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. 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. 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. 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. 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. 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. 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.