Polycystic Ovary Syndrome


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Polycystic Ovary Syndrome

  1. 1. Polycystic ovary syndrome (PCOS) What is polycystic ovary syndrome? Polycystic (literally, many cysts) ovary syndrome (PCOS or PCO) is a complex condition that affects the ovaries (the organs in a woman's body that produce eggs). In PCOS, the ovaries are bigger than average, and the outer surface of the ovary has an abnormally large number of small follicles (the sac of fluid that grows around the egg under the influence of stimulating hormones from the brain). In PCOS, these follicles remain immature, never growing to full development or ovulating to produce an egg capable of being fertilised. For the woman this means that she rarely ovulates (releases an egg) and so is less fertile. In addition, she does not have regular periods and may go for many weeks without a period. Other features of the condition are excess weight and excess body hair. The condition is relatively common among infertile women and particularly common among women with ovulation problems (an incidence of about 75 per cent). In the general population, around 25 per cent of women will have polycystic ovaries seen on ultrasound examination but most have no other symptoms or signs of PCOS and are perfectly healthy. The ultrasound appearance is also found in up to 14 per cent of women on the contraceptive pill. What causes PCOS? While it is not known if women are born with this condition, PCOS seems to run in families. This means that something that induces the condition is inheritable, and thus influenced by one or more genes. Interestingly, when PCOS is passed down the man's side of the family, the men are not infertile, but they do have a tendency to become bald early in life, before the age of 30. Ongoing research is trying to clarify whether there is a clearly identifiable gene for PCOS. It seems likely that in the future one or two genes will be identified that play a fundamental role in determining a woman's likelihood of developing this condition. Even if PCOS has a genetic basis, it is likely that not all women with the gene or genes will develop the condition. It is more likely to develop if there is a family history of diabetes (especially Type 2, the less severe type usually controlled by tablets), or if there is early baldness in the men in the family. Women are also more at risk if they are overweight. Maintaining weight or body mass index (BMI) below a critical threshold is probably very important to determine whether some women develop the symptoms and physical features of the condition. Just how much weight (or what level of BMI) is difficult to say because it will be different for each individual. Certainly, for patients who are considered obese (with BMI greater than 30) or overweight (BMI 25 to 30), weight loss improves the hormonal abnormalities and
  2. 2. improves the likelihood of ovulation and thus pregnancy. Can PCOS be prevented? If there is a genetic influence, then some people are more likely to get PCOS than others. However, it seems likely that you cannot alter your predisposition to PCOS. There is no current proof of any benefit of preventative weight loss, but the best advice for overall health is to maintain a normal weight or BMI, especially if you have strong indicators that PCOS could affect you. These indicators are: • a tendency in the family towards non-insulin dependent (Type 2) diabetes. • a tendency towards early baldness in the men in the family (before 30 years of age). • the knowledge that a close relative already has PCOS. What are the symptoms? The ways in which PCOS shows itself include: • absent or infrequent periods (oligomenorrhoea): a common symptom of PCOS. Periods can be as frequent as every five to six weeks, but might only occur once or twice a year, if at all. • increased facial and body hair (hirsutism): usually found under the chin, on the upper lip, forearms, lower legs and on the abdomen (usually a vertical line of hair up to the umbilicus). • acne: usually found only on the face. • infertility: infrequent or absent periods are linked with very occasional ovulation, which significantly reduces the likelihood of conceiving. • overweight/obesity: a common finding in women with PCOS because their body cells are resistant to the sugar-control hormone insulin. This insulin resistance prevents cells using sugar in the blood normally and the sugar is stored as fat instead. • miscarriage (sometimes recurrent): one of the hormonal abnormalities in PCOS, a raised level of luteinising hormone (LH - a hormone produced by the brain that affects ovary function), seems to be linked with miscarriage. Women with raised LH have a higher miscarriage rate (65 per cent of pregnancies end in miscarriage) compared with those who have normal LH values (around 12 per cent miscarriage rate). These symptoms are related to several internal changes. • Hormonal abnormalities, including: • raised luteinising hormone (LH) in the early part of the menstrual cycle. • raised androgens (male hormones usually found in women in tiny amounts). • lower amounts of the blood protein that carries all sex hormones (sex-hormone-binding globulin). • a small increase in the amount of insulin and cellular resistance to its actions. • Characteristic changes in the appearance of the ovaries on ultrasound scan. The ovaries are polycystic, with many small follicles scattered under the surface of the ovary (usually more than 10 or 15 in each ovary) and almost none in the middle of the ovary. These follicles are all small and immature, generally do not exceed 10mm in size and rarely, if ever, grow to maturity and ovulate. Most women with PCOS will have the ultrasound findings, whereas the menstrual cycle abnormalities are found in around 66 per cent of women and obesity is found in 40 per cent. The increase in hair and acne are found in up to 70 per cent
  3. 3. whereas the hormone abnormalities are found in up to 50 per cent of women. It is likely that there are different stages of the disease throughout life. Younger women tend to have substantial difficulties with their periods, whereas older women have other problems such as diabetes and hypertension (high blood pressure), though their period patterns tend to become more regular. Women with PCOS also have an increased risk of strokes and heart attacks, but their death rate from these conditions is not increased (Wild et al, 2000). Women with PCOS may also have an increased risk of endometrial cancer (cancer of the lining of the womb), particularly if they have infrequent or absent periods. How is PCOS diagnosed? The diagnosis is based on the patient's symptoms and physical appearance. If the diagnosis seems likely because the patient's history contains many of the symptoms described already, certain investigations are done to provide confirmatory evidence or to indicate another cause for the symptoms. These include: • blood tests such as: • female sex hormones (at a certain point in the cycle if possible) • male sex hormones • sex-hormone-binding globulin • glucose • thyroid function tests • other hormones, eg prolactin. • ultrasound examination. Your own GP can do the initial blood investigations, ensuring they are carried out at the correct time of the cycle if appropriate. Your GP may be able to arrange an ultrasound scan. Once the diagnosis is made, nothing more needs to be done for some women, eg if their fertility is not an issue, if their weight is within normal limits, and if they do not have excess body hair. If any of the symptoms are an issue, then further advice and treatment, and possibly specialist referral is needed. What else could it be? The other conditions likely to cause abnormal periods include raised levels of prolactin and of thyroid stimulating hormone (TSH). Both these hormones are produced from a particular part of the brain, the anterior pituitary. Raised prolactin levels can occur together with headaches and some disturbances of vision whereas raised TSH levels indicate low thyroid hormones (hypothyroidism). Both these conditions lead to suppressed ovulation and infertility.
  4. 4. Increased hair and acne reflect an increase in male hormones (androgens) in the blood. Other conditions can cause such an increase. Rarely, adrenal disorders or tumours cause increased androgens. In these conditions, hirsutism usually develops quite rapidly; previously normal periods may also stop and, occasionally, muscle weakness occurs. Loss of, or changes in, female aspects of body shape and appearance (secondary sexual characteristics), especially reduction in breast size, may also occur. As the androgen excess progresses, the voice can deepen and the clitoris can increase in size (clitoromegaly). If these serious medical disorders are present, the male hormone levels will be considerably increased, way above those found in PCOS, and specialist treatment should be arranged. What can you do for PCOS? There are several things that an individual can do if they have a tendency towards developing some or all of the elements of PCOS. Much of this involves lifestyle changes to ensure that your weight is kept within normal limits (BMI between 19 and 25). In addition, because there is a likelihood of developing diabetes in later life and a slightly higher risk of heart disease, low-fat and low- sugar options should be considered when making choices about what to eat or to drink. Weight loss, or maintaining weight below a certain level, will have the short-term benefit of increasing the likelihood of successful treatment and the long-term benefits of reducing the risk of diabetes and heart disease (Galtier-Dereure et al, 1997). 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).
  5. 5. Table 1: Treatments to improve fertility in women with polycystic ovary syndrome Drug and mode of action Benefits Risks Effects on life quality Clomifene (eg Clomid): 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 (eg Glucophage): 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 (eg Glucophage) 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).
  6. 6. 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. References Farquhar C, Vanderkerckhove P et al (2000). Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome (Cochrane Review). Cochrane Database Syst Rev 2000; (2): CD001122. Galtier-Dereure F, Pujol P et al (1997). "Choice of stimulation in polycystic ovarian syndrome: the influence of obesity. Hum Reprod 1997; 12 (Suppl 1): 88-96.
  7. 7. Homberg R (1998). Adverse effects of luteinizing hormone on fertility. London: Balliere Tindall, 1998. Hughes E, Collins J et al (2000a). Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea (Cochrane Review). Cochrane Database Syst Rev 2000; (2): CD000056. Hughes E, Collins J et al (2000b). Gonadotrophin-releasing hormone analogue as an adjunct to gonadotropin therapy for clomiphene-resistant polycystic ovarian syndrome (Cochrane Review). Cochrane Database Syst Rev 2000; (2): CD000097. Hughes E, Collins J et al (2000c). Ovulation induction with urinary follicle stimulating hormone versus human menopausal gonadotropin for clomiphene- resistant polycystic ovary syndrome (Cochrane Review). Cochrane Database Syst Rev 2000: (2): CD000092. Lee O, Farquhar C et al (2000). Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne (Cochrane Review). Cochrane Database Syst Rev 2000; (2): CD000194. Pirwany IR, Yates RW et al (1999). Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea. Hum Reprod 1999; 14(12): 2963-68. Wild S, Pierpoint T et al (2000). Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. Human Fertility 2000; 3(2): 101-05. Wild S, Pierpoint T et al (2000). Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000; 52(5): 595-600. Winters SJ, Talbott E et al (2000). Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome. Fertil Steril 2000; 73(4): 724-29.