PCOS

1
PCOS

• Dr. Mridula A Benjamin
• Dept of Obs and Gyn
• RIPAS Hospital, Brunei

2
Introduction

• Heterogenous problem
• Commonest hormonal disturbance
• Ovarian expression of metabolic syndrome
• Long term consequences - strategies to screen
• Stein Leventhal syndrome

3
ASRM/ ESHRE

• Rotterdam May 2003
• Two of three Oligomenorrhoea or anovulation
• Hyperandrogenism
  Clinical/biochemical
• PCO on USG 12 or
  more, 2-9mm,10cm3
• Single PCO
• The follicle distribution increase in stromal
  echogenecity volume should be omitted
• Chronic anovulation hyperandrogenism in absence
  of other endocrine disorders
• January issue of Fertility Sterility J, 2004

4
Ultrasound

• Polycystic ovaries
• Bilateral
• Multiple cysts
• Cyst diam lt2-9mm
• Stroma increased

• Multicystic ovaries
• Bilateral
• Multiple cysts
• Cyst diam gt 6-10 mm
• Stroma not increased

5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
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

9
(No Transcript)
10
(No Transcript)
11

• The best biochemical markers of hyperandrogenism
  are
• free testosterone levels or free androgen index
• Not all patients with PCOS have elevated
  circulating androgen levels
• Routine measurement of androstenedione cannot be
  recommended
• DHEAS is raised in small fraction of patient with
  PCOS levels

12

• LH levels are elevated in 60 women with PCOS
• 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
• Implications?? High miscarriage / low fertility
• The chances of ovulation or pregnancy rates using
  CC or HMG are unaffected

13

• 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)

14

• Thyroid disorders in PCOS patients are not more
  common than in other young women, and TSH is
  unnecessary
• In hyperandrogenic females Prolactin

15
Metabolic syndrome 3 of the following 1.
Waist circumference gt88cm 2. Triglycerides gt150
mg/dl 3. HDL lt50 mg/dl 4. Blood pressure gt
130/85 5. Fasting Blood glucose 110-126 /or 2-h
glucose 140-199 mg/dl
16
Prevalence

• PCO on ultrasound - 20-33
• Oligomenorrhea - 4 21
• Oligomenorrhea hyperandrogenism - 3.5 9

17
Pathogenesis (etiology?)

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

18
OVARIAN STEROIDOGENESIS
LH
Theca cell
Cholesterol
17-20 Lyase
17 hydroxylase
Pregnenolone
17 OH-Pregnenolone
DHEA
T
17 OH-Progesterone
Androstenandion
Progesterone
Granulosa cell
Estrone
FSH
estradiol
19
Obesity
Insulin
IGF-1
SHBG
5-alfa reductase activity is stimulated
Free testosterone
IGF insulin like growth factor
20
Obesity and insulin resistance

• Diminished biological response to insulin
• In both obese and non obese
• In 40
• More in obese and oligomenorrhoeic
• Euglycaemia at expense of hyperinsulinaemia
• Obesity more of central -35-60

21
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
22
Presentation

• Amenorrhea-
• Oligomenorrhea
• Infertility
• Hirsutism
• Obesity
• Acne Vulgaris
• Asymptomatic

23
(No Transcript)
24
Laboratory studies

• Increased androgen levels in blood (testosterone
  and androstendione)
• Increased LH, exaggerated surge
• Increased fasting insulin
• Increased prolactin
• Increased estradiol and estrone levels
• Decreased SHBG levels

25
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)

26
Long term consequences

• Possible
• Hypertension
• Cardiovascular disease
• Gestational diabetes mellitus
• Pregnancy-induced hypertension
• Ovarian cancer
• Unlikely
• Breast cancer

27
Management

• Symptom oriented
• Diet exercise
• Wt. loss
• Improves both symptoms endocrine profile
• BMI gt30kg/ m2
• Keep CHO content down, avoid fatty food
• Obesity clinics

28
Contd

• Menstrual irregularities
• OCP- Yasmin, Dianette
• ET gt10mm(oligo), gt15mm(amen)-Withdrawal bleed
• Fails - Endometrial sampling

29
STEPWISE APPROACH FOR OVULATION INDUCTION IN PCOS
(ACOG,2002) 1. Weight loss If BMI gt30 K/m2 2.
Clomiphene citrate 3. CC corticosteroids if
DHES gt 2ug/ml 4. CC Metformin 5. Low dose FSH
injection 6. Low dose FSH injection
Metformin 7. Ovarian drilling 8. IVF
30
(No Transcript)
31
Mx of Hirsutism

• Cosmetic
• Medical- 6-7 months
• Cyproterone acetate EE, Spironolactone
• Reliable contraception
• Flutamide Finasteride - Rare

32
Reproductive Endocrinologist

• S.testosterone gt 5nmol/L
• Rapid onset hirsutism
• IGT/ Type2 DM
• Refractory symptoms
• Amen. gt 6 months
• Subfertility

33
Guidelines (RCOG, May 2003)

• 1-Patients presenting with PCOS particularly if
  they are obese, should be offered measurement of
  fasting blood glucose and urine analysis for
  glycosuria. Abnormal results should be
  investigated by a glucose tolerance test
• Such patients are at increased risk of
  developing type II diabetes (Evidence level
  IIbC)

• 2- Women diagnosed as having PCOS before
  pregnancy should be screened for gestational
  diabetes in early pregnancy
• Refer to specialized obstetric diabetic service
  if abnormalities detected (evidence level IIbB)

34
Guidelines (RCOG, May 2003)

• 3-Measurement of fasting cholesterol, lipids and
  triglycerides should be offered to patients with
  PCOS, since early detection of abnormal levels
  might encourage improvement in diet and exercise
  (Evidence level IIIC)

• 4- Olig- and amenorrhoeic women with PCOS may
  develop endometrial hyperplasia and later
  carcinoma. It is good practice to recommend
  treatment with progestogens to induce withdrawal
  bleed at least every 3-4 months (Evidence level
  IIaB)

35
Guidelines (RCOG, May 2003)

• 5- Evidence has accumulated demonstrating safety
  and efficacy of insulin-sensitizing agents in
  the management of short-term complications of
  PCOS, particularly anovulation. Long-term use of
  these agents for avoidance of metabolic
  complications of PCOS cannot as yet be
  recommended (Evidence level IVB)

• 6- No clear consensus regarding regular screening
  of women with PCOS for later development of
  diabetes and dyslipidemia
• Obese women with strong family history of cardiac
  disease or diabetes should be assessed regularly
  in a general practice or hospital outpatient
  setting. Local protocols should be developed and
  adapted (Evidence level IVC)

36
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 IIIC)

37
Thank you