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What is Polycystic Ovarian Syndrome?

Polycystic Ovarian Syndrome PCOS refers to an endocrine disorder characterized by ovaries with multiple cysts (polycystic ovary), an imbalance of the female hormones, menstrual disturbance, disturbances in ovulation and high levels of androgens (steroid male hormones that promote male characteristics).

The age of onset is often around the age when menses just started before bone age reaches16 years old. Between 1 in 10 and 1 in 20 women of child bearing age is diagnosed with polycystic ovarian syndrome PCOS.
What causes Polycystic Ovarian Syndrome PCOS?

The exact cause of polycystic ovarian syndrome is unknown. Experts identify certain factors that contribute to PCOS. These include insulin resistance, increase levels of androgens (steroid male hormones that promote male characteristics), female hormones (estrogen and progesterone) imbalance causing menstrual disturbance and certain genetic predisposition.

Insulin is a hormone produced by the pancreas that controls our blood sugar level. After a meal, insulin will be released to lower our blood serum sugar level. Insulin resistance develops when the body cells do not respond to the effects of insulin, so the level of glucose in our blood increases up to a certain level and cause diabetes mellitus.

Insulin resistance will also induce more insulin to be released to control the blood sugar level, condition called hyperinsulinemia which is associated with hyperlipidemia (Metabolic Syndrome). Insulin resistance is also associated with acanthosis nigricans which is thickened darken velvety skin patches often at the neck, axilla and groin area.

Patients with PCOS have higher than normal levels of androgens which will prevent ovulation and may lead to subfertility and irregular/infrequent or absent menses. Androgens also cause male characteristic hair growth, acne and weight gain.

A woman with PCOS is likely to have a sister or mother who has the condition too. However researchers have yet to identify any particular genes or inheritance trait in PCOS. 
Clinical symptoms of polycystic ovarian syndrome PCOS

1.    Menstrual disorders: Patients may experience infrequent menstrual periods, absent menses and irregular menstrual periods. The menses may also be heavy resulting in dysfunctional uterine bleeding. Menstrual disorders are due to the disturbance in ovulation as a result of the surge in androgens and imbalance of female hormones.

2.    Hyperandrogenism: Increase levels of androgens result in male pattern of excessive hair growth on the chest, abdomen, face and legs. This condition is called hirsutism. This affects up to 70% of PCOS patients. Other associated symptoms with increased androgens are acne with oily skin, male pattern hair loss (androgenic alopecia), increase muscle mass, enlarged clitoris and deepening of voice.

3.    Infertility: As patients with PCOS only ovulate infrequently/intermittently the chance of pregnancy is lowered. PCOS is the most common cause of female infertility. There is also increased risk of miscarriage.

4.    Obesity and metabolic syndrome: More than 50% of patients with PCOS are obese. PCOS patients are also predisposed to metabolic syndrome. Metabolic syndrome is a condition whereby patients have central obesity, raised triglycerides, reduced HDL cholesterol, raised blood pressure and raised fasting serum glucose which predisposes patients to cardiovascular diseases.

5.    Diabetes Mellitus: As PCOS patients tend to have insulin resistance which predisposes them to diabetes mellitus. American college of obstetricians and gynecologists  recommend diabetes screening for patients with PCOS from 40 years onwards.

6.    Obstructive sleep apnea: Many women with PCOS tend to have Obstructive Sleep Apnea OSA characterize by episodes of apnea/hypoapnea (temporary cessation of breathing during sleep) associated with daytime somnolence. Patients with OSA should undergo a sleep study.

7.    Acanthosis Nigricans: PCOS patients may have patches of thickened velvety darkened skin over the neck, axilla and groin area. This is associated with insulin resistance.

8.    Multiple cysts on ovaries: Patients will have multiple ovarian cysts as the name suggest polycystic ovarian syndrome.
Physical examination signs of Polycystic Ovarian Syndrome

General appearance: Patients will have male pattern hair loss, male distribution of hair (hirsutism), increased muscle mass and a deepened voice. They will also have acanthosis nigricans skin changes.

Measurements: Patients will also have central abdomen obesity with a waist circumference bigger than 88 cm. Their Body Mass Index is also raised. Their blood pressure, blood cholesterol and blood glucose level may also be raised as in metabolic syndrome.

Abdomen and pelvic examination: usually there will be no pain/mass on palpation of the ovaries unless they are enlarged. The clitoris may be enlarged due to the increased androgens.
Complications of polycystic ovarian syndrome

1.    Diabetes Mellitus and gestational diabetes: As PCOS patients have insulin resistance they are at risk of diabetes during pregnancy and also early onset adult diabetes. Diabetes also has its own cardiovascular risks. Patients with PCOS should be screened for diabetes.

2.    Metabolic syndrome: Combination of obesity, raised cholesterol levels, raised blood pressure and blood glucose levels all predispose patients to increase risk of stroke, heart attack, peripheral vascular disease and other cardiovascular conditions. Hence annual check-up and screening for these diseases, regular exercise and keeping a normal body mass index are highly important.

3.    Non-alcoholic steatohepatitis: Due to the raised cholesterol levels, this will result in fat accumulation in the liver (fatty liver) and resulting in inflammation of the liver.

4.    Sleep apnea: Patients with obstructive sleep apnea need to go through a sleep study and some may need oxygen therapy during sleep if severe.

5.    Endometrial cancer: Patients with PCOS has associated increased endometrial thickening (lining of uterus) as there is constant stimulation of the endometrium without progesterone. Endometrial hyperplasia (thickened uterine lining) will increase the risk of endometrial (uterine) cancer. Hence Royal College of Obstetricians and Gynecologists (RCOG) recommend inducing menstrual bleeding with progestogens with a minimum of every 3 to 4 months.
Differential Diagnosis of Polycystic Ovarian Syndrome

There are conditions that may present similarly as Polycystic Ovarian Syndrome that need to be ruled out before PCOS can be confirmed. These conditions include:

1.    Congenital Adrenal Hyperplasia
2.    Ovarian Hyperthecosis
3.    Hypothyroidism
4.    Drugs like danazol, androgenic progestins
5.    Familial or idiopathic hirsutism
6.    Cushing Syndrome
7.    Hyperprolactinemia
8.    Masculinizing tumors of adrenal glands
9.    Anabolic steroid consumption
10. Stromal Hyperthecosis
11. Ovarian Cancer
12. Acromegaly

Tests and diagnosis of Polycystic Ovarian Syndrome

To diagnose Polycystic Ovarian Syndrome PCOS is to exclude the possible conditions above that could also cause menstrual disturbances and Hyperandrogenism. A number of tests to confirm diagnosis of PCOS can be done as listed below:

1.    Laboratory tests:
  • serum 17-hydroxyprogesterone levels to rule out congenital adrenal hyperplasia
  • serum prolactin level to rule out Hyperprolactinemia
  • thyroid function test to rule out thyroid disease
  • serum cortisol test and overnight dexamethasone suppression test to rule out Cushing syndrome
  • serum insulin-like growth factor (IGF) ̶ 1 level should be checked to rule out acromegaly
  • In PCOS the follicle-stimulating hormone (FSH) is low and luteinizing hormone (LH) is raised hence the LH:FSH ratio is usually greater than 3 in patients with PCOS
  • Androgens level like testosterone level and dehydroepiandrosterone sulfate (DHEA-S) levels will be raised in patients with PCOS
  • Oral glucose tolerance test and cholesterol test: patients with PCOS should be screened for diabetes and high cholesterol.

2.    Imaging:
  • Ovarian ultrasonography can be performed to assess ovarian morphology. Ultrasound images of the ovaries will reveal multiple peripheral follicles on the ovary in patients with PCOS
  • CT/MRI scans: In cases when ovarian cancer is suspected, CT and MRI scans are good modality to visualize the ovaries and other organs.
Treatment of polycystic ovarian syndrome

Lifestyle modifications: American College of Obstetricians and Gynecologists ACOG recommend lifestyle modifications like healthy diet, regular exercise and weight loss will help reduce the risk of diabetes mellitus, hypertension, high cholesterol and other cardiovascular diseases in patients with PCOS. These lifestyle changes will also help regulate ovulation and effects of high androgen levels.

Drug therapy: Medications can be used to regulate menses and ovulations, treat metabolic derangements and improve hirsutism.

1.    Fertility medications: Patients with PCOS has fertility issues because of lack of ovulation. Medications like clomiphene citrate induce ovulation and increase chance of pregnancy. However it increases the risk of multiple pregnancies. Another option is in vitro fertilization (IVF). IVF offers the best chance of becoming pregnant in any given cycle.

2.    Oral Contraceptives: For patients not keen to get pregnant, oral contraceptive help to regulate menses, reduce the male androgen hormones and improve acne.

3.    Insulin sensitizer drugs: Metformin used in diabetic treatment can be used in PCOS. Metformin improves insulin sensitivity, reduces androgens, facilitate weight loss and improve cholesterol levels.

4.    Hirsutism control: Anti-androgens drugs like spironolactone will reduce androgen effects on the skin and control abnormal hair growth. However spironolactone is not safe for usage in pregnancy. Eflornithine (Vaniqa) cream slows facial hair growth in women. Long-term, more permanent measures for unwanted hairs include electrolysis and laser treatment.

5.    Anti-acne treatment: Topical antibiotics, topical anti-acne creams, oral antibiotics, topical retinoids and oral retinoids can be used to control acne in patients with PCOS.

Surgery: Laparoscopic surgery involving small incisions in the abdomen to conduct ovarian drilling to induce ovulation by using electrical or laser energy to burn holes in follicles on the surface of the ovaries. Potential complications from surgery include formation of adhesions and ovarian atrophy. It does not have risk of multiple pregnancies like ovulation inducing drugs.
Follow up on Polycystic Ovarian Syndrome

PCOS patients are at risk of hypertension, diabetes and high cholesterol hence regular follow-up with screening tests are recommended.

PCOS patients also have an increased risk of endometrial cancer (uterine cancer) hence they should be followed up with their gynecologists. Hence Royal College of Obstetricians and Gynecologists (RCOG) recommend inducing menstrual bleeding with progestogens with a minimum of every 3 to 4 months.

Pregnant women with PCOS have increased risk of miscarriage, preterm labor, pre-eclampsia and gestational diabetes.
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