PCOS- Polycystic ovarian syndrome Khalid

This document provides an overview of polycystic ovarian syndrome (PCOS). It discusses the introduction, aetiology, pathophysiology, clinical features, diagnostic criteria, investigations, treatment, and complications of PCOS. PCOS is the most common endocrine disorder in women of reproductive age and is characterized by menstrual irregularity and signs of hyperandrogenism. The cause is unknown but thought to involve genetic and environmental factors like obesity and insulin resistance. Diagnosis involves evaluating clinical signs, lab tests, and ultrasound imaging. Treatment aims to address symptoms and is individualized, involving lifestyle changes, medications, or surgery in some cases.

1. PCOS
Khalid Akkour, MD FRCSC

2. Objectives
•Define PCOS
•Understand pathophysiology
•Form an appropriate differential diagnosis
•Establish the work-up for PCOS
•Develop an array of therapies to treat complaints and
prevent bad outcomes

3. POLYCYSTIC OVARIAN SYNDROME (PCOS)
OVERVIEW
•PCOS is a complex endocrine disorder affecting
women of childbearing age characterized by
increased androgen production and ovulatory
dysfunction
•Prevalence 6-8% of normal population
•Leading cause of anovulatory infertility and
hirsutism
•Women with PCOS have an increased risk of
miscarriage, insulin resistance, hyperlipidemia,
type 2 diabetes, cardiovascular disease, and
endometrial cancer

4. PCOS and Stein-LeventhalSyndrome
oPCOS was first identified by Stein and
Leventhal in 1935
oThey described a group of women who were
obese and infertile, with enlarged ovaries
with multiple cysts
oFew of these original features are now
considered consistent findings in PCOS

5. PATHOPHISIOLOGY

6. •Insulin secretion and action
•Gonadotropin secretion and action
•Androgen biosynthesis and action
•Weight and energy regulation
•Environment factor

8. DIAGNOSTIC CRITERIA
AND
CLINICAL MANIFESTATIONS

9. •NIH Criteria
•Menstrual irregularity due to anovulation or oligo-ovulation
•Evidence of clinical or biochemical hyperandrogenism
•Hirsutism, acne, male pattern baldness
•High serum androgen levels
•Exclusion of other causes (CAH, tumors, hyperprolactinemia)

10. •RotterdamCriteria (2 out of 3)
•Menstrual irregularity due to anovulation oligo-ovulation
•Evidence of clinical or biochemical hyperandrogenism
•Polycystic ovaries by US
•presence of 12 or more follicles in each ovary measuring 2 to 9 mm
in diameter and/or increased ovarian volume
* In addition, other etiologies (congenital adrenal hyperplasias,
androgen-secreting tumors, Cushing's syndrome) must be excluded.

11. •AES criteria
presence of three features
•androgen excess (clinical and/or biochemical
hyperandrogenism)
•ovarian dysfunction (oligo-anovulation and/or polycystic
ovarian morphology)
•exclusion of other androgen excess or ovulatory disorders

12. MENSTRUAL DYSFUNCTION
•Oligo or amenorrhea
•Menstrual irregularity typically begins in the
peripubertal period
•Delayed menarche
•Reduction in ovulatory events leads to
deficient progesterone secretion
•Chronic estrogen stimulation of the
endometrium with no progesterone for
differentiation—intermittent breakthrough
bleeding or dysfunctional uterine bleeding
•Increased risk for endometrial hyperplasia
and/or endometrial CA

13. 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Hormone
Level
Estradiol
Progesterone
FSH
LH
Menstrual Cycle Day
Ovulation
Endometrial
Thickness
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Normal
Menstru
al Cycle

14. Hormone
Level
Estradiol
Progesterone
Endometrial
Thickness
0 2 4 6 8 10 12 14 16 18
20
0 2 4 6 8 10 12 14 16 18
20
Weeks
Breakthrough
Withdrawal
Anovulatory
Bleeding in
PCOS
Lower limit
of normal

15. HYPERANDROGENISM
•Hirsutism, acne, male pattern balding, alopecia
•50-90% patients have elevated serum androgen levels
•Free testosterone levels is the most sensitive
•Rare: increased muscle mass, deepening voice, clitormegaly
(should prompt search for underlying neoplasm)

16. OVARIAN ABNORMALITIES
•Thickened sclerotic cortex
•Multiple follicles in peripheral location
•80% of women with PCOS have classic cysts

18. Polycystic
Ovaries
Cystic
Follicles
Uterus
Tube
Anatomic Features of
the Polycystic Ovary

19. INFERTILITY
•Intermittent ovulation or anovulation
•Inherent ovarian disorder—studies show reduced rates of
conception despite therapy with clomid

20. OBESITY
•Prevalence of obesity varies from 30-75%
•2/3 of patients with PCOS who are not obese have excessive
body fat and central adiposity
•Obese patients can be hirsute and/or have menstrual
irregularities without having PCOS

21. OBESITY AND INSULIN RESISTANCE
•½ patients with PCOS are obese
•> 80% are hyperinsulinemic and have insulin resistance
(independent of obesity)
•Hyperinsulinemia contributes to hyperandrogenism through
production in the theca cell and through its suppressive
effects on sex hormone binding globulin production by the
liver

22. Acanthosis Nigricans
•Velvety plaques
on nape of neck
and intertriginous
areas
•Epidermal
hyperkeratosis
•Associated with
insulin resistance

23. DIFFERENTIAL DIAGNOSIS
1.Hyperprolactinemia
Prominent menstrual dysfunction
Little hyperandrogenism
2.Congenital Adrenal Hyperplasia
morning serum 17-hydroxyprogesterone
concentration greater than 200 ng/dL in the early
follicular phase strongly suggests the diagnosis
confirmed by a high dose (250 mcg) ACTH
stimulation test: post-ACTH serum 17-
hydroxyprogesterone value less than 1000 ng/dL

24. 3. Ovarian and adrenal tumors
•serum testosterone concentrations are always higher than 150
ng/dL
•adrenal tumors: serum DHEA-S concentrations higher than 800
mcg/dL
•LOW serum LH concentrations
4. Cushing’s syndrome
5. Drugs: danazol; OCPs with high androgenicity

25. TESTING
•Serum HCG
•Serum prolactin
•Thyroid function test
•FSH: r/o ovarian failure
•Serum luteinizing hormone (LH)—elevated
•Serum estradiol—normal
•Serum estrone—elevated

26. TESTING
•Fasting glucose: elevated
•2 hour OGTT: elevated
•Fasting insulin: elevated
•Free testosterone: elevated
•DHEA-S: normal
•17-hydroxyprogesterone: normal
•Pelvic US
•Lipids

27. Total Testosterone (T)
DHEA-S (DS)
17-hyroxyprogesterone (17-OHP)
T > 200 ng/dl
DS > 700 μg/dl
Suspect Tumor
17-OHP > 2 ng/ml
Suspect CAH
T Elevated
±
DS Elevated
DS Elevated
T & DS Normal
PCOS
Adrenal
Idiopathic
Laboratory Evaluation

28. TREATMENT

29. •Depends on goal of treatment

30. WEIGHT LOSS
•Weight loss
•Weight loss
•Weight loss

31. Hirsutism
•Mechanical hair removal
•OCPs with minimal androgenicity
•OCP plus antiandrogen (spironolactone)
•Spironolactone, 50-200 mg per day
•Flutamide
•Potential hepatic dysfunction

32. Oral Contraceptives
•Suppress ovarian androgen
•Increase SHBG
•Regular menstrual cyclicity
•Estrogen opposition
•Contraception

33. Anti-androgens
•Spironolactone
•Flutamide
•Finasteride

34. Spironolactone
•Androgen receptor blockade
•Steroid enzyme inhibition
•Aldosterone antagonism
•Lower blood pressure
•Potassium sparing
•Dose: 100-200 mg/day

35. Flutamide
•Non-steroidal, selective anti-
androgen
•Liver function tests
•Dose: 125-250 mg/day

36. Oligomenorrhea
•Combination estrogen-progestin pill first line when fertility is
not desired
•Decrease in LH secretion and decrease in androgen production
•Increase in hepatic production of sex-hormone binding globulin
•Decreased bioavailablity of testosterone
•Decreased adrenal androgen secretion
•Regular withdrawal bleeds
•Prevention of endometrial hyperplasia

37. TREATMENT—NO FERTILITY DESIRED
•Monophasic antiandrogenic OCP
•ON 1/35 (norethindrone)
•Orthocyclen (norgestimate)
•Desogen or Orthocept (desogestrel)
•Yasmin

38. insulin-sensitizing agents
•Metformin
•will restore ovulation and menses in >
50% of patients
•Treat with cyclic progestin to reduce
endometrial hyperplasia if regular
menses not attained
•10 mg for 7 to 10 days every two to four
months

39. METFORMIN
•Decreases hepatic glucose production
•Reduces need for insulin secretion
•Improves insulin sensitivity (increases peripheral glucose
uptake and utilization)
•Antilipolytic effect—reduces fatty acid concentrations and
reduces gluconeogenesis

40. SIDE EFFECTS
•Diarrhea, nausea, vomiting, flatulence,
indigestion, abdominal discomfort
•Caused by lactic acid in the bowel wall
•Minimized by slow increase in dosage
•Lactic acidosis—rare
•Avoid in CHF, renal insufficiency, sepsis
•Discontinue for procedures using contrast
(withhold X 48 hours)
•Temporarily suspend for all surgical procedures
that involve fluid restriction
•Cimetidine causes increased metformin levels

41. INFERTILITY TREATMENT
•Metformin
•Metformin 500 mg once a day with breakfast for 4 days
•Metformin 500 mg twice a day with breakfast and dinner for 4
days
•Metformin 500 mg with breakfast and 1,000 mg with dinner for
4 days
•Metformin 1,000 mg twice daily
•Clomid
•50 mg days 3-7 for 3 months
•100 mg days 3-7 for 3 months

42. METFORMIN DOSING
•Target—1500-2000 mg per day
•Clinically significant responses not regularly observed at
doses less than 1000 mg per day

43. Infertility
•Weight loss—reduction in serum testosterone
concentration and resumption of ovulation
•Clomid: 80% will ovulate, 50% will conceive
•Metformin: when added to clomid, improves
ovulatory rates
•Laparoscopic surgery: wedge resections,
laparoscopic ovarian laser electrocautery
•IVF

44. Key points
•PCOS is the most common endocrine disorder in
reproductive-aged women.
•PCOS is a lifelong disease beginning in fatal life and
extending into the postmenopausal period.
•Hyperinsulinemia is the mainfactor in the
pathogenesis.
•PCOS is an inherited disorder thatfollows an
autosomal dominant inheritance pattern although the
gene or genes involve are unknown

45. •Hyperandrogenemia with or without
hyperandrogenism along with
oligomenorrhea are hallmark features of
PCOS
•Anovulationresulting in infertility is a
common presentation
•Obesity worsens metabolic abnormalities
such as hyperinsulinemia and
hyperandrogenemia.

46. •Diabetes, lipid disorder, heart disease and
endometrial cancer are metabolic
sequelae of PCOS.
•Insulin-sensitizing agent heave
dramatically changes the management of
PCOS. Metformin, an insulin-sensitizing
agent, is now first choice for the
treatment of anovulation in PCOS. Weight
loss and exercise are the best long term
therapy to decrease the metabolic
sequelae of PCOS.

47. References
•Berek & Novak’s Gynecology
•Clinical gynecology / [edited by] Eric J. Bieber, Joseph S. Sanfilippo,
Ira R. Horowitz
•Uptodate.com
•Polycystic ovary syndrome : a guide to clinical management / Adam
Balen ... [et al.]
•Polycystic ovary syndrome / edited by R. Jeffrey Chang, Jerrold J.
Heindel, Andrea Dunaif.
•ACOG practice bulletin, polycystic ovary syndrome
•The ovary / editors, Peter C.K. Leung, Eli Y. Adashi
•Clinical gynecologic endocrinology and infertility / Leon Speroff,
Marc A. Fritz

48. Thank You