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Polycystic Ovarian Syndrome

Polycystic Ovarian syndrome is a complex hormonal condition that may cause infertility, excessive weight gain, acne or excessive hair growth.  It is a highly complex disorder and so I shall try to simplify it. 

What is Polycystic ovarian syndrome?

A syndrome is a collection of symptoms and signs that appear together. Usually when we talk of a syndrome, it is because we do not know the actual disease process that produces the symptoms. So it is with PCOS. PCOS is not just about the ovaries, it is a "whole body disease". 
It has been defined by the European Society for Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM) PCOS Consensus Workshop Group.  (Rotterdam Criteria)
This has suggested a broader definition for PCOS, with two of the three following criteria being diagnostic of the condition:

● polycystic ovaries (either 12 or more peripheral follicles or increased
ovarian volume greater than 10 cm3 )
● oligo- or anovulation  (little or no egg production)
● clinical and/or biochemical signs of hyperandrogenism  (the effect of too much male hormone).


A raised luteinising hormone/follicle-stimulating hormone ratio is no longer a diagnostic criterion for PCOS owing to its inconsistency.  It should be noted that the diagnosis of PCOS can only be made when other aetiologies have been excluded. The recommended baseline screening tests are thyroid function tests, a serum prolactin and a free androgen index (total testosterone divided by sex hormone binding globulin (SHBG) x 100 to give a calculated free testosterone level). In cases of clinical evidence of hyperandrogenism and total testosterone greater than 5 nmol/l, 17-hydroxyprogesterone should be sampled and androgen-secreting tumours excluded. If there is a clinical suspicion of Cushing syndrome, this should be investigated according to local practice.

It would seem to affect, to some extent, perhaps 30% of the female population of child bearing age.
We know that it is a disorder of the normal control of the menstrual cycle. The Pituitary gland instructs the ovaries to ovulate (release the egg) and then to produce the hormone progesterone with the release of a burst of luteinising hormone (LH) in the normal cycle but in this condition, the circulating LH is high throughout the month. It seems that the ovary is unable to respond by producing progesterone and instead produces hormones that are related to progesterone but act much more like androgens (male hormones). These produce many of the distressing symptoms.

Excess fat could be caused by these hormones which are like the anabolic steroids used by body builders. However, obesity could be a cause of the problem as it counteracts the action of insulin (insulin resistance). This leads to excess production of insulin by the body. There are changes in chemicals which signal satiation (having eaten enough) possibly leading to over eating.  .  There is some evidence suggesting that a relative insulin resistance is developed during intrauterine life and is the cause of this syndrome. 

If pregnancy occurs, it is important to mention the PCOS to your Obstetrician in view of this relative Insulin resistance.
Also there is a reduction in sex hormone binding globulin (SHBG). This will usually bind the small quantities of testosterone (male hormone) in the blood rendering the bound portion inactive. A reduction in SHBG, therefore, makes more testosterone active.
The lack of progesterone is recognised by the brain which instructs the pituitary gland to produce more LH and so a vicious cycle is set up.

The incorrect instructions to the ovarian follicles means that they do not develop to the stage of producing an egg (or is it their inability to develop properly that is the cause of all this? We do not know). The arrested follicles take up a position just under the surface of the ovary giving rise to the name of the syndrome and a particular picture on ultrasound examination.  There is also a thickened capsule to the ovary.

How does PCOS present to us in the clinic?

Most commonly, PCOS is found in my subfertility clinic.  Women who have none of the gross symptoms or signs of PCOS, are found on investigation to have a raised LH (on more than one occasion in a cycle) and a typical ultrasound picture.
Secondly, irregular or absent periods in women who are not seeking a pregnancy may lead to this diagnosis.

Rarely, women attend simply because of facial hair growth. Although many cases are due to a racial variant of normal, it is distressing that they have often spent many years and many pounds relying on cosmetics without a diagnosis.
The extreme presentation of a fat hairy woman with absent periods and huge polycystic ovaries as described by Stein and Leventhal in the 1930s is very rare.

How can we treat PCOS?

The treatment depends very much upon the distressing symptom and the desires of the woman for pregnancy.

Cosmetic approach:  Weight loss is vital and may be all that is necessary for normal ovulation to resume. It might be helpful, for those who are unable to lose weight by diet and exercise, to take a course of a drug such as Xenical (Roche Ltd) which interferes with fat absorption or Reductil (Abbott Labs).
Electrolysis, laser treatment and depilatory creams are often used to reduce facial hair. Recently, a new cream has been licensed for this purpose. Vaniqa (eflornithine 11.5% cream, Shire Pharmaceuticals Ltd.) is not an anti-androgen but slows hair growth in the area to which it is applied. It should not be used before proper investigation of the reason for the hirsutism.

Anti-androgen drugs:       The oral contraceptive pill Dianette contains the anti-androgen cyproterone acetate and is the treatment of first choice for a woman with androgenic symptoms (e.g. acne or hirsutism) and who does not wish to conceive. (Other drugs which may sometimes be used include: cyproterone in higher dose, spironolactone, flutamide or finasteride. none of these is actually licensed for use in PCO.)

Fertility drugs:      Clomifene citrate is usually the first line of treatment for those seeking a pregnancy. More complicated fertility treatment may be appropriate for some women.

Drugs affecting insulin resistance:       Metformin is used for non-insulin dependent diabetics. It is being used more and more for obese women with PCOS to reduce the insulin resistance

Surgical treatment:         Wedge resection of the ovary has been found to be helpful. However this is an open operation and risks adhesion formation. We, therefore, usually drill a series of holes in the ovarian capsule at laparoscopy. This seems to be as effective and  may allow normal ovulation or permit a greater response to a lower dose of clomifene

Ovarian Drilling

Ovarian Drilling

What other risks might I have?
Sleep apnoea is an independent cardiovascular risk factor and has been found to be more common in PCOS. The difference in prevalence of sleep apnoea between PCOS and controls remained significant even when controlled for BMI.  It has been reported that the strongest predictors for sleep apnoea were fasting plasma insulin levels and glucose-to-insulin ratios.  This leads to disturbed sleep and daytime fatigue.
It has been suggested that women with PCOS may have a higher cardiovascular risk than weight-matched controls with normal ovarian function.  They have increased cardiovascular risk factors such as obesity, hyperandrogenism, hyperlipidaemia and hyperinsulinaemia.  Despite the increase in cardiovascular risk factors, morbidity and mortality from coronary heart disease among women with PCOS has not been shown to be as high as predicted. 
Women who have been diagnosed as having PCOS before pregnancy (such as those requiring ovulation induction for conception) should be screened for gestational diabetes before 20 weeks of gestation, with referral to a specialist obstetric diabetic service if abnormalities are detected. 
It has been known for many years that severe oligo- and amenorrhoea in the presence of premenopausal levels of estrogen can lead to endometrial hyperplasia and carcinoma. In women with PCOS intervals between menstruation of more than 3 months may be associated with endometrial hyperplasia.  Regular induction of a withdrawal bleed with cyclical progestogens for at least 12 days, oral contraceptive pills or the Mirena® intrauterine system would be advisable in oligomenorrhoeic women with . No 33  December 2007

http://www.rcog.org.uk/files/rcog-corp/uploaded-files/GT33_LongTermPCOS.pdf

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