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Tracy’s health counseling certification is from Columbia University for the Institute of Integrative Nutrition in New York.

She has completed ongoing training and is working on a certification in understanding the root causes of chronic illness with the Institute of Functional Medicine and on an additional Masters degree in Human Nutrition at Bridgeport University.

She holds a Masters degree in Engineering from MIT and a Masters degree in Management from The Sloan School at MIT.

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SAFM Deep Dive Clinical Courses2

Hormones DemystifiedPart 3

This presentation is copyrighted by Purpose Inc. with all rights reserved, available for student reuse strictly subject to the terms outlined in the SAFM student program agreement.

Today’s Agenda

A Brief Refresher Support for Countering PCOS Estrogen Receptors, Phytoestrogens, and Individuality Male Hormone Balance Looking Toward Part 4

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And completely beyond this diagram, there are receptors!

Agonists and antagonists. And many things besides hormones can

affect hormone receptors in either direction e.g. AR and ERα/ERβ.

Different tissues express different levels of the enzymes that convert hormones

e.g. DHT in the prostate.

For women, three common imbalances:1. Estrogen dominance2. Androgen dominance3. Insufficient hormones (progesterone in

perimenopause and estrogen in menopause in thinner women)

For men, three common imbalances:1. Estrogen dominance2. DHT dominance3. Insufficient hormones (especially overall

testosterone or free testosterone, esp. as men age, in concert with low DHEA)

So Many Things Can “Go Wrong” with Balance

Hormone Imbalance

Toxins/Chemicals Insomnia Low nutrient intake Infections Chronic Stress Physical Stress/Trauma Worry/Anxiety Smoking Maldigestion/malabsorption Genetic Tendency Refined, inflammatory foods Poor Ability to Detoxify Obesity Social Isolation Food Sensitivities Constipation Hypothyroid function Dysbiosis

The Root Causes of hormone imbalance are also the same Root Causes and contributors to other

dis-ease progression!

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Dance of the Hormones

Epinephrine/Norepinephrine

CortisolInsulin

EstrogenProgesterone

ThyroidTestosterone

DihydroTestosterone(DHT)Many hormones affect one

another directly and indirectly across systems.

In women, excess insulin can promote higher testosterone and

anovulation. Resulting lower progesterone can then increase

estrogen dominance.

…in an interactive Soup!

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Epidemic of PCOS

PCOS is affecting more and more women (especially young women) as a result of high insulin-stimulating diets (high in refined carbohydrates, sugars) and high toxic exposure in modern society (both in utero and life-long).

High insulin causes ovaries to make excess testosterone which impairs ovulation.

It’s actually a hormonal, quadruple whammy! High insulin drives high body fat which spawns earlier

menses and overall higher estrogen levels throughout. Use of contraceptives hormones to “fix” PCOS may make this issue worse long-term.

Typically, women with PCOS do not ovulate, so there is insufficient protective progesterone. Thus, they are more vulnerable to that higher estrogen! Over time, they may struggle with symptoms of excess androgens as well (e.g. acne, hair loss on head, excess facial/body hair, overweight).

Commonly presents as “skinny fat girls” and “muffin tops”.

Over time, this dynamic increases the risk of many cardio-metabolic impairments and disease (e.g. hypertension, prediabetes, obesity. PCOS in adults is also associated with an increased (nearly 10X!) incidence of sleep apnea (which is attributed to the levels of testosterone) increases sympathetic neural activity.*

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* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574283/ , https://www.physiology.org/doi/full/10.1152/japplphysiol.00264.2002

PCOS Interventions

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Countering PCOS - 1

Low glycemic diet. WS tip: Increasing vegetable intake and ensuring ample protein intake while taking our all sweeteners, fruit juices, & grains entirely (not just refined grains) for 3-6 mos is potent in reversing insulin resistance alongside a few targeted supplements. Reversing Diabetes DDCC covers this in detail.

Reduce stress. Increased sympathetic activation increases ovarian testosterone secretion, in mechanisms separate from ACTH (adrenal stimulation). (This is why beta blocker drugs have been shown to reduce ovarian cysts formation caused by adrenergic stimulation). Stress impairs fertility, actively. *

Assess and address hypothyroidism. High coincidence of hypothyroidism and polycystic ovaries. Increased TRH increases TSH and also prolactin, which inhibits ovulation; FSH/LH ratio also shifts. In PCOS, higher bodyfat increases estrogen, and excess estrogen can impair thyroid function via higher TBG. Interesting theory that metformin helps PCOS not just via reducing IR but also reducing TSH. ** Be aware that metformin can depleted Vitamin B12 (Serum B12, MCV, & ideally MMA: check regularly!)

Inositol – a sugar alcohol shown to restore ovulation in PCOS along with restoration of insulin sensitivity. 2500-3000mg once daily (loose powder).***

Vitex – chastetree berry can restore ovulation & progesterone in a variety of anovulation and luteal insufficiency situations (via dopamine?). Low dose (~200mg) may increase prolactin; high dose (500-1000mg)will reduce it (i.e. for PCOS), for days 14-28 of menstrual cycle. #

Improve Insulin sensitivity with intake of targeted key nutrients e.g. chromium, biotin, alpha lipoic acid, B vitamins.

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* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166402/ , https://www.ncbi.nlm.nih.gov/pubmed/22328164/** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287775/, https://www.ncbi.nlm.nih.gov/pubmed/23505173/ , https://www.ncbi.nlm.nih.gov/pubmed/21521311/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746091/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821496/ *** https://www.schoolafm.com/ws_qa/inositol-and-insulin-resistance/# https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528347/ , https://www.aafp.org/afp/2005/0901/p821.html

Countering PCOS - 2

Berberine – If insulin resistance has progressed to drive significantly elevated blood sugar (e.g. HbA1c 5.6% or higher), I often recommend use of berberine for a few months as triage until this drops. 400-500mg taken 2-3x/day prior to meals of the day with greatest carbohydrate intake. *

Magnesium – Insulin resistance promotes magnesium deficiency, and the latter promotes the former. Check RBC Mg to ensure in upper third of reference range. If not, consider magnesium glycinate, perhaps 200-300mg twice daily. **

Omega-3 essential fatty acids – Reduces testosterone and insulin resistance (and improves associated lipid markers) and also improved menstrual regularity in those with PCOS. 1.5 to 3 grams actual omega-3s (high EPA) in divided doses with food. Consume ground flaxseed (provides O3 but also lignans!) #

Stop birth control pills (OCP) as a triage remedy. WS tip: Always support other possible estrogen dominance drivers first (e.g. estrogen clearance). Then once the above actions have been in place for about a month, stop OCP; this drug increases cortisol and increases sex hormone binding globulin which will reduce available progesterone as the body begins making more of it. The effect is universal but varies in intensity by ingredients.***

Reduce any excessive (or eliminate) alcohol intake

Interventions already discussed for countering Estrogen Dominance (ED) may also be appropriate depending on the extent of ED in a unique person e.g. evening primrose oil, Vit D.##

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* https://www.schoolafm.com/ws_clinical_know/blood-sugar-busting-berberine/, http://www.eje-online.org/content/166/1/99.long, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722087/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073878/** https://www.ncbi.nlm.nih.gov/pubmed/7714113 , http://cjasn.asnjournals.org/content/2/2/366.full.pdf+html ,

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820051/ , https://www.ncbi.nlm.nih.gov/pubmed/28526383*** https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845679/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766352/# https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963626/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941370/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752973/ , ## https://www.ncbi.nlm.nih.gov/pubmed/28742409

Xeno and Phyto: What’s the Difference?

Xenoestrogens are chemicals (e.g. bisphenol-A) that have estrogenic potentiating effects. Generally considered to be harmful.

Phytoestrogens are foods/herbs (e.g. soybeans) that have estrogen potentiating effects. Generally considered to be beneficial.

Huh?!? Of course it’s not an exact science.

Phytoestrogens include substances such as lignans & polyphenols (e.g. isoflavones such as genisten). Isolated food “extracts” can end up many, many more times more potent in estrogenic effect than the whole food.

Dosage matters. It’s one thing to fill up estrogen receptors with a weaker estrogen than estradiol; it’s another to add so much that overall estrogen effect is increased.

Phytoestrogens tend to bind both ERα and ERβ receptors but much, much more strongly to ERβ. Most isoflavones bind and activate both ERα and ERβ more readily than synthetic EDCs including BPA.

It’s NOT just about estrogen receptors. Phytoestrogens also often feature anti-inflammatory and antioxidant properties. Many xenoestrogen chemicals feature pro-inflammatory or oxidative components.

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* See “The Pros and Cons of Phytoestrogens” in the Documents section for this course.

Male Hormone Balance

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Expanding on Androgens & What Goes Wrong14

With appreciation to Precision Analytical, the makers of DUTCH labs, for this excellent hormone biochemistry flow diagram.

Makin’ it Manly! Androgens

Androgen hormones are critical for men for libido, bone cell formation, metabolism, muscle retention, overall drive for achievement, fat storage control, cardiovascular health, general energy, mental clarity, and overall sense of wellbeing.

Sex Hormone Binding Globulin (SHBG) has particularly high affinity for androgens and especially DHT. Androgens also bound (more weakly) to albumin (included in “bioavailable testosterone”). WS tip: Stinging nettle root (not leaf) is effective for reducing SHBG.***

Testosterone metabolized by 5-alpha- and 5-beta-reductase enzymes; 5-alpha pathway creates DHT. These enzymes also metabolize progesterone and cortisol.

Dihydrotestosterone (DHT) and Testosterone (T) are the most potent androgens, with DHT having ~ 3X potency of T. DHT is especially important for early life development. DHT has primarily local action, esp. in skin and prostate (in prostate, 10X more DHT than T - and has many androgen receptors!). *

Androgen receptor mutation or gene amplification are implicated in prostate cancer.** As usual, endogenous hormones are witless exacerbators vs. true root causes of cancer.

Excess DHT in men can promote head hair loss, acne, benign prostate hyperplasia (BPH), excessive body/facial hair, irritability/rage, and perhaps hypertension.*

Obesity and high insulin increase expression of 5-alpha-reductase enzyme

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An excellent technical overview of androgens: https://www.ncbi.nlm.nih.gov/books/NBK279000/* https://www.bu.edu/news/2012/03/07/study-examines-the-relative-roles-of-testosterone-and-its-metabolite-dihydrotestosterone-dht-in-men/, https://www.sciencedirect.com/topics/neuroscience/dihydrotestosterone , https://onlinelibrary.wiley.com/doi/epdf/10.1002/j.1939-4640.1992.tb01621.x , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081639/** https://www.ncbi.nlm.nih.gov/pubmed/8912473/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165281/*** https://www.ncbi.nlm.nih.gov/pubmed/9434605 , https://www.ncbi.nlm.nih.gov/pubmed/17509841

BPH: The Modern “Perimenopause” of Manhood?42

Benign Prostate Hyperplasia Typical symptoms include urinary issues e.g. urgency, difficulty initiating, leakage, and

excessive overnight. WS tip: But also embarrassment, frustration, disturbed sleep, stress. Often occurs coincident with other symptoms of elevated DHT (dihydrotestosterone)

such as top of head hair loss, acne, irritability, and increased body/facial hair growth. There is some interesting data* showing

coincidence of prostate cancer with top-of-head balding (don’t confuse with receding hairline).

But on the other hand, low serum DHT levels at diagnosis are associated with reduced survival from prostate cancer.**

But as usual, the Devil is in the Detail! DHT is a paracrine hormone. Blood leveldoesn’t correlate with prostate levels.#

Blood levels of E1 (and perhaps E2)correlate well with virulence of prostate cancer. But xenoestrogens, ERα/ERβ balance, and E clearance appear to play key roles! ##

* https://www.health.harvard.edu/mens-health/testosterone-prostate-cancer-and-balding-is-there-a-link-thefamilyhealth-guide** https://www.ncbi.nlm.nih.gov/pubmed/17482753 # https://academic.oup.com/edrv/article/38/3/220/3788611## https://www.ncbi.nlm.nih.gov/pubmed/18337090 , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2972405/ , https://www.ncbi.nlm.nih.gov/pubmed/15663993/ , https://www.ncbi.nlm.nih.gov/pubmed/17786930 , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830606/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891116/ , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291886/ , https://www.ncbi.nlm.nih.gov/pubmed/18381236

BPH Remedies42

All aspects of an anti-inflammatory lifestyle are key! Also, optimal hydration. Reduce or eliminate alcohol.

Better balance 5-alpha and 5-beta enzyme action for a unique person. WS Tip: this is where urinary hormone data is powerful (e.g. DUTCH).

Zinc. Picolinate is most bioavailable form; citrate or amino acid chelate next best. 30mg 2x/day for men for 1-2 mos to rebuild low levels; typically can sustain at 1x/day. May need Zn/Cu combination depending on aggregate dietary intake. Check with RBC Zinc. Alkaline phosphatase less than 60 IU/L is suspect.

Generally research shows that herbal combinations work best at reducing 5-alpha reductase activity vs. any single agent. Consider saw palmetto, pumpkin seeds, pygeum, rye grass pollen, beta sistosterol.

Address estrogen dominance. As covered in webinar #2. Some men need progesterone. Eat ground flaxseed. Fascinating study shows major positive impact and strong placebo. *

As an aside, there is a lot of confusion about therapeutic intake of ground flaxseed in men and possible testosterone suppression. As usual, the point is to consider the goal. IF there is a need to reduce 5aR activity or effect of strong estrogens (e.g. insulin resistance), then ground flaxseed may be useful. If estrogens are already optimal with no excess DHT issues, then this is likely a less beneficial food. Avoid black-and-white thinking! And always make sure downstream pathways are addressed first (e.g. estrogen clearance).

A good lay article re: research into BPH and natural remedies: https://draxe.com/enlarged-prostate/ and http://www.berkeleywellness.com/supplements/herbal-supplements/article/can-herbs-shrink-enlarged-prostate* https://www.ncbi.nlm.nih.gov/pubmed/18358071 , https://www.ncbi.nlm.nih.gov/pubmed/25546379

Testosterone Truths42

Yes, andropause is “a thing”. Production reduces as we age! And it starts earlier from about age 30 and onward (1-2%/year on average reduction, not necessarily linear).

Men typically produce more estrogen as they age due to increased bodyfat (insulin) and increased aromatase (which converts testosterone to estradiol).

Common symptoms of Low Testosterone (or suboptimally low T/E ratio) include increased body fat and reduced muscle mass, low libido, fatigue, low motivation, and insulin resistance (vicious cycle). If estrogen too high: male breasts, thicker thighs/hips, softer skin. Natural aromatase inhibitors can be quite helpful in shifting this balance (e.g. chrysin, lignans), plus reducing insulin by addressing insulin resistance.

Alcohol impairs testosterone synthesis and speeds up its metabolism.*

Resistance training increases testosterone. L-carnitine supplement (e.g. acetyl- or fumarate forms) can ensure fatty acid oxidation is efficient (e.g. 1000mg 1-2x/day acetyl-).

You know by now: Xenoestrogens matter! Insulin and aromatase matter.

Again, it’s about balance! A combination of both low testosterone and low estradiol is associated with a 100% increase in deathfrom all causes in elderly men. **

* https://www.nejm.org/doi/full/10.1056/NEJM197610072951501 , https://pubs.niaaa.nih.gov/publications/arh25-4/282-287.htm** * https://www.ncbi.nlm.nih.gov/pubmed/19401373

Erectile dysfunction is often a combination of suboptimal

testosterone, estrogen dominance, high cortisol, and poor circulation, especially due to insulin resistance.

DHEA

Major androgen for women throughout life, but also for men later in life (as T from testes wanes).

Can be converted into estrogen (the major source of estrogen post-menopause). Increases libido in women. WS tip: Key awareness for your menopausal clients.

Produced in the adrenal gland and also stimulated by ACTH but regulated by other enzymes as well. WS tip: Any steroid supplementation suppresses ACTH.

Cortisol and DHEA mediate largely opposing biologic, neurologic, & immunologic functions. WS tip: High cortisol exerts more toxic effects long-term in the presence of suboptimal DHEA.

Increased cortisol often drives a countering, lower production of DHEA in order to allow cortisol to have maximal effect. This varies by person, by tissue, by situation. DHEA can protect tissues from sustained cortisol negative effects.

The ratio of enzymes to produce DHEA vs. cortisol falls progressively over time as we age.

Primary raw material for testosterone production in women throughout life. Too much may promote excessive hair growth, head hair loss, irritability, aggression, and/or PCOS.

WS tip: Use supplemental DHEA only when you like what’s happening downstream. Modulate balance 1st!

* DHEA-S is a sulfated metabolite of DHEA that is more stable in blood and has a long half-life (compared to DHEA). http://www.aquarianlaboratories.com.au/dhea-overview-causal-factors-symptoms-and-treatment/ . https://www.ncbi.nlm.nih.gov/pubmed/12007895, https://www.ncbi.nlm.nih.gov/pubmed/11972140 , https://people.clas.ufl.edu/dkertes/files/Kamin_Kertes_HB_2017.pdf

Estrogen for Men: Delicate Balance

Yes! Women need androgens for optimal functioning; men need estrogen and progesterone as well. As usual, it’s all about balance.

Low estradiol associated with higher risk of osteoporosis in men. Low E2 also independently associated with higher risk of fracture (but not testosterone). #

Both high and low estrogen are associated with higher rate of death in men with cardiovascular disease (4X higher in the lowest E2 group than the median one). Highest estradiol quintile in men (>70 y/o) had 2X the risk of stroke. * No surprise. This is true in postmenopausal women too! Highest quintile free estrogen

(endogenous or exogenous!) had 2X the risk of strike vs. the lowest and even higher correlation for women with high central adiposity (insulin as mediator!?) *

Testosterone (T) gel therapy increased total arterial plaque volume dramatically in group of men (>65 y/o) with high incidence of IR, T2D, and metabolic syndrome. The authors focused on possible role of T, but notably their E2 also went up -on average by 50%(to upper quartile of RR). Prior studies showed no change in coronary calcium score. **

Men in 60s with low total T (<300 ng/ml). In groups with lower (<20%) pre-existing CVD, T therapy associated with 50% reduced mortality. But in groups with much higher (<80%) pre-existing CVD, testosterone therapy increased mortality. Estrogen not measured in either study! ***

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# https://www.ncbi.nlm.nih.gov/pubmed/18518773 and https://www.ncbi.nlm.nih.gov/pubmed/19308628* https://jamanetwork.com/journals/jama/fullarticle/183891 , https://www.ncbi.nlm.nih.gov/pubmed/17310026 , and https://jamanetwork.com/journals/jamaneurology/fullarticle/799274** https://jamanetwork.com/journals/jama/fullarticle/2603929 and https://www.ncbi.nlm.nih.gov/pubmed/26262795*** https://academic.oup.com/jcem/article/97/6/2050/2536693 and https://jamanetwork.com/journals/jama/fullarticle/1764051

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A Typical “Real Life” Patient (2)

Very busy, over-committed, middle-aged man

Too busy to exercise. Typical corporate desk job. Stressed and going aggressively after a promotion.

Feels exhausted and unrested in the morning.

Typical cafeteria lunch each day. Feels he tends to choose “healthy” options e.g. sandwich on whole wheat bread, low-fat chips, and fat-free yogurt.

Self-medicating with a few beers on the couch every evening.

Low libido. Short, weaker erections most of the time.

Even higher triglycerides, LDL, & blood sugar. Latest visit to doc was a wake-up call. Blood pressure was shockingly high.

More belly fat. Having to use the last notch on his belt.

Urinary urgency during day and then seems to “go all night”. Rough sleep getting up so often on top of lying awake ruminating after the job opportunity.

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Many Signs and Contributors to Hormone Imbalance – None of which are Uncommon!

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Putting the Hormone Puzzle Pieces Together

Overwhelmed. Anxious. High cortisol.

High cortisol impairs melatonin synthesis overnight. Poor sleep.

Stress and high intake refined carbohydrates increases insulin and percentage bodyfat.

High insulin increases aromatase activity. Lower testosterone-to-estrogen ratio.

Ongoing, excessive alcohol intake impairs testosterone secretion.

Stress increases SHBG and further reduces available testosterone.

Combination of stress and higher blood sugar are increasing arterial inflammation which promotes higher LDL and hypertension.

Likely episodes of higher adrenaline as well. Unknown COMT SNPs are impairing both catecholamine and estrogen detoxification.

Insulin resistance impairs cellular uptake of magnesium which is also likely contributing to hypertension.

Low testosterone and endothelial damage in arteries combine for erectile dysfunction.

Increase blood sugar promotes storage of excess as increased triglycerides. Risk of full conversion to metabolic syndrome and cardiovascular disease increases.

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It’s the Hormone Soup Dance!

High cortisol Low melatonin Increased inflammationHigh insulinLow testosteroneHigh SHBGHigher body fatExcessive estrogen action Insufficient nutrients for detoxificationPro-inflammatory dietary fat intake.

Is it any wonder that he struggles with “low t” (that is being in a Low Testosterone state)?

Again, this is Not an atypical scenario. Your expertise in this area is NEEDED.

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False Expectations?

We are not designed to be in a chronic, low-gradeStressed, Toxic, Inflamed, Infected, Malnourished, & Unrested

state and yet still easilyThrive, Grow, Reproduce, be Thin, feel Well,

Eat Anything we want, enjoy perfect BMs, and have Great Sex.

This combination would be Not Natural.

Looking Toward Part 4

Webinar #4 Perimenopause & Menopause Overt Hormone Supplementation Key Medication Considerations Hormone Testing Considerations Resources for More Learning

We highly recommend experiencing this (Part 3) webinar again

before moving on to Part 4.

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This presentation is copyrighted by Purpose Inc. with all rights reserved, available for student reuse strictly subject to the terms outlined in the student program agreement.

Thank You for Joining Us!

Hormones DemystifiedPart 3