Polycystic Ovarian Syndrome is heterogeneous, multisystem endocrinopathy in women of reproductive age characterized by chronic anovulation resulting in infertility, irregular bleeding, obesity and hirsutism. Most common, although the least understood, cause of androgen excess. Initially it was described in 1935.Also known as Stein-Leventhal syndrome The slide includes: Introduction Incidence Pathophysiology Pathology Clinical features Investigation Treatment

1. Polycystic Ovarian Syndrome (PCOS)
Prepared by:
Anish Dhakal (Aryan)

2. Contents:
1. Introduction
2. Incidence
3. Pathophysiology
4. Pathology
5. Clinical features
6. Investigation
7. Treatment

4. INTRODUCTION
• Heterogeneous, multisystem endocrinopathy
in women of reproductive age
• Chronic anovulation resulting in infertility,
irregular bleeding, obesity, hirsutism
• Most common, although the least understood,
cause of androgen excess
• Initially described in 1935
• Also known as Stein-Leventhal syndrome

5. INTRODUCTION
Rotterdam criteria
• Two out of the following three criteria should
be present:
1. Oligomenorrhoea and/or anovulation
2. Hyperandrogenism (clinical and/or
biochemical)
3. Polycystic ovaries, with the exclusion of
other aetiologies

8. INCIDENCE
• Affects 4–6% of women
• Incidence is fast increasing due to change in lifestyle
and stress
• Most common cause of anovulation
• 20–25% of women with normal ovulation
demonstrate ultrasound findings typical of polycystic
ovaries

11. PATHOPHYSIOLOGY
• Remains incompletely clear
• Insulin resistance with resultant hyperinsulinaemia
initiates PCOS in 50–70% cases. Cause of
hyperinsulinaemia and insulin resistance is also not
entirely known
Obesity in PCOS excess adipose tissue
Increase secretion of leptin, adiponectin and cytokines
interfere with insulin signaling pathways in the liver and
muscle insulin resistance and hyperinsulinaemia

13. Pathophysiology:
Chronic anovulation: Steady state LH/FSH.
No progesterone. Irregular bleeding
Increased androgens: LH stimulation of theca cells &
decreased SHBG from liver. Free testosterone rises
(Hirsutism)
Enlarged ovaries: Multiple peripheral cystic follicles
fail to mature an apoptosis ceases due to increased
androgens. Premature follicle atresia despite follicle
stimulation from steady state FSH

14. Causes for Increased Androgen Level:
Increased frequency of GnRH pulses, so LH
rises
Insulin stimulates theca cells with LH to
produce androgens
Insulin also synergistically act with androgens
to decrease hepatic production of SHBG, thus
increasing free or active testosterone

15. ENDOCRINOLOGICAL CHANGES:
• Oestrone/E2 level rises
• LH level is raised over 10 IU/mL
• FSH level remains normal, LH/FSH level >3
• SHBG level falls due to hyperandrogenism
• Testosterone and epi-androstenedione levels rise
• Thyroid function tests may be abnormal
(hypothyroidism)
• Cytochrome P450c17:a multifunctional enzyme that
converts C21 steroids to the C19 sex steroid precursor
DHEA might be increased

16. PATHOLOGY
• Ovaries are usually 2–5 times the normal size,
graywhite with a smooth outer cortex, and studded
with subcortical cysts
• Multiple cysts (12 or more) of 2–9 mm size are
located peripherally along the surface of the ovary

17. PATHOLOGY
• Ovary which amounts to more than 10 cm3 in
volume
Enlarged ovaries secondary to:
1. Excessive follicles
2. Theca cells and Stromal hyperplasia
3. Thickened capsule

18. CLINICAL FEATURES
• Young woman; Central obesity (BMI>30kg/m3)
• Oligomenorrhoea (87%), amenorrhoea (26%) followed
by prolonged or heavy periods. Dysmenorrhoea is absent
• Infertility (20%)
• Pregnancy loss (20–30%)
• Hyperandrogenism : Hirsutism, Acne, Acanthosis
nigricans

20. INVESTIGATION:
• Ultrasound is diagnostic of PCOS
 It shows 12 or more small follicles each of 2–9 mm
in size placed
peripherally
 It rules out ovarian
tumor
 It shows endometrial
hyperplasia if present

22. Management:

23. Goal of management
• To cure a women with menstrual disorder
• To treat hirsutism
• To treat infertility
• To prevent long term effect of X syndrome in
later life

24. Non
pharmacological
Pharmacological Surgical
Management

25. Non pharmacological Therapy:
• Weight loss:
– Weight loss of more than 5% of previous weight alone is
beneficial in mild hirsutism
– It restores the hormonal milieu
– It increases secretion of sex hormone binding globulin
from liver thereby reducing testosterone level.
– Reduces insulin level
• Lifestyle:
– smoking cessation (lowers E2 levels and raises DHEA and
androgen levels)

27. Pharmacological
To maintain regular menstruation cycle
– Oral combined pills
– OC and cyproterone acetate
– OC and spironolactone (spironolactone inhibit 5
alpha reductase so less DHT formation)
– Ketoconazole (200 mg daily of ketoconazolereduces
testosterone secretion)

28.  Suppresses androgens and adrenal hormones
(DHEA)
 Raises the secretion of SHBG in the liver, which
binds with testosterone, reduces free testosterone
 Also suppresses LH
 Given as low-dose combined pills, having
progestgen with lesser androgenic effect
Oestrogen

29. • 4th generation combined pills (containing 30 μg E2
and 2-3 mg drospirenone progestogen with anti-
androgenic action)
– Reduces acne and further hirsutism
– Prevents water retension and reduces weight.
– Maintain lipid profile
• Progestogen- to induce menstruation in
amenorrhoeic woman prior to initiating hormonal
cyclical therapy
• OC with cyproterone - if the woman has hirsutism

31. Hirsutism:
• Acne can be managed by 1% clindamycin lotion or 2%
erythromycin gel if pustules form
• For severe acne, isotretinoin is used (MUST be avoided in
pregnancy)
– Takes 3-6 months to show the effect effect on hirsutism
• Antiandrogens like cyproterone, spironolactone, Flutamide
can be given for hirsutism
• Dexamethasone (0.5 mg) at bedtime reduces androgen
production
– used in some infertile women with clomiphene if DHEA-S > 5
ng/mL.

32. Treatment of Infertility:

33. Infertility:
• Clomiphene, 1st line treatment for PCOS with infertility
• Class of drug: Partial Estrogen Agonist
• MOA:
– It induces GnRH secretion in women by blocking estrogenic
feedback inhibition of pituitary. The amount of LH/FSH
released at each secretory pulse is increased. In response,
the ovaries enlarge and ovulation occurs if the ovaries are
responsive to gonadotropins.
• Antagonism of peripheral actions of estrogen results in
hot flushes
• Endometrium and cervical mucus may be modified

34. How to prescribe?
• Can be started at any time if women suffers from
amenorrhoea
• In normal cycles, Day 2 of cycle (50mg), once daily for 5
days
• Monitoring by USG starting from 10th day onwards until
signs of ovulation is observed, normal daily rise in size
of follicle is 1-2mm
• After dominant follicle reaches 20mm, hCG 5000 IU is
injected IM

35. Contd..
• 36-40 hours after hCG administration, ovulation
occurs– so couples are advised to have intercourse
around this time
• Cyclical therapy is advised for 6 months after which
break is given for 2-3 months
• If follicular size not more than 20mm, increase dose
upto 150mg or same dose for seven days
• Clomiphene + dexamethasone improves fertility

36. Side Effects of Clomiphene:
• Ovarian enlargement
• Hot flushes, sweating
• Visual disturbances
• Headache, dizziness, allergic skin reactions
• Anti estrogenic in cervical mucus and
endometrium
• >1 year: low grade ovarian cancer
• Ovarian hyperstimulation syndrome
• Multiple pregnancy(10%)

37. Contraindications
• Ovarian cyst- the cyst can increase in size
• Chronic liver diseases- metabolized in liver
• Scotoma

38. Failure to Clomiphene
• In resistant case: Tamoxifen 20-40 mg daily for 5
days or off-label letrozole (2.5 mg daily for 5 days or
20 mg single dose on day 3) should be tried
• Failure to above therapy: FSH, LH or GnRH analogues
are used
• A woman with insulin resistance requires metformin
in addition
• For raised level of homocysteine, N-acetyl-cysteine
1.2 g may be added to clomiphene therapy
• N-acetyl-cysteine (NAC) is a mucolytic drug and
insulin-sensitizer

39. Metformin
• To treat root cause, rectifies endocrine and metabolic
functions, improves fertility rate, is used as insulin
sensitizer
Class of drug: Biguanide
– Inhibition of hepatic glucose production
– Decrease intestinal glucose absorption, increase peripheral
insulin sensitivity
– Also reduces the level of total and free testosterone and
increases the sex hormone binding globulin

40. Clomiphene superior to Metformin?

41. Both are shown to be equally
efficacious in many studies

43. Side effects:
• GI disturbances and lactic acidosis
• Contraindicated in hepatic and renal disease
(so acarbose 300mg is used)
• Starting with 500 mg daily, the dose is
gradually increased to 500 mg three times a
day (taken just before meals)

44. Surgery
• Reserved for
– Medical therapy fails
– Hyperstimulation occurs
– Infertile women
– Previous pregnancy losses
– Surgery comprises laparoscopic drilling or puncture of not
more than four cysts in each ovary either by laser or by
unipolar electrocautery
– Restores endocrine milieu, improves fertility for a year or so.
– Pelvic adhesions caused by surgery may again reduce fertility
rate.

46. • Tubal testing with chromotubation can be performed
simultaneously.
• Other causes of infertility, i.e. endometriosis looked for.
• One-time treatment
• Intense and prolonged monitoring not required.
• Cost effective compared to IVF
• Reduces androgen and LH production
• Following surgery, single ovulation occurs with drugs, and
hyperstimulation and multiple pregnancy are avoided
• Ovulation occurs in 80-90% and pregnancy in 60-70%
Advantages of Surgery:

47. Disadvantages of Surgery:
• Surgery involves anaesthesia and laparoscopy
• Adhesions may form postoperatively
• Premature ovarian failure due to destruction
of ovarian tissue if cautery is used. For this
reason, many now prefer simple puncture of
the cysts

50. Appropriate Counselling:
• PCOS can recur
• Any form of treatment: to give temporary
relief, may be required to be repeated,
varied at various times during her
reproductive years
• To ensure that in the long term diabetes and
endometrial cancer may develop

51. Prevention
• Not entirely preventable
• Adequately treated at earliest.
• Obesity in adolescents avoided and corrected
• Lifestyle changes recommended

52. References:
• Padubidri V.G., Daftary S. N., Howkins and Bourne Shaw’s
Textbook of Gynaecology, 16th edition, chapter 32
“polycystic ovarian syndrome” page 431-434.
• Gyanecology by Ten Teachers
• DC Dutta’s Textbook of Gyanecology
• William’s Gynecology
• B. Roebrt, Treatment of PCOS in adults,
https://www.uptodate.com/contents/treatment-of-
polycystic-ovary-syndrome-in-adults
• E. David et al,
https://www.uptodate.com/contents/diagnosis-of-
polycystic-ovary-syndrome-in-adults