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Dr.S.Sethupathy,M.D.,Ph.D.,
Professor and Head,
Department of Biochemistry,
Rajah Muthiah Medical College,
Annamalai University.
 It is an endocrine, reproductive and
metabolic disorder.
 4-12 % are affected, common cause for
infertility
Characterized by
 Irregular menstrual cycles
 Hyperandrogenism/ Hirsutism
 Obesity
 Polycystic ovaries
 Insulin resistance
 Infertility
 Type2 diabetes (15-20%)
 Hypercholesterolemia
 Hypertension
 CVD
 Thyroid disease
 Endometrial cancer
 Follicular phase
 One ovarian follicle matures by FSH
 Maturing follicle releases estrogen which causes
release of LH from pituitary( positive feed back)
 Ovulation ( 14th day) – LH peak initiate ovulation-
egg released from dominant follicle
 Luteal phase
 Ruptured follicle becomes corpus luteum and
secretes estrogen and progesterone
 High levels of them inhibit FSH and LH release-
negative feed back
 LH induces theca and granulosa cells to
secrete progesterone
 Theca externa releases proteolytic enzymes
which cause thinning of outer membrane.
 Rapid vascularization and prostaglandins
cause plasma leak into follicle and its
swelling
 Both factors cause rupture of follicle and
release of ovum
 FSH stimulate granulosa cells - estradiol
by aromatase during the follicular
phase .
 After ovulation- the granulosa cells
become granulosa lutein cells
 Produce progesterone -to maintain a
potential pregnancy –
 It causes a thick cervical mucus to
inhibit sperm entry into the uterus.

 Thecal cells from the stromal layer
surrounding the granulosa cells and oocyte.
 Thecal cells are not capable of producing
estrogen but do produce androgens in
response to LH
 They are converted into estrogen by FSH
induced aromatase in the neighboring
granulosa cells of selected growing follicles.
 Oligo-ovulation – cycles longer than 36 days
and less than 8 times a year
 Menstrual dysfunction, anovulation
 Signs of hyperandrogenism.
 Hirsutism
 Infertility
 Obesity
 Diabetes
 Obstructive sleep apnea
 Metabolic syndrome
 Guidelines from the NHLBI and AHA, metabolic
syndrome is diagnosed when a patient has at
least 3 of the following 5 conditions:
1) Fasting glucose ≥100 mg/dL (or on drugs)
2) Blood pressure ≥130/85 mm Hg (or on drugs)
3) Triglycerides ≥150 mg/dL (or on drugs)
4) HDL-C <40 mg/dL in men or <50 mg/dL in
women
5) Waist circumference ≥102 cm (40 in) in men or
≥88 cm (35 in) in women;
If Asian American, ≥90 cm (35 in) in men or
80 cm (32 in) in women
 Virilizing signs
 Acanthosis nigricans
 Hypertension
 Enlarged ovaries- evaluate for an ovarian
mass
 Exclude - adrenal or ovarian tumors, thyroid
dysfunction, congenital adrenal hyperplasia,
hyperprolactinemia, acromegaly, and Cushing
syndrome.
 Severe acne or hirsutism or both
 Frontotemporal balding
 Deepening of the voice
 A decrease in breast size
 Clitorial hypertrophy
 Increased muscle mass
 Amenorrhoea / Oligomenorrhoea
 Absent (0): Not detectable on close inspection
 Present (1): Clearly present on close visual
inspection, not visible to the casual observer,
extent not measurable
 Mild (2): Limited to the base of the skull, usually
does not extend to the lateral margins of the
neck
 Moderate (3): Extends to the lateral margins of
the neck but not visible anteriorly
 Severe (4): Visible anteriorly
 Severe (5): Circumferential
 Girls whose oligomenorrhea persists 2-3
years past menarche – look for ovarian or
adrenal dysfunction.
 First-line monotherapy- metformin
 or combination therapy with oral
contraceptive agents and antiandrogen
agents.
 Plasma glucose –F and PP
 Lipid profile
 Insulin – F - > 12 mIU significant
 Insulin – PP - > 25 mIU significant
 TSH – hypothyroidism
 FSH/LH ratio- normal- FSH > 3-4 LH Reversal
of ratio significant
 Total testosterone > 3.6 ng/ml significant
 USG- volume of one ovary more than 10 cc
with “ string of pearl appearance”
 Androstenedione increased in ovarian
pathology
 Very high Prolactin due to pituitary tumour
 17 hydroxy progesterone increased in late
onset CAH
 Dehydroepiandrosterone –SO4 (DHEAS)
elevated in adrenal pathology
 Dihydro testosterone – indicates peripheral
conversion of testosterone
 BMI negatively correlates with
estrogen level
 Glyphosate – a broad spectrum
herbicide
 Inhibitor of cyp450 enzymes,
aromatase.
 Affects gut bacteria and increase
the risk for celiac disease,
Autism, Parkinson’s disease ,
cancer, PCOS
 Complex carbohydrates and Whole grains-
fiber, B comp vitamins, trace minerals
 Fruits- fibers, antioxidants,
 Legumes- proteins, macronutrients, pinitol
 Pinitol improves insulin resistance.
 Whole foods - whole grains , fruits,
vegetables, meats, fish, seaweeds and
spices.
 75% of the diet should be whole foods.
 MUFA-olive and canola oil, avocados, cashew,
peanuts and sesame seeds.
 Omega3 fatty acis – Alpha linoleic acid (ALA)-
flax seeds, canola, walnuts, and chia seeds.
 Eicosa petanoic acid(EPA) and docosa
hexaenioc acid (DHA) reduce risk of heart
disease
 Found in salmon, trout, tuna, sardines,
mackerel and fish oil capsules.
 Omega 6 – sunflower oil, sesame oil ,olive oil
 Refined carbohydrates – cause spikes in BG
 Processed foods- poor quality fats, many
artificial flavours which are not good for
health
 Trans fats- margarine (Dalda) -raise LDL and
lower HDL, promote inflammation and
increase the risk for CVD
 Non organically grown foods and meat may
contain glyphosate
 Vitamin D
 Chromium
 N-acetyl cysteine
 Inositol
 Fish oil capsules
 Magnesium
 B comp vitamins
 Antioxidants
 Exercise
 Insulin sensitizing agents-
metformin
 Fertility treatment- clomiphene
citrate , gonadotropins
 Oral contraceptives
 Ovarian drilling
 Acne treatment
 Herbal treatment- eg: cinnamon
bark, liquorice etc
 AMH is secreted by the granulosa
cells of ovarian follicles.
 AMH -protein hormone related
to inhibin and activin
 It is increased in PCOS
 Its level indicates ovarian reserve.
 Bisphenol A (BPA) - starting material for the
synthesis of plastics, polycarbonates and epoxy
resins, polysulfones
 BPA-based plastic - clear and tough- made into
consumer goods, such as plastic water bottles,
sports equipment, CDs, and DVDs.
 Epoxy resins containing BPA -used to line water
pipes, as coatings on the inside of many food
and beverage cans
 For making thermal paper- used in sales
receipts.
 4 million tonnes of BPA chemical-used for
manufacturing polycarbonate plastic
 One of the highest volume of chemicals
produced worldwide.
 Estrogen-mimicking, hormone-like
properties
 U.S. Food and Drug Administration (FDA)
has ended its authorization of the use of
BPA in baby bottles and infant formula
packaging
 Proposed mechanisms for BPA exposure to
increase the risk of obesity
 BPA-induced thyroid dysfunction
 Activation of the PPAR-gamma receptor, and
disruption of neural circuits that regulate feeding
behavior.
 BPA works by imitating the natural hormone 17B-
estradiol.
 BPA alter glucose and lipid metabolism in animal
studies.
 BPA exposure modifies insulin sensitivity and
insulin release without affecting weight
 BPA is a thyroid-disrupting
chemical
 Affect pregnant women, neonates
and small children.
 A 2009 review summarized BPA
adverse effects on thyroid
hormone action.
 Exposure to BPA in the uterus and
during childhood
 Cause poor behavioral outcomes
 Higher levels of anxiety, depression,
hyperactivity, and aggression in
children.
 Effects on fetal and infant brain
development and behavior.
 Lower sperm quality.
 miscarriage is associated with
BPA levels
 Decreased male sexual
function
 Microbial degradation
 The fungus Cunninghamella elegans degrade
synthetic phenolic compounds like bisphenol
A.
 Plant degradation
 Portulaca oleracea efficiently removes
bisphenol A
 Photodegradation
 Main method of natural
weathering in the environment,
via the Photo Fries rearrangement.
 It occurs at wavelengths less than
300 nm.
 Combustion
 Oxidation of BPA by Ozone
 Those who'd dined out the day before
- higher urine levels of phthalates,
versus people who'd had all meals at
home.
 Old-fashioned home-cooked meals
reduce health risks.
 Phthalates are added to plastics to
make them more flexible and difficult
to break.
 Table mushroom has anti-aromatase
properties
 Chinese women who consumed greater than
10 grams of fresh mushrooms or greater than
4 grams of dried mushrooms per day had an
approximately 50% lower incidence of breast
cancer.
 Chinese women who consumed mushrooms
and green tea had a 90% lower incidence of
breast cancer.
Thank you

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Pcos overview

  • 1. Dr.S.Sethupathy,M.D.,Ph.D., Professor and Head, Department of Biochemistry, Rajah Muthiah Medical College, Annamalai University.
  • 2.  It is an endocrine, reproductive and metabolic disorder.  4-12 % are affected, common cause for infertility Characterized by  Irregular menstrual cycles  Hyperandrogenism/ Hirsutism  Obesity  Polycystic ovaries  Insulin resistance
  • 3.  Infertility  Type2 diabetes (15-20%)  Hypercholesterolemia  Hypertension  CVD  Thyroid disease  Endometrial cancer
  • 4.
  • 5.  Follicular phase  One ovarian follicle matures by FSH  Maturing follicle releases estrogen which causes release of LH from pituitary( positive feed back)  Ovulation ( 14th day) – LH peak initiate ovulation- egg released from dominant follicle  Luteal phase  Ruptured follicle becomes corpus luteum and secretes estrogen and progesterone  High levels of them inhibit FSH and LH release- negative feed back
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.  LH induces theca and granulosa cells to secrete progesterone  Theca externa releases proteolytic enzymes which cause thinning of outer membrane.  Rapid vascularization and prostaglandins cause plasma leak into follicle and its swelling  Both factors cause rupture of follicle and release of ovum
  • 11.  FSH stimulate granulosa cells - estradiol by aromatase during the follicular phase .  After ovulation- the granulosa cells become granulosa lutein cells  Produce progesterone -to maintain a potential pregnancy –  It causes a thick cervical mucus to inhibit sperm entry into the uterus. 
  • 12.  Thecal cells from the stromal layer surrounding the granulosa cells and oocyte.  Thecal cells are not capable of producing estrogen but do produce androgens in response to LH  They are converted into estrogen by FSH induced aromatase in the neighboring granulosa cells of selected growing follicles.
  • 13.
  • 14.
  • 15.  Oligo-ovulation – cycles longer than 36 days and less than 8 times a year  Menstrual dysfunction, anovulation  Signs of hyperandrogenism.  Hirsutism  Infertility  Obesity  Diabetes  Obstructive sleep apnea  Metabolic syndrome
  • 16.  Guidelines from the NHLBI and AHA, metabolic syndrome is diagnosed when a patient has at least 3 of the following 5 conditions: 1) Fasting glucose ≥100 mg/dL (or on drugs) 2) Blood pressure ≥130/85 mm Hg (or on drugs) 3) Triglycerides ≥150 mg/dL (or on drugs) 4) HDL-C <40 mg/dL in men or <50 mg/dL in women 5) Waist circumference ≥102 cm (40 in) in men or ≥88 cm (35 in) in women; If Asian American, ≥90 cm (35 in) in men or 80 cm (32 in) in women
  • 17.
  • 18.  Virilizing signs  Acanthosis nigricans  Hypertension  Enlarged ovaries- evaluate for an ovarian mass  Exclude - adrenal or ovarian tumors, thyroid dysfunction, congenital adrenal hyperplasia, hyperprolactinemia, acromegaly, and Cushing syndrome.
  • 19.  Severe acne or hirsutism or both  Frontotemporal balding  Deepening of the voice  A decrease in breast size  Clitorial hypertrophy  Increased muscle mass  Amenorrhoea / Oligomenorrhoea
  • 20.
  • 21.
  • 22.
  • 23.
  • 24.  Absent (0): Not detectable on close inspection  Present (1): Clearly present on close visual inspection, not visible to the casual observer, extent not measurable  Mild (2): Limited to the base of the skull, usually does not extend to the lateral margins of the neck  Moderate (3): Extends to the lateral margins of the neck but not visible anteriorly  Severe (4): Visible anteriorly  Severe (5): Circumferential
  • 25.
  • 26.
  • 27.  Girls whose oligomenorrhea persists 2-3 years past menarche – look for ovarian or adrenal dysfunction.  First-line monotherapy- metformin  or combination therapy with oral contraceptive agents and antiandrogen agents.
  • 28.
  • 29.
  • 30.  Plasma glucose –F and PP  Lipid profile  Insulin – F - > 12 mIU significant  Insulin – PP - > 25 mIU significant  TSH – hypothyroidism  FSH/LH ratio- normal- FSH > 3-4 LH Reversal of ratio significant  Total testosterone > 3.6 ng/ml significant  USG- volume of one ovary more than 10 cc with “ string of pearl appearance”
  • 31.  Androstenedione increased in ovarian pathology  Very high Prolactin due to pituitary tumour  17 hydroxy progesterone increased in late onset CAH  Dehydroepiandrosterone –SO4 (DHEAS) elevated in adrenal pathology  Dihydro testosterone – indicates peripheral conversion of testosterone
  • 32.
  • 33.
  • 34.  BMI negatively correlates with estrogen level  Glyphosate – a broad spectrum herbicide  Inhibitor of cyp450 enzymes, aromatase.  Affects gut bacteria and increase the risk for celiac disease, Autism, Parkinson’s disease , cancer, PCOS
  • 35.  Complex carbohydrates and Whole grains- fiber, B comp vitamins, trace minerals  Fruits- fibers, antioxidants,  Legumes- proteins, macronutrients, pinitol  Pinitol improves insulin resistance.  Whole foods - whole grains , fruits, vegetables, meats, fish, seaweeds and spices.  75% of the diet should be whole foods.
  • 36.
  • 37.  MUFA-olive and canola oil, avocados, cashew, peanuts and sesame seeds.  Omega3 fatty acis – Alpha linoleic acid (ALA)- flax seeds, canola, walnuts, and chia seeds.  Eicosa petanoic acid(EPA) and docosa hexaenioc acid (DHA) reduce risk of heart disease  Found in salmon, trout, tuna, sardines, mackerel and fish oil capsules.  Omega 6 – sunflower oil, sesame oil ,olive oil
  • 38.  Refined carbohydrates – cause spikes in BG  Processed foods- poor quality fats, many artificial flavours which are not good for health  Trans fats- margarine (Dalda) -raise LDL and lower HDL, promote inflammation and increase the risk for CVD  Non organically grown foods and meat may contain glyphosate
  • 39.  Vitamin D  Chromium  N-acetyl cysteine  Inositol  Fish oil capsules  Magnesium  B comp vitamins  Antioxidants
  • 40.  Exercise  Insulin sensitizing agents- metformin  Fertility treatment- clomiphene citrate , gonadotropins  Oral contraceptives  Ovarian drilling  Acne treatment  Herbal treatment- eg: cinnamon bark, liquorice etc
  • 41.  AMH is secreted by the granulosa cells of ovarian follicles.  AMH -protein hormone related to inhibin and activin  It is increased in PCOS  Its level indicates ovarian reserve.
  • 42.  Bisphenol A (BPA) - starting material for the synthesis of plastics, polycarbonates and epoxy resins, polysulfones  BPA-based plastic - clear and tough- made into consumer goods, such as plastic water bottles, sports equipment, CDs, and DVDs.  Epoxy resins containing BPA -used to line water pipes, as coatings on the inside of many food and beverage cans  For making thermal paper- used in sales receipts.
  • 43.  4 million tonnes of BPA chemical-used for manufacturing polycarbonate plastic  One of the highest volume of chemicals produced worldwide.  Estrogen-mimicking, hormone-like properties  U.S. Food and Drug Administration (FDA) has ended its authorization of the use of BPA in baby bottles and infant formula packaging
  • 44.  Proposed mechanisms for BPA exposure to increase the risk of obesity  BPA-induced thyroid dysfunction  Activation of the PPAR-gamma receptor, and disruption of neural circuits that regulate feeding behavior.  BPA works by imitating the natural hormone 17B- estradiol.  BPA alter glucose and lipid metabolism in animal studies.  BPA exposure modifies insulin sensitivity and insulin release without affecting weight
  • 45.  BPA is a thyroid-disrupting chemical  Affect pregnant women, neonates and small children.  A 2009 review summarized BPA adverse effects on thyroid hormone action.
  • 46.  Exposure to BPA in the uterus and during childhood  Cause poor behavioral outcomes  Higher levels of anxiety, depression, hyperactivity, and aggression in children.  Effects on fetal and infant brain development and behavior.
  • 47.  Lower sperm quality.  miscarriage is associated with BPA levels  Decreased male sexual function
  • 48.
  • 49.  Microbial degradation  The fungus Cunninghamella elegans degrade synthetic phenolic compounds like bisphenol A.  Plant degradation  Portulaca oleracea efficiently removes bisphenol A
  • 50.  Photodegradation  Main method of natural weathering in the environment, via the Photo Fries rearrangement.  It occurs at wavelengths less than 300 nm.  Combustion  Oxidation of BPA by Ozone
  • 51.  Those who'd dined out the day before - higher urine levels of phthalates, versus people who'd had all meals at home.  Old-fashioned home-cooked meals reduce health risks.  Phthalates are added to plastics to make them more flexible and difficult to break.
  • 52.
  • 53.  Table mushroom has anti-aromatase properties  Chinese women who consumed greater than 10 grams of fresh mushrooms or greater than 4 grams of dried mushrooms per day had an approximately 50% lower incidence of breast cancer.  Chinese women who consumed mushrooms and green tea had a 90% lower incidence of breast cancer.