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com/Article/1790

Treatment strategies in PCOS patients


Juergen M Weiss began his medical career at the Department of Gynecology and
Obstetrics, University of Schleswig-Holstein, Campus Lübeck in 1996 and specialized in
gynaecology and obstetrics in 2001. He became a consultant in 2002 and gained his PhD
in 2004.

Dr Juergen M Weiss

Sascha Tauchert, Annika K Ludwig, K Diedrich, Juergen M Weiss1


Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee
160, 23538 Luebeck, Germany
1Correspondence: Tel: +49 451 5002155; Fax: +49 451 5004905; e-mail: jmweiss1@hotmail.com

Abstract
Polycystic ovary syndrome (PCOS), with a prevalence of up to 7%, is the most common endocrinopathy in women of
reproductive age. It is a complex metabolic–endocrine disorder with severe long-term health consequences, such as a higher
risk of type 2 diabetes and cardiovascular diseases. According to prospective studies, women with PCOS have abnormal
glucose tolerance and diabetes mellitus in 31.0–35.0% and 7.5–10.0% respectively. This risk is 2–3 times higher than
normal. Insulin resistance plays a key role in the pathophysiology of this syndrome, and this makes the use of oral anti-
diabetic drugs most compelling. The majority of studies have shown amelioration of typical symptoms such as
hyperandrogenism and cycle irregularities following the use of oral anti-diabetics, and ovulation and pregnancy rates
increased. Furthermore, these drugs might be cardioprotective by improving insulin sensitivity and reducing the risk for type
2 diabetes. The best-investigated drug is metformin. Metformin is not approved for PCOS treatment in Germany and is a
class B drug in pregnancy. In sterile PCOS patients, clomiphene citrate is still the first choice. The combination of
clomiphene with metformin and lifestyle changes such as weight reduction and exercise might be superior to clomiphene
alone. This article covers the use of different oral anti-diabetic drugs in the treatment of PCOS, and their influence on
fertility and long-term health.

Keywords: cardiovascular risk, insulin resistance, oral anti-diabetic drugs, polycystic ovary syndrome (PCOS), type 2 diabetes

Introduction Insulin resistance plays a key role in the pathophysiology of


this syndrome (Book and Dunaif, 1999). This makes the use of
Polycystic ovary syndrome (PCOS) is believed to be the most oral anti-diabetic drugs most compelling. Besides oral anti-
frequent endocrinopathy in women of reproductive age diabetic drugs, other forms of therapeutic strategies are
(Franks, 1995; Carmina and Lobo, 2001). These women, important in dealing with PCOS patients. A change in lifestyle,
besides hyperandrogenism, cycle irregularities and infertility, weight loss, physical activity and other forms of medication
have profound insulin resistance, alterations in β-cell function might improve this complex syndrome.
(Dunaif, 1997), and moreover an increased cardiovascular risk
(Mather et al., 2000). Thus, PCOS is more than just a cosmetic The association between a disorder of glucose metabolism and
and reproductive problem; it is a major health problem that hyperandrogenism was first described in 1921, and was called
shortens life expectancy. ‘diabetes of the skin’. Achard and Thiers observed this
relationship, reporting a bearded woman who was also diabetic
The aetiology of PCOS remains unclear and may be (Achard and Thiers, 1921). The majority of PCOS patients
multifactorial, involving a variable combination of ovarian and show a phenotype similar to syndrome X, the combination of
adrenal hyperandrogenism, insulin resistance, obesity and insulin resistance, type 2 diabetes, hypertension,
alterations in gonadotrophin secretion. Family studies have dyslipidaemia, endothelial dysfunction and coronary heart
identified PCOS as a genetic disorder, and identification of disease.
relevant genes is under intensive investigation (Franks et al.,
1997). Nutrition could ameliorate symptoms of excessive Teenage PCOS patients complain of the clinical manifestations
androgen production, anovulation and metabolic disorder such of hyperandrogenism, for example hirsutism and alopecia.
as glucose intolerance or type 2 diabetes that confer a high risk Besides cycle irregularities in the form of oligomenorrhoea
of developing cardiovascular disease. and/or amenorrhoea, signs of obesity appear. In reproductive
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PCOS treatment strategies - S Tauchert et al.

age, women with PCOS may be unable to become pregnant. binding globulin, LH/FSH ratio >2, insulin resistance with
The first signs of glucose intolerance are shown by an oral hyperinsulinaemia and dyslipidaemia. Clinical manifestations
glucose tolerance test. Post-menopausal women could suffer are obesity with an increased waist-to-hip-ratio over 0.8 (50%
eventually from type 2 diabetes, coronary heart disease and of all PCOS patients), hirsutism, oligo-/amenorrhoea,
hypertension, and life expectancy could be decreased. infertility, alopecia and skin problems.

In all, 31–35% of PCOS patients have impaired glucose Strategy of diagnosis


tolerance when they are diagnosed with PCOS; the prevalence
of type 2 diabetes is between 7.5 and 10% (Ehrmann et al., In practice, an efficient and fast diagnosis should be made. A
1999; Legro et al., 1999), including both obese and lean work-up does not exist which suits each PCOS patient. Other
women. Overall, type 2 diabetes affects 3–5% of the adult possible reasons for cycle irregularities and hyperandrogenism
European and US population. have to be excluded. Regarding the ESHRE/ASRM consensus
of Rotterdam in 2003, adrenal hyperplasia, androgen
In PCOS, conversion from glucose tolerance to type 2 diabetes producing tumour and Cushing’s syndrome must be clinically
is increased by 5- to 10-fold compared with healthy patients and biochemically excluded (Rotterdam ESHRE/ASRM
(Ehrmann et al., 1999; Legro et al., 1999). PCOS Consensus 2003). To find out whether a patient suffers
from these problems, a careful ultrasound examination of the
Retrospective US studies have shown, that 27% of ovaries and the suprarenal glands should be made, and the
premenopausal diabetic women suffered from PCOS (Peppard concentrations of 17-hydroxy-progesterone, prolactin and
et al., 2001), and an English study diagnosed polycystic TSH should be determined.
ovaries by vaginal ultrasound in 82% of examined women
with diabetes (Conn et al., 2000). A positive family history An oral glucose tolerance test (OGTT) shows possible
regarding type 2 diabetes and obesity increases the risk for impaired insulin tolerance; determination of lipids such as
PCOS patients developing type 2 diabetes. In conclusion, cholesterol, high density lipids, and low density lipids and
patients with PCOS of all ages have a high risk of developing triglycerides give information on increased cardiovascular
type 2 diabetes compared with an age-matched population. risk.

A review by Urman et al. described assisted reproduction in Yildiz et al. suggested that women with PCOS should be
the treatment of PCOS. In reproductive age, an unfulfilled screened for glucose intolerance. Detection by a 2-h OGTT is
pregnancy wish is, besides clinical manifestation of preferable to a fasting plasma glucose alone. The OGTT can
hyperandrogenism, the most important problem. The authors determine both impaired glucose tolerance and diabetes
showed that the outcome in terms of pregnancy and (Yildiz and Gedik, 2004).
implantation rates is similar for patients with PCOS compared
with patients undergoing IVF for other indications (Urman et Parameters useful in the diagnosis of PCOS are summarized in
al., 2004). Table 1.

Diagnosis of PCOS Therapy strategies


Some efforts were made to find a new classification of PCOS. Improvement by exercise and diet
An exact diagnosis and classification is essential to begin the
correct therapy. One of the most controversial criteria is the The reproductive problems of PCOS patients are linked to
ultrasound picture of the polycystic ovaries. More than 10 insulin resistance and resulting hyperinsulinaemia. In former
follicles with a diameter of at least 10 mm are necessary to studies, it was shown that a decrease in hyperinsulinaemia
confirm the ultrasound picture as ‘polycystic ovaries’. Not all could also decrease concentrations of androgens. Weight loss
patients with polycystic ovaries show the endocrinological and is well known to decrease androgen concentrations and restore
metabolic disorders that lead to the diagnosis of PCOS. ovulation.

Typical biochemical characteristics are: elevated testosterone, In one small study, 28 women were randomized to a 3-month
androstendione, DHEA and prolactin, decreased sex hormone- diet with either a high or low dose of proteins. Improvements

Table 1. Possible diagnostic parameters in polycystic ovarian syndrome.

Exclusion of a tumour or/and pathophysiology of the suprarenal glands


Total testosterone and clinical manifestations of hyperandrogenism
Prolactin, oestradiol, progesterone, FSH, LH
Lipid profile
Oral glucose tolerance test
Basal thyroid simulating hormone
Ultrasound
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PCOS treatment strategies - S Tauchert et al.

in menstrual cyclicity, lipid profile, insulin resistance and a was conducted by Fleming et al. (2002), treating 92 women
decrease in weight (7.5%) occurred in both groups, with metformin 850 mg twice a day. On average, the
independent of diet composition (Moran et al., 2003). metformin-group ovulated on day 23.6 compared with the
placebo group, whose first ovulation was on day 41.8. Patients
Improvements in menstrual cyclicity were associated with in the metformin group showed a significant weight loss
greater decreases in insulin resistance and fasting insulin. compared with the placebo group, who gained weight.
Crosignani et al. (2003) showed that weight loss through a Moghetti et al. (2000) treated 23 PCOS patients with 500 mg
controlled low-calorie diet and exercise improved metformin three times daily, or a placebo for a period of 6
anthropometric indices in obese PCOS patients reduced months. Insulin concentrations under metformin therapy were
ovarian volume and microfollicle number and restored reduced by 33% and androgen concentrations by 21%, while
ovulatory cycles, resulting in spontaneous pregnancies. under placebo there were no changes.

These results show that lifestyle modifications must be the Kumari et al. (2005) showed in January 2005 that metformin
basic step of therapy. Patients should be informed about the monotherapy (3 × 500 mg daily) for 12 weeks was effective in
importance and the great benefits of exercise and diet. Any improving ovulation and pregnancy rates in lean women with
medical intervention described in this article should be PCOS as compared with obese women. In the lean group, 15
accompanied by lifestyle intervention. out of 17 women (88%) ovulated and 11 of 17 (65%) women
became pregnant. In the group of obese women, the ovulation
Further studies are needed to investigate whether diet and rate was 29% and pregnancy rate only 18%.
exercise can help lean patients with a PCOS.
Stadtmauer et al. (2004) conducted a study to determine if
Oral anti-diabetics metformin improves ovarian stimulation and IVF outcomes in
patients with clomiphene-resistant PCOS. In total, 72 cycles of
The most commonly used agent that increases tissue IVF–embryo transfer with intracytoplasmic sperm injection
sensitivity to insulin is metformin, a biguanide (ICSI) were performed in clomiphene-resistant PCOS patients
antihyperglycaemic drug. It decreases hepatic glucose treated or not treated with metformin. The metformin-treated
production (Inzucchi et al., 1998) and has some positive group showed an increase in the mean number of mature
effects on increasing peripheral glucose uptake in response to oocytes, oocytes fertilized and cleaving embryos.
insulin. The number of insulin receptors increases (Fantus and
Brosseau, 1986) and insulin and androgen concentrations are Recently, a prospective study was conducted in 21 Brazilian
reduced. Improvements in the clinical manifestation of women with PCOS who were treated with 1500 mg metformin
hyperandrogenism have been described (Moghetti et al., per day for 8 weeks. Spontaneous menstruation was observed
2000). in 81% of the women, with no changes in weight or BMI.
However, the insulin sensitivity and the lipid profile improved
Nausea, vomiting and diarrhoea could be possible side effects; as well as the serum testosterone concentration (Santana et al.,
a gradual increase in the dose can alleviate this problem. 2004).

Thiazolidinediones (TZD), e.g. troglitazone, rosiglitazone and A review of seven randomized controlled trials published in
pioglitazone, sensitize tissues to insulin action by up- 2004 described evidence that metformin improves ovulation
regulating the nuclear insulin receptor (Hauner, 2002). and menstrual cyclicity, but these improvements were variable
Troglitazone is, due to its hepatotoxicity, no longer available. and modest. Spontaneous ovulation and normal menstruation
Trials reported so far have shown improved insulin sensitivity were achieved rapidly overall within 3 months of the start of
as well as reduction of androgen concentrations and a higher therapy (Harborne et al., 2003).
pregnancy rate (Ehrmann et al., 1997). Research is currently
concentrating on rosiglitazone and pioglitazine, which have A meta-analysis by Kashyap in 2004 reviewed eight
been available in the United States since 1999. randomized controlled trials addressing the use of metformin
or clomiphene for treatment of PCOS, looking at ovulation and
Success of metformin in treatment of pregnancy. A benefit of metformin was shown, but a longer
PCOS duration of therapy (>3 months) did not show an improvement
(Kashyap et al., 2004). Further studies are needed to
A meta-analysis that reviewed 13 randomized controlled trials, investigate whether long-term use of metformin leads to a loss
including 543 women with PCOS, gave good evidence that of efficacy.
metformin increases ovulation rate, and that metformin in
combination with clomiphene effectively increases ovulation In contrast to the mentioned studies is a study by Ng et al. (2001),
and pregnancy rates when compared with clomiphene alone. who treated clomiphene-resistant PCOS patients with metformin
In detail, this analysis showed that metformin could achieve (1500 mg/day) and clomiphene or placebo. Ng et al. found a
ovulation in 46% of patients when used alone, compared with reduction in insulin concentration of 25% and a reduction in
24% in the placebo arm. When a metformin/clomiphene androgen concentration of 33%, but the ovulation rate was not
combination was used, 76% of PCOS patients ovulated, significantly improved under clomiphene with metformin (1500
compared with 42% receiving clomiphene alone (Lord et al., mg/day) compared with placebo with metformin. However, the
2003). inclusion criterion for this study was polycystic ovaries on
ultrasound, so that some included patients had a normal cycle and
The largest double-blind placebo-controlled randomized study normal androgen concentrations. 69
PCOS treatment strategies - S Tauchert et al.

Some studies did not show the benefit of metformin in the In a study with 12 obese PCOS patients with severe insulin
treatment of PCOS. However, the inclusion criteria sometimes resistance, the effectiveness of rosiglitazone was evaluated. All
differ from the definition of PCOS. One of these studies women were treated with 4 mg of rosiglitazone daily for 6
recruited patients with hirsutism, while it remains unclear if months. Eleven women reverted to regular ovulatory cycles
other features of PCOS were present (Crave et al., 1995). during the treatment period, insulin resistance improved and
ovarian androgen production decreased (Sepilian and
In a recent review, Cheang and Nestler (2004) described Nagamani, 2005).
metformin as a first-line therapy for women with PCOS,
resulting in amelioration of the metabolic syndrome leading to Newer TZD such as rosiglitazone and pioglitazone appear not
prevention of long-term cardiovascular and diabetes to cause the hepatic side effects reported for troglitazone, and
complications. have shown their effectiveness alone and in combination with
clomiphene in improving cyclicity, insulin sensitivity and
Randomized, placebo-controlled studies using metformin in the biochemical parameters. However, more studies have to be
treatment of PCOS are summarized in Table 2. performed to prove these so far positive clinical effects of
TZD.
Unfortunately, most published papers do not give any
information about how ovulation was determined. In future Another oral antidiabetic drug, acarbose, an inhibitor of the
studies, it would be useful to include such information. alpha-glucosidase enzyme, was used by Ciotta et al. (2001) in
a study in 2001. In this clinical trial, clinical symptoms of
Troglitazone, rosiglitazone, pioglitazone hyperandrogenism improved after 3 months therapy with 200
mg acarbose daily. Eight of 15 patients ovulated regularly.
and acarbose in the treatment of PCOS
Less information exists on the effects of TZD in the treatment of Recently, Sonmez et al. (2005) compared the effects of
PCOS. Troglitazone, which has been researched the most, had to acarbose and metformin on ovulation rates in clomiphene-
be taken off the market due to hepatotoxicity. resistant PCOS patients. Group I was treated with 100 mg
clomiphene citrate and 300 mg acarbose daily, group II with
The use of pioglitazone for 3 months increased normal regular 100 mg clomiphene and 1700 mg metformin daily for 3
cycles and ovulations over placebo in a trial of 40 patients (41.2 months. Total testosterone decreased and ovulation rates
versus 5.6%) (Brettenthaler et al., 2004). Romualdi et al. treated increased in both groups. Reduction in weight and BMI was
PCOS patients for a period of 6 months with 45 mg piogliatzone only significant in the acarbose group.
daily. Cycle irregularities improved in 83% of
hyperinsulinaemic PCOS patients and in 33% of The American Association of Clinical Endocrinologists
normoinsulinaemic PCOS women. Insulin sensitivity improved recommends using metformin 850 mg twice daily to treat the
in the hyperinsulinaemic group, and in both groups hirsutism hyperandrogenic state of PCOS (AACE, 2001). The use of
and acne decreased (Romualdi et al., 2003). Glueck et al. (2003) TZD regarding the AACE guidelines is less clear due to
used pioglitazone to treat 13 patients who failed to respond limited evidence and risk of teratogenicity.
successfully to metformin. When pioglitazone was added,
concentrations of insulin, glucose and DHEAS, as well as Table 3 summarizes studies investigating the treatment of
insulin resistance, decreased and menstrual regularity improved PCOS patients with rosiglitazone and pioglitazone.
without severe side effects.
Oral anti-diabetics and type 2 diabetes
Two small randomized controlled trials studied the use of
rosiglitazone combined with clomiphene. Improvements in Women with PCOS have, due to insulin resistance, an
menstrual regularity (Shobokshi and Shaarawy, 2003) and both increased risk of developing type 2 diabetes. Two studies have
spontaneous and clomiphene-induced ovulation rates (Ghazeeri shown that improved insulin sensitivity had a positive
et al., 2003) were achieved. Ghazeeri et al. randomized 25 influence on developing type 2 diabetes. Insulin resistance
clomiphene-resistant women with PCOS in two groups. Group may be the earliest detectable abnormality in individuals who
1 (n = 12) received 4 mg rosiglitazone twice daily and a placebo develop type 2 diabetes, and is a recognized risk factor for
on days 5–9 of the cycle. The second group received clomiphene diabetes (Erickson et al., 1990).
instead of placebo. In total, 56% ovulated, 33% in the placebo
group and 77% in the clomiphene group. Two major outcome studies showed that interventions to
improve insulin sensitivity can delay the development of type
Recently, Baillargeon et al. (2005) showed in a randomized 2 diabetes in individuals with a high risk profile. A Finnish
controlled, double-blind trial testing metformin, rosiglitazone, a study reported that insulin sensitivity was improved by a
combination of both and a placebo over a period of 6 months that combination of diet and exercise, and that progression to type
compared with placebo, fasting insulin concentrations and 2 diabetes was reduced by 58% over 4 years in obese men with
insulin sensitivity improved significantly after metformin or impaired glucose tolerance (Tuomilehto et al., 2001).
combination therapy, but not after rosiglitazone. Ovulation rates
at 6 months were markedly increased in all groups except the The Diabetes Prevention Program, a study of the National
placebo group. Combination treatment did not yield additive Institutes of Health (NIH) of 3234 individuals at high risk for
results for either ovulation or menstrual bleeding. Androgen diabetes, had to be stopped early after an average follow-up of
concentrations decreased significantly with active treatment 3 years because intensive lifestyle interventions consisting of
70 (Baillargeon et al., 2005). diet and exercise reduced the risk of progression to type 2
PCOS treatment strategies - S Tauchert et al.

Table 2. Randomized, placebo-controlled studies with metformin.

Author Group Dose Rate of ovulation Effect

Nestler et al., 35 metformin, 3 × 500 mg, 34% metformin; 4% placebo; Insulin sensitivity ↑
1998 26 placebo followed by 90% metformin plus
clomiphene clomiphene; 8% placebo
plus clomiphene
Moghetti et al., 10 metformin, 3 × 500 mg 50% metformin; 0% placebo HDL ↑, insulin
2000 13 placebo sensitivity ↑
Pasquali et al., 10 metformin, 2 × 850 mg metformin > placebo Hirsutism ↓
2000 8 placebo
Fleming et al., 45 metformin, 2 × 850 mg 23% metformin, 13% placebo HDL ↑, LDL ↓
2002 47 placebo
Kocak et al., 27 metformin, 2 × 850 mg, 78% metformin, 14% placebo, Androgens ↓,
2002 28 placebo followed by pregnancy rate, (non significant) BMI ↓, LH ↓
clomiphene
HDL = high density lipoprotein; LDL = low density lipoprotein; BMI = body mass index; ↑ = increased; ↓ = decreased.

Table 3. Studies with rosiglitazone and pioglitazone.

Author Group: Dose Rate of ovulation (%) Effect

Zheng et al., 30: 4 mg rosiglitazone 50 Androgens ↓


2002
Ghazeeri et al., 25: group I, 12 subjects, Group I, 33 (1 pregnancy/ Fasting glucose
2003 4 mg rosiglitazone plus 1 live birth); group II, concentrations ↓,
placebo; group II, 13 77 (2 pregnancy/1 live birth) SHBG ↑, LH ↓
subjects, 4mg
rosiglitazone plus
clomiphene
Shobokshi and 50: group I, 48; 72 Androgens ↓, LH ↓
Shaarawy, 2003 clomiphene;
group II, rosiglitazone
plus clomiphene
Romualdi et al., 18: 45 mg pioglitazone 83 (hyperinsulinaemic), Hirsutism ↓, acne ↓,
2003 33 (normoinsulinaemic) insulin sensitivity ↑
Sepilian and 12: 4 mg rosiglitazone Insulin sensitivity ↑,
Nagamani, 2005 androgens ↓
SHGB = sex hormone-binding globulin; ↑ = increased; ↓ = decreased.

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PCOS treatment strategies - S Tauchert et al.

diabetes by 58%, while therapy with metformin only led to a Long-term studies on cardiovascular events in PCOS are still
reduction of 31% (Knowler et al., 2001). This study proved missing, but multiple studies have demonstrated the increased
that medical interventions should always go hand-in-hand with prevalence of risk factors for cardiovascular diseases in these
lifestyle interventions. patients. Therefore, the influence of insulin-sensitizing drugs
on amelioration of cardiovascular risk factors in PCOS is
Patients with a history of gestational diabetes are also at higher mostly indirect, as studies showed the improving effect on
risk of developing type 2 diabetes. In a prospective placebo- several cardiovascular risk factors. Metformin, combined with
controlled study, 114 patients with a history of gestational a diet, can ameliorate many of the features of the metabolic
diabetes were treated with troglitazone and 121 patients with a syndrome (Glueck, 2003). Apart from its influence on the
placebo. After a median follow-up of 30 months, troglitazone development of type 2 diabetes, one cardiovascular risk factor,
reduced the development of type 2 diabetes by 56% compared metformin decreases serum triglycerides (Velazquez, 1994),
with placebo (Buchanan et al., 2001). the concentration of endothelin-1 (Diamanti-Kandarakis et al.,
2001) and PAI-I (Velazquez et al., 1997) and reduces blood
Although it is not evidence-based yet, it seems to be pressure (Velazquez et al., 1994). Vribikova et al. (2002)
reasonable to transfer results from the prevention studies reported that metformin therapy for only 4 weeks decreased
mentioned above to the group of women with PCOS. The the concentration of homocysteine significantly. Studies
positive effect of insulin-sensitizing drugs on fertility has been investigating the effects of anti-diabetic drugs on
shown, but studies to analyse preventive effects from type 2 cardiovascular diseases in PCOS patients do not exist so far,
diabetes are still lacking. It is necessary to wait for controlled but they have been published for patients with type 2 diabetes.
studies for evidence. The United Kingdom Prospective Diabetes Study showed a
reduced incidence of myocardial infarction in obese patients
Oral anti-diabetics and cardiovascular with type 2 diabetes who received metformin (UKPDS, 1998).
diseases
Conclusion
PCOS is associated with multiple cardiovascular risk factors
such as obesity, insulin resistance and dyslipidaemia. In PCOS is a severe health problem due to its long-term
addition, there might be genetic intrinsic factors that caused an consequences and not only a cosmetic and fertility problem.
increased cardiovascular risk in PCOS patients (Dunaif, 1997). Insulin resistance, dyslipidaemia and hypertension increase the
Several studies showed a higher prevalence of cardiovascular cardiovascular risk, PCOS becomes a form of syndrome X.
diseases in PCOS patients (Talbott et al., 2000; Tuomilehto et
al., 2001). Dahlgren et al. reported that the risk of PCOS Amelioration of insulin sensitivity can normalize endocrine
patients suffering a myocardial infarction is increased by 7.4 and reproductive disorders. The use of insulin-sensitizing
compared with normal age-matched controls (Dahlgren et al., drugs, particularly metformin, can help to restore cycle
1992). Compared with age- and weight-matched controls, irregularities and increase pregnancy rates in clomiphene-
women with PCOS have a higher incidence of cardiovascular resistant women. Regarding long-term results, studies that
risk factors such as hypertension (Björntorp, 1996) and investigate metformin effects are needed.
dyslipidaemia (Wild, 1995). In 2000, Wild et al. (2000)
published a retrospective cohort study over a period of 31 Patients should be advised about the benefits of lifestyle
years. In 786 women with PCOS the incidence of interventions such as diet and physical activity. A reduction in
hypertension, type 2 diabetes and dyslipidaemia was increased BMI in women with PCOS can reduce the incidence of type 2
compared with age-matched controls. Besides dyslipidaemia, diabetes and can improve ovulation rates and fertility.
plasminogen-activiting inhibitor (PAI) (Legro et al., 2001) and
C-reactive protein (Morin-Papunen et al., 2003) are increased Patients and doctors have to be aware of the long-term
in PCOS. consequences and the importance of prevention. PCOS
patients, lean or obese, should be informed about the necessity
Rautio et al. (2005) recently randomized 30 women with of healthy food and physical activity. A regular determination
PCOS either to metformin therapy or to an ethinyl oestradiol- of lipid profile and glucose tolerance should be discussed.
cyproterone acetate contraceptive pill. The metformin
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