Polycystic ovarian syndrome (PCOS) is a condition affecting women that causes various symptoms including obesity, male pattern hair growth, a lack of periods and infertility. It is thought that a high level of insulin leads to the persistence of immature egg follicles1 in the ovaries, leading to excess production of male hormones. It is these multiple follicles that give the disease its name – 'polycystic'2 is, in a sense, a misnomer. The condition occurs in 5-10% of women in their reproductive years, though it does not always cause symptoms. Furthermore, one in five women who menstruate normally will have large numbers of follicles in their ovaries, but two thirds of these women will not have PCOS. Treatment depends on the individual case: some women have little in the way of symptoms whereas others are severely affected, and some seek to become pregnant and thus have treatment to increase their fertility.
The production of hormones by the ovaries is controlled by the pituitary, which secretes luteinising hormone (LH) and follicle stimulating hormone (FSH). These hormones act on two types of cell in the egg follicle: LH causes the thecal cells to produce weak androgens, and FSH causes the granulosa cells to convert the androgens into oestrogens. It is thought that a high level of insulin in the blood due to insulin resistance3 can prevent the death of the thecal cells, with the result that instead of being released at ovulation4, the egg follicles remain in the ovary. The retained follicles lose their granulosa cells, with the result that the weak androgens made by the thecal cells are converted into testosterone instead. As oestrogen production falls, the pituitary produces more LH in an attempt to increase weak androgen and thus oestrogen production, but this simply results in the production of more testosterone.
It is thought that PCOS may be triggered in multiple ways, including enlargement of the adrenal gland, a failure of correct hormone coordination at the start of reproductive life, an alteration in LH secretion by the pituitary due to high insulin levels, or a change in hormone levels following an eating disorder. Insulin resistance, diabetes and obesity are associated with an increased risk of PCOS.
Fewer periods. Women with PCOS may experience fewer periods (oligomenorrhoea) or no periods at all (amenorrhoea). The length of periods and time in between may vary greatly from cycle to cycle.
Infertility. Women with PCOS may ovulate less than usual or not at all – if ovulation does not occur, a woman will be unable to conceive. However, PCOS would seem to affect fertility in more ways that one, as women with PCOS who ovulate may still have difficulty conceiving. Also, the insulin resistance that may underlie PCOS leads to an increased risk of miscarriage.
Effects of testosterone. The increased levels of testosterone seen in PCOS can lead to acne, oily skin, thinning of scalp hair, increased hair on the face and chest (hirsutism), and deepening of the voice.
Obesity. High levels of insulin in the blood due to insulin resistance can cause weight gain, and half of all women with PCOS are overweight or obese.
Emotional disturbance. Raised testosterone may also cause mood swings, and the burden of the condition may lead to depression.
Following a detailed history and examination looking for the above, the woman may have a blood test for hormone levels and be sent for a transvaginal ultrasound scan5. A diagnosis can generally be made with three of the following:
- Oligomenorrhoea or amenorrhoea
- Acne or hirsutism
- Polycystic ovaries on ultrasound
- An increase of the LH:FSH ratio from the normal 1:1
- An increased level of free testosterone
- A reduced level of sex hormone binding globulin (SHBG)6
The simplest treatment for PCOS is for the woman to improve her lifestyle by eating healthily and exercising regularly. Weight loss is of great help in overweight women, as it may reduce insulin resistance and restore normal menstruation and ovulation. Treatment of any eating disorder present is important. Meanwhile, excess facial and body hair may be removed using laser treatment7, and acne may be treated using various topical creams and drugs if needs be.
Metformin, a drug that reduced blood sugar levels, has been shown to improve insulin resistance and may also improve the other symptoms of PCOS. The drug also assists with weight loss provided that the woman eats less, and may reduce the risk of later developing type II diabetes. Acarbose, a drug that reduces digestion of carbohydrates into sugars and thus reduces absorption of glucose into the bloodstream, has been shown to improve menstrual regularity in women with PCOS.
The oral contraceptive pill may be used to increase oestrogen levels, reducing production of LH by the pituitary and thus the androgens produced by the ovaries. This reduces further cyst formation and improves the androgen-related symptoms such as acne and hirsutism. Spironolactone, a diuretic and androgen-blocking drug, can also be used to reduce the effects of androgens, and may also improve insulin resistance. Dianette, an oral contraceptive containing an oestrogen and an anti-androgen, may also prove useful.
Clomiphene citrate is a drug that blocks the effect of oestrogen on the hypothalamus, thus leading to an increase in both LH and FSH levels. Appropriate treatment with the drug leads to ovulation in the majority of women and increases the chances of conception to a greater extent than metformin. However, there is a small risk of a multiple pregnancy, which though seemingly welcome may have a poor outcome. Very rarely, the drug will lead to ovarian hyperstimulation syndrome, a potentially dangerous condition in which the ovaries become grossly enlarged, and may increase the risk of ovarian cancer. Clomiphene is thus added after weight loss and metformin treatment have failed to result in a return to normal ovulation. Various other drugs and forms of artificial fertilisation may also be used by gynaecologists to treat infertility due to PCOS, and will not be covered here.
Progesterone may be used to induce menstruation and thus reduce the possible risk of endometrial cancer in women whose endometrium8 has become thickened. The intra-uterine system9, which is placed inside the uterus and releases progesterone over time, may be used to prevent thickening of the endometrium, but has a contraceptive effect.
Surgery can reduce the size of the ovaries, reducing androgen levels and thus leading to a return to ovulation in the majority of women. It is used in women who do not ovulate following several cycles of clomiphene treatment in order to prevent the risk of multiple pregnancy due to the drug. Originally, surgery consisted of a rather brutal procedure in which the ovaries were sliced open and each had a wedge removed: a 'wedge resection'. One complication that could occur following this operation was that of adhesions10 around the Fallopian tubes11, thus leading to a risk of infertility or ectopic pregnancy due to damaged tubes. The current technique, 'ovarian drilling', is performed laparoscopically12 and involves puncturing and destroying a handful of follicles using diathermy (electrical cautery).
The likelihood of successfully conceiving following appropriate treatment varies. Only some women who successfully return to ovulation will achieve conception, and out of those that become pregnant some will miscarry. Various studies provide different estimates, but it would appear that clomiphene and surgery are equally effective, leading to ovulation in 80% of women and an eventual live birth in 60%, half of whom will successfully conceive within the first year of treatment.
Meanwhile, although treatment of androgen-related symptoms is reasonably successful, one fifth of women with PCOS will develop type II diabetes or impaired glucose tolerance, a pre-diabetic state. There are also suggestions of an increased risk of endometrial cancer in women who do not ovulate for a number of years, though to date research has still proven inconclusive.