Polycystic ovarian syndrome symptoms

Polycystic ovary syndrome

Polycystic ovary syndrome, or Stein-Leventhal syndrome as it was previously known, is a clinical condition with a combination of hyperandrogenism (acne, hirsutism, male pattern baldness but no virilization) and anovulation (menstrual irregularity, infertility) with typical ultrasound changes in the ovaries.

Epidemiology

Polycystic ovary syndrome is the most common endocrine disorder of women of reproductive age, affecting at least 8% of women using clinical criteria alone and 20% using ultrasound findings. It occurs in up to 20% of Caucasians and 50% of Asians. It is thought to be the cause of 95% of cases of hirsutism referred to endocrinology and dermatology outpatient clinics.

Pathology

The characteristic pathological findings are enlarged ovaries with multiple small cysts which are multiple follicles at various stages of development. The ovarian capsule is often thickened or scarred. The follicles fail to mature (possibly due to abnormalities in FSH/LH and androgen levels) and take on the appearance of fluid-filled sacs. Excess androgens are thought to arise from excessive production by the ovaries.

Scope of disease

Patients may have mild symptoms only, with the diagnosis made incidentally on ultrasound scanning. Disruption to the menstrual cycle and lack of ovulation can lead to infertility. Polycystic ovary syndrome has genetic associations with insulin resistance, although obesity and type 2 diabetes mellitus (7-fold increased risk) are common associated features. Polycystic ovary syndrome is also associated with obstructive sleep apnoea, endometrial carcinoma and cardiovascular disease.

Clinical features

Common symptoms are menstrual irregularity, obesity, excessive body and facial hair, acne and male-pattern baldness. Infertility is also an occasional presenting complaint. On examination, hypertension and signs of diabetes may also be evident.

Some patients with the syndrome may have some but not all of the classical findings. The 2003 international criteria are listed in , where two out of three criteria are required for diagnosis:

-Presence of polycystic ovaries on ultrasound examination

-Oligo-/anovulationClinical

-biochemical evidence of androgen excess

Initial investigations

Serum testosterone level

Elevated testosterone levels provide biochemical evidence of hyperandrogenism; however, it is usually within the normal range. Other causes of raised androgen levels include congenital adrenal hyperplasia and androgen-secreting tumours.

Sex hormone binding globulin

Sex hormone binding globulin (SHBG) is low in 50%.

Serum LH and FSH

Raised LH occurs in up to 70%: the higher the LH level, the more likely it is that fertility is affected. There is also an increased LH:FSH ratio.

Pelvic ultrasound scan

Typically (in 90% of cases) there is an increase in ovarian stroma with more than 8 follicular cysts that are <10 mm in size. Transvaginal ultrasound will also detect most solitary virilizing ovarian tumours.

Further investigations

Once the diagnosis is confirmed, further tests are often performed to screen for associated diseases or differential diagnoses associated with androgen excess (based on any associated clinical features).

Screening for associated diseases

Oral glucose tolerance test

An oral glucose tolerance test is recommended in women over the age of 30 because up to 40% can have impaired glucose tolerance associated with this insulin-resistant state and up to 15% develop type 2 diabetes at some time in their lives.

Serum lipid profile

Screening for hyperlipidaemia and hypertriglyceri-daemia is undertaken to assess the cardiovascular risk profile.

Screening for endometrial cancer

Patients who have not had a menstrual period for more than a year should be assessed for the risk of endometrial cancer. This may be done through ultrasonic measurement of the endometrial thickness, or through endometrial biopsy.

Screening for differential diagnoses

Screening for adrenal disease

17-OH progesterone levels are performed to exclude late-onset congenital adrenal hyperplasia . Dehydroepiandrosterone and androstenedione can also be significantly raised with adrenal disease.

Screening for prolactinoma

Mild hyperprolactinaemia is seen in 30% of patients but is usually less than 2000 mU/L.

Screening for Cushing's syndrome

Urinary free cortisol and an overnight dexamethasone suppression test should be performed if cortisol excess is suspected.

Initial management

Patient education

Dietary modification to follow a low glycaemic index, low-fat diet can be used and may aid in weight reduction. This may improve insulin resistance and symptoms such as hirsutism.

Medical management

The aims of treatment are symptomatic improvement and reduction of the risk of complications from metabolic and cardiovascular abnormalities

Suppression of hyperandrogenism

Suppression of hyperandrogenism reduces symptoms such as acne and hirsutism. This can be achieved using oestrogen therapy such as the combined oral contraceptive pill. Oestrogen suppresses LH and the subsequent overproduction of androgens in the ovaries. The progestogen component protects against unopposed oestrogenic stimulation of the endometrium which can cause endometrial cancer. However, synthetic progestogens derived from male hormones should be avoided. In addition to relief of acne and hirsutism, the contraceptive pill restores menstrual regularity. However, the adverse effects include worsening of insulin resistance and increased risk of vascular thrombosis.

Other competitive androgen receptor blockers such as cyproterone acetate (benefits 60%), spironolactone (benefits 45%) and flutamide (benefits 50%) may be used in combination to achieve a greater response. Glucocorticoids have been used but have significant side effects.

Management of infertility

Induction of ovulation is required if the patient wishes to become pregnant. Clomifene is an orally available agent which blocks oestrogen receptors in the hypothalamus, thus triggering additional gonadotrophin release.

Pulsatile gonadotrophin therapy is associated with a 40% conception rate after 4 cycles. Surgical treatment includes laparoscopic diathermy or laser drilling that can restore ovulation in up to 80%. If all these therapies do not help, in vitro fertilization can be successful in up to 80% after 6 cycles.

Management of insulin resistance

Metformin, a biguanide drug used to treat type 2 diabetes mellitus, has been used in treatment of insulin resistance found in polycystic ovary syndrome. Benefits include reduction in fasting insulin levels, blood pressure and low-density lipoprotein cholesterol. In addition, metformin significantly increased the likelihood of ovulation (in up to a third of patients), with an odds ratio of 3.88 (confidence interval (CI) 2.25 to 6.69) compared to placebo. The most common adverse effects of metformin are gastrointestinal disturbance such as nausea and vomiting.

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