (SNPs) in MTHFR and COMT

▶ COMT is upregulated by:

▶ Methyl donors

▶ SAMe, B vitamins, TMG, choline, folate, and methionine

Case History-R.R.

▶ 22 y/o male w hx of ADHD

▶ Obese

▶ Poor S.A.D. Diet

▶ Poor Motivation

▶ Occupation: “Gamer?”

▶ VS

▶ 73”, 382 pounds, BMI 50.40

▶ BP 132/78, T 98.2, R 18, P 92, O2 Sat 95%

▶ PH

▶ Infected cyst low back removed 4 years ago w continuous drainage.

▶ 2 rounds of antibiotics when first developed without relief.

▶ Drained by surgery q 6 mo. to year.

▶ Mate dresses wound and expresses as much fluid out as possible

▶ Lack of Energy, “Tired but Wired”, Insomnia

▶ No Sex Drive

▶ Loss of Muscle

▶ Depressed

▶ Poor Memory Case History-R.R.

▶ PE

▶ Exam: Obese, in no acute distress. Tender mid thoracic to Upper lumbar area midline w slight drainage. Otherwise normal.

▶ Initial Assessment

▶ Cyst of skin [ICD-10: L72.9]

▶ Cellulitis of skin [ICD-10: L03.90]

▶ Morbid obesity [ICD-10: E66.01]

▶ Plan

▶ Cleocin 300 MG Oral Capsule Take 1 capsules (600 mg) by mouth every 8 hours for 28 days As Reflected in the Steroidogenic Pathway, What is Wrong? R.R. Case Study ▶ Labs

▶ H/H 16.1./47.3

▶ FBS/Insulin/IR 79/11.2 (Range 2.6-24.9)/2.18 (normal <2.9)

▶ cRP 3.1 (Range 0.0-4.9)

▶ Chol/Trig/HDL/LDL 166/177/31/103

▶ Testosterone Total x2 am 228/178 (347-1197)

▶ Free Testosterone 6.2/6.0 (9.3-26.5)

▶ DHEA 230

▶ Prolactin 12.0 (4.0-15.2)

▶ Estradiol 46.1 (<40)

▶ TSH/free T3/TPO/TAG/rT3 1.83, 2.6, 10, <1, 34

▶ 25 OH Vitamin D 10.6 (30-100)

▶ Homocysteine 8.4 (<11)

▶ SHBG 62 (16.5-55.9) FAI 13.02 (30-130)

▶ Cortisol (AM) 35 (7-28, ideal 10-15) R.R. Case Study-Affected Pathways? Recommendations?

▶ Stress Reduction

▶ Emotional/Mental – breathing exercises, prayer, meditation, yoga, etc

▶ Infection – antimicrobials/antifungals –

▶ Inflammation – dietary (low sugar/high protein) gluten free

▶ Anti-inflammatories (omega-3 fatty acids, curcumin, etc) ▶ Hormone Support

▶ Pregnenolone 30 mg 2x/d

▶ DHEA 25 mg/d

▶ Testosterone Yes or No?

▶ Hint (HCG 500 IU SQ twice weekly x 8 weeks) or Clomiphene citrate 50 mg 2-3x/wk

▶ Aromatase

▶ Green Tea, Zinc citrate 50 mg/d, Flaxseed, Chrysin, Progesterone 2% Cream w gynecomastia

▶ Adaptogenic Herbs

▶ – Panax Ginseng, Rhodiola, Ashwagandha

▶ Vitamin D3

▶ 8000 IU @ bedtime Follow Up

▶ 8 Weeks ▶ 52 Weeks ▶ More strength, feels better, more energy ▶ Weight 295 ▶ Weight 365, following diet 80%, exercising 4 days/wk. ▶ Began Community College ▶ Wound closed, no drainage for first time in 4 year ▶ Wound healed

▶ Plan : D/C antibiotics, vitamin e oil for ▶ Testosterone 874, free 17.1 wound care

▶ Cont. Hormone Regimen 2 mo. then off a ▶ Estradiol 19.6 month ▶ 25 OH Vitamin D 49 ▶ 20 weeks

▶ Weight 344 ▶ Regimen

▶ Testosterone 527, free 14.3 ▶ Gluten Free Diet 2000-2400 cal/d ▶ Estradiol 27.4 ▶ Tribulus/Tongkat ali combo for Testosterone ▶ 25 OH Vitamin D 34.6 Boost ▶ Cortisol 19 ▶ Continues Adrenal Regimen-No glandulars ▶ ED Gone ▶ Vitamin D3 2000 IU @ bedtime T.G.-Case History

▶ 34 year old female with history of:

▶ Prolonged, painful menses, scanty flow at times

▶ Hirsutism, Acne

▶ Infertility

▶ Overweight

▶ Depression

▶ Sensitive to sugar, needs to eat every 2-3 hours or becomes light headed

▶ PE

▶ Ht: 61”, Wt. 201#, BMI 37.98

▶ BP 120/64, P82, R18, PO2 95% T.G. Labs

▶ H/H 12.5/39.7

▶ FBS/Insulin/IR 82/29.5 (Range 2.6-24.9)/5.97 (normal <2.9)

▶ cRP 27.3 (Range 0.0-4.9)

▶ Chol/Trig/HDL/LDL 232/1118/71/127

▶ Testosterone Total 46 (10-55)

▶ Free Testosterone 7.1 (0-4.2)

▶ DHEA 292

▶ Estradiol 28 day saliva

▶ Progesterone 28 day saliva

▶ TSH/free T3/TPO/TAG/rT3 3.11, 3.5, 8, <1, 16

▶ 25 OH Vitamin D 27.9 (30-100)

▶ Homocysteine 5.5 (<11)

▶ SHBG 31 (16.5-55.9)

▶ Cortisol (AM) 28 (7-28, ideal 10-15)

▶ Ferritin 70 (90-120) 28 Day Saliva Evaluation

P/

Luteal Phase P/E2 = 7 Goal 30-40 28 Day Saliva Test

▶ Progesterone: Low

▶ Estrogen: Production is normal.

▶ DHEA: Average DHEA-3 ng/ml. Reference Range: 3-10 ng/ml

▶ Testosterone: Average testosterone level is 39 pg/ml.

▶ The borderline range is 6-9 pg/ml, normal is 10-38 pg/ml.

▶ Balance: Favors estrogenic activity. Insufficient progesterone.

▶ Distinct estrogen dominance What Relationships Do You See? Remedy Array

▶ Stress reduction ▶ Interventions

▶ Diet – Paleo, Anti-inflammatory, Low ▶ BCP Glycemic Index, Low Phytoestrogens, Fiber ▶ Less androgenic: Desogestrel or norgestimate) ▶ Mental/emotional ▶ Progesterone ▶ Inflammatory ▶ Saw Palmetto ▶ Infections ▶ D‐Chiro‐Inositol/D‐Pinitol/myo‐inositol ▶ Oxidative ▶ N-acetyl-cysteine ▶ Interventions ▶ Black Cohosh, Chaste Berry ▶ Metformin ▶ ECGC (Green Tea) ▶ Adaptogens ▶ Licorice ▶ Spironolactone, Cimetidine ▶ Ovulation Inducers ▶ Zinc ▶ Clomiphene ▶ Nettle ▶ HCG What Questions Will You Ask?

Estrogen Estrogen Excess Progesterone

1.Hot Flashes 1. Cysts 1. Agitation 2.Night Sweats 2. Breast Tenderness 2. Irritability a. Ovarian, Breast 3. Sleep Disturbance 3.Brain Fog b. Uterine (Fibroids) 4. Panic Attacks 4. Belly Fat c. Gallstones 5. Poor Libido 3. Anxiety 6. Headaches 5. Memory Loss 4. Spotting, Irreg menses 7. Short Tempered 6. Bone Loss Cramping 5. Infertility 7. Heart S/S DOE 6. Joint pain 7. Wt. Gain 8. PMS What Questions Will You Ask?

Testosterone Testosterone Excess Thyroid

1. Anxiety 1. Oily Skin 1. Dry Skin 2. Depression 2. Oily Hair 2. Dry Hair 3. Poor Sense of Well 3. Acne 3. Hair loss evenly on scalp Being 4. Skin Breakout 4. Fingernails 4. Muscle Tone neck and shoulder a. Crack/Break 5. Urinary 5. Road rage 5. Constipation Incontinence 6. Higher BPs 6. Weight Gain 6. Vaginal 7. ASVD (Long term) 7. Tired All Day Dryness/ED 8. Acne 8. Eyebrows Thin At outer 7. Poor Libido edge 8. Poor Sexual 9. Oral Temp <97.6 Performance What Questions Will You Ask?

Cortisol Growth Hormone Insulin

1. Tired Upon Rising 1. Strength/Energy 1. Excess 2. Need Stimulant in 2. Memory a. Thirst mid morning 3. Task Initiation b. Excess Urination 3. Nap in afternoon 4. Planning and Prioritizing c. Abdominal Pain 4. Exhausted by 5. Organization d. Visual Disturbance Dinner time 6. Ability to Switch Between 5. Second Wind after Tasks 2. Deficiency 8 PM 7. Completing Tasks a. Sweating 6. Sugar/Salt 8. Paranoia b. Tired Cravings 9. Dark Moods c. Hunger 7. Nods off easily 10. OCD d. Easily Irritable e. Feels Shaky

1. Deficiency a. Lightheaded b. Needs to Eat Every 2 hours c. Irritable d. Moodiness What Questions Will You Ask?

DHEA Pregnenolone Low Prolactin

1. Flabby Muscles 1. Memory loss 1. Treatment Resistant: 2. Aging Faster than 2. Stress intolerant a. Anxiety Peers 3. Crave Salty Food b. Depression 3. Prone to Infections 4. Thing are dim vs. 2. Poor Immune Responses 4. Feels less well the past

5. Noise intolerant 5. Less hair High Prolactin 6. 1. Unexplained headaches. 2. Visual impairment. 3. Reduced sex drive or fertility problems. 4. Erectile dysfunction 5. Abnormal lack of body and facial hair. 6. Irreg or no menses 7. Galactorrhea 8. Menopausal S/s

Let AMMG Know You Want the Johnny Castle Tradition to Continue I’ve Had