Polycystic ovary syndrome is not purely a gynaecological problem.
Diagnosis can be made if the patient has at least two of the following: menstrual disorder (infrequent menstrual periods - cycle more than 35 days - or amenorrhoea), hyperandrogenism, polycystic ovaries.
Polycystic ovary syndrome is associated with reduced insulin sensitivity which may lead to increased health risks.
Prevalence and consequences
The prevalence of PCOS is estimated to be 5-15% in women of reproductive age.
PCOS will mean increased morbidity at various stages throughout the woman's life.
Gynaecological problems
Patients usually present with menstrual irregularities, hirsutism and infertility problems.
Pregnancies appear to be associated with a higher risk of miscarriage, hypertension and diabetes. The increased risk is, however, likely to be associated with obesity rather than with PCOS as such.
Long-term oestrogenic activity with simultaneous lack of luteal hormone activity predispose to endometrial hyperplasia and thus increase the risk of cancer of the uterine corpus. It has been reported that the risk of uterine cancer is increased 2-6 -fold in women with PCOS as compared with the general population. However, it is difficult to distinguish between the increased risk caused by obesity and that by PCOS, and large-scale epidemiological studies are needed.
There is no evidence of a link with breast or ovarian cancer.
Metabolic disturbances
Women with PCOS often have reduced insulin sensitivity which is associated with truncal obesity and disturbances in lipid metabolism.
Depending on the population, 20-70% of the women with PCOS are overweight.
Insulin resistance and the resulting compensatory increased concentration of insulin are more marked in overweight patients with PCOS than in otherwise overweight controls.
Typical findings include low plasma HDL-cholesterol concentration and hypertriglyceridaemia.
PCOS appears to increase the risk of developing type 2 diabetes at a considerably early age (the risk is 5-10-fold) and hypertension (the risk is 2-3-fold).
The risk of venous thrombosis is 1.5-2-fold and the risk of stroke 2-fold in women with PCOS.
The risk of cardiovascular diseases seems to be increased already at young age.
The risk of complications associated with cerebrovascular disease and diabetes is increased.
Other disturbances
Women with PCOS have additionally an increased risk of many other diseases, such as thyroid diseases (3-fold), asthma (1.5-fold), depression (3-fold), anxiety disorders (1.4-fold) and migraine (2-fold).
Diagnosis
Diagnosis is based on the history, clinical findings (menstrual irregularities, male pattern of hair distribution, acne) and, if necessary, on hormone studies.
A gynaecological ultrasound examination is used to verify the diagnosis; polycystic morphology of the ovaries is evident.
Two of the following criteria must be present for PCOS diagnosis:
anovulation characterized by menstrual irregularities (oligomenorrhoea, i.e. cycle duration more than 35 days, or amenorrhoea)
clinical (male pattern of hair distribution) or biochemical hyperandrogenism (serum testosterone > 2.7 nmol/l or > 2.3 nmol/l depending on the method and laboratory)
polycystic morphology of the ovaries, verified by ultrasound examination (presence of 20 or more follicles in each ovary measuring 2-9 mm in diameter, and/or increased ovarian volume).
Exclude thyroid disease, hyperprolactinaemia, androgen-secreting tumours and disturbances in adrenal function.
If the patient presents with menstrual irregularities, measure serum TSH and prolactin to exclude other causes. Remember to exclude eating disorders.
If the patient presents with hirsutism and/or acne, measure serum testosterone.
Serum FSH and LH concentrations should be determined for differential diagnostics of menstrual disorders. Serum oestradiol assay is not usually of diagnostic benefit.
Due to the risk of metabolic disturbances the following screening is indicated, particularly in overweight patients:
blood glucose, lipids (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and blood pressure at regular intervals (for example every one to two years)
HbA1c in overweight and obese persons as well as in persons with substantial increase in weight, followed by regular testing (for example every 2-3 years).
Treatment
The most important treatment form is weight reduction down to the patient's normal weight. Weight reduction may
significantly reduce the risk of miscarriage during early pregnancy as well as other pregnancy-associated risks
enhance the safety and efficacy of ovulation induction treatments and reduce the risk of late complications associated with PCOS, such as type 2 diabetes Lifestyle Changes in Women with Polycystic Ovary Syndrome and coronary heart disease.
Exercise reduces insulin resistance .
Smoking cessation is important due to the increased risk of vascular diseases.
In the treatment of hirsutism, no difference in the effectiveness of various combined oral contraceptives has been shown.
Combined oral contraceptives containing 35 µg of ethinyloestradiol and cyproterone acetate are not recommended due to their risk profile (e.g. higher risk of venous thrombosis).
To prevent endometrial hyperplasia cyclic progestogen (dydrogesterone, norethisterone or lynestrenol) has to be prescribed (for example, for 10 days on days 15-24 of the cycle or for 14 days every 2 or 3 months).
During spironolactone therapy, monitor plasma electrolytes (sodium and potassium) at regular intervals, for example after the first 3 months after instigating treatment and annually thereafter.
Treatment of anovulatory infertility
Refer a PCOS patient at an earlier stage than usual to a gynaecologist familiar with infertility treatments.
Metformin
Metformin, combined with lifestyle changes, may have beneficial effects on metabolic risk factors and restoration of ovulation Metformin for Polycystic Ovary Syndrome. Not enough evidence is available on whether long-term use of metformin reduces the risk of developing metabolic diseases.
Always consult a gynaecologist before prescribing metformin to discuss its use on an individual basis.
If there is no urgent need for infertility treatment, metformin may be helpful also in losing weight.
Metformin started 3 months earlier and combined with ovulation induction drug (gonadotropin) improves both pregnancy and live birth rates by up to 15%.
For the time being there are no studies on combining metformin and aromatase inhibitor drugs, but such combination therapy is nowadays routinely used (see Other treatments of anovulation).
Although metformin may further weight loss, there is not enough evidence on whether metformin is more effective in overweight PCOS women compared with normal-weight PCOS women.
Metformin does not appear to decrease the risk of miscarriage in women with PCOS.
According to current practice, metformin is discontinued when a pregnancy test is positive.
If the patient has earlier had gestational diabetes, the further use of metformin during pregnancy should be discussed with an obstetrician with expertise in the topic.
Metformin has been presumed to possibly reduce the occurence of gestational complications, such as pre-eclampsia and gestational diabetes, but no significant effect has been verified in adequately large placebo-controlled studies.
Use of metformin during pregnancy may reduce the risk of prematurity.
Other treatments of anovulation
All other ovulation induction treatment is carried out by a gynaecologist who has expertise in fertility treatment.
Aromatase inhibitors (letrozole and the more rarely used anastrozole) are the primary drugs for inducing ovulation in PCOS and they have in Finland completely replaced clomiphene which was used earlier.
Aromatase inhibitors are drugs used in breast cancer therapy. They prevent oestrogen production in the ovaries. As a result, the inhibitory effect of oestrogens on gonadotropin secretion decreases and the secretion of gonadotropins increases, which stimulates ovarian follicle growth.
Letrozole is used as tablets in the beginning of the menstrual cycle. Development of follicles and the endometrium is monitored by ultrasonography and, as required, by monitoring serum progesterone concentration.
The next step is ovarian diathermy (”drilling”) or the use of gonadotropins. Gonadotropin treatment is more problematic than letrozole treatment and it is expensive.
Gonadotropins are injected daily, and ovulation induction may take a long time. The treatment requires repeated ultrasound examinations, and still the risk of multiple pregnancy or hyperstimulation remains.
Laparoscopic ovarian drilling has recently regained popularity along with the development of new techniques. Treatment costs are considerably lower than those of gonadotropin treatment, and the method has been found to be equally effectiveLaparoscopic ”drilling” for Ovulation Induction in Polycystic Ovary Syndrome and to reduce the risk of multiple pregnancy. The choice between drilling and gonadotropins is made on an individual basis.
If conception does not occur with ovulation induction, in vitro fertilization is considered.
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