Polycystic Ovary Syndrome

Polycystic Ovary Syndrom

Definition: It is a syndrome of ovarian dysfunction & endocrine problems associated with hyperinsulinemia. The diagnostic criteria of which include the following:
• Evidence of hyperandrogenism, biochemical or clinical(hirsutism acne & male pattern baldness).
• Ovulatory dysfunction; amenorrhoea;oligomenorrhoea.
• Morphological polycystic ovaries.

Women who have at least two of these criteria are said to have polycystic ovary syndrome. Polycystic ovaries diagnosed by ultra-sound should not be confused with PCOS. The ultrasonic picture of polycystic ovary is the presence of 12 or more follicles measuring 2-9 mm in diameter & increased ovarian volume (>10 cm3) on transvaginal ultrasound. A woman having PCO in the absence of an ovulation disorder or hyperandrogenism (asymptomatic PCO) should not be considered as having PCOS, although she may develop symptoms over time, e.g if she gain weight.

Prevalence: PCOS affect around 15-20% of women of reproductive age group.

Aetiology:
The exact aetiology is unknown.
• Genetic factor: the syndrome clusters in families, the prevalence in first degree relatives is 5-6 times higher than in the general population.
• Hormonal factors: Hypersecretion of androgens by theca cells lead not only to the cardinal clinical features of the syndrome, hyperandrogenism, but also lead to inhibition of follicular growth with resultant excess of immature follicles. Hypersecretion of LH stmulate excess production of testosterone by the ovary.
Insulin resistance occur in up to 60 % of women with PCOS especially in those with high BMI. The resultant hyperinsulinaemia stimulate LH- induced androgen production from the ovaries. In the liver elevated insulin causes a decreased production of sex-hormone binding globulin increasing the level of free androgen in the circulation.

Diagnosis:
Clinical features:
• Oligomenorrhoea/ amenorrhoea: related to chronic anovulation.
• Hirsutism.
• Subfertility.
• Obesity.
• Recurrent miscarriage.
• Acanthosis nigricance: areas of increased skin pigmentation occur in axillae & other flexures.

Laboratory test:
• Increased LH level
• Elevated LH:FSH ratio
• Elevated testosterone & androstenedione levels
• Decreased sex hormone-binding globulin
• Increased fasting insulin level or impaired glucose tolerance assessed by GTT.
• Increased prolactin level.

Ultrasound: twelve or more subcapsular follicular cysts <10mm in diameter with increased ovarian stroma (ovarian volume >10cm3 ).









Long-term health implications of PCOS:
include the following:
• Increased incidence of multiple pregnancy, gestational diabetes & pregnancy-induced hypertension.
• Increased incidence of type II diabetes mellitus, hypertension & hyperlipidaemia due to insulin resistance & hyperandrogenism respectively.
• Increased incidence of endometrial hyperplasia & endometrial carcinoma due to unopposed estrogen stimulation.



Treatment:
Treatment should be directed at the symptoms that the patient complains of, as follows:

Obesity:
in obese women (BMI >30 kg/m2) with PCOS, significant improvement in symptoms, endocrine profile & the likelihood of ovulation can occur with weight reduction. However this is difficult to achieve. Change in lifestyle with altered diet & exercise might be effective. The right diet for an individual is one that is practical, sustainable & compatible with her lifestyle.

Oligomenorrhoea/amenorrhoea:
estrogen level is normal or high, because of chronic anovulation there is unopposed estrogenic stimulation of the endometrium with the increased risk of endometrial cancer. Oligomenorrhoeic women tend to have infrequent but heavy bleeds. For these reasons, cyclical progesterone is useful to induce withdrawal bleeds & to protect the endometrium. Oral progesterone (e.g. medroxyprogesterone acetate 10 mg daily is given for 10 days every 1-3 months. The woman will bleed few days after the progesterone is stopped.
Alternatively for those who do not want to conceive oral contraceptive pills can be used. This will results in artificial cycles & regular shedding of the endometrium.

Infertility:
treatment include a number of steps:
• Weight loss : improve both spontaneous & drug induced ovulation.
• Clomiphene citrate: anti-estrogen used for ovulation induction by blocking estrogen receptors in the pituitary with a resultant increase in endogenous FSH production. It is given from day 2-6 of a natural or induced cycle. It is successful in inducing ovulation in 80% of women ,however pregnancy occur in only 40%. It should be prescribed only in a setting where US is available to minimize the 10% risk of multiple pregnancy & to ensure that ovulation is taking place. It can be used for six months.
• Gonadotrophin therapy: recombinant FSH & human menopausal gonadotrophin are both effective for ovulation induction in those with clomiphene-resistant PCOS. Because the polycystic ovary is very sensitive to exogenous hormones, it is very important to start with very low doses of gonadotrophins & follicular development must be carefully monitored. Also these women are at increased risk of developing ovarian hyperstimulation syndrome (OHSS). This occurs if too many follicles (> 10 mm) in diameter are stimulated & results in abdominal distension, discomfort, nausea, vomiting & sometimes difficult breathing.
• Laparoscopic ovarian drilling: with either diathermy or laser, this can lead to normalization of LH level with increasing ovulation & pregnancy rates. It is free of the risk of multiple pregnancy & ovarian hyperstimulation & does not require intensive US monitoring.
• Metformin: this biguanide inhibit the production of hepatic glucose & enhances the sensitivity of peripheral tissues to insulin, thereby reducing insulin secretion. it has a beneficial role in reducing insulin resistance which has a central role in the pathogenesis of PCOS. Metformin may also improve menstrual regularity & improve ovarian response to clomiphene. It is given in a dose of 850 mg bd or 500 mg tds. Side effects include anorexia, nausea, flatulence & diarrhea & may be reduced by taking metformin just before food & gradually increasing the dose from 850 mg nocte to 850 mg bd after 1 week.

Hirsutism:
The aim of treatment is to reduce the androgen level, increase sex hormone-binding globulin or reduce the activity of 5?-reductase enzyme at the level of the hair follicle.
Options include:
? Oral contraceptive pills: suppress ovarian androgen production & increase sex hormone-binding globulin.
? Cyproteron acetate: an anti-androgen which competitively inhibit androgen receptors.
? Spironolactone: aldosterone antagonist with anti-androgenic properties.
? Finasteride: 5?-reductase inhibitor.
? Physical methods of hair removal: bleaching, shaving, electrolysis of hair follicle & weight loss.



Acne:
is chronic inflammation of pilosebaceous unit. Increased androgen production cause an increased size of sebaceous glands & thus increased sebum production which then become colonized with abnormal microbial flora leading to inflammation.
Acne can be treated with keratolytic agents, antimicrobials & anti-androgenic drugs.