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Transcript
Polycystic ovarian syndrome
Lec.4
Dr.Alyaa
2016/2017
Background
Rotterdam criteria for diagnosing PCOS
Requires the presence of two out of the following
three variables and
exclusion of other disorders:
• Irregular or absent ovulations.
• Clinical or biochemical signs of
hyperandrogenism:( acne, hirsutism, alopecia.)
• Polycystic ovaries on pelvic USS: ≥ 12 antral
follicles on one ovary or ovarian volume >10mL.
Aetiology: genetics
Pathophysiology and labrotory finding:
- Hyperandrogenism and anovulation in PCOS is caused by
endocrine abnormality
- High intraovarian androgen concentration inhibit follicular
maturation.
- E1 level is increased.
- Elevated LH and LH:FSH ratio and elevated prolactin level in
25% of patients.
- There is insulin resistance and compensatory
hyperinsulinaemia as a result of PCOS and obesity. Insulin
is a potent stimulus for secretion of androgen by the ovary
also it suppress the synthesis of SHBG by the liver thus
elevate the free androgen index. Patient are at increased
risk of glucose intolerance or frank diabetes.
Clinical features
The clinical features of PCOS are as follows:
• oligomenorrhoea/amenorrhoea in up to 75 percent
• hirsutism;
• subfertility in up to 75 per cent of women;
• obesity in at least 40 per cent of patients; central
type with higher waist to hip ratio
• recurrent miscarriage in around 50–60 per cent of
women;
• acanthosis nigricans
• may be asymptomatic.
Investigations
• Basal (day 2–5): LH, FSH, TFTs, prolactin, and
testosterone.
• If hyperandrogenisim:
- dehydroepiandrosterone sulphate (DHEAS)
- androstenedione
- SHBG.
• Exclude other causes of secondary
amenorrhoea.
• Pelvic USS.
These investigation will show the following results:
Ultrasound: increased stromal thickness and increased
ovarian volume (>10 cm3)(specific for PCOS),and the
presence of 12 or more follicles measured 2-9 mm in
diameter.
Serum endocrinology:
Increase serum LH
Increase serum LH : FSH ratio
Increase serum androgen (testosterone and
androstenedione)
Decrease SHBG
Increase estradiol and estrone
Increase serum prolactin.
Increase serum insulin level.
Impaired glucose tolerance .
Gross appearance of polycystic ovary.
Ultrasound picture of polycystic ovary.
Examination
• BMI.
• Signs of endocrinopathy, hirsutism, acne, alopecia,
acanthosis nigricans.
Long-term health consequences of PCOS
• Ischaemic heart disease(7 fold increase in MI).
• Type II diabetes is a known risk of obesity and insulin
resistance, and pregnant women with PCOS are at
increased risk of gestational diabetes, abortion & preeclampsia .
• endometrial hyperplasia and, endometrial carcinoma.
• There is also increased morbidity in obese PCOS who fails
to reduce their weight.
Management of PCOS:
The options should focus on the main concern
of the woman:
- Lifestyle modification:
- Menstrual irregularities:
- Hyperandrogenism and hirsutism :
- Treatment of infertility in PCOS:
Lifestyle modification
weight loss through exercise and diet has been
proven effective in restoring ovulatory cycles and
achieving pregnancy.
Menstrual irregularities:
• Weight loss.
• COCP: low dose combined oral contraceptive
preparation.
Progesterone as medroxy progesterone acetate
(provera) Or dydrogesterone (duphastone) for 12
days every 1-3 months to induce withdrawal
bleeding.
• Metformin.
Hyperandrogenism and hirsutism :
modified Ferriman and Gallway score may be used to
evaluate the degree of hirsutism before and during
treatment .
1. Physical treatment (Cosmetic) :depilatory cream,
waxing & bleaching, electrolysis, shaving, plucking,
Laser and photothermolysis .
2. Medical treatment:
a. COCP:
- First line is diane (ethinylestradiol 30 Mg with
cyproterone acetate 2mg.CPA may cause liver
damage, diane increase the risk of
thromboembolism.
- reduces serum androgen levels by increasing SHBG
levels
- providing a regular monthly withdrawal bleed and
beneficial antiandrogenic effects.
b. Antiandrogens such as eflornithine facial cream,
finasteride, flutamide or spironolactone(is a weak
diuretic with antiandrogenic properities can be
used at a daily dose of 25-100 mg ). they:
- can be used to help with acne and hirsutism
- can take 6–9mths to improve hair growth
- avoid pregnancy with usage of contraception
(feminizes a male fetus).
Hirsutism in PCOS patient
After hormonal treatment
Treatment of infertility in PCOS:
1. life style modification
2.Medical Induction of ovulation in PCOS
patient by
a. antioestrogen : - clomiphene citrate . Tamoxifene.
b. gonadotrophin :
c. GnRH analogues
d. Metformin
3. Surgical method of ovulation induction
4. IVF
2.Medical Induction of ovulation in PCOS patient by
a. antioestrogen : - clomiphene citrate . : is an orally
active synthetic non steroidal compound with
oestrogenic and non oestrogenic properties.
It displace the oestrogen from it’s receptor at the
hypo-thalamic pituitary axis reduce it’s negative feed
back and encourage GnRH secretion.
It’s administered at 50 mg daily dose on day 2-6
A course of 6-12 cycles can be used with monitoring by
ultrasound for follicular response.
Ovulation is expected in 80% and pregnancy in 40% .
Adverse reaction to such treatment:
-Antioestrogenic side effect including thickening of
the cervical mucos and hot flushes in 10% of
women.
-abdominal pain ,nausea , vomiting .
-headache and visual disturbance.
-breast tenderness.
-reversible hair loss.
- ovarian hyperstimulation syndrome is rare in
<1%.
-Multiple pregnancy in 10%.
-Ovarian cancer.
Tamoxifen: has structure similar to
clomiphene .the recommended dose is 2040 mg per day from day 3 for 5 days it have
the same pregnancy rate as clomiphene
with less potent antioestrogenic action on
the cervical mucos.
b. Medical induction by gonadotrophin
used when the patient do not respond to
clomifene or fails to conceive after 6-12
ovulatory cycles.
- recombinant FSH or purified urinary hMG (FSH
and LH). Gonadotrophin treatment result in
cumulative Pregnancy rates of 40-50% and 1-2%
rate of OHSS.
c. GnRH analogues in ovulation induction : it’s
used in conjunction with gonadotrophin to
achieve pituitary down regulation to facilitate
cycle control
d. Metformin : this is an oral biguanide decrease the
secretion of insulin and treat hyperinsulinaemia.
decrease hyperandrogenism and abnormalities of
gonadotrophin secretion and can restore menstrual
cyclicity and fertility.
The usual dose is 850 mg bid or 500 mg t.d.s. taken Before
meal .
Side effect of metformin: nausea ,vomiting , flatulance and
diarrhoea .
Metformin is not usually cause Lactic acidosis in non diabetic
patient with PCOS with normal liver and renal Function.
Regular checking of renal and liver function, metformin
should discontinued for 3 days after iodine containing
compound and should be discontinued during pregnancy.
3. Surgical method of ovulation induction
Laparoscopic ovarian diathermy LOD: by diathermy or
Laser, slim patient with high LH level. A unipolar
coagulating current is used to deliver four punctures
to a depth of 4 mm in each ovary . fewer multiple
pregnancy rate with the cumulative pregnancy rate
similar to those obtained with 3-6 cycle of
gonadotrophin.
LOD has replaces the wedge resection of the ovaries as
it result into extensive peri-ovarian and peritubal
adhesion.
4. IVF if ovulation cannot be achieved or does not
succeed in pregnancy.
- increased risk of (OHSS).