Polycystic Ovary Syndrome

What is it?

Polycystic ovarian syndrome (PCOS) is a common condition, affecting up to a quarter of women of childbearing age. The disorder is one of the most common hormonal abnormalities in women of reproductive age and is a leading cause of infertility. Although the underlying cause is not well understood, PCOS is generally characterised by an excess production of androgens (male hormones - usually testosterone), lack of ovulation i.e. anovulation (the egg is not released by the ovary) and absence of menstrual periods (amenorrhoea), and by a varying degree of insulin resistance. The ovaries usually have many fluid-filled sacs (cysts) hence the name of the condition.

Androgens are normally created in small amounts by a woman's ovaries and adrenal glands. Even a slight overproduction can lead to symptoms such as hirsutism and acne. In extreme cases, they can lead to virilization.

There is frequently increased secretion of luteinising hormone (LH) from the pituitary gland and all these hormone imbalances affect the menstrual cycle in PCOS, causing infertility problems. Most women with this condition do not have regular periods. Often they have chronic anovulation and amenorrhoea, but they may also experience irregular periods and uterine bleeding. With PCOS, both ovaries tend to be enlarged as much as 3 times their normal size. In many women with PCOS, an ultrasound of the ovaries will reveal cysts (small immature egg-bearing follicles, fluid-filled follicles) that can be seen on the surface of the ovary. When the egg is not released and a woman is not menstruating, sufficient progesterone is not produced. This leads to a hormonal imbalance in which oestrogen acts "unopposed." This can lead to an overgrowth of the lining of the uterus (endometrial hyperplasia) and increases a woman's risk of developing endometrial cancer. Women with PCOS who do ovulate and become pregnant tend to have an increased risk of complications including gestational diabetes, premature delivery, caesarean delivery and miscarriage.

Although the cause of PCOS is not well understood, some think that insulin resistance may be a key factor. Insulin is vital for the transportation and storage of glucose at the cellular level; it helps regulate blood glucose levels and has a role in carbohydrate and lipid metabolism. When there is resistance to insulin's use at the cellular level, the body tries to compensate by making more. This leads to hyperinsulinaemia (elevated levels of insulin in the blood). Some believe that hyperinsulinaemia may be at least one cause for an increased production of androgens by the ovaries.

Most women with PCOS have varying degrees of insulin resistance, obesity, and lipid dysfunction. Insulin resistance tends to be more pronounced in those who are obese and do not ovulate. These conditions put those with PCOS at a higher risk of developing type 2 diabetes and cardiovascular disease.

Signs and Symptoms

PCOS is said to be heterogeneous; that is, patients may experience a wide variety of different symptoms to a greater or lesser degree, and vary over time. Also, a uniform and precise definition of the syndrome is lacking. Women often go to their doctor because they are having menstrual irregularities, experiencing infertility, and/or are having symptoms associated with androgen excess. They may experience:

  • Abnormal uterine bleeding
  • Acanthosis nigricans
  • Acne
  • Amenorrhoea or irregular periods (oligomenorrhoea)
  • Decreased breast size
  • Deeper voice (rare)
  • Enlarged ovaries
  • Hirsutism involving male hair growth patterns such as hair on the face, sideburn area, chin, upper lip, lower abdominal midline, chest, areola, lower back, buttock, and inner thigh
  • Weight gain/truncal obesity; fat distribution in the centre of the body
  • Skin tags in the armpits or neck
  • Thinning hair, with male pattern baldness
Tests

PCOS is to some extent a diagnosis which is reached after excluding other disorders. PCOS remains a syndrome (a collection of signs and symptoms) with no single clinical feature which can make the diagnosis. Your doctor will carry out tests to rule out other causes of anovulation and infertility. He will usually request a variety of hormone tests to help determine whether hormone overproduction may be due to PCOS, an adrenal or ovarian tumour, or an overgrowth in adrenal tissue (adrenal hyperplasia). Ultrasound is often used to look for cysts in the ovaries and to see if the internal structures appear normal.

Your doctor will use the combination of laboratory results and clinical findings to make a diagnosis. If the diagnosis is PCOS your doctor may then request further tests such as lipid profiles and glucose levels to monitor your risk of developing future complications such as diabetes and cardiovascular disease

PCOS is more difficult to diagnose in adolescent girls, as the changes associated with puberty overlap with the symptoms seen in PCOS. Acne, irregular periods and polycystic ovaries are normal features of puberty which make the diagnosis of PCOS difficult. Ultrasound is not used, but your doctor may request some or all of the laboratory tests below. If you are adolescent and have some of the features of PCOS but your doctor isn’t able to give you a formal diagnosis, he will reassess you around 8 years after your periods started.

Laboratory Tests

  • FSH (Follicle Stimulating Hormone), may be normal or low with PCOS
  • LH (Lutenizing Hormone), may be elevated
  • LH/FSH ratio. This ratio is normally about 1:1 in premenopausal women, but a ratio of greater than 2:1 or 3:1 may provide supporting evidence for a diagnosis of PCOS
  • Prolactin may be normal or mildly elevated
  • Testosterone, usually elevated
  • DHEAS (may be measured to rule out a virilising adrenal tumour in women with rapidly advancing hirsutism), frequently mildly elevated with PCOS
  • Oestrogens, may be normal or elevated
  • Sex hormone binding globulin, may be reduced
  • Androstenedione, may be elevated
  • Anti-Müllerian Hormone is a relatively new test used by some centres and has been found to be increased 2-3 times in PCOS. At present, this test is not routinely used in the investigation of PCOS in the UK, although this could change as a result of ongoing research.
  • hCG (Human chorionic gonadotropin), used to check for pregnancy, negative
  • Lipid profile, (collected after a fast), (low HDL, high LDL, and cholesterol, elevated triglycerides)
  • Glucose, fasting and/or a glucose tolerance test, may be elevated
  • HbA1c may be elevated
  • Insulin, (collected after a fast), often elevated
  • TSH (Thyroid stimulating hormone) some women who have PCOS are also hypothyroid
  • Cortisol to rule out Cushing's syndrome
  • 17-hydroxyprogesterone to exclude adrenal hyperplasia
  • Insulin-like growth factor (IGF-1) to exclude acromegaly

The above tests may not all be requested or performed at the same time. Some will only be performed as directed by clinical findings and initial laboratory test results.

Non-Laboratory Tests
Ultrasound is used to evaluate enlarged ovaries. This may be transvaginal or pelvic. With PCOS, the ovaries may be enlarged and characteristically have 12 or more follicles per ovary, with each follicle less than 10 mm in diameter. These ultrasound findings are not diagnostic; not all women with PCOS have polycystic ovaries, and some women have polycystic ovaries but do not have PCOS.

Treatment

There is no cure for PCOS. Although there have been cases involving the spontaneous resumption of periods, most women will have progressive symptoms until after menopause. Treatment of PCOS is aimed at reducing its symptoms and helping to prevent future complications. The goals are to promote ovulation, prevent endometrial hyperplasia, counterbalance the effects of androgens, and reduce insulin resistance. Treatment options depend on the type and severity of the individual patient's symptoms and on the patient's desire to become pregnant. Low-dose oral contraceptives are often used to stabilise hormones and oppose stimulation of the endometrium. Over several months, low-dose oral contraceptives can usually regulate menstrual periods, eliminate or minimise uterine bleeding, and reduce androgen levels (improving hirsutism and clearing up acne).

Anti-androgens, such as spironolactone (aldactone), flutamide (Drogenil) and cyproterone (Androcur, Cyproterone acetate) are sometimes combined with oral contraceptives to help address more severe hirsutism and acne. Standard hair removal treatments such as waxing or shaving may be used to remove unwanted hair, and antibiotics or retinoic acids may be used to treat acne.

Weight loss and exercise are recommended to help decrease insulin resistance and to minimize lipid abnormalities. Weight reduction can also decrease testosterone, insulin, and LH levels.

Although sometimes performed, surgery is a rare PCOS treatment option. One surgical option, a "wedge resection", involves removing the part of the ovary that contains the cystic follicles to try to restore ovulation. Another option, ovarian drilling, involves using a needle with an electric current to make holes in the ovary. Both of these procedures may temporarily increase fertility but may also lead to scarring and adhesions.

If a woman with PCOS wants to become pregnant, she is usually given clomiphene citrate (Clomifene, Clomid), a drug that helps induce ovulation. She may also be given human menstrual gonadotrophins (Merional, Menopur), although this drug increases the risk of multiple pregnancies.