Pathogenesis of PCOS

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Pathogenesis of PCOS Powered By Docstoc
					          Year 5 Medicine



Polycystic Ovary Syndrome and Hirsutism




                      Stella Milsom
              Overview

diagnosis of PCOS-new Rotterham Consensus

symptoms of PCOS

future health risks associated with PCOS

relevant investigation of woman with likely symptoms

management of hirsutism related to PCOS
  
What is polycystic ovary syndrome?


 syndrome of ovarian hyperandrogenisation

 associated symptoms of androgen excess

 anovulation leads to menstrual irregularity

 most common gynaecological condition
 affecting women of childbearing age

 also associated with the metabolic syndrome
POLYCYSTIC OVARIAN SYNDROME
POLYCYSTIC OVARIAN SYNDROME




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  Normal ovaries        Polycystic ovaries
   volume < 8 cm3       mildly enlarged
   scattered follicles  generally > 8 cm3
                         peripheral distribution
                          of follicles
                               increased stroma
          Pathogenesis of PCOS

    LH           insulin/IGF1     cytochrome P450

                                    
obesity
            ovarian androgen production
                          
              disturbed folliculogenesis
Diagnosis of polycystic ovary syndrome


symptoms of androgen excess
 irregular menses
 acne, hirsutism



biochemical androgen excess
  total / free testosterone,  androstenedione,  LH



 pelvic ultrasound
 1 or both ovaries enlarged, >12 peripheral follicles
       Anovulation in PCOS


presents as:
    absence of periods
    infrequent periods ( > 35 day cycle)
    dysfunctional uterine bleeding
    occasionally regular periods

risk of endometrial cancer
     Biochemistry in PCOS


Raised LH or LH:FSH ratio

One or more androgen levels raised
 testosterone
 androstendione
 DHEAS
Polycystic Ovaries




 Normal ovaries          Polycystic Ovaries
 volume < 8 cm3        Generally >8cm3
 scattered follicles   peripheral distribution
                         of follicles
                         increased stroma
2004 Consensus PCOS Definition


2 out of the following 3 features

  anovulation

  clinical and/or biochemical evidence of androgen excess

  polycystic ovaries on ultrasound:

1 or more ovaries ≥10mls in size and ≥12 follicles

                 Human Reproduction, 2004
                    PCOS

PCOS is also associated with a characteristic
 metabolic syndrome that includes:

  insulin resistance
  dyslipidemia
  hypertension

These features are linked with increased risks
 of type 2 diabetes and possibility of premature
 cardiovascular disease
   Metabolic abnormalities in PCOS due
          to insulin resistance

 impaired GTT         40%

 Diabetes – 5x more likely than weight matched
  controls     OGTT vs FG

 gestational diabetes increased risk

 dyslipidemia                 HDL LDL TG
                    potential cardiovascular risk
Associations of PCO with clinical
           conditions

PCO present in

 75% cases of anovulatory infertility (Adams 1986, Hull 1987)
 87% cases of oligomenorrhoea       (Adams 1986)
 80% cases of hirsutism and regular menses
                                      (Adams 1986, Hull 1987)
 83% women presenting with acne to dermatology clinic
                                     (Bunker 1989)
 30-40% women with amenorrhoea (Adams 1986)
     What tests are useful?


androgens, FSH, LH, estradiol


prolactin, thyroid function, pregnancy test
 (causes of secondary amenorrhea)


ultrasound pelvis
     What tests are useful?

remember to exclude secondary causes of PCOS

 androgen secreting tumour

 acromegaly

 non classical CAH
       Management of PCOS


 symptom orientated

 long term risk
  reduction
       Management of PCOS
        - Current Symptoms

determine which predominates-infertility or androgen
 excess

then consider antiandrogen versus ovulation induction
 therapy

consider state of endometrium

first line medical management from diagnosis to
 reproduction most likely be OCP
            Hirsutism and PCOS


defined as coarse terminal hair in a male distribution

do not confuse with lanugo hair

assessed by the Ferriman-Galwey score

does not always correlate with androgen levels
       Management of androgen excess
            symptoms in PCOS


symptoms include:

hirsutism

acne

androgenic alopecia
      Management of androgen excess
           symptoms in PCOS


First line treatment for mild hirsutism

  weight loss and exercise


  oral contraceptive (Estelle and Yasmin)


  metformin
    Effect of lifestyle in hirsute PCOS

 weight gain causes an increase in insulin resistance and androgen

  production in PCOS women

 antiandrogen therapy is less efficacious

 modest weight loss and increase in exercise e.g. 5-10% weight loss will

  often improve hirsutism by reducing androgen production
           OCP and hirsutism

first line treatment for hirsutes (manages endometrium and
  contraception also)
synthetic E2 suppresses gonadotropin driven androgen
  production
increase in SHBG decreases bioavailable T to hair follicle
addition of low dose CPA (Estelle) provides antiandrogenic
  progesterone
    Metformin and hirsutism

useful alternative to OCP in woman with hirsutism who also
desires fertility


common to have gut side effects


commence slowly, work up to 1500mg/day


moniter with liver and renal function ( occasional hepatotoxicity,
theoretical risk of lactic acidosis)
     Metformin and hirsutism

In both lean and overweight women with PCO

improves insulin sensitivity and lipids

decreases hyperandrogenism

increases frequency of ovulation (40-70%) compared
 to placebo
     Management of androgen excess
          symptoms in PCOS

Treatment of more severe hirsutism (refer)

  OCP plus additional antiandrogen therapy:
  spironolactone 200mg/day
  cyproterone in reverse sequential regime (specialist)
  flutamide 250mg/day (specialist)
  finasteride unfunded and less effective

  for the future: vaniqa cream (ornithine decarboxylase
    inhibitor)
      Combination antiandrogen
              therapy

 use in conjunction with OCP
 specialist prescription
 require monitoring (liver function)
 used in more severe hirsutism or unresponsive women
 course up to 36 months
 require contraception
 6 months before effect but may improve up to 2 years
  after initiating therapy (50% reduction in FG score)
Management of PCOS-longer term

consider OCP, metformin, progestins, antiandrogens,
 ovulation induction, lipid lowering agents, antihypertensives
 as necessary


surveillance for diabetes, hypertension and dyslipidemia
 especially if positive family history and overweight


monitor endometrium


active weight loss and exercise programme

				
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