Polycystic ovarian syndrome
Dr.Alyaa
2016/2017
1
Background
• PCOS is the most common endocrine disorder in women.
• Responsible for 80% of all cases of anovulatory subfertility.
• Estimated prevalence is 5–10% of women of childbearing age.
• USS evidence of polycystic ovaries is seen in 25% of women.
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
The aetiology of PCOS is not completely clear, but there is often a family
history. It seems likely that a gene is important in its development.
Pathophysiology and labrotory finding:
- Hyperandrogenism and anovulation in PCOS is caused by endocrine
abnormality mainly in the ovary with the total testosterone level is usually
not more than twice the upper normal range(20-80 ng/dl).
- High intraovarian androgen concentration inhibit follicular maturation.
- E1 level is increased as a result of peripheral aromatization of
hyperandrogenisim .
- There is abnormal estrogen feed back at the hypothalamic pituitary gland
result in elevated LH and LH:FSH ratio and exhibit 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 by the presence of different type of receptor doesn’t exhibit
insulin resistance 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:
Polycystic ovarian syndrome
•
oligomenorrhoea/amenorrhoea in up to 75 percent of patients, predominantly
related to chronic anovulation;
•
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 (areas of increased velvety skin pigmentation occur in the
axillae and other flexures);
•
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 (not measured routinely as Very wide rang of
values).
Increase serum prolactin.
Increase serum insulin level.
Impaired glucose tolerance .
Examination
• BMI.
• Signs of endocrinopathy, hirsutism, acne, alopecia, acanthosis nigricans.
Long-term health consequences of PCOS
• Obesity, insulin resistance, and metabolic abnormalities including
Polycystic ovarian syndrome
dyslipidaemia are all risk factors for 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 & pre-eclampsia .
• Long periods of secondary amenorrhoea, with resultant unopposed
oestrogen, are a risk factor for endometrial hyperplasia and, if
untreated, 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
This is the cornerstone to managing PCOS in overweight women. Even a modest
weight loss (5%) can improve symptoms. Moreover, 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 :
A standirized scoring system as the 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: stop further progression and decrease the rate of hair
growth.
a. COCP:
- First line is diane (ethinylestradiol 30 Mg with cyproterone acetate 2mg.CPA
may cause liver damage, so require regular checking and once response is
achieved we should be switched to other COCP because diane can increase the
risk of thromboembolism.
- reduces serum androgen levels by increasing SHBG levels
Polycystic ovarian syndrome
- 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).
Treatment of infertility in PCOS:
1. life style modification
including diet reduction and exercise. A loss of 5-10%
of body weight in obese PCOS patients improve the prospect of both
spontaneous and drug induced ovulation
2.Medical Induction of ovulation in PCOS patient
by
a. antioestrogen : - clomiphene citrate . - Tamoxifene.
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 of a spontaneous and induced
menstrual cycle (increased by 50 mg /day till ovulation occur for a max. Dose.
A course of 6-12 cycles can be used in women who respond to treatment 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 enlargement, and ovarian hyperstimulation syndrome is rare in <1%.
-Multiple pregnancy in 10%.
-Ovarian cancer described in women receive treatment for more than 12 cycles.
Tamoxifen:
has structure similar to clomiphene .the recommended dose is 20-
40 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 :
Polycystic ovarian syndrome
Gonadotrophin are used when the patient do not respond to clomifene or fails to
conceive after 6-12 ovulatory cycles.
Preperation in common use include recombinant FSH or purified urinary human
menopausal gonadotrophin (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 inhibits the production of hepatic
glucose ,enhance the sensitivity of peripheral tissue to insulin thus decrease the
secretion of insulin and treat hyperinsulinaemia.
Metformin is shown to 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 . (these
can be reduced by taking the drug before the meal and by gradually increasing
the dose start with 850 mg nocturnal then 850 mg bid for the next week.
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 (although there is no evidence of Teratogenesis).
3. Surgical method of ovulation induction
Laparoscopic ovarian diathermy LOD: by diathermy or Laser, it appear to be
more successful in a 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 .The
principle advantage of ovarian drilling is monofollicular ovulation resulting in
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.
- Women with PCOS who undergo IVF are at increased risk of ovarian
hyperstimulation syndrome(OHSS).