Polycystic ovary syndrome (PCOS)

Written by Dr David Cahill, consultant senior lecturer on obstetrics and gynaecology

What can your doctor do?

Your family doctor will be able to provide many of the drug treatments available (although these are probably best taken in consultation with a specialist). Treatments aim to improve several aspects of PCOS, including:

fertility, via the stimulation of ovulation

reduction of the insulin resistance

reduction of the increased hair.

Treatments

The range of treatments available and their application are listed in Tables 1 and 2.

Table 1 deals with the treatments for improving fertility in women with PCOS (Homberg, 1998; Pirwany et al, 1999; Farquhar et al, 2000; Hughes et al, 2000a; Hughes et al, 2000b; Hughes et al, 2000c).

Table 2 deals with the treatments for other features of PCOS including hirsutism, irregular or absent periods and obesity. The evidence in favour of using of these medications to improve symptoms is not strong (Lee et al, 2000).

Table 1: Treatments to improve fertility in women with polycystic ovary syndrome
Drug and mode of action	Benefits	Risks	Effects on life quality
Clomifene: mild stimulant of ovarian function (Hughes et al, 2000a).	Effective method to achieve ovulation.	1. Very low risk of ovarian hyperstimulation syndrome.	1. Simple easy method of treatment with tablets to be taken by mouth, for five days each month.
		2. Possible risk of multiple pregnancy if several mature follicles develop.	2. Minimal effects while taking tablets, though some develop headaches.
		3. Increased risk of ovarian tumours in women having more than 12 cycles of treatment.	3. Obvious benefit if pregnancy ensues (pregnancy also lowers the increased risk of ovarian tumour back to that of the normal population).
Gonadotrophin injections: direct stimulation of the ovarian follicles to grow.	Ovulation rates of over 90 per cent in most women and pregnancy rates of 20-25 per cent per cycle.	1. Ovarian hyperstimulation syndrome.	1. Require daily injections of hMG or FSH derived from urine or recombinant FSH (Hughes et al, 2000c).
		2. Multiple pregnancy if many mature follicles develop.	2. Several studies suggest the benefits of taking a second drug in conjunction. This should suppress LH and improves the chances of an ongoing pregnancy.
Metformin: many actions - eg reduction of male steroid production by the ovaries.	Improves the uptake of sugars into cells by insulin. Ovulation rates up to 90 per cent of cycles (Pirwany et al, 1999, Galtier-Dereure et al, 1997).	No significant associated risk.	Considerable gastrointestinal upset reported - particularly diarrhoea - which is somewhat improved by reducing the daily dose.
Gonadotrophin releasing hormone agonists: stimulate the release of natural sex hormones from the brain.	Lowers LH concentrations and reduces the likelihood of miscarriage (Homberg, 1998, Hughes et al, 2000b).	Needs to be used in conjunction with FSH injections and therefore all the above risks also are present. GnRH agonists themselves have little risk in short-term use.

Table 2: Treatments for other features of polycystic ovary syndrome
PCOS feature	Available treatment	Comments
Raised androgen (male sex hormone) level	Metformin	1. Metformin reduces the abnormal findings of raised androgens and decreased sex-hormone binding protein in the blood, but it can cause considerable gastrointestinal upset - particularly diarrhoea - which is somewhat improved by reducing the daily dose. It is less effective in women of normal weight and does not improve hirsutism.
Irregular periods	Metformin	1. Return of periods in 90-95 per cent of women.
Obesity	Metformin	1. Several studies have examined the effect on weight loss; the majority support its effectiveness.
Hirsutism	Combined oral contraceptives, especially containing the anti-androgen cyproterone acetate (eg Dianette).	1. These increase the levels of the sex hormone carrier in the blood, leaving less androgen free to cause hirsutism.
		2. It may take six months before any noticeable improvement occurs and two to three years to achieve the maximum benefit from anti-androgens because of the length of the growth-cycle of hair.
Hirsutism	Finasteride	1. Finasteride reduces the amount of hair by preventing androgen getting into cells. It can cause headache and depression, and contraception is essential to avoid accidental exposure to a foetus. It is useful as a second-line drug for the treatment of excess hair but is not licensed for this purpose, and some pharmacies have made inappropriate comments to my patients when filling prescriptions, affecting their likelihood of taking the treatment.
Endometrial cancer (cancer of the womb lining)	Progestogens, medroxyprogesterone acetate.	1. Stops endometrium (womb lining) from developing, and counteracts any tendency towards cell abnormalities and cancer. Occasional bloating and fluid retention occur.

The increased risk of endometrial cancer is thought to be due to certain hormonal abnormalities that result in continuous stimulation of the lining of the womb by oestrogen. However, the mild increase in insulin found in these women may also have negative effects.

It does seem sensible to advise women with absent or very infrequent periods to take occasional progestogen therapy to 'oppose' the oestrogen and minimise the risk of endometrial cancer.

Non-drug treatments

Ovarian diathermy (surgery that uses heat to alter ovarian function) is thought to reduce the amount of androgen secreting tissue in the ovaries, leading to resumption of ovulation in up to 80 per cent of women. The risks include those of having a laparoscopy and a theoretical risk of ovarian damage from the diathermy. The benefits include resumption of ovulation in a simple manner, with effects lasting six to nine months (Farquhar et al, 2000; Homberg, 1998).

There is a range of non-drug treatments available for hirsutism. Once a serious increase in male hormone levels has been excluded, then local cosmetic options can safely be considered. These include:

bleaching

depilatory preparations

waxing

plucking

laser hair removal

electrolysis

shaving.

Each is usually effective but expert advice should be taken, because each method has its own problems.

Bleaching and depilatory preparations can occasionally cause a local allergic reaction.

Waxing and plucking often break the hair shaft rather than actually remove it from the hair follicle and, therefore, should be considered to be little more effective than shaving.

Electrolysis and laser hair removal usually give the most prolonged action but both are expensive and cannot tackle large areas of the skin. Electrolysis is painful and laser removal may not be permanent.

Damage to skin or follicles can also occur with either. Waxing, plucking and shaving can lead to inflammation and infection of hair follicles, requiring topical antibiotic creams.

Sugaring is less likely to provoke this result than waxing. Best results will be obtained from shaving if hypoallergenic shaving soaps and razors are used. There is no evidence that plucking, waxing or shaving will encourage increased hair growth.

What is the outlook?

Living with PCOS means different things for different women. This is because women experience the condition in different ways and have more or less severe symptoms depending on their situation. In addition, as women get older, some symptoms change with age; hirsutism become less as hair distribution patterns change with advancing age and as the male hormones in the blood revert to more normal levels (Winters et al, 2000).

Women with PCOS are more prone to some serious conditions. These include an increase in the likelihood of developing diabetes (usually Type 2 diabetes (non-insulin dependent diabetes) and of developing cancer of the womb lining (endometrial cancer).

They also are more at risk of hypertension (high blood pressure) and high cholesterol, though if weight is controlled, high blood pressure is less likely to occur (Wild et al, 2000). Therefore, it makes sense to watch for symptoms suggestive of these conditions and to see your doctor should any suspicious symptoms be present.

For endometrial cancer, these include irregular spotting or bleeding in the 40 to 50 year age group or any bleeding after themenopause. For diabetes, these include unusual thirst requiring large amounts of fluids, tiredness, and passage of increased amounts of urine, particularly at night.

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