Polycystic Ovary Syndrome(PCO)

By: Prof. Dr. Rizwana Chaudhri

Head of the Gynae/Obs Unit - I

Holy Family Hospital, Rawalpindi.

Rawalpindi Medical College, Rawalpindi.

Holy Family Hospital, Rawalpindi. Faisal Mosque & Margalla Hills, Islamabad.

College of Physicians & Surgeons Pakistan.

PCO

Commonest endocrine disorder in women.

Prevalence- 15- 20%.

Complex Interaction of Environmental and

Genetic factors.

Runs in families , effecting 50% first degree

relatives.

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

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

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)

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

PAINTINGS OF BEARDED WOMEN

Brigida del Rio (1590)

Painted by

Sanchez Cotán (1560-1645))

Maddalena Ventura

Painted by

José de Ribera (1631)

PATHOPHYSIOLOGY

Hyperandrogenism.

Menstrual disturbances.

Infertility.

Obesity.

Asymptomatic.

SYMPTOMS

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

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

SERUM ENDOCRINOLOGY

↑Fasting insulin

↑Androgens.

↑LH, normal FSH.

↓SHBG.

↑Oestradiol.

↑Prolactin.

POSSIBLE LATE SEQUELAE

Diabetes mellitus.

Dyslipidemia.

Hypertension.

Cardiovascular disease.

Endometrial carcinoma.

Breast cancer.

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

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

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

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

23

TRIGGERING SIGNALSTRIGGERING SIGNALS

MANAGEMENT

Mainly symptom oriented

Loose weight: BMI < 30 Kg/m2.

Diet/Dietician help.

Exercise.

Drugs.

OBESITY

MENSTRUAL IRREGULARITY

Dianne 35

Low Dose OCP

Progestogens

Induction of ovulation

HYPERANDROGENISM / HIRSUTISM

1. Physical treatment.

2. Medical treatment.

1. PHYSICAL TREATMENT:

Waxing

Electrolysis

Bleaching

Laser

Photothermolysis

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

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

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

THE 3 STEPS OF ANDROGEN METABOLISMIN WOMEN

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

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

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

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

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

HYPERINSULINAEMIA

METFORMIN:

Ameliorates hyperinsulinaemia and

hyperandrogenism.

No effect on weight loss.

Dose: 850mg bd/500mg tds.

Further long term evaluation required.

INFERTILITY

Ovulation Induction:

WEIGHT REDUCTION IMP, to improve the prospects of both spontaneous and drug

induced ovulation.

Medical Method.

Surgical Method.

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.

2. PARENTRAL GONADOTROPHINS:

hMG, hCG, FSH.

6 month- CCR and LBR- 62%- 54% resp.

12 month-CCR and LBR-73%- 62% resp

SIDE EFFECTS:

Multiple pregnancy;

05 -10%.

Ovarian Hyperstimulation syndrome (OHSS);

0.5-10%.

SURGICAL OVULATION INDUCTION

1. Ovarian Wedge Resection.

2. Ovarian Diathermy

1. OVARIAN WEDGE RESECTION:

Used to be done in 1970’s.

Abandoned b/c:

* Extensive tissue loss.

* Extensive periovarian and tubal adhesions.

2. Laparoscopic Ovarian Diathermy (LOD)

• Technique40w, 04points, 04sec.

• Unilateral/Bilateral.

Laparoscopic Ovarian Diathermy

Laparoscopic Ovarian Diathermy

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.

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:

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%.

Risk of anaesthesia.

Risk of minimal adhesions.

Requires expertise.

DISADVANTAGES OF LOD

CONCLUSION

PCO syndrome is a mixed

clinical entity and should

be dealt with according to

the problems of the patients

hope we all have a better tomorrow

Thank You