Polycystic Ovarian Syndrome

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Polycystic Ovarian Syndrome

• Christina C Ding
• Consultant in Obstetrics and gynaecology
• Subspecialist in Reproductive Medicine and
  Surgery

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Overview

• Definition (and Prevalence)- much debated
• Diagnostic Criteria update
• Management update
• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Definition -PCOS

• Why is reaching consensus difficult?
• Problems with the lack of unified definition?
• New criteria in 2003

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Definition- PCOS Challenges in reaching a
consensus

• Heterogeneity in symptom and sign
• For an individual, these may change over time
• PCO can exist without clinical signs of the
  syndrome, which may become expressed overtime

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Range of presenting complaints

• Menstrual irregularities (unopposed E2)
• Anolulatory Infertility
• Hyperandrogenism (Acne/Hirsutism/Alopecia)
• Obesity
• Metabolic Risks (DM, H/T, CVD)
• Asymptomatic incidental Scan finding of PCO

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DefinitionProblems without a consensual
definition

• Progress in Clinical Research hampered
• Inconsistencies and poor delivery of clinical care

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Definition Revised 2003 Rotterdam diagnostic
criteria

• Two out of three
• Oligo / Anovulation
• Hyperandrogenism clinical or biochemical
• USS Features
• gt12 follicles of 2-9 mm in diameter , or
• ovarian volume gt10 cm3 in one or both ovaries
• Excluding thyroid dysfunction, congenital
  adrenal hyperplasia, hyperprolactinaemia,
  androgen-secreting tumours and Cushing syndrome

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Prevalence

• NIH criteria 1990
• 6-7
• Rotterdam consensus 2003
• 20-25 UK Caucasian
• 52 UK South Asian immigrant

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SHBG decrease
atresia
Wt. increase
Insulin increase
Insulin receptor disorder
IGFBP-I decrease
Free estradiol increase
Theca (IGF-I)
Free testosterone increase
High LH Low FSH
hirsutism
Androstenandione increase
Testosterone increase
Endometrial cancer
Estrone increase
IGFBP insulin like growth factor binding
protein
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Clinical Challenges

• Menstrual irregularities (unopposed E2)
• Anolulatory Infertility
• Hyperandrogenism (Acne/Hirsutism/Alopecia)
• Obesity
• Metabolic Risks (DM, H/T, CVD)

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Life Style Changes

• The best diet and exercise regimens are unknown,
  but caloric restriction and increased physical
  activity are recommended.
• RCOG guideline

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Management Update

• General
• Life style changes
• insulin sensitising agent
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Metformin

• Not licensed outside DM treatment
• Safe (not established in pregnancy)
• Short term benefits (Wt. loss, OI, hirsutism)
• No long term benefits

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Cancer risks

• Endometrial Cancer
• Risk is 3.1 x higher (95 C I 1.1- 7.3)
• Coulam et al, 1983 (1270 chronic anovulation pt)
• Breast Cancer
• No significant increased risks
• Pierpoint et al., 1998 Coulam et al., 1983
  Anderson et al., 1997
• Ovarian Cancer
• No significant increased risks
• Pierpoint et al., 1998

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Long term risks CVD

• PCOS metabolic abnormalities suggesting
  increased cardiovascular risk
• Observation Reference
• Triglycerides?, HDL? Rajkhowa et al. (1997)
  Orio et al. (2004)
• C-reactive protein? Taponen et al. (2004)
  Boulman et al. (2004)
• Homocysteine? Carmina et al. (2005)
• Leucocytes? Orio et al. (2005)
• Fibrinolytic activity? Yildiz et al. (2002)
• Metabolic syndrome? Apridonidze et al. (2005)
• The ESHRE Capri Workshop Group, Hormones and
  cardiovascular health in women, Human
  Reproduction Update, 2006

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Long term risks DM,H/T

• Follow-up studies of PCOS
• Authors Patients Intermediate outcomes
  CVD outcomes
• Dahlgren et al. (1992) 33 followed for 2231
  years More diabetes and hypertension
• Pierpoint et al. (1998) 786 diagnosed between
  1930 -79 SMR 0.9 (95 CI 0.7, 1.2)
• Wild et al. (2000) 240 PCOS diagnosed before
  1979 More cerebral disease and diabetes
  Similar CHD mortality
• Elting et al. (2001) 346 followed for 232
  years More diabetes and hypertension
• SMR, Standardized Mortality Ratio

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Long term risks obstetric

• Meta analysis of 15 studies involving 720
  women presenting with PCOS and 4505 controls
• Higher risks of
• Gestational DM (OR 2.94 95 CI 1.705.08)
• Pregnancy-induced H/T (OR 3.67 95 CI
  1.986.81)
• Preterm birth (OR 1.75 95 CI 1.162.62)
• Perinatal mortality (OR 3.07 95 CI 1.039.21)
• Hum. Reprod. Update 2006, A meta-analysis of
  pregnancy outcomes in women with PCOS

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Psychological Quality of Life

• Symptoms such as acne, hirsutism, irregular
  menses, amenorrhoea, obesity and subfertility are
  a major source of psychological morbidity and can
  negatively affect quality of life (QoL).
• Systematic review PCOS has a significant
  negative impact on a womans health-related
  quality of life
• Health-related quality of life measurement in
  women with polycystic ovary syndrome a
  systematic review. Jones et al, Human
  Reproduction Update (2008)

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Antiobesity Drug

• Orlistat (Xenical)
• gastric/pancreatic Lipase inhibitor
• Sibutramine (Reductile)
• SNRI
• Withdrawn since Jan 2010 due to increased heart
  attack and stroke risks

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Bariatric Surgery

• Two groups malabsorptive restrictive
  procedures
• Malabsorptive procedures induce decreased
  absorption of nutrients by shortening the
  functional length of the small intestine. The
  created short-bowel syndrome leads to a negative
  energy balance and weight loss.
• Restrictive operations reduce the storage
  capacity of the stomach and as a result early
  satiety arises, leading to a decreased caloric
  intake.

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Figure 1 Bariatric procedures. (a) Jejunoileal
bypass (b) biliopancreatic diversion (c)
biliopancreatic diversion with duodenal switch
(d) vertical banded gastroplasty (e)
laparoscopic adjustable gastric band and (f)
Roux-en-Y gastric bypass.
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Bariatric Surgery

• Benefits
• Average weight loss 2040 kg
• Recovery from type 2 diabetes in 76.8
• Risks
• Mortality early (lt30/7) 0.1-2
• Morbidity
• VTE (0.4-3.1)
• Infection
• Anastomotic leak / stenosis (20-30)

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Hyperandrogenism

• Acne
• Hirsutism
• Male pattern hair loss
• Sign of severe androgen excess (virilization)

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Hirsutism

• 5-10 women of child bearing age
• 70 PCOS
• 23 idiopathic
• 4.3 CAH
• 0.2 A S tumour (ovarian or adrenal)
• Hx sudden onset, rapid virilization
• Ix testosterone, free testosterone.
• If testosterone gt 5nmol/L gt DHEA-S
  androstenedione to exclude an adrenal or
  ovarian tumour

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Hirsutism - treatment options

• Systemic (over 3-6 months)
• COCP less androgenic progesterone cyproterone
  acetate Diannette , drospirenone Yasmin
• Antiandrogens (uncommonly used)
• Spironolactone (Aldactone), an aldosterone
  antagonist
• Cyproterone acetate
• Flutamide is a pure nonsteroidal antiandrogen
  that acts as an androgen receptor blocker.
• Finasteride is a potent inhibitor of the type 2
  isoenzyme of 5-á-reductase, which blocks the
  conversion of testosterone to 5-á-dihydrotestoster
  one
• Corticosteroids late onset CAH
• Topical
• Eflornithine cream (Vaniqa)
• Cosmetic
• Direct Hair Removal plucking, waxing,
  electrolysis, laser removal

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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Ovulation Induction stepwise approach (RCOG)

• 1. Weight loss If BMI gt30 K/m2
• 2. Clomiphene citrate
• 3. CC Metformin
• 4. Low dose FSH injection
• 5. Ovarian drilling
• 6. IVF

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Laparoscopic ovarian drilling

• Diathermy or laser
• Clomid resistant anovulatory PCOS
• Benefits
• Ovulation rate gt70
• Pregnancy rates gt50
• Similar pregnancy and
• miscarriage rates to Gonadotrophins
• No increase in multiple pregnancies and reduces
• ovarian hyperstimulation.

• Risks
• Risk of loss of ovarian tissue and thus reducing
  the ovarian reserve
• Risk of surgery
• ?Adhesions

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Ovarian drilling
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Management Update

• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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Mx of a/oligomenorrhea

• Progesterone induced Bleeding
• 3 monthly
• Reduce risks of E hyperplasia and E carcinoma

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Overview

• Definition (and Prevalence)- much debated
• Diagnostic Criteria update
• Management update
• General
• Life style changes
• insulin sensitising agents
• Prevention of long term health risks (CVD,
  Cancers, Psychological)
• Specific symptomatic control
• Obesity Mx Antiobesity drugs, Bariatric surgery
• Hyperandrogenism Tx
• Infertility Anoulatory cycles
• Menstrual irregularities

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