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PCOS- Spotlights

VIEWS: 4 PAGES: 31

									Polycystic Ovary Syndrome
              Jamal Zaidi

 Consultant Obstetrician & Gynaecologist
   East Sussex Healthcare NHS Trust
                  Objectives
•   Definition & Prevalence
•   Pathogenesis
•   Diagnosis
•   Clinical Features
•   Management
•   Long term consequences
                              Definition
                            ASRM/ ESHRE
• Rotterdam: May 2003
• Two of three: Oligomenorrhoea & or anovulation
                 Hyperandrogenism; Clinical/biochemical
                 PCO on USG; 12 or more follicles in each ovary, 2-
  9mm,and/ or increased ovarian volume to over 10cm3
• Single PCO
• The follicle distribution & increase in stromal echogenicity &
  volume should be omitted
• Chronic anovulation & hyperandrogenism in absence of other
  endocrine disorders
• January issue of Fertility & Sterility J, 2004
Ultrasound
    Gross appearance of ovaries
• Enlarged bilaterally and have a smooth thickened
  avascular capsule

• On cut section, subcapsular follicles in various
  stages of atresia are seen

• Microscopically luteinizing theca cells are seen
                 Prevalence

• PCO on ultrasound - 20%-33%
• Oligomenorrhoea - 4 – 21 %
• Oligomenorrhoea + hyperandrogenism - 3.5 – 9 %

• PCOS – approx 18% (community-based
  prevalence study based on Rotterdam criteria).
  Importantly, 70% of women in this recent study
  were undiagnosed
                 Pathogenesis

• Insulin resistance ?
• Hypersecretion of adrenal androgens?
• Hypersecretion of ovarian androgens?
• A genetic disorder with an autosomal dominant
  mode of inheritance?
• A multifactorial genetic disorder?
                                      Obesity


                                      Insulin

                         SHBG                      IGF-1
                                            5-alfa reductase activity is
                                            stimulated


                                        Free
                                    testosterone
IGF*** insulin like growth factor
                                              Insulin
                                              Resistance


                                              Hyperinsulinaemia
                                              -                                              -

              Hepatic IGF-BP-1 production                                     Hepatic SHBG production
                                          +                                                      +

                                    ↑Free IGF-1                                    ↑ Free testosterone
                                                                                                 +
                                                                                                               Atresia
                                                                     +
                                                                                                              Hirsutism
↑Adipose tissue leptin                                                       ↑Thecal cell & adrenal
                                                                                  androgens

                                     +                                                           +

                                         ↑Pulse Freq                                  ↑ Oestrogens
                                                                                                 -

        LH production                                                              FSH production
                           +


 IGF-BP-1; insulin growth factor binding protein: IGF-1; insulin growth factor 1: SHBG; Sex hormone binding
 globulin: LH; Luteinising Hormone: FSH; Follicle Stimulating Hormone.
                Diagnosis

History Taking
• Menarche
• Menstrual pattern
• Weight issues
• Hirsutism
• Other aspects of gynae history
                      Diagnosis
                 Biochemical tests

The best biochemical markers of hyperandrogenism are
Increased free testosterone levels or free androgen index;
Reduced SHBG levels

Not all patients with PCOS have elevated circulating
androgen levels

DHEAS is raised in small fraction of patient with PCOS
levels (measured to exclude adrenal causes)
                          Diagnosis
                     Biochemical Tests

•LH/FSH ratios can be elevated in up to 95% of women with
PCOS if women with recent ovulation are excluded
LH levels are not necessary for clinical diagnosis of PCOS

• May have increased Prolactin levels

• Increased oestradiol/oestrone levels

• Normal TFTs

• Increased fasting insulin
•PCOS should be excluded from other disorders in which
hirsutism and menstrual irregularities are prominent
Congenital adrenal hyperplasia
Cushing's syndrome
Androgen-secreting tumors


•In oligo/anovulation:
 E2 & FSH to exclude hypogonadotrophic hypogonadism
(central origin of ovarian dysfunction)
                             Diagnosis
                        Pelvic Ultrasound
Small ovarian follicles; result of disturbed ovarian function
In PCOS, there is a so called "follicular arrest", i.e., several follicles
develop to a size of 5–7 mm, but not further.
According to the Rotterdam criteria, 12 or more small follicles
should be seen in an ovary on ultrasound examination. The follicles
may be oriented in the periphery, giving the appearance of a ‘string
of pearls’
                Clinical Features

•   Amenorrhoea
•   Oligomenorrhoea
•   Irregular periods
•   Infertility
•   Hirsutism
•   Obesity
•   Acne Vulgaris
•   Asymptomatic
                       Management
•   Symptom control
•   Diet & exercise
•   Wt. loss
•   Improves both symptoms & endocrine profile
•   Aim for BMI < 30kg/ m2
•   Keep CHO content down, avoid fatty food
•   Obesity clinics
                     Contd

Menstrual irregularities
• OCP- COCP, Yasmin, Dianette
• Withdrawal bleed – regular bleed with
  progestagen
• Consider Endometrial sampling
 STEPWISE APPROACH FOR OVULATION INDUCTION
              IN PCOS (ACOG,2002)


1. Weight loss: If BMI >30 Kg/m2
2. Clomiphene citrate
3. CC +/- Metformin
4. Low dose step up protocol - FSH injection
5. Ovarian drilling
8. IVF
                Mx of Hirsutism


•   Cosmetic
•   Medical- 6-7 months
•   Cyproterone acetate+ EE, Spironolactone
•   Reliable contraception
•   Flutamide & Finasteride - Rare
     Reproductive Endocrinologist /
            Gynaecologist
•   S.testosterone > 5nmol/L
•   Rapid onset hirsutism
•   IGT/ Type2 DM
•   Refractory symptoms
•   Amen. > 6 months
•   Subfertility
           Long term risks in PCOS

Definite

• Type 2 diabetes(15%), IGT( 18-20%)

• Dyslipidemia (Hypercholesterolemia with
  diminished HDL2 and increased LDL)

• Endometrial cancer (OR 3.1 95% CI 1.1 -7.3)
Possible

•   Hypertension
•   Cardiovascular disease
•   Gestational diabetes mellitus
•   Pregnancy-induced hypertension

Unlikely

• Breast cancer
  Guidelines (RCOG, May 2003)
• 1-Patients presenting with         • 2- Women diagnosed as having
  PCOS particularly if they are        PCOS before pregnancy should
  obese, should be offered             be screened for gestational
  measurement of fasting blood         diabetes in early pregnancy
  glucose and urine analysis for     • Refer to specialized obstetric
  glycosuria. Abnormal results         diabetic service if abnormalities
  should be investigated by a          detected (evidence level IIb[B])
  glucose tolerance test
• Such patients are at increased
  risk of developing type II
  diabetes (Evidence level IIb[C])
  Guidelines (RCOG, May 2003)
• 3-Measurement of fasting           • 4- Olig- and amenorrhoeic
  cholesterol, lipids and              women with PCOS may
  triglycerides should be offered      develop endometrial
  to patients with PCOS, since         hyperplasia and later
  early detection of abnormal          carcinoma. It is good practice to
  levels might encourage               recommend treatment with
  improvement in diet and              progestogens to induce
  exercise (Evidence level III[C])     withdrawal bleed at least every
                                       3-4 months (Evidence level
                                       IIa[B])
  Guidelines (RCOG, May 2003)
• 5- Evidence has accumulated       • 6- No clear consensus regarding
  demonstrating safety and            regular screening of women
  efficacy of insulin-sensitizing     with PCOS for later
  agents in the management of         development of diabetes and
  short-term complications of
  PCOS, particularly anovulation.     dyslipidemia
  Long-term use of these agents     • Obese women with strong
  for avoidance of metabolic          family history of cardiac
  complications of PCOS cannot        disease or diabetes should be
  as yet be recommended               assessed regularly in a general
  (Evidence level IV[B])              practice or hospital outpatient
                                      setting. Local protocols should
                                      be developed and adapted
                                      (Evidence level IV[C])
 Guidelines (RCOG, May 2003)
• Young women diagnosed with PCOS should be
  informed of the possible long-term risks to health
  that are associated with their condition. They
  should be advised regarding weight and exercise
  (Evidence level III[C])
Thank you

								
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