pcos, metabolism & lifestyle: putting it into practice dr jim ... dr jim parker...rat, ewe & primate...
TRANSCRIPT
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PCOS, Metabolism & Lifestyle:
Putting it into Practice
Dr Jim Parker
No conflicts of interest
practice point
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Learning Objectives
1. Define revised criteria for the diagnosis PCOS
2. Explain the emerging role of nutritional and
environmental factors in the pathogenesis PCOS
3. Summarise the principles of management of PCOS
using lifestyle-based approaches
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practice point
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https://www.trybooking.com/book/sessions?eid=424944&ses=1254243
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Polycystic Ovary Syndrome
• Affects 8-13% of women worldwide
• most common endocrine disorder and cause of infertility
• first degree relative → 25% risk (polygenic inheritance)
• Widespread health consequences
• Significant proportion gynaecological consultations
• Challenging Mx problems - lifestyle/nutritional
• Significant economic burden ($4.36 billion/yr US)
• Significant contribution to chronic diseases epidemic
Diagnosis of PCOS
• Rotterdam criteria (2 of 3 features)
• oligomenorrhoea
• biochem/clinical elevated androgen
• ↑Testosterone, ↑FAI, ↓SHBG
• ultrasound features of PCOS (>10 cysts 2-8mm)
practice point
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Health Consequences of PCOS
• Reproductive dysfunction
• menstrual disturbance, acne, hirsuitism, alopecia, infertility
• Weight disorders
• management of obesity and prevention of weight gain
• Metabolic disturbance
• insulin resistance (70%), Gestational Diabetes & Type 2 Diabetes (↑3-5 fold)
• ↑ lipids, metabolic syndrome, CV disease, endometrial cancer (x2-6)
• Psychological disability
• anxiety, depression, quality of life (infertility concern most common)
• Not just a cosmetic & fertility problem but major health problem
PCOS and Insulin Resistance(Marshall JC. All women with PCOS should be treated for insulin resistance. Fertil Steril. 2012 January ; 97(1): 18–22)
• IR & compensatory hyperinsulinaemia affects
• 65-70% PCOS overall
• 70-80% obese (BMI >30) PCOS
• 25-30% lean (BMI
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MJA InSight: Prof Robert Norman
# “the impetus to develop the guideline came from patients”
# “we consistently had complaints that doctors knew less about PCOS than patients did”
# “the metabolic aspects of PCOS have been emphasised in the guidelines”
# “the guideline sought to reassure patients with PCOS that they could have a normal fertility potential”
National Health and Medical Research Council Polycystic Ovary Syndrome Centre for Research Excellence
71 countries201 pages166 recommendations
practice point
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1. Lifestyle2. OCP3. Letrozole
Integrative Medicine Resources
• PCOS mindset
• control
• mindfulness
• nurturing
• Nutrition
• food intolerances
• personalised plan
• Exercise
• Stress reduction
• Circadian rhythms
practice point
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metabolic hormonal
maternal
paternalfamilial polygenic condition associated
with a varietyof symptoms
depending on genetic background and superimposed
lifestyle factors
Pathogenesis of PCOS
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Developmental Origins of Health and DiseaseNEM epigenetic effects start in-utero
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https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiagYb5sMzgAhULT30KHeX0DkgQjRx6BAgBEAU&url=https://www.sciencenewsforstudents.org/article/silencing-genes-understand-them&psig=AOvVaw2XmnLU40a7yRWhffMDn0my&ust=1550823088079633http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjCy5KlsszgAhUGVH0KHR_ZAZoQjRx6BAgBEAU&url=http://thyroidnosurgery.com/thyroid-cancer/environmental-chemicals-causing-thyroid-cancer-a-wake-up-call-to-action/&psig=AOvVaw37Om5brloRWRXSxzm21fvZ&ust=1550823525097126https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=2ahUKEwiu6ZDMt8zgAhVUfisKHRSLBtAQjRx6BAgBEAU&url=https://www.everydayhealth.com/pcos/symptoms-diagnosis/&psig=AOvVaw0iyRuizrKNJ0auNdQTPJpy&ust=1550825034051490
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Developmental Origins of PCOSFetal Androgen Excess
• Maternal
• PCOS , obesity, IR, GDM, DM
• Endocrine disrupting chemicals
• CAH & adrenal tumor
• Fetal
• ↑glucose → ↑insulin → ↑androgen
• congenital adrenal hyperplasia
• Placental
• ↓ aromatase
• Rat, ewe & primate studies
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Androgenic Endocrine Disruptors
• Triclocarban – enhanced testosterone action
• Glyphosate (Roundup) aromatase inhibitor, leaky gut
• BPA (bisphenol A) – effects E2 & androgen metabolism
• Tributyltin - boat paint → seafood. Direct toxicity to HPG axis
• Perfluorinated compounds (PFOA, PFOS)(teflon)
• Nicotine – ↑ serum testosterone in women with PCOS Marraudino M et al. Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food
Intake and Energy Metabolism. Frontiers in endocrinology 9 January 2019. doi: 10.3389/fendo.2018.00766
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Polycystic Ovarian Syndrome & the Thrifty Phenotype Hypothesis
A pregnant woman programs her fetus forthe metabolic world in which she lives, and
in which it is expected her child will live
The “messages” passed to the child may have come down from many generations
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Polycystic Ovary Syndrome(evolutionary paradox)
• Not a disease
• Syndrome = collection of symptoms and test results
• Systemic whole-body disorder affecting• metabolism, immune, CV, gut, skin, mind, fertility
• Ancient disorder• described by Hippocrates 400BC
• How could a condition that impedes fertility persist in 10% of the female population?
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PCOS in Hunter-Gatherers
• Ancient PCOS different to modern PCOS
• Mild inherited condition that bestowed advantages
• Slightly higher Testosterone levels• more muscle mass, denser bones, slightly stronger
• “Thrifty genes” & ↑IR more fat storage for famines
• Anovulation and mild subfertility• fewer and better spaced pregnancies
• maternal survival advantage in times of high MM
• Adaptation to hunter-gatherer nomadic life
Pathophysiology of PCOS in Modern Society
• Metabolic dysregulation• SAD diet, microbiome dysbiosis, systemic inflammation• insulin resistance and hyperandrogenism• metabolic-circadian desynchronisation• metabolic, endocrine and reproductive dysfunction
• Environmental disruption• endocrine disrupting chemicals
• Circadian dysregulation• extended light exposure• extended feeding window• shift-work• disturbed oestrogen function
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https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiTpMvayrzgAhUMTo8KHSPbCUUQjRx6BAgBEAU&url=https://www.lookandlearn.com/history-images/B001732/Cavemen-dinosaur-and-volcano-for-an-article-about-special-effects?t%3D4%26n%3D12450&psig=AOvVaw09n_xSRMujUvCe0Nz3H62L&ust=1550280406547695
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Pathogenesis of PCOSDOGMA (dysbiosis of gut microbiota) Theory
(Tremellen K, Pearce K. dysbiosis of Gut Microbiota. Med Hypotheses 2012)
Insulin Resistance
Hyperandrogenaemia
Chronic Inflammation
DIET
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Pathogenesis of Polycystic Ovary Syndrome(Parker J. Emerging concepts in the pathogenesis and treatment of PCOS.
2014; 10(2): 107-112. Current Women’s Health Reviews)
Genetic Predispositiongonadotrophin genesdiabetes genes
Environmental factorspoor quality dietenvironmental chemicals
In-utero epigenetic effects androgen excess
Childhood risk factorsintractable obesitymetabolic syndromepremature adrenarche
Adolescent onsetoligomenorrhoea, acne, hirsuitism
Adult sequelaeinfertility, menstrual disturbancediabetes, cardiovascular, cancer
Altered bowel flora↓ lactobacillus & bifidobacteria↑ gram negative, clostridium
Bacterial productsLPS, cytokines, metabolites
Immune system activation
(mucosal damage & ↑ permeability)
Chronic inflammation
Insulin resistance hyperandrogenism
practice point
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Management of PCOS
• Medical model fragmented
• menstrual symptoms or fertility problem – gynaecologist
• acne – dermatologist
• hirsuitism – endocrinologist
• anxiety/depression - psychologist/psychiatrist
• gut problems (IBS or reflux) – gastroenterologist
• Integrative practitioner
• integrates treatment of all systems
Optimise LIFESTYLE to Support Metabolic Health
• Wholefood nutrition
• Exercise
• Weight reduction
• Environmental expos
• Stress reduction
• Smoking & Alcohol
• Community
• Circadian rhythms
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COULD WE PREVENT PCOS IN GIRLS?Interventions in pregnancy, infants and girls
• Healthy nutrition intervention for all pregnant women
• Screening for IR in high risk patients (obese/PH GDM)
• Optimise blood sugar control in diabetics & GDM
• Vaginal birth to optimise microbiome
• Breastfeeding & minimise antibiotics
• Avoid Endocrine Disrupting Chemicals
PCOS and the DoHAD Cycle of Life
poor quality diet & environmental effects
activate thrifty phenotype
in-utero epigenetic
effects
obesity, diabetes, GDM, metabolic syndrome, PCOS
obesity, diabetes, GDMmetabolic syndrome, PCOS
(adult)
(offspring)
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1. Wholefoods Nutrition2. Dysbiosis3. Trace Elements4. Micronutients5. Supplements6. Insulin Resistance7. Acne8. Weight Loss
Clinical Management of PCOS
• Acute emergencies
• Acute symptom management
• Chronic symptom management
• Prevention
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Case Presentation
• 14 yo girl with 7 yr history of recurrent LAP
• Prepubertal US showed enlarged ovaries & normal hormone
• Pubertal development 11 yrs, menarche 13yrs, normal wt
• Mother had PCOS and GDM
• Presented with acute LAP not relieved by narcotics
• ↑HR, ↑temp, normal BP, RIF tender, guarding & rebound
• ↑WBC, US enlarged ovaries and ? right ovarian torsion
shown with patients permission26
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https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiYj6X77dbPAhXogVQKHWTgAT0QjRwIBw&url=https://www.studyblue.com/notes/note/n/lecture-22-female-reproductive-system/deck/8882865&psig=AFQjCNFLTk8P_IwWNy_ILCYWJ-EOI4ZgLg&ust=1476416429973437
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Postoperative History
• 14yo 18mth oligomenorhoea (42-56d)
• Diet history shows SAD diet
• Normal weight (BMI =23) and regular exercise
• No acne or hirsuitism
• No PH of medical problems
• ? investigations
Assessment and Evaluation of PCOSEstablish your baseline
• Menstrual cycle
• Track with calendar or app
• Anthropomorphic
• Weight and BMI, BP
• waste & hip circumference, waist to hip ratio
• Medical tests
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Investigation of PCOS
• Elevated LH:FSH ratio
• Normal prolactin, TSH, T3, T4, DHEAS, tumour marker
• Elevated FAI & testosterone and low normal SHBG
• Normal FBC, LFT, UEC, homocysteine, Vit D, Mg, Zn
• Elevated fasting insulin and normal BSL and HbA1C
• Elevated hsCPR and cholesterol
practice point
Diagnosis & Treatment
• Oligomenorrhoea, ↑T, ↑LH:FSH ratio = PCOS
• ↑hsCRP and diet history = ? dysbiosis
• ? insulin resistance
• insulin 11 (
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Pathogenesis of Polycystic Ovary Syndrome(Parker J. Emerging concepts in the pathogenesis and treatment of PCOS.
2014; 10(2): 107-112. Current Women’s Health Reviews)
Genetic Predispositiongonadotrophin genesdiabetes genes
Environmental factorspoor quality dietenvironmental chemicals
In-utero epigenetic effects androgen excess
Childhood risk factorsintractable obesitymetabolic syndromepremature adrenarche
Adolescent onsetoligomenorrhoea, acne, hirsuitism
Adult sequelaeinfertility, menstrual disturbancediabetes, cardiovascular, cancer
Altered bowel flora↓ lactobacillus & bifidobacteria↑ gram negative, clostridium
Bacterial productsLPS, cytokines, metabolites
Immune system activation
(mucosal damage & ↑ permeability)
Chronic inflammation
Insulin resistance hyperandrogenism
practice point
Nutritional Management of PCOS
• Evidenced Based
• Clinical Guidelines
• 3,000 health professionals &
consumers worldwide
• 201 pages
• 608 references
To achieve weight lossin those with excess weight,
an energy deficit of30% or 500 - 750 kcal/dayas per general population
recommendation
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https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS-Evidence-Based-Guideline.pdf
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What is the Optimal Diet to Prevent PCOS?Wholefoods Diet
practice point
Prevention and Treatment of PCOSWholefoods Diet
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http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjn46Ck4LnLAhUnGaYKHTmtDbEQjRwIBw&url=http://www.thefitdecision.com/&bvm=bv.116573086,d.dGY&psig=AFQjCNE2kJXNaUI-NCGDBTd60SUNBQ3fDA&ust=1457824058957165https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiNxvCwwZvhAhUZeysKHVW5ATwQjRx6BAgBEAU&url=https://www.123rf.com/photo_68877666_steamed-fish-in-lemon-sauce-on-white-plate.html&psig=AOvVaw13wgdF9-rIAIXL3YanDRK9&ust=1553542071787544http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjawf7lwZvhAhVVSX0KHTb9AHgQjRx6BAgBEAU&url=/url?sa%3Di%26rct%3Dj%26q%3D%26esrc%3Ds%26source%3Dimages%26cd%3D%26ved%3D%26url%3Dhttps://www.foodandwine.com/recipes/green-lentil-curry%26psig%3DAOvVaw3Hvusj-JSfu73fqNaAMabd%26ust%3D1553542176679460&psig=AOvVaw3Hvusj-JSfu73fqNaAMabd&ust=1553542176679460https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwje-a-rwr7bAhVKO7wKHUkVCt4QjRx6BAgBEAU&url=https://en.wikipedia.org/wiki/Olive_oil&psig=AOvVaw3k-sFZmfKxAM2OkcG71_96&ust=1528356592915477https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiu5-nbwb7bAhXFWbwKHdQvAEsQjRx6BAgBEAU&url=https://www.tesco.com/groceries/en-GB/products/254918067&psig=AOvVaw0-rjoNxluOCvEfUg9xMzEU&ust=1528356476561329https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwicnIvywb7bAhUEW7wKHfrADCgQjRx6BAgBEAU&url=https://www.shutterstock.com/search/margarine&psig=AOvVaw09izat7mQVJc32PCSns8IM&ust=1528356529124743https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwje-a-rwr7bAhVKO7wKHUkVCt4QjRx6BAgBEAU&url=https://en.wikipedia.org/wiki/Olive_oil&psig=AOvVaw3k-sFZmfKxAM2OkcG71_96&ust=1528356592915477https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiz14rCwr7bAhVKy7wKHYFACekQjRx6BAgBEAU&url=https://www.shutterstock.com/search/coconut%2Boil&psig=AOvVaw1Xyc3EyRByo37Pnj4O4R1y&ust=1528356696996324https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwii-sLnwr7bAhXKwbwKHYXbD_sQjRx6BAgBEAU&url=https://www.istockphoto.com/photos/glass-of-water&psig=AOvVaw14KJ-lvGG5zGhFkAWL84dU&ust=1528356764444787https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiR-Z2Nw77bAhVFNrwKHb0CDGEQjRx6BAgBEAU&url=https://www.echo.net.au/2018/02/drinking-soft-drink-linked-cancer-risk/&psig=AOvVaw26emwHOFmu2ULynEJCY163&ust=1528356831636428https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiVzf3GxL7bAhUFU7wKHSXdAG4QjRx6BAgBEAU&url=https://www.dreamstime.com/photos-images/bread.html&psig=AOvVaw3HKzcF_KYS-hzgOs0n0bh8&ust=1528357243980124http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwi7zdHRv5vhAhUBSX0KHf78D4gQjRx6BAgBEAU&url=/url?sa%3Di%26rct%3Dj%26q%3D%26esrc%3Ds%26source%3Dimages%26cd%3D%26ved%3D%26url%3Dhttps://www.123rf.com/photo_8297195_orange-juice-and-slices-of-orange-isolated-on-white.html%26psig%3DAOvVaw11Aa4UWYDl1Gf2Pui44EhB%26ust%3D1553541605081400&psig=AOvVaw11Aa4UWYDl1Gf2Pui44EhB&ust=1553541605081400
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Prebiotics: PCRMpractice point
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practice point
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shown with permission from patient and dietitian
practice point
HEALTHCOACHES
DIETITIAN
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Minimise Environmental Chemical Exposure
1. Eat organic foods (glyphosate and pesticides)2. Natural personal careproducts for lotion, shampoo, conditioner, sunscreen (carcinogens, reproductive toxicants, substances that cause allergies/immune problems, EDC=triclocarban, phthalate)3. Avoid BPA in food packaging and receipts4. Non-toxic cleaning products5. Create a healthy home
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https://secure.ewg.org/p/salsa/web/common/public/signup?signup_page_KEY=5977&_ga=2.243402949.1749597768.1550632581-524426321.1550632581http://www.corvallisadvocate.com/wp-content/uploads/2013/01/Spraying-Pesticides.jpg
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2 years later
• Presentation• acute onset of widespread acne (back & chest)
• oligomenorrhoea
• not adherent to diet
• still exercising and normal weight
• Management• GP referral dermatologist
• minocycline and skin wash
• Dietary advice
PCOS Related Acne
Most common skin condition on earth
Affects 85% of teenagers in western societies
Affects 50% of adults into their 30’s
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Incidence of Acne inDeveloped vs Developing Nations
(Lynn D et al. The epidemiology of acne in late adolescence. Adolescent health, medicine and therapeutics 2016;7: 13-25)
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Kitivan Adolescents & AcneAcne Vulgaris: A Disease of Western Civilisation
(Cordain L. Arch Dematol 2002; 138: 1584-1590)
• NE New Guinea - No acne
• 1990 phones,cars,electricity
• 1200/300 adolescent 15-26
• Rich in fresh, natural foods such as tubers, fruit, coconut & fish (wholefoods)
• Low GI→↓insulin→↓T
• Hi fish=hi omega 3 (↓IGF1)
• No dairy →↓mTOR Inuit Eskimos 1971
Ache hunter-gathers Paraguay 1997-2001
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https://www.google.com.au/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwj10tXIpafbAhWGUrwKHXJaAcEQjRx6BAgBEAU&url=https://sporteluxe.com/us/kitava-skin-diet/&psig=AOvVaw23wGj1l74_bZk35cx7xKN-&ust=1527558594285717https://www.google.com.au/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwip9IGfpqfbAhVPhrwKHTGqACYQjRx6BAgBEAU&url=http://coachmikeblogs.com/you-are-not-a-kitavan-islander/&psig=AOvVaw23wGj1l74_bZk35cx7xKN-&ust=1527558594285717
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DHT
Acne Vulgaris: A Disease of Western Civilisation(Cordain L. Arch Dematol 2002; 138: 1584-1590)
DHT
Nutritional Management of AcneWhole-foods diet (Kitivan)
• Low GI diet
• ↓ IR → ↓ IGF-1 → ↓ hyperkeratinisation of sebaceous gland & unblocks follicle
• ↓ IR reduces androgens by 20% via ? ↓ ovarian androgen production
• High fibre diet
• testosterone secreted in bile and removed rather than enterohepatic circulation
• Minimise or avoid dairy
• inflammatory and leads to higher androgens
• Eat more omega-3 fa which are anti-inflammatory
• wild-caught fish, oysters, nuts and seeds
• Avoid Endocrine Disrupting Chemicals
• Vitamin D, Zinc, Probiotics, Berberine
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Diagnosis & Treatment of PCOS
• Dysbiosis and “proof of concept studies”
• Hyperandrogenism
• Obesity
• Menstrual symptoms
• Infertility
• Insulin resistance
• Supplementation
Fasting Insulin
1. Physiological IR
2. Fasting hyperglycaemia
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Testing for Insulin ResistanceReference ranges for HOMA-IR in normal weight & obese young caucasians. Shashaj B et al. Acta diabet 2015
euglycaemic hyperinsulinaemic clamp, IV GTT, OGTT, QUICKI, FGIROGTT derived adipocytokine surrogate markers
(physiological insulin resistance, fasting hyperglycaemia)
HOMA-IR = insulin(11) x glucose(5.2) = 2.5 22.5
practice point
Supplements and PCOSPundir J et al. Overview of systematic reviews of non-pharmacological interventions in women with pcos. Hum Reprod Update.. March-April 2019. 25;2:243–256.
• Trace elements: Mg, Cu, Fe, selenium, Zn
• N-acetyl cysteine: medication vs supplement
• Inositol: insulin signalling pathway, neurotransmitter pathways
• Antioxidants: vitamins A, C, E, selenium, resveretrol
• Vitamins D and B group vitamins
• Probiotics
• Fish oil: omega-3 fatty acids
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Conclusions: Polycystic Ovary Syndrome
• Common inherited metabolic disorder
• Significant contribution to chronic disease epidemic
• Diagnosis by revised Rotterdam criteria
• Pathogenesis: nutritional and environment factors
• Mx by lifestyle interventions +/- supplementation
• Ideal opportunity for prevention of chronic disease
Wholefoods DietEndocrine Disrupting Chemicals
foodrelaxation
sleep movement
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