In The Name Of God

1
In The Name Of God
2
PCO AND METABOLIC SYNDROM
3
Polycystic ovarian syndrome (PCOS) is an
extremely common disorder affecting 4 to 12
of women of reproductive age. Despite being
heterogeneous in nature, the hallmarks of the
disease are hyperandrogenism and chronic
anovulation
4

• What's name?
• . Is it PCO or polycystic ovary disease (PCOD)
  or polycystic ovary syndrome (PCOS)? Since the
  name includes the word "polycystic" does that
  mean that all women with this problem have cysts
  in their ovaries?
• Not all women with polycystic ovary syndrome
  (PCOS) will present the same way or have the same
  symptoms or laboratory findings. Confused?

5
The poly cystic ovary

• The characteristic polycystic ovary emerges when
  a state of anovulation persists for any length of
  time.
• Because there are many causes of anovulation
  there are many causes of polycystic ovaries.

6
Ovarian hystologic characteristics

• The surface area is doubled
• average volume increases 2.8 times.
• The number of growing and atretic follicles
  doubled.
• Each ovary may contain 20- 100 cystic
  follicles(2-10mm)
• The thickness of tunica is increased by 50.
• A 5-fold increase in stroma are noted.

7
(No Transcript)
8
Ultrasonography Finding

• Enlarged ovaries and necklace like pattern
• Large number (gt10) of tiny follicles (cysts)
  just under the surface of the ovaries
• The center of the ovaries is echogenic (highly
  reflective on ultrasound) and with very few
  follicles seen.
• Women with ultrasound findings are said to have
  polycystic appearing ovaries (PAO).

9
Ultrasonography as a diagnostic tool for PCOs is
unnecessary.

• Frome 8 - 25 of normal women will demonstrate
  ultrasonographic picture.
• This woman are endocrinology normal and
  polyscystic ovaries observed with ulteasonography
  are associated with impaired fertility only when
  accompanied by symptoms of menstural
  irregularities and hyperandrogenism.

10
The cause of PCOS is most likely multiple
factors, and genetic abnormalities may be involved

• PCOS as a heterogeneous disorder of unknown cause
  with various clinical features that can be
  divided into 3 categories clinical, endocrine,
  and metabolic.

11

• What signs and symptoms can be found in women
  with polycystic ovary syndrome (PCOS)?
  Ovulation problemsAnovulation
• Oligo-ovulation
• Infrequent or irregular ovulation
• Irregular menstrual cycles (results from not
  ovulating regularly)Amenorrhea
• Oligomenorrhea 20-50
• Infrequent periods
• Hypermenorrhea
• Metorrhagia 30
• Menometorrhagia

12
Elevated androgen levels can result in the
development of some signs and symptoms in women

• Hirsutism
• Unwanted hair growth. Usually on the lip- cheeks-
  chin neck-in between the breasts(70).
• Acne
• Alopecia

13
Endocrin abnormality

• Steady state of gonadotropins and sex stroids
• The higher mean concentrations of LH but low or
  low-normal levels of FSH.( LH/FSH )
• The average daily productin of Estrogen and
  Androgens is increased and dependent on LH
  stimulation
• 50 reduction in circulating levels of SHBG

14

• The higher concentration of Testestron
• Andrestendion
• DHA- DHEAS
• 17OHP
• EStron.

15

• The circulating estron levels are due to
  peripheral conversion of the increased amounts of
  androstendion to estron.

16
Etiology of increasing LH/FSH

• Increased frequency of GNRH pulsatile secretion.
• Increase in LH pulse frequency and pituitary
  response to GNRH are characteristic of the
  anovulatory state and are independent of obesity.

17

• Because the FSH levels are not totally depressed
  ,new follicular growth is continuosly stimulated
  but not to the point of full maturation and
  ovulation.
• FSH new follicular
• growth
  
• and atresy

18

• Theca cell
• LH
• Granolosa cell
• FSH

Cholestronl testestron

Andrestandion

Estron Estradiol
19
(No Transcript)
20
(No Transcript)
21
Hyperandrogenism effect in ovary

• Androgens convertion to 5a-reduced metabolites
  that inhibit aromatase avtivity
• Preventing normal cycle and ovulation
• Preventing follicular development and indusing
  premature atresia of follicul

22
Hyperandrogenism effect in ovary

• Atresia
• degenerating granulosa
• leaving the theca cells to the stromal
• Andrgens

23

• Increaseed free estradiol and estron
• FSH LH/FSH

24
Genetic concideration

• X- linked dominant transmission
• Autosomal- dominant and Premature bladness in
  males
• The stimulatory effect of insulin on ovarian
  androgen production is influenced by gegnetic
  predisposition

25
Insulin Resistance and Hyperandrogenism

• The association between increased insulin
  resistance and PCO is now well recognized.

26
Questions

• 1- Which coms first , the hyperinsulinemia or the
  hyperandrogenism?
• 2- How does hyperinsulinemia produce
  hyperandrogenism?
• 3- Are all women with PCOS have hyperinsulinemia?

27
1_ Hyper insulinemia is the primery factor

• GNRH agonist and correction hyper androgenism
• Administeration of insulin and glucose
• Weight loss
• Invitro , insulin stimulates theca cell androgen
  production

28
2_ How does hyperinsulinemia produce
hyperandrogenism?

• Insulin binds to IGF-1 reseptors
• increase androgen product
• in theca cells

29
(No Transcript)
30
(No Transcript)
31
Are all women with PCOS have hyperinsulinemia?

• Not every women with PCOS has hyperinsulinemia
  not even every overweigt.
• Hyperinsulinemia can be an underlying disorder.

32
4 - why not all women who are insulin resistant
are hyperandrogenic?

• The answer to this question is not known. But a
  logical speculation is that an ovarian genetic
  susceptibility is required or existence of
  long-term anovulation must be present and even
  preced huperinsulinemia.

33
Obesity

• Central body (android) obesity is associated with
  cardiovascular risk factors
• Waist/hip gt0/85
• Waist circumference gt100cm (40inches) in men
• andgt90cm(35 inches) in women.

34
Obesity Prevalance (35-60)

• Hyperinsulinemia and hyprandrogenism are not
  confined to anovulatory women who are overweight.
• The obes unovulatory women
• Insulin - LH - SHBG -IGFBG-1
• In normal weight women
• Insulin - LH

35
Metabolic Syndrom
36
(No Transcript)
37
Prevalence

• Overall estimated 24 higher in women( 40 by
  age 60)
• In normal GTT 10
• Imppaired GGT 40
• Type 2 diabet 85
• Normal weight 5
• Obes 60

38
Metabolic syndrom

• multiple studies indicate that women with PCO are
  at increased risk for the development of glucose
  intolerance or frank type 2 diabetes mellitus,
  hypertension, dyslipidemia, and atherosclerosis.
• In recent studies, the prevalence of MS in women
  with PCOS is approximately 4347.

39
Hyperinsulinemia and coronary disease

• HT
• Triglycerides
• HDL
• PAI-1

40
Clininical consequens

• Infertility
• AUB
• Hirsutism-acne and alopecia
• Endometrial cancer and perhaps breast cancer.
• Cardiovascular disease
• Diabetes melituse in patients with insulin
  resistant

41
Cardiovascular disease

• Advers lipid and lipoprotein profile
• Subclinical atherosclerosis by corotid ultra
  sonography in premenoppausal women with PCO.
• In women who undergoing cronary angiography the
  prevalence of PCO is increased.

42
Laboratory tests to exclude other problem

• TSH
• Prolactin
• Lipid and lipoprotein profile
• Screen for Cushing s
• Endometrial biopsy
• If presence of signs of exess androgens
• Total testestron
• 17-OHP

43
Who should be tested for Hyperandrogenism

• In anovulatory women and their brother and
  sisters
• Central obesity

44
How to test

• Measurement of 2- hours glucose and insulin level
  after a 75gr glucose.
• Glucose response
• Normal lt140mg/dl
• Impaired 140-199
  mg/dl
• Diabet typ 2 gt200 mg/dl
• Insulin response
• Insulin resistant very likely 100-150 uU/ml
• Insulin resistant 151-300uU/ml
• Sever insulin resisrant gt300 uU/ml

45
(No Transcript)
46
(No Transcript)
47

• Treatment
• Hyperandrogenism
• Endometrium protect
• Hyperinsulinemia
• prevent of CVD
• Induced ovulation

48
Endometrium protection

• Endometrial Biopsy
• 1- Duratin of exposure to unopposed estrogen is
  critical.
• 2- Endometrial Thickness is greater than 12mm

49

• Medroxy progestron 14 days every month
• OCP
• 1- Androgen suppression
• 2- Improvement in lipid profile
• 3 - protectin of endometrium

50
Insulin Resistance

• The best therapy is weight lossgt5
• BMIlt27
• Lifestyle improvement with proper diet and
  exercise
• Druge agent Metformin and Glitazones

51
Metformin

• Weight loss
• Ovulation
• Diabete risk reduction
• CVD risk reductin
• It is important component of health care of
  women with PCO.

52
Cunclusion

• In past we treated the specific problems of
  infertility-AUB and hirsutism but now we must
  effect on quality and quantity of life of this
  womens.

53
THE Best Wish For You