EVIDENCE BASED MANAGEMENT FOR PCOS

1. CLINICAL FEATURES AND
MANAGEMENT OF
POLYCYSTIC OVARIAN
SYNDROME
DR. Okechukwu Ugwu

2. OUTLINE
• Introduction
• Epidemiology
• Pathophysiology
• Diagnostic criteria
• Clinical features
• Management
• Recent advances
• Conclusion
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3. INTRODUCTION
• PCOS is a public health issue with reproductive, metabolic and
psychological features
• It is one of the most common Endocrinological conditions in
reproductive aged women
• Frequently begins around time of puberty.
• It is a heterogeneous collection of signs/symptoms- spectrum
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4. EPIDEMIOLOGY
• PCOS is the most common condition associated with chronic anovulation
• It affects 8-13% of reproductive-aged women
• It’s prevalence among infertile women is 15% to 20%.
• with up to 70% of affected women remaining undiagnosed
• Presentation varies by ethnicity
• Studies in Nigeria : 18.1% (Ugwu et al) to 31.22% (Adelusi et al) in infertile women.
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5. PATHOPHYSIOLOGY-1
• In contrast to the cyclic pattern of hormone concentrations that
occurs during the normal cycle, the endocrine milieu in women with
chronic anovulation is characterized by a “steady state” in which
gonadotropin and sex steroid concentrations vary relatively little
• Disruption of HPO axis
• Hyperinsulinemia and hyperandrogenism
• Familial and genetic link
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6. PATHOPHYSIOLOGY-2
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7. DIAGNOSTIC CRITERIA
• (ESHRE/ASRM) –
1. Oligo- and/or anovulation.
2. Hyperandrogenism (clinical and/or biochemical).
3. Polycystic ovaries (12 or more peripheral follicles, 2-9 mm
diameter & ovarian vol. (> 10cm3) on TVS.
One single ovary may fulfill this sonographic criteria.
Exclude other causes of androgen excess.
Elevated LH/FSH ratio- inconsistency
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8. CLINICAL FEATURES
• Women with PCOS present with diverse features
• Psychological (anxiety, depression, body image)
• Reproductive (irregular menstrual cycles, hirsutism, infertility and
pregnancy complications)
• Metabolic features (insulin resistance (IR), metabolic syndrome,
prediabetes, type 2 diabetes (DM2) and cardiovascular risk factors)
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9. Menstrual irregularity
• This occurs in 60-85% of women with PCOS (>35 days)
• It is the most common reason for a gynaecological presentation.
• Classically, menstrual dysfunction in women with PCOS has a
premenarcheal onset
• Fewer than nine menstrual periods in a year
• Approximately 15–40% are eumenorrheic despite evidence of oligo-
anovulation
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10. INFERTILITY
• Chronic anovulation
• Oocyte quality
• Endometrial or implantation abnormalities- hostile androgen
environment
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11. OBESITY
• The prevalence of obesity is approximately 50%
• Although they can also have normal body mass index (BMI) or even
underweight.
• Obesity predisposes to chronic anovulation in at least three distinct
ways:
• a) Increased peripheral aromatization of androgens, resulting in
chronically elevated oestrogen concentrations.
• b) Decreased levels of hepatic SHBG production, resulting in
increased circulating free estradiol and testosterone.
• c) Insulin resistance
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12. ACNE/OILY SKIN
• Its prevalence among women with PCOS varies with ethnicity.
• it is unclear whether acne is more prevalent among women with PCOS than in the
general population.
• The extent to which PCOS may increase risk for developing acne, if at all, is
therefore uncertain
• Approximately one-third of PCOS patients have acne.
• Increased levels of androgens stimulate enlargement of the sebaceous glands.
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13. HIRSUTISM
• Hirsutism is the growth of terminal hairs on the face or body in a male pattern.
• It is the most obvious clinical indicator of androgen excess and is an important
feature of PCOS.
• PCOS accounts for 65 to 75 % of hirsutism
• The modified Ferriman-Gallwey score is the most common method for grading
the extent of hirsutism, assigning a score from 0–4 in each of 9 androgen-sensitive
areas.
• The threshold value that defines hirsutism ranges from 4 and 6.
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14. SCALP ALOPECIA
• PCOS can be associated scalp hair loss.
• Uncommon feature, occurring in <5% of women with PCOS
• Typically, the hair loss is limited to the crown and does not involve the
frontal hair line
• 25% or more of scalp hair must be lost before thinning becomes
apparent
• widening of the hair parting is an early sign of androgenic alopecia
• The Ludwig visual score is preferred for assessing the degree and
distribution of alopecia.
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15. ACANTHOSIS NIGRICANS/HAIR-AN SYNDROME
• It is reported in up to 5% of women
with PCOS.
• Acanthosis nigricans is a
mucocutaneous condition leading to a
dark and velvety appearance.
• Insulin resistance leads to
keratinocytes and dermal fibroblast
growth causing increased keratin
deposits and pigmentation.
• The lesions are most common in the
axillae, nape of the neck, under the
breasts and in skin flexures.
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16. GLUCOSE INTOLERANCE
• Insulin resistance is a common feature in obese and, to a lesser extent, lean women
with PCOS
• prevalence ranges between 50% and 75%.
• Insulin sensitivity is decreased by an average of 35–40% in women with PCOS
• Up to 35% of these women exhibit IGT and 7–10% meet criteria for type 2
diabetes mellitus.
• Conversely, women with type 2 diabetes are 6-fold more likely than non-diabetic
women of similar age and weight to have PCOS.
• This happens when the pancreatic islet cells can no longer compensate with
Hyperinsulinemia.2/20/2019 16Okey Ugwu

17. ENDOMETRIAL HYPERPLASIA/CANCER
• Unopposed oestrogen secretion is a risk factor for endometrial
hyperplasia and carcinoma.
• women with PCOS and abnormally heavy or prolonged bleeding
should be investigated for endometrial pathology by endometrial
biopsy.
• 3 fold risk of endometrial cancer.
• No increase risk of breast or ovarian cancer.
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18. CARDIOVASCULAR DISEASE
• It is recognised that obesity, hyperandrogenism, hyperlipidaemia and
hyperinsulinaemia are cardiovascular risk factors.
• The long-term risk of developing atherosclerosis, hypertension and
myocardial infarction is greater.
• Despite the increase in cardiovascular risk factors, morbidity and
mortality from coronary heart disease among women with PCOS has
not been shown to be as high as predicted.
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19. RECURRENT PREGNANCY LOSS
• Mechanism not clear.
• Risk of 30 to 50 % for early miscarriage compared to 15 % base line.
• Possible aetiologies: hyper LH secretion and Insulin resistance .
• Women with a history of recurrent miscarriage in the presence of
PCOS should still have investigations to exclude other possible
causative factors.
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20. OBSTRUCTIVE SLEEP APNOEA
• They exhibit increased risk of sleep disorders including increased
daytime fatigue/somnolence and snoring
• Sleep apnoea is an independent cardiovascular risk factor and has
been found to be more common in PCOS
• The strongest predictors for sleep apnoea were fasting plasma insulin
levels and glucose-to-insulin ratios
• Very rare
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21. PRINCIPLES OF MANAGEMENT
• Symptom- based.
• Restore menstruation, ovulatory cycles & fertility
• Improve Acne & Hirsutism
• Prevent endometrial hyperplasia/ Carcinoma
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22. HISTORY
• Menstrual history
• History of androgenic symptoms
• Body-weight changes, eating and exercise habits.
• Past history of infertility or recurrent miscarriages.
• Family history of PCOS, diabetes, hypertension obesity, premature
balding
• History of skin darkening
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23. EXAMINATION
• Assessment of obesity: weight, height, BMI, waist and hip
circumference and waist– hip ratio.
• Assessment of hyper -androgenism and rule out virilization.
• Blood pressure measurements.
• Thyroid and breast examination.
• Pelvic examination: clitoral inspection
• Loss of vagina rugae may suggest virilization
• Bimanual examination can sometimes confirm enlargement of the
ovaries
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24. INVESTIGATIONS
• Pregnancy test (B-HCG)
• Hormonal profile: FSH, LH, Prolactin, TSH, mid-luteal phase progesterone.
• Testosterone
• SHBG
• Glucose tolerance test
• Lipid profile
• Ultrasound (transvaginal) examination of ovaries and endometrial thickness
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25. INVESTIGATIONS
• Free androgen index
• progesterone challenge test
• Endometrial biopsy
• Infertility work up: SFA /MCS, HSG, Laparoscopy
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26. TREATMENT
• The management of women with PCOS should seek to correct or prevent both its
immediate and longer-term clinical consequences
• which may include :
• Menstrual abnormalities.
• Endometrial hyperplasia and neoplasia.
• Hyperandrogenism (hirsutism, acne, alopecia).
• Infertility.
• Increased risk for developing type 2 diabetes.
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27. TREATMENT-2
• Counsel on weight loss
• Lifestyle modification through diet and exercise
• Weight loss reduces insulin and androgen levels .
• Ovulation and normal menses can be restored with just 10 % weight
loss.
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28. TREATMENT -3
Menstrual irregularity and prevention of endometrial
hyperplasia
• COCPS first line- avoid Norgestrel and Levonorgestrel
• Progesterones (Provera 5-10mg for 12days every 4-8 weeks ).
• Mirena IUS.
• Metformin can restore ovulatory menses in many women with PCOS
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29. TREATMENT- 4
Hirsutism
Physical Rx. Shaving,Chemical depilation&/bleaching, waxing,plucking
,electrolysis and Laser.
Medical Rx. 1. Oral contraceptives Estrogen+Non androgenic
progesterone- Norgestimate, norethindrone, desogestrel.
2. Diannete- EE (30mcg) + CPA (2mg)
3. Spironolactone 25-100mg dly.
4. EE + Drospirenone (Yasmin)
5. Other anti androgens – Ketoconazole, finasteride &
Flutamide.
6. Eflorthinine (vaniqua) Topical cream.
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30. TREATMENT- 5 ACNE
• Combined oral contraceptive pills
• May include anti androgens ( flutamide)
• 5alpha reductase inhibitors ;eg (finestride)
• Topical and systemic antibiotics (erythromycin, doxycycline)
• Benzoyl peroxide
• Topical retinoid
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31. TREATMENT-6
INFERTILITY
• Letrozole
• Clomiphene citrate
• Insulin sensitizing agents such as Metformin
• Tamoxifen
• Gonadotropins
• Laparoscopic ovarian drilling with laser or diathermy
• Invitro fertilisation/ET
• Dexamethasone/prednisolone
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32. LETROZOLE
• First line agent in medical induction of ovulation
• Non-steroidal compounds
• Aromatase enzyme inhibitor
• No effect on hypothalamic oestrogen receptors, thus NFB mechanism
remain intact
• Multiple folliculogenesis/pregnancy is reduced
• No deleterious effect on cervical mucus and endometrium
• Dose is 2.5 – 5mg daily, from day 2, 3, 4 or 5
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33. CLOMIPHENE CITRATE
• Selective estrogen receptor modulator
• Non steroidal triphenyl ethylene derivative
• Has both oestrogen agonist and antagonist properties.
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34. CLOMIPHENE CITRATE contd
• Dose 50 – 150mg daily for 5 days starting day 2, of
menstrual cycle.
• Doses > 150mg do not seem to confer any significant
increase in ovulation or pregnancy rate.
• Ovulation is achieved in 75% of cases and pregnancy in 35-
40% of women with PCOS
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35. CLOMIPHENE CITRATE contd
• Side effects include hot flushes, bloating ,abdominal distension,
multiple pregnancy and OHSS.
• Women with anovulation resistant to CC may respond to various
adjuvants to clomiphene .
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36. ROLE OF METFORMIN
• An oral biguanide and insulin sensitizer
• Does not cause hypoglycemia in normoglyceamic patients
• Dose is 1500-2500 mg daily in divided doses
• Reduces ovarian Androgen production by:
a) Reduction in insulin resistance and secretion
b) As well as direct action on ovarian theca cells
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37. TAMOXIFEN
• An anti-oestrogen.
• Mode of action similar to clomiphene.
• Administered 20-40mg daily from day 3 over 5 days
• Result similar to clomiphene
• Less anti-oestrogenic effect
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38. GONADOTROPINS
Indicated In failure to respond to clomiphene or failure of conception after 6-12 cycles.
Regimens-
Standard step up protocol
• starts with 150iu/day .
• Multiple pregnancy rate of 34%.
• OHSS rate of 4.6%
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39. LAPAROSCOPIC OVARIAN DRILLING
RULE OF 4
4 points in each ovary
4mm depth
40watts
4 seconds
Has replaced ovarian wedge resection
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40. In-vitro fertilisation (IVF)
• IVF +ET
• IVF ± intracytoplasmic sperm injection
• metformin commencement at the start of GnRH agonist treatment
• metformin use at a dose of between 1000mg to 2550mg daily
• metformin cessation at the time of the pregnancy test or menses
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41. Recent advances
• Extended regimen of clomiphene citrate for 10 days
• Aromatase inhibitors
• Thiazolidinediones (troglitazone, rosiglitazone and pioglitazone)
• InoFolic
• Myo-Inositol
• D-chiro-inositol
• Orlistat
• Rimonabant – weight reduction/improvement in cardio-metabolic profile
• Sibutramine- not recommended in women with systolic hypertension
• Bariatric surgery- in selected women with morbid obesity.
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42. CONCLUSION
• Polycystic ovary syndrome is a polygenic disorder likely involving the
interaction of numerous genomic variants and the influence of
environmental factors with varied manifestation. Diagnosis and
treatment is therefore important to correct the immediate and long
term complications.
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43. References
1. Clinical gynaecological endocrinology by Leon Speroff
2. International evidence based guideline on the assessment and
management of PCOS
3. Monash PCOS
4. CREPCOS
5. PCOS Network
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