Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is an endocrine (hormonal) condition in which a woman produces too much androgen hormone. Elevated androgens cause the ovaries to enlarge and develop many small cysts. PCOS is commonly associated with hirsutism (excess body hair growth), acne, irregular menstrual cycles and infertility.

Other Names


PCOS has several names:


 * Polycystic ovarian syndrome
 * Stein-Leventhal syndrome (original name, used when first described in 1935)
 * Syndrome O
 * Hyperandrogenic Chronic Anovulation
 * Polycystic Ovary Disease
 * Functional Ovarian Hyperandrogenism
 * Ovarian Dysmetabolic Syndrome

Symptoms
Below are some symptoms of PCOS:


 * Infertility
 * Irregular periods or absent menstrual periods
 * Hirsutism (excess body hair on the face, chest, stomach. Note that the amount of body hair that a woman has can be closely related to her ethnicity. For example, women of mediterranean and middle eastern descent normally tend to have more body hair than Asian women.)
 * Acne
 * Male-pattern thinning of hair
 * Acanthosis nigrans (velvety areas of darkened skin behind the neck, in the groin and in the armpits)

Conditions associated with PCOS:


 * Obesity
 * Type 2 diabetes or impaired glucose tolerance (also called prediabetes)
 * Gestational Diabetes (diabetes in pregnancy)
 * Metabolic Syndrome

Cause
In order to understand why the ovary does not ovulate (release a mature egg) in PCOS, it is important to first understand why the normal ovary does ovulate.

Normally, the pituitary gland in the brain makes several different kinds of hormones including LH (lutenizing hormone) and FSH (follicle stimulating hormone). Hormones go out into the blood stream and act as messengers to different organs in the body.

FSH’s function is to go to the ovary to stimulate a follicle to grow and produce a mature egg. A follicle is a fluid-filled sac (functional cyst) located just beneath the surface of the ovary. It contains an egg and it is lined with special cells. The follicle increases in size during the first half of the menstrual cycle in normal women because it is stimulated by FSH.

LH is normally released in low levels from the pituitary during the first half of the menstrual cycle while the egg matures. Healthy women get a surge or spike in the LH level in the middle of the menstrual cycle and this causes the follicle to rupture and release the egg. The egg is then picked up by the fallopian tube.

In PCOS, high levels of LH combined with low or normal levels of FSH cause the ovaries to make excess androgen hormones. This inhibits the proper development of a follicle and a mature egg and inhibits ovulation. The PCOS ovaries have many small follicles or cysts, but none of these follicles becomes large enough to ovulate because of the abnormal hormonal environment.

High levels of androgens increase the risk of hirsuitism (abnormal body hair growth), infertility, abnormal thickening of the uterine lining which can cause heavy periods and if untreated can lead to uterine cancer.

Patients with PCOS also often have high insulin levels. The high insulin can also cause the ovaries to make too much androgen hormone which also inhibits ovulation. In addition, high insulin levels are also associated with type 2 diabetes, heart disease, high cholesterol an high blood pressure.

Diagnosis
A set of diagnostic criteria for PCOS was determined by a conference held in Rotterdam in 2003 &lt;ref&gt; Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004 Jan;19(1):41-7. Abstract&lt;/ref&gt;. According to these guidelines, a woman must have at least two of the following three conditions to be diagnosed with PCOS:


 * Infrequent or absent ovulation (associated with irregular or absent periods)
 * Signs of increased androgen effects (either with elevated androgen hormone levels in the blood or clinical signs of male-pattern baldness, acne, hirsuitism)
 * Polycystic ovaries (as seen on ultrasound)

Medical histories and physical exams, including a pelvic exam, are used for diagnosis. Sometimes a vaginal ultrasound and blood tests (hormone levels)are performed.

Medical history
Several conditions noted in a medical history are relevant to a diagnosis of PCOS:


 * irregular menstrual cycles or absence of menstrual cycles
 * acne and oily skin
 * abnormal body hair growth (hirsuitism)
 * family history of PCOS

Physical examination
Below are some physical findings that are suggestive of PCOS:


 * Abnormal hair growth (either male-pattern hair loss or body hair growth in a more traditional "male" pattern - sideburns, neck, inner thighs and lower back.)
 * Acne and oily skin
 * Acanthosis Nigrans - dark, thickened skin usually seen on the neck, armpits and groin. Skin tags may also be seen in these areas. Acanthosis nigrans is not diagnostic of PCOS - it can be seen with other diseases such as diabetes, obesity, high blood pressure and even cancer.
 * Obesity is very often present in PCOS. A patient's body fat is generally distributed around the mid-section of the body ("apple-shape"). A body mass index (BMI) can easily be calculated in the doctor's office. Waist size measurements can also be helpful.
 * The physician may be able to feel slightly enlarged ovaries during a pelvic examination. The doctor can then perform a transvaginal ultrasound to better examine the ovaries.

Laboratory tests
Laboratory tests are used to check for abnormal concentrations of hormones and other markers.

Endocrine (hormone) tests
Blood hormone levels to check if a woman is not ovulating and PCOS is suspected:


 * LH is usually elevated in PCOS.
 * FSH is usually low or normal in PCOS.
 * Testosterone
 * DHEA and 17-hydroxyprogesterone (adrenal gland hormones) are measured to rule out an adrenal gland tumor or problem such as Congenital Adrenal Hyperplasia.
 * Prolactin is another pituitary hormone that can cause irregular or absent periods if elevated.
 * TSH (thyroid stimulating hormone) levels are measured to rule out a thyroid gland problem that could be causing irregular periods.
 * HCG is a pregnancy test eliminates the possibility that the irregular menses and weight gain is due to a pregnancy.

Blood chemistry tests
Blood tests are also used to measure cholesterol levels and detect diabetes. The latter is determined by testing fasting blood sugar and glucose tolerance tests (glucose level after a loading dose of sugar is consumed).

Ultrasound
PCOS can be diagnosed with a pelvic (transvaginal) ultrasound. This test can detect 10 or more cysts that are 2–9 mm in diameter.&lt;ref&gt; Jonard S, Robert Y, Cortet-Rudelli C, Pigny P, Decanter C, Dewailly D. Ultrasound examination of polycystic ovaries: is it worth counting the follicles?. Hum Reprod. 2003; 18(3): 598-603. Abstract | Full Text | PDF&lt;/ref&gt; In addition, the ovaries in PCOS are enlarged (ovarian volume more than 10 cm3) - usually to 1 1/2 to 3 times normal size. &lt;ref&gt;Sikka P, Gainder S, Dhailwal LK, Bagga R, Sialy R, Sahdev S. Ultrasonography of the ovaries and its correlation with clinical and endocrine parameters in infertile women with PCOS. Int J Fertil Womens Med 2007;52(1):41-7. Abstract&lt;/ref&gt;

Treatment
Treatment of PCOS has four main goals:


 * Restoration of menstrual cycles (to prevent heavy vaginal bleeding and possible uterine cancer if the uterine lining builds up too much)
 * Increasing Fertility (by restoring ovulation)
 * Treatment of Symptoms (abnormal hair growth, acne)
 * Lowering insulin levels.

PCOS should be treated in the long term because of the increased risk of heart disease, diabetes and uterine cancer associated with PCOS.

Treatment Options
Treatment options include:


 * Medications
 * Weight loss
 * Ovarian stimulation with special fertility medicines
 * Laser hair removal or electrolysis
 * Surgery is a last resort

Medications
Most PCOS symptoms can be controlled by medication. Details about several of these medications are given below:


 * Menstrual cycle regulation:
 * Birth control pills can regulate menstruation, reduce androgen levels and clear acne. They may also lower the risk of some female reproductive cancers.
 * Progesterone pills can also regulate the menstrual cycle, but they do not prevent pregnancy.
 * PCOS patients who are insulin resistant may ovulate when treated with metformin (Glucophage). Metformin is mostly used in type 2 diabetes to increase the body’s sensitivity to insulin.


 * Hirsuitism and acne treatments:
 * Birth control pills can also decrease acne.
 * Spironolactone may be used to decrease hair growth in combination with birth control pills.
 * Anti-androgen medications are not used often.


 * Infertility caused by anovulation (lack of ovulation):
 * Clomiphene Citrate (Clomid) and Letrozole (Femara) are anti-estrogens that trick the brain into increasing FSH levels. The FSH stimulates follicle growth and therefore leads to ovulation.
 * Injectible Gonadotropin medicines (fertility injections) such as Gonal-F, Pergonal, etc which contain high doses of FSH can be used to cause ovulation. However, these medicines can stimulate many follicles and eggs and therefore they have an increased risk of causing twins and triplets.


 * Other medications are used to control blood pressure and cholesterol levels.

Lifestyle changes
Lifestyle changes such as regular exercise can aid weight loss and help reduce blood sugar levels and regulate insulin levels more effectively. Weight loss can help lessen many of the health conditions associated with PCOS. Many women with PCOS will start to have regular periods and will start to ovulate again if they are able to get closer to their ideal body weight. Even modest decreases in weight can help.

Surgery
Surgical treatment may also be an option, but it is not recommended as initial therapy. Medications have become so effective that surgery is not usually necessary. In the past, laparascopic ovarian drilling and ovarian wedge resection were used.

Cures
PCOS has no cure, but many symptoms can be managed with weight loss and with medication. Early diagnosis and treatment helps prevent associated problems.

Chances of Developing PCOS
The prevalence of polycystic ovaries (diagnosed via pelvic ultrasound) in premenopausal women is estimated at 20%. Half of these women (up to 10% of the population) meet the criteria for a diagnosis of PCOS. In addition, as many as 75% of women with secondary amenorrhea (the absence of menses in someone who has had menstrual cycles in the past) have PCOS. &lt;ref&gt; Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997 Dec;18(6):774-800. Abstract | Full Text | PDF&lt;/ref&gt;

The risk of developing PCOS may be as high as 40% for a woman with an affected sibling and 19% if the woman has an affected mother. &lt;ref&gt; Kahsar-Miller M, Azziz R. The Development of the Polycystic Ovary Syndrome: Family History as a Risk Factor. Trends Endocrinol Metab. 1998 Feb;9(2):55-8. Abstract&lt;/ref&gt;

Complications
Because women with PCOS do not release eggs during ovulation, PCOS is the most common cause of female infertility. Although it may be harder for women with PCOS to get pregnant, many do get pregnant, naturally or using assistive reproductive technology. However, women with PCOS are at higher risk for miscarriage if they do become pregnant. Metformin (Glucophage) has been shown to decrease the miscarriage rate in some studies.&lt;ref&gt; Thatcher SS, Jackson EM. Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin. Fertil Steril. 2006 Apr;85(4):1002-9. Epub 2006 Mar 9. Abstract&lt;/ref&gt;.

Other conditions associated with PCOS include the following:


 * Diabetes and impaired glucose tolerance
 * Cardiovascular disease—including heart disease and high blood pressure
 * Cholesterol abnormalities (low HDL "good cholesterol", high triglycerides)
 * Abnormal uterine bleeding and uterine cancer (because of the disruption of hormones)
 * Metabolic syndrome

Clinical Trials
Polycystic Ovary Syndrome Clinical Trials

ClinicalTrials.gov

Research
The role of insulin in PCOS is an intense area of research. In 2007, the U.K. charity WellBeing of Women funded a study to look at how cells in the ovary metabolize glucose in women with and without PCOS.&lt;ref&gt;Medical News Today. New Project To Analyze Why Polycystic Ovary Syndrome And Insulin Resistance Are So Closely Linked&lt;/ref&gt; The results will help in understanding the role of insulin resistance in the development of PCOS, which could lead to new treatments.

PubMed has a long list of research articles relating to PCOS.

Prevalence
Approximately 1 in 15 women worldwide have PCOS.&lt;ref&gt;Norman RJ, Dewailly D, Legro RS, Polycystic ovary syndrome. Lancet. 2007 Aug 25;370(9588):685-97. Press Release.&lt;/ref&gt; Occurence in women of reproductive age in the United States ranges from 4% to 12%.&lt;ref name=khan&gt;Khan MI. emedicine. Polycystic Ovarian Syndrome.&lt;/ref&gt; Studies in Europe have suggested a prevalence of 6%–7%.&lt;ref name=khan /&gt; PCOS is noted to be much higher in certain ethnic groups.

Notable Experts

 * The American Society of Reproductive Medicine (ASRM) has a listing of Reproductive Endocrinologists and Infertility specialists all of whom have special training to take care of women with PCOS. ASRM Physician Search


 * Society for Reproductive Endocrinology and Infertility: Physician Search


 * American Association of Clinical Endocrinologists: PCOS Public Awareness Campaign