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

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. Polycystic Ovarian Morphology
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
Reduce Androgen excess
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
Reduce Androgen excess
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
Reduce Androgen excess

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 mg / day
Cyproterone Acetate mg (5-15days Induction / Maintenance)
*Ensure adequate contraception / Prevent under virilisation of the male foetus*
S/E: GI distress, Breast tenderness, Headache, Increased weight, Emotional lability

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
Ovulation induction / Androgen symptoms /Menstrual irregularity
S/E: GI distress, Breast tenderness, Headache, Increased weight, Emotional lability

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
Ovulation induction / Androgen symptoms /Menstrual irregularity
S/E: GI distress, Breast tenderness, Headache, Increased weight, Emotional lability

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

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 AGENTS
Letrozole
Clomiphene Citrate
CC + Metformin
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
2.5mg/d usual dosage
Doses exceeding 2.5mg/d may cause reduced libido
Competitively blocks production by binding to the haeme of its CP450 unit: Action specific to Letrozole
Long-term use not advised >> S/S of hypo-oestrogenism, esp Osteoporosis >> Usually prescribed with Fosamax (Bisphosphonate)

32. OVULATION INDUCTION AGENTS
Letrozole
Clomiphene Citrate
CC + Metformin
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
50mg / 100mg / 150mg
Half-life: 5 – 7 days
Time to peak: 4 – 10 days
Average 7 days
Rare cases ovulation may occur late (14 days from last day of treatment)

33. OVULATION INDUCTION AGENTS
Clomiphene Citrate
Rare cases ovulation may occur late (14 days from last day of treatment)

34. Mx of PCOS
Support Groups
#PCOSsupport

36. Take Home Message