MODERN APPROACH TO PCOS

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MODERN APPROACH TO PCOS Powered By Docstoc
					MODERN APPROACH TO PCOS


  J. SERNA MD. PhD.
  IVI Madrid
Physiology and Diagnosis


  What is PCOS?
  How to Diagnose it?
  How to Treat it?
 High prevalent disease
 Multiorganic: ovaries, HH,
  adrenal, fat, skin, pancreas, etc...
 Different degrees of organ
  involvement
 Main feature: ovarian
  hyperandrogenism
 Multiple phenotypes
    PCOS: HETERGENEOUS


          Reproductive disorders
          •Hyperandrogenism
          •Anovulation: Menstrual
          disorders, infertility
          •Polycystic ovaries
          •Miscarriage


Metabolic disorders
•IR and                         General Health
Hyperinsulinism                 Disorders
•Obesity (male                  •Acantosis nigricans
pattern)                        •Cardiovascular
•Impaired Glucose               disease
Tolerance and DM2               •Endometrial cancer
•Hyperlypemia
         PCOS Dg CRITERIA


Anovulation and/or dysovulation

Clinical and/or Biochemical Hyperandrogenism

Polycystics ovaries

     and exclusion of other aetiologies (CAH,
     tumours, HPRL, etc)

      The Rotterdam ESHRE/ASRM sponsored PCOS consensus
                                   workshop group, 2003
Anovulation/dysovulation work-up
           FSH,LH,PRL,TSH, 17 βE2

  PRL                                PRL N

                 FSH(N /  )
                                                  FSH

           FSH/LH < 1            FSH/LH > 1
           Estrogens N         Hypoestrogenism


WORK-UP                         Hypo-hypo
            PCOS                                 WORK-UP
                               Amenorrhea
hyperPRL                                          POF

  Type       Type                   Type           Type
   IV         II                     I             III
                    PCOS


Anovulation and/or dysovulation

Clinical and/or Biochemical Hyperandrogenism

Polycystics ovaries

     and exclusion of other aetiologies (CAH,
     tumours, HPRL, etc)

      The Rotterdam ESHRE/ASRM sponsored PCOS consensus
                                   workshop group, 2003
       Percentage of patients with PCOS and
            altered biochemical markers

  80              78,7
                         75,1
                                                      62,4
  60

                                41,4
% 40


  20    19,2                            17,2

                                               3,25
   0
         TT       SHBG   FTI    A4     17 OHP DHA-S LH/FSH



          N=198
          Percentage of patients with PCOS and
               altered biochemical markers


    100                                      98,3


     95

                           90,1
%    90
              86,7

     85


     80
            TT+SHBG   TT+SHBG+17OHP   TT+SHBG+17OHP+A4
       PCOS DIAGNOSIS
Biochemical hyperandrogenism


1. Normal boundaries established by laboratories
   RIA:
   •   95-97%
   • Control population?
2. High variability among normal population (absence
   of feed-back mechanism)

Diverse androgens: TT,ITL, 17OHP, DHA-S, A4,
  etc.
                    PCOS


Anovulation and/or dysovulation

Clinical and/or Biochemical Hyperandrogenism

Polycystics ovaries

     and exclusion of other aetiologies (CAH,
     tumours, HPRL, etc)

      The Rotterdam ESHRE/ASRM sponsored PCOS consensus
                                   workshop group, 2003
    PCOS DIAGNOSIS


Polycystic ovary
Presence of 12 or more
follicles 2-9 mm 
and/or ovarian volume
higher than 10 mL
(one ovary is enough)

Non suitable to women on OCP or with a
dominant follicle (>10 mm)


      The Rotterdam ESHRE/ASRMsponsored PCOS consensus workshop
      group, Hum Reprod 2004,19:41-7
              Polycystic ovaries. Pitfalls


False positives: 20% normal women
False negatives: 30% PCOS


US scan cannot make differential
diagnosis between multycystic ovaries and
polycystics ovaries


Time required for measurements
                    PCOS


Anovulation and/or dysovulation

Clinical and/or Biochemical Hyperandrogenism

Polycystics ovaries

     and exclusion of other aetiologies (CAH,
     tumours, HPRL, etc)

      The Rotterdam ESHRE/ASRM sponsored PCOS consensus
                                   workshop group, 2003
                             PCOS DIAGNOSIS
Clinical and/or                                           Anov/dysovulation
Biochemical
Hyperandrogenism
                                                        HiperPRL, HA, POF, etc

     Idiopathic Hirsutism
     CAH, Tumors

                                                              Dysovulation wo
Normal cycle                                       ??        hyperandrogenism
and hyperandrogenism         ??
   Infertility and
  miscarriages
  Exaggerated response
  to OI
  Multiple pregnancy
                                      PCO
                 The Rotterdam ESHRE/ASRMsponsored PCOS consensus workshop
                 group, Hum Reprod 2004,19:41-7
  Insulin-resistance in PCOS patients


                                          Insulino
                                        resistentes


         75,3%(n=149)


No insulino                                    N=198
resistentes


 HOMA (Homeostasis model assesment): Glucose x18,1/Insulin
 x0,139 (Insulin-resistance: Obese <5,09, Lean <5,48)
Prevalence of Impaired Glucose Tolerance and Diabetes in POCS
in two American Studies (New York, Pensylvania y Chicago) and
                     in a Spainish Survey


  40                                  35
          31,1
  30


% 20
                                               10             8,95
  10              7,5
                                                                       4,47

   0
         Legro, 1999             Ehrmann, 1999                  HSPSC


           Legro. J Clin Endocrinol Metab 1999. N=244.
           Ehrmann. Diab Care 1999. N=122 (WHO, 1985)
           HSPSC N=67                                    Criteria: WHO, 1999.
    Methods for insulin-resistance work-up


Index                          Formula                                           Normal ranges
        Basal Insulin                         Insulin (U/ml)                           < 20
 Glucose/insulin index                Glucose (mg/dL)/Insulin (U/Ml)                < 4,5
 HOMA (Homeostasis               glucose (mg/dL) x insulin (U/mL) / 405             ≥ 3,8
  model assessment)               glucose (mmol /lL) x insulin (U/mL) /
                                                     22.5
 QUICKI (Quantitative             1 / log insulin (U/mL) + log glucose (mg          < 0,33
insulin sensitivity check                            /dl)
          index)




                        Insulin: U/ml x 7,175 = pmol/l pmol/l x 0,139 = U/ml
                        Glucose: mg /dl x 0,0551 = mmol/l mmol/l x 18 = mg/dl
     Methods for Insulin-Resistance work-up

      Gold Standard test IR is euglucemic clamp
      .
      Due to its complexity, Oral Glucose Tolerance Test
      or Basal Glucose and Insulin measurements instead
      .
      OGTT is the main test in the diagnosis of Impaired
      Glucose Intolerance or Type II Diabetes

Other indexes are less used in clinical routine
                              IR
                       hyperinsulinism




                              ¿?



Hyperandrogenic Anovulation
Metabolic Syndrome
       WHO                     Adult Treatment Panel
   Diabetes Mellitus             Central obesity (Waist)
   IGT                           Dyslipidaemia TG
   IFG or IR                     Dyslipidaemia HDL-C
   And 2 of                      ≥130/85
        ≥ 140/90 mmHG            Fasting glucose >100 mg/dL
        Dyslipidaemia
        Central Obesity
                                   At least 3
             Wais:hip ratio
             BMI
        Microalbuminuria
Cardiovascular disease in women

•Near 2,5 million women hospitalized each year due to
CVD

•1st death cause in women (over the next 14 together)

•Half of these deaths are from MCI

•Annual cost estimated to be 28,65 billion dolars

Tsang y cols. Risk of caronary heart disease in women: current understanding. Mayo
Found Med Educ Research, 2000
Clinical hyperandrogenism

1. Different prevalence among different populations:
   ethnicity

2. Absence of consensus on how to evaluate clinically
   the hyperandrogenism

3. Semiquantitative staging methods (Ferriman-
   Gallwey). Limitations:

   1. Subjective: intra and inter-observer variability
   2. Previous pharmacological or cosmetical treatments
   3. Non validated
              Hirsutism Prevalence in
               Women with SOPQ


  80                              72,2
             63,57
  60


% 40


  20


   0
       Sant Pau( n=198)   Azziz, 2004(n=873)
Genes in PCOS
TREATMENT
TREAT WHAT?
        Imparied             Treatment Options
                         Metformin
                         Clomiphene
Infertility              Letrozole
                         Gonadotropins
                         Ovarian cautery
                         OCP + antiandrogen (spironolactone,
Skin                     flutamide, finasteride)
                         GnRH agonists
                         Cyclic progesterone
Dysfunctional bleeding   OCP


                         Diet/lifestyle
Weight/Metabolic         Metformin
TREAT WHAT?
        Imparied             Treatment Options
                         Diet/lifestyle
Weight/Metabolic         Metformin


                         Cyclic progesterone
Dysfunctional bleeding   OCP


                         Metformin
                         Clomiphene
Infertility              Letrozole
                         Gonadotropins
                         Ovarian cautery
                         OCP + antiandrogen (spironolactone,
Skin                     flutamide, finasteride)
                         GnRH agonists
Metabolic Syndrome
    Caloric restriction +/- weight loss ( 6-7 months )




                                                                 Leptine

Insulin Resistance                            SHBG
                                              IGFBP



Improvement in Gonadotropins metabolism                  Ovulatory cycles
                                                         Improve Hirsutism
                             androgens                            Acanthosis
                             citochrome P450scc
                             17-αhidroxilase
Insulin-Sensitizing Agents

    α-Glucosidasa Inhibitors
    Sulfonilureas
    Methiglinidas
    Biguanides
    Thiazolidindiones
TREAT WHAT?
Imparied                     Treatment Options
                         Diet/lifestyle
Weight/Metabolic         Metformin


                         Cyclic progesterone
Dysfunctional bleeding   OCP

                         Metformin
                         Clomiphene
Infertility              Letrozole
                         Gonadotropins
                         Ovarian cautery
                         OCP + antiandrogen (spironolactone,
Skin                     flutamide, finasteride)
                         GnRH agonists
TREAT WHAT?
Imparied                     Treatment Options
                         Diet/lifestyle
Weight/Metabolic         Metformin


                         Cyclic progesterone
Dysfunctional bleeding   OCP

                         Metformin
                         Clomiphene
Infertility              Letrozole
                         Gonadotropins
                         Ovarian cautery
                         OCP + antiandrogen (spironolactone,
Skin                     flutamide, finasteride)
                         GnRH agonists
                                      Laparoscopic Electrocoagulation
                                      Laparoscopic Ovarian Diathermy

                                      Several energy sources:
                                      Monopolar, LASER (CO2, Argon,
                                      KTP, YAG)




Mechanism of action
    Not well established
    Removal of androgen-producing stroma
    Total and free testosterone reduction to 40-50% basal levels
    LH pulses amplitude decreases
    Better prognosis for patients with LH > 10 UI/l before surgery
         LAPAROSCOPIC ELECTORCAUTERY

                   Year    Patients   Previous ttm       % Ovulation     % Spont preg



Gjonnaess          1985      58           ----                72              41


Weise              1991      39        CC, HMG               ---              59


Naether            1993      104       CC, HMG                55              34


Saravelos          1996      21           CC                  76              30


Merchan            1996      74        CC, HMG                88              57


Pelosi             1996      30        CC, HMG                83              70


Total                        720                             79.7            51.5


            29.1% had adherence at a 2nd laparoscopy

                                                 Campo, S. Obst Gyn Surv 1998;53:297-308.
   LAPAROSCOPIC LASER VAPORIZATION
                 Year      Patients     Prevıous ttm       % Ovulatıon   % Spont Preg


Daniell (CO2)    1989        85              CC                71            41

Kojima (YAG)     1989         12          CC, HMG              83            58

Gurgan (YAG)     1992        40              CC                70            50

Sinha (YAG)      1993        20            CC,                100            40
                                         HMG,FSH
Heylen Argon     1994        44              CC                80            55

Fukaya (YAG)     1995        26           CC, HMG              23            23

Total                        322                              71.5           43.7


        50% had adherence at a 2nd laparoscopy


                Campo, S. Obst Gyn Surv 1998;53:297-308.
TREAT WHAT?
Imparied                     Treatment Options
                         Diet/lifestyle
Weight/Metabolic         Metformin


                         Cyclic progesterone
Dysfunctional bleeding   OCP

                         Metformin
                         Clomiphene
Infertility              Letrozole
                         Gonadotropins
                         Ovarian cautery
                         OCP + antiandrogen (spironolactone,
Skin                     flutamide, finasteride)
                         GnRH agonists
Skin
 Systemic              Cutaneous
   Antiandrogens           Eflornitine
     Spironolactone        Creams
     Finasteride           Electrolysis
     Flutamide             Laser
   OCP
   GnRH analogs
Thank you

				
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posted:8/17/2011
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