- PCOS is a common endocrine disorder affecting women of reproductive age, characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries. - Its pathophysiology involves increased androgen production by the ovaries and ovaries containing arrested follicles. - Treatment involves lifestyle modifications, medication to induce ovulation or reduce androgen levels, and a multidisciplinary approach involving dietitians, physicians, and fertility specialists.

1. POLYCYSTIC OVARIAN
SYNDROME (PCOS)
TL KHUMALO
30 AUGUST 2018

2. • Dr TL Khumalo hails from Durban, KwaZulu-Natal, currently practicing as a
Specialist Obstetrician and Gynaecologist in Edendale Regional Hospital
(Pietermaritzburg)
• She obtained her undergraduate degree at the Nelson R. Mandela School of
Medicine and obtained her Fellowship in Obstetrics and Gynaecology via the
University of KwaZulu-Natal in 2016
• She has keen interests in seeing both Maternal health and the stigmatized
Disorders of Sex development improve
• She has research interests in Infertility management in low resource
settings
• Her research interests are in the field of Sexual Reproductive Health

3. DISCLOSURES
• NIL DISCLOSURES

4. OUTLINE
• BACKGROUND
• DEFINITION / PREVALENCE
• ISSUES RELATED TO PCOS
• APPROACH TO MANAGEMENT

6. SYNDROME
Greek Etymology
Sun
~
TOGETHER
DRAMEIN
~
TO RUN
SYNDROME
SunDRAMEIN
~
TO RUN TOGETHER

7. BACKGROUND
• 1935 : Stein IF and Leventhal ML designated PCO as a syndrome
• ’80s/’90s : Addition of ultrasound criteria
• 2003 : Rotterdam Consensus Conference
• 2018 : International evidence-based guideline for the
assessment and management of polycystic ovary syndrome 2018

8. BACKGROUND
2018:
International evidence-based guideline for the assessment and management
of polycystic ovary syndrome 2018
• Over 3 000 delegates
AIMS
SUPPORT OPTIMAL PATIENT CARE
ASSIST CLINICAL DECISION MAKING
PROVIDE CLEAR INFORMATION

9. BACKGROUND
• Ovarian Theca Cells >> Under the control of LH/IGF-1 >> Produces
Testosterone >> Granulosa cells convert (Aromatase enzyme) to active
Oestradiol
• Increased androgen production
• Increased free androgens

10. PCOS

11. CONTROVERSIES
• Rotterdam criteria is over 10yrs old
• Serum AMH is under intense debate
• Misnomer of the term poly“cystic” which is referring to aarested
follicles not cysts
• COCP and the WHO MEC (2015)
• Ethics of Distributive Justice

12. PATHOPHYSIOLOGY

13. PCOS
OA
~
Oligo-Anovulation
HA
~
Hyper-androgenism
PCOM
~
Polycystic Ovarian Morphology

14. OA:Oligo-Anovulation
• Primary / Secondary Amenorrhoea
• Oligomenorrhoea
• Less than 8 episodes of menses a year
• Cycle length exceeding 35 days (n:21-35)
• Complications PCOM diagnosis on US > No longer recommended in
the presence OA

15. OA:Oligo-Anovulation Mx
AIM
• Balance the steroid hormones (ER/PR)
Compete with Oestrogen at
receptor level /Hypothalamic level
Block conversion to active
hormone – Inhibit Aromatase
enzyme
Anti-oestrogenic action
Anti-androgenic /
Anti-oestrogenic action

16. OA:Oligo-Anovulation Mx
• Increase SHBG
• Suppress of FSH/LH > Negative Feedback on the axis
• Reduction in free circulating Androgens
• Regulation of menses > Risk reduction of endometrial hyperplasia / EC
Low dose COCP

17. OA:Oligo-Anovulation Mx
• 35mcg Ethinyloestradiol + Cyproterone Acetate not for 1st line in PCOS
• Consider combining with Metformin in Adolescents or BMI ≥ 25kg/m²
• Regulation of menses > Risk reduction of endometrial hyperplasia / EC
Low dose COCP

18. HA: Hyperandrogenism

19. HA: Hyperandrogenism
Biochemical
FSH:LH Ratio
Testosterone
DHEAS
AMH
Clinical
Hirsutism
Acne
Alopecia
Virilisation
• Grade the Hirsutism > modified Ferriman-Gallwey score
• Mx: Block the peripheral action of hair follicle 5α Reductase >
Testosterone to Di-hydrotestosterone therefore blocked

20. HA: Hyperandrogenism Mx
• Grade the Hirsutism > modified Ferriman-Gallwey score (1961)
• Rx: Block the peripheral action of hair follicle 5α Reductase >
Testosterone to Di-hydrotestosterone therefore blocked
• Lifestyle modification
• COCP + Drosperinone / Desogestrel / Norgestimate
• Anti-androgens :
• Spironolactone 50-200mg / day
• Cyproterone Acetate 50-100mg (5-15days Induction / Maintenance)
*Ensure adequate contraception / Prevent under virilisation of the male foetus*

21. HA: Hyperandrogenism Mx
Insulin Lowering / Increase Insulin Sensitisation
• Generally off-label / EBM practice
• Under the control of LH/IGF-1 : Ovarian Theca Cells produce
Testosterone
• Adjunctive BMI ≥ 25kg/m² for Ovulation induction
• Metformin 500mg tds > Slow release preferred
• Reduces Hepatic Glucose production / Lowering Insulin levels
• Possible improvement in Ovarian Steroidogenesis

22. HA: Hyperandrogenism Mx
GnRHa
• Blockade of GnRH > Blockade of FSH / LH
• Zoladex 3.6mg s/c (3-6 months)
• Leuprolide 3.75mg imi (3-6 months)
• Add-back therapy if intolerable side-effects
• 25-30mcg transdermal Oestradiol
• Tibolone is great for oestrogen withdrawal
• S/E: Hot flashes, Reduce Bone mineral density, Atrophic vaginitis, FSD

23. HA: Hyperandrogenism Mx
Anti-androgens + COCPs if no control of HA > 6mo

24. PCOM: Polycystic Morphology

25. PCOM: Polycystic Morphology
• Challenge is not so much the size or volume
• US has poor sensitivity in the background of OA /HA
• Arrest of Pre-antral follicles
• Failure of LH surge
• Leading to failure of Ovulation

26. MULTI-DISCIPLINARY TEAM
Gynaecologist Dietician
Physician/Endocrinologist Fertility Specialist
Support Groups

27. Mx of PCOS
Dietician
• Lifestyle modification
• Moderate exercise (30 minutes /week)
• Target to normalize BMI
• Reduction of adipose tissue > Reduces
peripheral sites for Androgen production
• Higher spontaneous pregnancy rates with
lifestyle adjustments

28. Mx of PCOS
• Metabolic control
• IGT / Insulin Resistance
• Risk of Metabolic syndrome
secondary to Obesity
• Higher incidence of Depressive /
Anxiety Disorders
Physician/Endocrinologist

29. PCOM: Infertility

30. Mx of PCOS
Gynaecologist Fertility Specialist
OVULATION INDUCTION AGENTS
• Letrozole
• Clomiphene Citrate (CC) 50mg / 100mg /150mg
• CC + Metformin

31. OVULATION INDUCTION
LETROZOLE
• Aromatase inhibition
• Anti-oestrogenic > Reduction up to
98% in Oestrogen levels
• FDA approved for HR+ Breast cancer
• Competitively blocks production by
binding to the haeme of its CP450
unit
• Does not reduce production of
mineralo-corticosteroids
OVULATION INDUCTION
AGENTS
• Letrozole
• Clomiphene Citrate
• CC + Metformin
• 2.5mg/d usual dosage
• Doses exceeding 2.5mg/d
may cause reduced libido

32. OVULATION INDUCTION
Clomiphene Citrate
• Mechanism of stimulating ovulation
remains elusive
• Anti-oestrogenic properties
• Competes with Oestrogen binding
sites
• Increase in FSH / LH
• Pre-ovulatory LH surge / Corpus
luteum maturation
OVULATION INDUCTION
AGENTS
• Letrozole
• Clomiphene Citrate
• CC + Metformin
• 50mg / 100mg / 150mg
• Half-life: 5 – 7 days
• Time to peak: 4 – 10 days
• Average 7 days

33. OVULATION INDUCTION
OVULATION INDUCTION
AGENTS
• Clomiphene Citrate

34. Mx of PCOS
Support Groups
www.pcosaa.org
#PCOSsupport

36. Take Home Message