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Polycystic Ovary Syndrome(PCO)
By: Prof. Dr. Rizwana Chaudhri
Head of the Gynae/Obs Unit - I
Holy Family Hospital, Rawalpindi.
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Rawalpindi Medical College, Rawalpindi.
Holy Family Hospital, Rawalpindi. Faisal Mosque & Margalla Hills, Islamabad.
College of Physicians & Surgeons Pakistan.
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PCO
Commonest endocrine disorder in women.
Prevalence- 15- 20%.
Complex Interaction of Environmental and
Genetic factors.
Runs in families , effecting 50% first degree
relatives.
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PCO Polycystic ovarian morphology seen by ultrasound
PCOS 1
favoured in the UK
Polycystic ovaries on ultrasound, plus: symptoms (obesity, hyper-androgenism, menstrual cycle disturbance) and/or: biochemical abnormalities (elevated serum concentrations of testosterone and/or LH)
PCOS 2
favoured in North America
Hyperandrogenism and menstrual cycle disturbance
DEFINITIONS OF PCOS
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DEFINITION OF PCOS
• NIH-Criteria 1990
– Chronic anovulation
– Clinical and / or biochemical signs of hyperandrogenemia and exclusion of other causes
• Rotterdam-Criteria 2003
– Oligo- and / or anovulation
– Clinical and / or biochemical signs of hyperandrogenism
– Polycystic ovaries (Ultrasound) and exclusion of other causes (Adrenal hyperplasia, androgen-producing tumor, Cushing Syndrome)
ESHRE/ ASRM-sponsored PCOS Workshop GroupHuman Reprod. 19, 41, 2004
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HETEROGENOUS SYMPTOM COMPLEX
ESHRE/ASRM Definition:
Two out of following 03 criteria:
Oligo – &/or anovulation
Hyperandrogenism (clinical/ biochem.)
Polycystic ovaries.
(≥12 follicles, 2-9 mm and ovarian volume >10
cm3)
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SONOGRAPHIC CRITERIA OF PCOS
Classical criteria
1. Enlarged ovaries
2. At least 8-10 follocles with 2-10 mm diameter, grouped peripherally
3. Stromal hyperplasia
New criteria
Presence of at least one criterium:
1. Enlarged ovaries (>10 cm3)
2. Increased number of follicles (at least 12 between 2-20 mm diameter)
3. It is sufficient that only one ovary is changed
Adams et al BMJ 293, 355, 1986
Scematic presentation
Balen et al Human Reprod. Update 9, 505, 2003
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PAINTINGS OF BEARDED WOMEN
Brigida del Rio (1590)
Painted by
Sanchez Cotán (1560-1645))
Maddalena Ventura
Painted by
José de Ribera (1631)
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PATHOPHYSIOLOGY
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Hyperandrogenism.
Menstrual disturbances.
Infertility.
Obesity.
Asymptomatic.
SYMPTOMS
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FREQUENCY OF SYMPTOMS IN PCOS
Goldzieher und Green
Symptom Cases (n) Average (%) Range (%)
Infertility 596 74 35-94
Hirsutism 819 69 17-83
Amenorrhea 640 51 15-77
Obesity 600 41 16-49
Functional bleeding 547 29 6-25
Dysmenorrhea 75 23
Virilisation 431 21 0-28
Cyclic bleeding 395 12 7-28
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CLINICAL FEATURES OF PCOS
• PCOS is the most frequent endocrine disturbance in the reproductive phase of women
• Increased ovarian androgensecretion with oligo-anovulation and signs of androgenisation
• Frequently: overweight, impaired glucose tolerance, hyperlipidenemia, hypertension, increased risk of diabetes mellitus type 2, infertility
• Less frequent: acanthosis nigricans, sleep-apnoe
• No virilisationSchöfl et al Dt. Ärzteblatt 101,
346, 2004Hahn et al J. Lab. Med. 27,53,2003
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SERUM ENDOCRINOLOGY
↑Fasting insulin
↑Androgens.
↑LH, normal FSH.
↓SHBG.
↑Oestradiol.
↑Prolactin.
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POSSIBLE LATE SEQUELAE
Diabetes mellitus.
Dyslipidemia.
Hypertension.
Cardiovascular disease.
Endometrial carcinoma.
Breast cancer.
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PCOS - OVERVIEWPCOS - OVERVIEW
Biochemical
parameter
Increased LH-/ FSH-Ratio
Elevated Androgens
Perhaps elevated
Prolaktin
SHBG ↓
IFGBP-1 ↓
Hyperinsulinemia
Dyslipidanemia
Hyper-
androgenimea
Acne
Hirsutism
Seborrhoe
Alopecia
Abnormalities
in reproduction
CLI
Anovulation
Infertility
Abortion
Gestationaldiabetes
Preeclampsia
Metabolic
Disturbances
Obesity
Dysfibrinolysis
Dyslipidemea
Diabetes mellitus
Hypertension
Cardiovascular
Disease
De Leo et al Minerva Ginecologica 56, 53, 2004
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The highest reported prevalence of PCOS
has been 52% amongst South Asian
immigrants in Britain, of whom 49 % had
menstrual irregularities.
Rodin et al Clin. Endocrinol. 49, 91, 1998
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PCOS is likely to parallel the increase in
prevalence of insulin resistance and type II
diabetes, which is currently being observed
in the Asian population.
Balen et al Taylor & Francis London NY, 2005, 51
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GENETIC ASPECTS OF PCOS I
• PCOS have a high heriditary component
– 24 % of all mothers
– 33 % of all sisters
do have PCOS
Kalsar-Miller et al Fert. Steril. 75, 53, 2001
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23
TRIGGERING SIGNALSTRIGGERING SIGNALS
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MANAGEMENT
Mainly symptom oriented
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Loose weight: BMI < 30 Kg/m2.
Diet/Dietician help.
Exercise.
Drugs.
OBESITY
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MENSTRUAL IRREGULARITY
Dianne 35
Low Dose OCP
Progestogens
Induction of ovulation
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HYPERANDROGENISM / HIRSUTISM
1. Physical treatment.
2. Medical treatment.
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1. PHYSICAL TREATMENT:
Waxing
Electrolysis
Bleaching
Laser
Photothermolysis
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TREATMENT OF ANDROGENISATION
1. Estrogen/progestogen combination with an antiandrogenic progestin for instance: Diane 35®
2. Non-steroidal antiandrogens (spironolactone, flutamide, finasteride)
1. Alone
2. Combined with Diane 35®
3. Insulin sensitizing drugs e.g metformin
1. Alone
2. Combined with Diane 35®
4. Sequential therapy
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PREVALENCE OF ANDROGEN-RELATED DISORDERS IN WOMEN
Most common female endocrinopathy
– affecting about 10-20 % of women in the fertile age
– characterized by excessive androgen action
Many women with androgenic skin changes have
normal androgen levels
– suggesting increased target organ (receptor)
sensitivity to androgens
Hyperandrogenism may be of ovarian or adrenal origin
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DIANE-35 INDICATION
Androgen-dependent diseases in women
– Seborrhea
–Acne
–Mild to moderate cases of hirsutism
–Androgenetic alopecia
In women who also need or accept contraception
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THE 3 STEPS OF ANDROGEN METABOLISMIN WOMEN
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REASONS FOR ANDROGEN-RELATED DISORDERS IN WOMEN
Increased secretion of testosterone from the ovaries or
adrenals
Increase in the level of freely circulating androgens not
bound to transport protein (SHBG)
Increased enzyme activity (5a-reductase) in target
organs, i.e. increased production of biologically active
dihydrotestosterone (DHT)
Increased sensitivity of the target organs to DHT
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DIANE-35 DIANE-35 (CPA 2 MG / EE 35 µG)(CPA 2 MG / EE 35 µG)
Highly effective in the treatment of androgen-related disorders– based on antiandrogenic effect of CPA– supported by antigonadotropic activity of CPA/EE
combination
Very reliable contraception– based on progestogenic effect of CPA and
antigonadotropic effect of CPA/EE combination– comparable to other oral contraceptives– Pearl index 0.1
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ANTI-ANDROGENIC EFFECT OF DIANE-35
Receptor level: By competition with binding of
testosterone and DHT to their nuclear receptors
Enzymatic: increasing androgen metabolic clearance
at the hepatic level and reducing the peripheral
activity of 5a-reductase at skin level
Antigonadotropic: Reduction of LH secretion and
suppression of ovarian androgen secretion
Increase in SHBG and decrease of free testosterone
The anti-androgenic treatment used most: Diane-35
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DIANE-35 IN ACNE: ANTIANDROGENIC EFFECT ON THE TARGET TISSUE
Acne is the most common skin disease– affecting 80% of
females at some time after the onset of puberty
Most patients seem to have sebaceous glands that are hypersensitive to androgens
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SUCCESSFUL TREATMENT OF HIRSUTISM REQUIRES MORE TIME THAN ACNE THERAPY
Reduction of overall Ferriman-Gallway score with
Diane-35 (n=63)
% reduction 6 cycles 24 cycles 48 cycles
-18% -55% -72%60 cycles treatment with Diane-35 (n=140)
– Acne resolved in all cases after 12-24 cycles
– Hirsutism resolved in 69% of cases
• Moderate hirsutism in 100% of cases
• Severe hirsutism became mild to moderate in
80% of cases
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HYPERINSULINAEMIA
METFORMIN:
Ameliorates hyperinsulinaemia and
hyperandrogenism.
No effect on weight loss.
Dose: 850mg bd/500mg tds.
Further long term evaluation required.
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INFERTILITY
Ovulation Induction:
WEIGHT REDUCTION IMP, to improve the prospects of both spontaneous and drug
induced ovulation.
Medical Method.
Surgical Method.
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MEDICAL OVULATION INDUCTION
1. ANTIESTROGEN - (Clomiphene Citrate)
50 – 100 mg.
Ovulation – 80%.
Conception – 40%
Cumulative conception rate (CCR) continues to
increase for up to 10-12 cycles.
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2. PARENTRAL GONADOTROPHINS:
hMG, hCG, FSH.
6 month- CCR and LBR- 62%- 54% resp.
12 month-CCR and LBR-73%- 62% resp
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SIDE EFFECTS:
Multiple pregnancy;
05 -10%.
Ovarian Hyperstimulation syndrome (OHSS);
0.5-10%.
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SURGICAL OVULATION INDUCTION
1. Ovarian Wedge Resection.
2. Ovarian Diathermy
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1. OVARIAN WEDGE RESECTION:
Used to be done in 1970’s.
Abandoned b/c:
* Extensive tissue loss.
* Extensive periovarian and tubal adhesions.
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2. Laparoscopic Ovarian Diathermy (LOD)
• Technique40w, 04points, 04sec.
• Unilateral/Bilateral.
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Laparoscopic Ovarian Diathermy
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Laparoscopic Ovarian Diathermy
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MECH. OF ACTION OF LOD
Exactly not known:
Ruptures thick ovarian capsule.
Sensitizes ovary to endogenous /exogenous FSH.
End result is a decrease in LH and androgen
levels, restoring normal ovulation.
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Improved endocrine profiles.
Spontaneous ovulation.
Reduction in gonadotropin doses for ovulation
induction and hence reduction in cost of further
stimulated cycles.
Reduction in multiple pregnancy rates.
Reduction in first trimester abortions.
ADVANTAGES OF LOD
Continued:
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Reduction in ovarian hyper stimulation.
No prolonged USG follow ups.
Tubal patency checked at the same time.
A meta analysis showed pregnancy rates greater with
06 months gonadotrophins treatment, compared with
LOD but same after 12 months.
Conception rate with LOD in 12 months is 60-80%.
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Risk of anaesthesia.
Risk of minimal adhesions.
Requires expertise.
DISADVANTAGES OF LOD
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CONCLUSION
PCO syndrome is a mixed
clinical entity and should
be dealt with according to
the problems of the patients
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hope we all have a better tomorrow
Thank You