POLYCYSTIC OVARIAN SYNDROME

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
2/20/2019 2Okey Ugwu

3. INTRODUCTION
• Most common endocrine disorder of reproductive aged women.
• It is a heterogeneous collection of signs/symptoms- spectrum
• With mild presentation in some but a severe disturbance of
reproductive , endocrine and metabolic function in others.
• Frequently begins around time of puberty.
• It is imperative not only to recognize it but also to delay or arrest its
metabolic sequelae
2/20/2019 3Okey Ugwu

4. HISTORICAL ASPECTS OF PCOS
• First described by Stein and leventhal in 1935- histological specimens taken
at wedge resection.
• Endocrinological criteria (elevated LH/FSH ratio) – 1960-70
• Pelvic Ultrasound/TVS in the l970s and l980s
• 1990 NIH criteria established for PCOS
• 2003 ESHRE/ASRM(Rotterdam, Netherlands) consensus definition of PCOS
2/20/2019 4Okey Ugwu

5. EPIDEMIOLOGY
• PCOS is the most common condition associated with chronic anovulation
• It affects 4–6% of reproductive age women
• It’s prevalence among infertile women is 15% to 20%.
• Studies in Nigeria : 18.1% (Ugwu et al) to 31.22% (Adelusi et al) in infertile
women.
2/20/2019 5Okey Ugwu

6. PATHOPHYSIOLOGY- 1
• PCOS is not a specific endocrine disorder having a unique cause or
pathophysiology.
• It is best viewed as a final common pathway in the chronic anovulatory
state.
• The characteristic PCO develops when a chronic anovulatory state persists
for a sufficient length of time.
• This results from a functional derangement, not from a specific central
or local defect.
2/20/2019 6Okey Ugwu

7. PATHOPHYSIOLOGY-2
• 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 increased androgen levels
• Familial and genetic link
2/20/2019 7Okey Ugwu

8. PATHOPHYSIOLOGY-3
2/20/2019 8Okey Ugwu

9. DIAGNOSTIC CRITERIA
• (ESHRE/ASRM) – sponsored PCOS consensus workshop group 2004)
agreed that presence of two of these three criteria.
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
2/20/2019 9Okey Ugwu

10. 2/20/2019 10Okey Ugwu

11. CLINICAL FEATURES
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
• Polymenorrhoea is very uncommon but can occur in <2% of untreated PCOS.
• Heavy break through bleeding can also occur.
2/20/2019 11Okey Ugwu

12. INFERTILITY
• Chronic anovulation is one of the most common causes of infertility
• Other causes include factors relating to oocyte quality or endometrial
and implantation abnormalities also might contribute
2/20/2019 12Okey Ugwu

13. 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
2/20/2019 13Okey Ugwu

14. 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.
• Peripheral conversion to more active metabolites like dihydrotestosterone lead to
further enlargement.
2/20/2019 14Okey Ugwu

15. 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 6 and 8.
2/20/2019 15Okey Ugwu

16. 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
• testosterone have been implicated as causative agents, with
conversion to dihydrotestosterone being the primary mechanism.
2/20/2019 16Okey Ugwu

17. 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 commonly in
the axillae, nape of the neck, under
the breasts and in skin flexures.
2/20/2019 17Okey Ugwu

18. 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 18Okey Ugwu

19. 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.
2/20/2019 19Okey Ugwu

20. 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.
2/20/2019 20Okey Ugwu

21. 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.
2/20/2019 21Okey Ugwu

22. 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
2/20/2019 22Okey Ugwu

23. PRINCIPLES OF MANAGEMENT
• Symptom- based.
• Restore menstruation, ovulatory cycles & fertility
• Improve Acne & Hirsutism
• Prevent endometrial hyperplasia/ Carcinoma
2/20/2019 23Okey Ugwu

24. 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
2/20/2019 24Okey Ugwu

25. 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 (mild clitoromegaly can occur
with PCOS)
• Loss of vagina rugae may suggest virilization
• Bimanual examination can sometimes confirm enlargement of the
ovaries
2/20/2019 25Okey Ugwu

26. INVESTIGATIONS
• Pregnancy test (B-HCG)
• Hormonal profile: FSH, LH, Prolactin, TSH, mid-luteal phase progesterone.
• Assessment of circulating androgens: free testosterone, 17-
hydroxyprogesterone, DHEAS.
• glucose insulin ratio measurement
• 24-hour urinary free cortisol
• Glucose tolerance test
• Lipid profile
• Ultrasound (transvaginal) examination of ovaries and endometrial
thickness
2/20/2019 26Okey Ugwu

27. INVESTIGATIONS
• progesterone challenge test
• Endometrial biopsy: in prolonged bleeding or thickened
endometrium on scan .
• Infertility work up: SFA /MCS, HSG, Laparoscopy
2/20/2019 27Okey Ugwu

28. TREATMENT
• The management of women with PCOS should seek to correct or
prevent both its immediate and longer-term clinical consequences
• which may include all of the following:
• Menstrual abnormalities.
• Endometrial hyperplasia and neoplasia.
• Hyperandrogenism (hirsutism, acne, alopecia).
• Infertility.
• Increased risk for developing type 2 diabetes.
• Increased risk for developing cardiovascular disease.
2/20/2019 28Okey Ugwu

29. 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.
2/20/2019 29Okey Ugwu

30. 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
2/20/2019 30Okey Ugwu

31. 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.
2/20/2019 31Okey Ugwu

32. 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
2/20/2019 32Okey Ugwu

33. TREATMENT-6
INFERTILITY
• Clomiphene citrate
• Insulin sensitizing agents such as Metformin
• Tamoxifen
• Letrozole
• Gonadotropins
• Laparoscopic ovarian drilling with laser or diathermy
• Invitro fertilisation/ET
• Dexamethasone/prednisolone
2/20/2019 33Okey Ugwu

34. CLOMIPHENE CITRATE
• Selective estrogen receptor modulator
• Non steroidal triphenyl ethylene derivative
• First line agent in medical induction .
• Has both oestrogen agonist and antagonist properties.
2/20/2019 34Okey Ugwu

35. 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
2/20/2019 35Okey Ugwu

36. 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 .
2/20/2019 36Okey Ugwu

37. 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
• Recent Studies have shown Metformin is significantly less effective
than clomiphene citrate alone and the addition of metformin
produced no significant benefit.
2/20/2019 37Okey Ugwu

38. METFORMIN contd
• Use of metformin is only recommended when there is impaired
glucose tolerance or type two diabetes mellitus.
• Might be tried in those that are clomiphene resistant.
• Retrospective studies suggest might help reduce pregnancy loss in
those with proven insulin resistance.
• A recent Cochrane review has also concluded no benefit of metformin
in achieving an increased rate of live birth either alone or in
combination.
2/20/2019 38Okey Ugwu

39. 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
2/20/2019 39Okey Ugwu

40. 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%
2/20/2019 40Okey Ugwu

41. LAPAROSCOPIC OVARIAN DRILLING
2/20/2019 41Okey Ugwu

42. 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.
2/20/2019 42Okey Ugwu

43. CONCLUSION
2/20/2019 43