MODERN APPROACH TO PCOS

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MODERN APPROACH TO PCOS

• J. SERNA MD. PhD.
• IVI Madrid

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Physiology and Diagnosis

• What is PCOS?
• How to Diagnose it?
• How to Treat it?

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• High prevalent disease
• Multiorganic ovaries, HH, adrenal, fat, skin,
  pancreas, etc...
• Different degrees of organ involvement
• Main feature ovarian hyperandrogenism
• Multiple phenotypes

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PCOS HETERGENEOUS

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

• General Health Disorders
• Acantosis nigricans
• Cardiovascular disease
• Endometrial cancer

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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

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Anovulation/dysovulation work-up
FSH,LH,PRL,TSH, 17 ßE2
PRL N
? PRL
FSH(N / ? )
? FSH
FSH/LH lt 1 Estrogens N
FSH/LH gt 1 Hypoestrogenism
Hypo-hypo Amenorrhea
WORK-UP hyperPRL
WORK-UP POF
PCOS
Type IV
Type I
Type II
Type III
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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

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Percentage of patients with PCOS and altered
biochemical markers
N198
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Percentage of patients with PCOS and altered
biochemical markers
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PCOS DIAGNOSIS

• Biochemical hyperandrogenism
• Normal boundaries established by laboratories
  RIA
• 95-97
• Control population?
• High variability among normal population (absence
  of feed-back mechanism)
• Diverse androgens TT,ITL, 17OHP, DHA-S, A4,
  etc.

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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

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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 (gt10 mm)
The Rotterdam ESHRE/ASRMsponsored PCOS consensus
workshop group, Hum Reprod 2004,1941-7
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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
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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

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PCOS DIAGNOSIS
Clinical and/or Biochemical Hyperandrogenism
Anov/dysovulation
HiperPRL, HA, POF, etc
Idiopathic Hirsutism CAH, Tumors

• Infertility and miscarriages
• Exaggerated response to OI
• Multiple pregnancy

PCO
The Rotterdam ESHRE/ASRMsponsored PCOS consensus
workshop group, Hum Reprod 2004,1941-7
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Insulin-resistance in PCOS patients
75,3(n149)
N198
HOMA (Homeostasis model assesment) Glucose
x18,1/Insulin x0,139 (Insulin-resistance Obese
lt5,09, Lean lt5,48)
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Prevalence of Impaired Glucose Tolerance and
Diabetes in POCS in two American Studies (New
York, Pensylvania y Chicago) and in a Spainish
Survey
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31,1
30
20

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8,95
7,5
10
4,47
0
Legro, 1999
Ehrmann, 1999
HSPSC
Legro. J Clin Endocrinol Metab 1999. N244.
Ehrmann. Diab Care 1999. N122 (WHO, 1985) HSPSC
N67
Criteria WHO, 1999.
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Methods for insulin-resistance work-up
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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
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IR hyperinsulinism
?
Hyperandrogenic Anovulation
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Metabolic Syndrome
WHO
Adult Treatment Panel

• Diabetes Mellitus
• IGT
• IFG or IR
• And 2 of
• 140/90 mmHG
• Dyslipidaemia
• Central Obesity
• Waiship ratio
• BMI
• Microalbuminuria

• Central obesity (Waist)
• Dyslipidaemia TG
• Dyslipidaemia HDL-C
• 130/85
• Fasting glucose gt100 mg/dL
• At least 3

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• 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

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• Clinical hyperandrogenism
• Different prevalence among different populations
  ethnicity
• Absence of consensus on how to evaluate
  clinically the hyperandrogenism
• Semiquantitative staging methods
  (Ferriman-Gallwey). Limitations
• Subjective intra and inter-observer variability
• Previous pharmacological or cosmetical treatments
• Non validated

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Hirsutism Prevalence in Women with SOPQ
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Genes in PCOS
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TREATMENT
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TREAT WHAT?
Imparied Treatment Options
Infertility Metformin Clomiphene Letrozole Gonadotropins Ovarian cautery
Skin OCP antiandrogen (spironolactone, flutamide, finasteride) GnRH agonists
Dysfunctional bleeding Cyclic progesterone OCP
Weight/Metabolic Diet/lifestyle Metformin
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TREAT WHAT?
Treatment Options
Imparied
Diet/lifestyle Metformin
Weight/Metabolic
Cyclic progesterone OCP
Dysfunctional bleeding
Metformin Clomiphene Letrozole Gonadotropins Ovari
an cautery
Infertility
OCP antiandrogen (spironolactone, flutamide,
finasteride) GnRH agonists
Skin
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Metabolic Syndrome
Caloric restriction /- weight loss ( 6-7 months )
Leptine
SHBG IGFBP
Insulin Resistance
Ovulatory cycles Improve Hirsutism Acanthosis
Improvement in Gonadotropins metabolism andro
gens citochrome P450scc 17-ahidroxilase
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Insulin-Sensitizing Agents

• a-Glucosidasa Inhibitors
• Sulfonilureas
• Methiglinidas
• Biguanides
• Thiazolidindiones

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TREAT WHAT?
Treatment Options
Imparied
Diet/lifestyle Metformin
Weight/Metabolic
Cyclic progesterone OCP
Dysfunctional bleeding
Metformin Clomiphene Letrozole Gonadotropins Ovari
an cautery
Infertility
OCP antiandrogen (spironolactone, flutamide,
finasteride) GnRH agonists
Skin
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TREAT WHAT?
Treatment Options
Imparied
Diet/lifestyle Metformin
Weight/Metabolic
Cyclic progesterone OCP
Dysfunctional bleeding
Metformin Clomiphene Letrozole Gonadotropins Ovari
an cautery
Infertility
OCP antiandrogen (spironolactone, flutamide,
finasteride) GnRH agonists
Skin
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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 gt 10 UI/l
  before surgery

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LAPAROSCOPIC ELECTORCAUTERY
Campo, S. Obst Gyn Surv 199853297-308.
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LAPAROSCOPIC LASER VAPORIZATION
Campo, S. Obst Gyn Surv 199853297-308.
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TREAT WHAT?
Treatment Options
Imparied
Diet/lifestyle Metformin
Weight/Metabolic
Cyclic progesterone OCP
Dysfunctional bleeding
Metformin Clomiphene Letrozole Gonadotropins Ovari
an cautery
Infertility
OCP antiandrogen (spironolactone, flutamide,
finasteride) GnRH agonists
Skin
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Skin

• Systemic
• Antiandrogens
• Spironolactone
• Finasteride
• Flutamide
• OCP
• GnRH analogs

• Cutaneous
• Eflornitine
• Creams
• Electrolysis
• Laser

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Thank you