RBMOnline - Vol 10. Suppl. 3 2005 67–74 www.rbmonline.

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

Polycystic ovary syndrome (PCOS) is believed to be the most
frequent endocrinopathy in women of reproductive age
(Franks, 1995; Carmina and Lobo, 2001). These women,
besides hyperandrogenism, cycle irregularities and infertility,
have profound insulin resistance, alterations in β-cell function
(Dunaif, 1997), and moreover an increased cardiovascular risk
(Mather et al., 2000). Thus, PCOS is more than just a cosmetic
and reproductive problem; it is a major health problem that
shortens life expectancy.
The aetiology of PCOS remains unclear and may be
multifactorial, involving a variable combination of ovarian and
adrenal hyperandrogenism, insulin resistance, obesity and
alterations in gonadotrophin secretion. Family studies have
identified PCOS as a genetic disorder, and identification of
relevant genes is under intensive investigation (Franks et al.,
1997). Nutrition could ameliorate symptoms of excessive
androgen production, anovulation and metabolic disorder such
as glucose intolerance or type 2 diabetes that confer a high risk
of developing cardiovascular disease.
this syndrome (Book and Dunaif, 1999). This makes the use of
oral anti-diabetic drugs most compelling. Besides oral anti-
diabetic drugs, other forms of therapeutic strategies are
important in dealing with PCOS patients. A change in lifestyle,
weight loss, physical activity and other forms of medication
might improve this complex syndrome.
The association between a disorder of glucose metabolism and
hyperandrogenism was first described in 1921, and was called
‘diabetes of the skin’. Achard and Thiers observed this
relationship, reporting a bearded woman who was also diabetic
(Achard and Thiers, 1921). The majority of PCOS patients
show a phenotype similar to syndrome X, the combination of
insulin resistance, type 2 diabetes, hypertension,
dyslipidaemia, endothelial dysfunction and coronary heart
disease.
Teenage PCOS patients complain of the clinical manifestations
of hyperandrogenism, for example hirsutism and alopecia.
Besides cycle irregularities in the form of oligomenorrhoea
and/or amenorrhoea, signs of obesity appear. In reproductive
67
 PCOS treatment strategies - S Tauchert et al.
age, women with PCOS may be unable to become pregnant.
The first signs of glucose intolerance are shown by an oral
glucose tolerance test. Post-menopausal women could suffer
eventually from type 2 diabetes, coronary heart disease and
hypertension, and life expectancy could be decreased.
In all, 31–35% of PCOS patients have impaired glucose
tolerance when they are diagnosed with PCOS; the prevalence
of type 2 diabetes is between 7.5 and 10% (Ehrmann et al.,
1999; Legro et al., 1999), including both obese and lean
women. Overall, type 2 diabetes affects 3–5% of the adult
European and US population.
In PCOS, conversion from glucose tolerance to type 2 diabetes
is increased by 5- to 10-fold compared with healthy patients
(Ehrmann et al., 1999; Legro et al., 1999).
Retrospective US studies have shown, that 27% of
premenopausal diabetic women suffered from PCOS (Peppard
et al., 2001), and an English study diagnosed polycystic
ovaries by vaginal ultrasound in 82% of examined women
with diabetes (Conn et al., 2000). A positive family history
regarding type 2 diabetes and obesity increases the risk for
PCOS patients developing type 2 diabetes. In conclusion,
patients with PCOS of all ages have a high risk of developing
type 2 diabetes compared with an age-matched population.
A review by Urman et al. described assisted reproduction in
the treatment of PCOS. In reproductive age, an unfulfilled
pregnancy wish is, besides clinical manifestation of
hyperandrogenism, the most important problem. The authors
showed that the outcome in terms of pregnancy and
implantation rates is similar for patients with PCOS compared
with patients undergoing IVF for other indications (Urman et
al., 2004).
Diagnosis of PCOS
Some efforts were made to find a new classification of PCOS.
An exact diagnosis and classification is essential to begin the
correct therapy. One of the most controversial criteria is the
ultrasound picture of the polycystic ovaries. More than 10
follicles with a diameter of at least 10 mm are necessary to
confirm the ultrasound picture as ‘polycystic ovaries’. Not all
patients with polycystic ovaries show the endocrinological and
metabolic disorders that lead to the diagnosis of PCOS.
Typical biochemical characteristics are: elevated testosterone,
androstendione, DHEA and prolactin, decreased sex hormone-
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
68
binding globulin, LH/FSH ratio >2, insulin resistance with
hyperinsulinaemia and dyslipidaemia. Clinical manifestations
are obesity with an increased waist-to-hip-ratio over 0.8 (50%
of all PCOS patients), hirsutism, oligo-/amenorrhoea,
infertility, alopecia and skin problems.
Strategy of diagnosis
In practice, an efficient and fast diagnosis should be made. A
work-up does not exist which suits each PCOS patient. Other
possible reasons for cycle irregularities and hyperandrogenism
have to be excluded. Regarding the ESHRE/ASRM consensus
of Rotterdam in 2003, adrenal hyperplasia, androgen
producing tumour and Cushing’s syndrome must be clinically
and biochemically excluded (Rotterdam ESHRE/ASRM
PCOS Consensus 2003). To find out whether a patient suffers
from these problems, a careful ultrasound examination of the
ovaries and the suprarenal glands should be made, and the
concentrations of 17-hydroxy-progesterone, prolactin and
TSH should be determined.
An oral glucose tolerance test (OGTT) shows possible
impaired insulin tolerance; determination of lipids such as
cholesterol, high density lipids, and low density lipids and
triglycerides give information on increased cardiovascular
risk.
Yildiz et al. suggested that women with PCOS should be
screened for glucose intolerance. Detection by a 2-h OGTT is
preferable to a fasting plasma glucose alone. The OGTT can
determine both impaired glucose tolerance and diabetes
(Yildiz and Gedik, 2004).
Parameters useful in the diagnosis of PCOS are summarized in
Table 1.
Therapy strategies
Improvement by exercise and diet
The reproductive problems of PCOS patients are linked to
insulin resistance and resulting hyperinsulinaemia. In former
studies, it was shown that a decrease in hyperinsulinaemia
could also decrease concentrations of androgens. Weight loss
is well known to decrease androgen concentrations and restore
ovulation.
In one small study, 28 women were randomized to a 3-month
diet with either a high or low dose of proteins. Improvements

in menstrual cyclicity, lipid profile, insulin resistance and a
decrease in weight (7.5%) occurred in both groups,
independent of diet composition (Moran et al., 2003).
Improvements in menstrual cyclicity were associated with
greater decreases in insulin resistance and fasting insulin.
Crosignani et al. (2003) showed that weight loss through a
controlled low-calorie diet and exercise improved
anthropometric indices in obese PCOS patients reduced
ovarian volume and microfollicle number and restored
ovulatory cycles, resulting in spontaneous pregnancies.
These results show that lifestyle modifications must be the
basic step of therapy. Patients should be informed about the
importance and the great benefits of exercise and diet. Any
medical intervention described in this article should be
accompanied by lifestyle intervention.
Further studies are needed to investigate whether diet and
exercise can help lean patients with a PCOS.
Oral anti-diabetics
The most commonly used agent that increases tissue
sensitivity to insulin is metformin, a biguanide
antihyperglycaemic drug. It decreases hepatic glucose
production (Inzucchi et al., 1998) and has some positive
effects on increasing peripheral glucose uptake in response to
insulin. The number of insulin receptors increases (Fantus and
Brosseau, 1986) and insulin and androgen concentrations are
reduced. Improvements in the clinical manifestation of
hyperandrogenism have been described (Moghetti et al.,
2000).
Nausea, vomiting and diarrhoea could be possible side effects;
a gradual increase in the dose can alleviate this problem.
Thiazolidinediones (TZD), e.g. troglitazone, rosiglitazone and
pioglitazone, sensitize tissues to insulin action by up-
regulating the nuclear insulin receptor (Hauner, 2002).
Troglitazone is, due to its hepatotoxicity, no longer available.
Trials reported so far have shown improved insulin sensitivity
as well as reduction of androgen concentrations and a higher
pregnancy rate (Ehrmann et al., 1997). Research is currently
concentrating on rosiglitazone and pioglitazine, which have
been available in the United States since 1999.
Success of metformin in treatment of
PCOS
A meta-analysis that reviewed 13 randomized controlled trials,
including 543 women with PCOS, gave good evidence that
metformin increases ovulation rate, and that metformin in
combination with clomiphene effectively increases ovulation
and pregnancy rates when compared with clomiphene alone.
In detail, this analysis showed that metformin could achieve
ovulation in 46% of patients when used alone, compared with
24% in the placebo arm. When a metformin/clomiphene
combination was used, 76% of PCOS patients ovulated,
compared with 42% receiving clomiphene alone (Lord et al.,
2003).
The largest double-blind placebo-controlled randomized study
PCOS treatment strategies - S Tauchert et al.
was conducted by Fleming et al. (2002), treating 92 women
with metformin 850 mg twice a day. On average, the
metformin-group ovulated on day 23.6 compared with the
placebo group, whose first ovulation was on day 41.8. Patients
in the metformin group showed a significant weight loss
compared with the placebo group, who gained weight.
Moghetti et al. (2000) treated 23 PCOS patients with 500 mg
metformin three times daily, or a placebo for a period of 6
months. Insulin concentrations under metformin therapy were
reduced by 33% and androgen concentrations by 21%, while
under placebo there were no changes.
Kumari et al. (2005) showed in January 2005 that metformin
monotherapy (3 × 500 mg daily) for 12 weeks was effective in
improving ovulation and pregnancy rates in lean women with
PCOS as compared with obese women. In the lean group, 15
out of 17 women (88%) ovulated and 11 of 17 (65%) women
became pregnant. In the group of obese women, the ovulation
rate was 29% and pregnancy rate only 18%.
Stadtmauer et al. (2004) conducted a study to determine if
metformin improves ovarian stimulation and IVF outcomes in
patients with clomiphene-resistant PCOS. In total, 72 cycles of
IVF–embryo transfer with intracytoplasmic sperm injection
(ICSI) were performed in clomiphene-resistant PCOS patients
treated or not treated with metformin. The metformin-treated
group showed an increase in the mean number of mature
oocytes, oocytes fertilized and cleaving embryos.
Recently, a prospective study was conducted in 21 Brazilian
women with PCOS who were treated with 1500 mg metformin
per day for 8 weeks. Spontaneous menstruation was observed
in 81% of the women, with no changes in weight or BMI.
However, the insulin sensitivity and the lipid profile improved
as well as the serum testosterone concentration (Santana et al.,
2004).
A review of seven randomized controlled trials published in
2004 described evidence that metformin improves ovulation
and menstrual cyclicity, but these improvements were variable
and modest. Spontaneous ovulation and normal menstruation
were achieved rapidly overall within 3 months of the start of
therapy (Harborne et al., 2003).
A meta-analysis by Kashyap in 2004 reviewed eight
randomized controlled trials addressing the use of metformin
or clomiphene for treatment of PCOS, looking at ovulation and
pregnancy. A benefit of metformin was shown, but a longer
duration of therapy (>3 months) did not show an improvement
(Kashyap et al., 2004). Further studies are needed to
investigate whether long-term use of metformin leads to a loss
of efficacy.
In contrast to the mentioned studies is a study by Ng et al. (2001),
who treated clomiphene-resistant PCOS patients with metformin
(1500 mg/day) and clomiphene or placebo. Ng et al. found a
reduction in insulin concentration of 25% and a reduction in
androgen concentration of 33%, but the ovulation rate was not
significantly improved under clomiphene with metformin (1500
mg/day) compared with placebo with metformin. However, the
inclusion criterion for this study was polycystic ovaries on
ultrasound, so that some included patients had a normal cycle and
normal androgen concentrations. 69
 PCOS treatment strategies - S Tauchert et al.
Some studies did not show the benefit of metformin in the
treatment of PCOS. However, the inclusion criteria sometimes
differ from the definition of PCOS. One of these studies
recruited patients with hirsutism, while it remains unclear if
other features of PCOS were present (Crave et al., 1995).
In a recent review, Cheang and Nestler (2004) described
metformin as a first-line therapy for women with PCOS,
resulting in amelioration of the metabolic syndrome leading to
prevention of long-term cardiovascular and diabetes
complications.
Randomized, placebo-controlled studies using metformin in the
treatment of PCOS are summarized in Table 2.
Unfortunately, most published papers do not give any
information about how ovulation was determined. In future
studies, it would be useful to include such information.
Troglitazone, rosiglitazone, pioglitazone
and acarbose in the treatment of PCOS
Less information exists on the effects of TZD in the treatment of
PCOS. Troglitazone, which has been researched the most, had to
be taken off the market due to hepatotoxicity.
The use of pioglitazone for 3 months increased normal regular
cycles and ovulations over placebo in a trial of 40 patients (41.2
versus 5.6%) (Brettenthaler et al., 2004). Romualdi et al. treated
PCOS patients for a period of 6 months with 45 mg piogliatzone
daily. Cycle irregularities improved in 83% of
hyperinsulinaemic PCOS patients and in 33% of
normoinsulinaemic PCOS women. Insulin sensitivity improved
in the hyperinsulinaemic group, and in both groups hirsutism
and acne decreased (Romualdi et al., 2003). Glueck et al. (2003)
used pioglitazone to treat 13 patients who failed to respond
successfully to metformin. When pioglitazone was added,
concentrations of insulin, glucose and DHEAS, as well as
insulin resistance, decreased and menstrual regularity improved
without severe side effects.
Two small randomized controlled trials studied the use of
rosiglitazone combined with clomiphene. Improvements in
menstrual regularity (Shobokshi and Shaarawy, 2003) and both
spontaneous and clomiphene-induced ovulation rates (Ghazeeri
et al., 2003) were achieved. Ghazeeri et al. randomized 25
clomiphene-resistant women with PCOS in two groups. Group
1 (n = 12) received 4 mg rosiglitazone twice daily and a placebo
on days 5–9 of the cycle. The second group received clomiphene
instead of placebo. In total, 56% ovulated, 33% in the placebo
group and 77% in the clomiphene group.
Recently, Baillargeon et al. (2005) showed in a randomized
controlled, double-blind trial testing metformin, rosiglitazone, a
combination of both and a placebo over a period of 6 months that
compared with placebo, fasting insulin concentrations and
insulin sensitivity improved significantly after metformin or
combination therapy, but not after rosiglitazone. Ovulation rates
at 6 months were markedly increased in all groups except the
placebo group. Combination treatment did not yield additive
results for either ovulation or menstrual bleeding. Androgen
concentrations decreased significantly with active treatment
70 (Baillargeon et al., 2005).
In a study with 12 obese PCOS patients with severe insulin
resistance, the effectiveness of rosiglitazone was evaluated. All
women were treated with 4 mg of rosiglitazone daily for 6
months. Eleven women reverted to regular ovulatory cycles
during the treatment period, insulin resistance improved and
ovarian androgen production decreased (Sepilian and
Nagamani, 2005).
Newer TZD such as rosiglitazone and pioglitazone appear not
to cause the hepatic side effects reported for troglitazone, and
have shown their effectiveness alone and in combination with
clomiphene in improving cyclicity, insulin sensitivity and
biochemical parameters. However, more studies have to be
performed to prove these so far positive clinical effects of
TZD.
Another oral antidiabetic drug, acarbose, an inhibitor of the
alpha-glucosidase enzyme, was used by Ciotta et al. (2001) in
a study in 2001. In this clinical trial, clinical symptoms of
hyperandrogenism improved after 3 months therapy with 200
mg acarbose daily. Eight of 15 patients ovulated regularly.
Recently, Sonmez et al. (2005) compared the effects of
acarbose and metformin on ovulation rates in clomiphene-
resistant PCOS patients. Group I was treated with 100 mg
clomiphene citrate and 300 mg acarbose daily, group II with
100 mg clomiphene and 1700 mg metformin daily for 3
months. Total testosterone decreased and ovulation rates
increased in both groups. Reduction in weight and BMI was
only significant in the acarbose group.
The American Association of Clinical Endocrinologists
recommends using metformin 850 mg twice daily to treat the
hyperandrogenic state of PCOS (AACE, 2001). The use of
TZD regarding the AACE guidelines is less clear due to
limited evidence and risk of teratogenicity.
Table 3 summarizes studies investigating the treatment of
PCOS patients with rosiglitazone and pioglitazone.
Oral anti-diabetics and type 2 diabetes
Women with PCOS have, due to insulin resistance, an
increased risk of developing type 2 diabetes. Two studies have
shown that improved insulin sensitivity had a positive
influence on developing type 2 diabetes. Insulin resistance
may be the earliest detectable abnormality in individuals who
develop type 2 diabetes, and is a recognized risk factor for
diabetes (Erickson et al., 1990).
Two major outcome studies showed that interventions to
improve insulin sensitivity can delay the development of type
2 diabetes in individuals with a high risk profile. A Finnish
study reported that insulin sensitivity was improved by a
combination of diet and exercise, and that progression to type
2 diabetes was reduced by 58% over 4 years in obese men with
impaired glucose tolerance (Tuomilehto et al., 2001).
The Diabetes Prevention Program, a study of the National
Institutes of Health (NIH) of 3234 individuals at high risk for
diabetes, had to be stopped early after an average follow-up of
3 years because intensive lifestyle interventions consisting of
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.

71
 PCOS treatment strategies - S Tauchert et al.
diabetes by 58%, while therapy with metformin only led to a
reduction of 31% (Knowler et al., 2001). This study proved
that medical interventions should always go hand-in-hand with
lifestyle interventions.
Patients with a history of gestational diabetes are also at higher
risk of developing type 2 diabetes. In a prospective placebo-
controlled study, 114 patients with a history of gestational
diabetes were treated with troglitazone and 121 patients with a
placebo. After a median follow-up of 30 months, troglitazone
reduced the development of type 2 diabetes by 56% compared
with placebo (Buchanan et al., 2001).
Although it is not evidence-based yet, it seems to be
reasonable to transfer results from the prevention studies
mentioned above to the group of women with PCOS. The
positive effect of insulin-sensitizing drugs on fertility has been
shown, but studies to analyse preventive effects from type 2
diabetes are still lacking. It is necessary to wait for controlled
studies for evidence.
Oral anti-diabetics and cardiovascular
diseases
PCOS is associated with multiple cardiovascular risk factors
such as obesity, insulin resistance and dyslipidaemia. In
addition, there might be genetic intrinsic factors that caused an
increased cardiovascular risk in PCOS patients (Dunaif, 1997).
Several studies showed a higher prevalence of cardiovascular
diseases in PCOS patients (Talbott et al., 2000; Tuomilehto et
al., 2001). Dahlgren et al. reported that the risk of PCOS
patients suffering a myocardial infarction is increased by 7.4
compared with normal age-matched controls (Dahlgren et al.,
1992). Compared with age- and weight-matched controls,
women with PCOS have a higher incidence of cardiovascular
risk factors such as hypertension (Björntorp, 1996) and
dyslipidaemia (Wild, 1995). In 2000, Wild et al. (2000)
published a retrospective cohort study over a period of 31
years. In 786 women with PCOS the incidence of
hypertension, type 2 diabetes and dyslipidaemia was increased
compared with age-matched controls. Besides dyslipidaemia,
plasminogen-activiting inhibitor (PAI) (Legro et al., 2001) and
C-reactive protein (Morin-Papunen et al., 2003) are increased
in PCOS.
Rautio et al. (2005) recently randomized 30 women with
PCOS either to metformin therapy or to an ethinyl oestradiol-
cyproterone acetate contraceptive pill. The metformin
treatment had beneficial effects on lipid profile and blood
pressure compared with the other group. Therefore, metformin
could be useful in the prevention of cardiovascular
complications.
The Nurses’ Health Study observed 8439 women during the
ages 20–35 years over a period of 14 years. The study showed
that the incidence of cardiovascular disease was increased in
women with irregular or prolonged menstrual cycles (RR: 1.25
for non-fatal and RR: 1.67 for fatal coronary disease). In
addition, this collective showed a higher risk of developing a
stroke (RR: 1.3) (Solomon et al., 2001).
The effects have been variable between the studies, but no
72 deterioration of cardiovascular risk factors has been described.
Long-term studies on cardiovascular events in PCOS are still
missing, but multiple studies have demonstrated the increased
prevalence of risk factors for cardiovascular diseases in these
patients. Therefore, the influence of insulin-sensitizing drugs
on amelioration of cardiovascular risk factors in PCOS is
mostly indirect, as studies showed the improving effect on
several cardiovascular risk factors. Metformin, combined with
a diet, can ameliorate many of the features of the metabolic
syndrome (Glueck, 2003). Apart from its influence on the
development of type 2 diabetes, one cardiovascular risk factor,
metformin decreases serum triglycerides (Velazquez, 1994),
the concentration of endothelin-1 (Diamanti-Kandarakis et al.,
2001) and PAI-I (Velazquez et al., 1997) and reduces blood
pressure (Velazquez et al., 1994). Vribikova et al. (2002)
reported that metformin therapy for only 4 weeks decreased
the concentration of homocysteine significantly. Studies
investigating the effects of anti-diabetic drugs on
cardiovascular diseases in PCOS patients do not exist so far,
but they have been published for patients with type 2 diabetes.
The United Kingdom Prospective Diabetes Study showed a
reduced incidence of myocardial infarction in obese patients
with type 2 diabetes who received metformin (UKPDS, 1998).
Conclusion
PCOS is a severe health problem due to its long-term
consequences and not only a cosmetic and fertility problem.
Insulin resistance, dyslipidaemia and hypertension increase the
cardiovascular risk, PCOS becomes a form of syndrome X.
Amelioration of insulin sensitivity can normalize endocrine
and reproductive disorders. The use of insulin-sensitizing
drugs, particularly metformin, can help to restore cycle
irregularities and increase pregnancy rates in clomiphene-
resistant women. Regarding long-term results, studies that
investigate metformin effects are needed.
Patients should be advised about the benefits of lifestyle
interventions such as diet and physical activity. A reduction in
BMI in women with PCOS can reduce the incidence of type 2
diabetes and can improve ovulation rates and fertility.
Patients and doctors have to be aware of the long-term
consequences and the importance of prevention. PCOS
patients, lean or obese, should be informed about the necessity
of healthy food and physical activity. A regular determination
of lipid profile and glucose tolerance should be discussed.
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