Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome (PCOS) is a term used to describe a group of conditions which cause the ovaries to produce excessive male hormones also known as androgens. It is a common endocrine (hormonal) disorder in women of reproductive age. A "syndrome" is defined as a set of symptoms associated with a disorder. PCOS is a syndrome because it manifests as a collection of symptoms related to infrequent ovulation, characterized by irregular menstrual periods and evidence of excess androgens (male hormones), which can cause excessive facial hair growth, acne, and/or male-pattern baldness. The ovaries may be enlarged with many small follicles (tiny sacs filled with fluid), hence the name polycystic. Although PCOS is primarily a problem of the ovaries, the condition alters hormone levels and affects tissues throughout the body. PCOS is a health problem that affects a woman's menstrual cycle, fertility, hormones, insulin production, heart, blood vessels, and appearance.

This syndrome was originally named Stein-Leventhal Syndrome in recognition of the two physicians who, in 1935, first described the condition. Other names for PCOS include Polycystic Ovarian disease, hyperandrogenic chronic anovulation and functional ovarian hyperandrogenism.

An estimated five to 10 percent of women of childbearing age have PCOS. As many as 30% of women have at least some characteristics of the syndrome. It is a leading cause of infertility. In fact, PCOS causes 75 percent of all cases of anovulatory infertility.

Normal Ovarian Function

An understanding of the normal menstrual cycle and how the ovaries normally work is important to gain an insight into the nature or physiology of PCOS. The ovaries serve two important functions in the reproductive age: they produce eggs and release two hormones, estrogen and progesterone into the blood.

A normal menstrual cycle is dependent upon regular cyclic changes in the blood hormone levels of estrogen and progesterone. A woman's ovaries have follicles, which are tiny sacs (cysts) filled with liquid that hold the eggs. Each month about 20 eggs start to mature, but usually only one becomes large and dominant. The growing follicle produces the hormone estrogen. As the one egg grows, the follicle accumulates fluid in it. When that egg matures, the follicle appears as a cyst on the surface of the ovary, breaks open or ruptures and releases the egg so that it can travel through the fallopian tube for fertilization. When the single egg leaves the follicle, ovulation takes place. Ovulation occurs approximately two weeks before the onset of the menstrual period. After ovulation occurs, the empty follicle in the ovary collapses (forms the corpus luteum) and produces progesterone in the second half of the menstrual cycle. Progesterone helps prepare the uterine lining for a possible pregnancy. If conception occurs, the egg fertilizes in the tube where it remains for 3-4 days, before entering the uterus where it embeds (implants) in the endometrium (uterine cavity lining). If there is no implantation, the levels of estrogen and progesterone declines, about 2 weeks after ovulation and the uterine lining is shed. This results in menstruation and the cycle begins again.

The development of follicles in the ovary is driven by two hormones called gonadotropins produced in the brain. In response to Follicle Stimulating Hormone (FSH), the follicles begin to grow. In response to Leutinizing hormone (LH), the follicle produces androgens and ovulation or the release of egg from the follicle occurs.

PCOS and Disruption on Normal Ovarian Function

The ovulatory cycle is easily disrupted by hormonal changes. The disruption may occur because of insufficient FSH or excessive LH production in the brain. In women with PCOS, the ovary doesn't make all of the hormones it needs for any of the eggs to fully mature. The follicles may start to grow and accumulate fluid. But no one egg becomes large enough. Instead, some may remain as immature follicles and continue to produce estrogen. Since no egg matures or is released, ovulation does not occur and the hormone progesterone is not made. Also, the immature follicles produce male hormones, which continue to prevent ovulation. Lack of ovulation results in infertility.

It is the abnormal hormone levels that lead to irregular periods in women with PCOS. As a result, the inside lining of the uterus - called the endometrium - is exposed to the hormone estrogen for great lengths of time without being exposed to the hormone progesterone. It is the cyclic rise and fall in both estrogen and progesterone that cause menstrual bleeding. In the case of PCOS, there can be prolonged lengths of time without the production of progesterone. During this time the endometrium is continuously exposed to estrogen. The result of this prolonged estrogen exposure is the buildup /growth of the endometrium. When the endometrium becomes too thick, heavy and irregular bleeding can occur. Also when the endometrium is exposed to estrogen for prolonged periods of time, cell changes can occur in which the cells of the endometrium become abnormal and, if not treated appropriately, can develop into cancer of the uterus. Progesterone prevents this build-up of the endometrium.

If elevated androgen levels persist for a long time, hirsutism and acne may occur.

The exact cause of PCOS is unknown. Women with PCOS frequently have a mother or sister with PCOS. Some studies are looking at the possibility of a genetic link to this disorder. Researchers are also looking at the relationship between PCOS and the body's ability to make insulin. Since some women with PCOS make too much insulin, it's possible that the ovaries react by making too many male hormones, called androgens. This can lead to acne, excessive hair growth, weight gain, and ovulation problems.

Signs and Symptoms of PCOS

Signs and symptoms of PCOS often begin around the time of puberty, but for others, symptoms do not develop until adulthood. Symptoms vary among women, but can include:

Appearance of small, multiple cysts on the ovary, enlarged ovaries visible by ultrasound
Irregular periods, infrequent menses or lack of menstruation (amenorrhea) due to infrequent or absent ovulation
Infertility and miscarriage
Elevated blood levels of male hormones (androgens), especially testosterone
Adult acne /oily skin/seborrhea
Excess facial and body hair (hirsutism)
Male-pattern baldness, hair loss or thinning hair (alopecia)
Weight problems especially around the midsection (central obesity)
High blood pressure (hypertension)
Abnormal lipid levels including elevated tricylercides and high cholesterol
Impaired glucose tolerance, insulin resistance, hyperinsulinemia, & type II diabetes
Skin tags (acrochordons) and dark velvety patches of thickened and dark brown or black skin on the neck, arms, breasts, or thighs (acanthosis nigricans)
Chronic pelvic pain
Sleep apnea (excessive snoring and breathing stops at times while asleep)

Any or all of these symptoms may be present, but some women have none of these symptoms and still can carry the diagnosis. These tend to be very lean, athletic women who may be even underweight and this may mask the PCO syndrome.

Diagnosis of PCOS

There is no single test to diagnose PCOS. A physician can often diagnose PCOS by obtaining a detailed medical and gynecological history and performing a physical exam. At the physical exam, evaluation of the areas of increased hair growth will be important. During a pelvic exam, the ovaries may be enlarged or swollen by the increased number of small cysts. Blood hormone levels such as testosterone levels are often measured to confirm the diagnosis. Additionally, glucose or sugar levels, as well as insulin blood hormone levels may be measured. A vaginal ultrasound may be performed to help distinguish PCOS from other disorders that cause multiple cysts in the ovaries. The ultrasound exam can also identify a thickened uterine lining. If menstrual periods have been irregular or absent, an endometrial biopsy may be necessary to rule out a pre-cancerous endometrial condition.

The current criteria for the diagnosis of PCOS include the following three items:

Irregular or absent periods
Signs of excess androgens (male hormones) in the form of excess hair growth or blood tests that show elevated levels of androgen "
Lack of any other conditions that would explain the above two conditions, such as problems with the pituitary, thyroid or adrenal glands

The combination of a detailed history, physical exam and blood testing is usually adequate to diagnose PCOS. A genetic predisposition to PCOS has been proposed. Women whose mothers had PCOS should watch carefully for symptoms. Early diagnosis and treatment may decrease the development of acne and hirsutism.

Health Problems Associated with PCOS

Although PCOS is primarily a problem of the ovaries, the condition alters hormone levels and affects tissues throughout the body. Because PCOS is not fully understood, it is often difficult to determine why it is associated with a variety of health problems.

Weight gain and obesity - PCOS is associated with gradual weight gain and obesity in about one-half of the women with this condition. Obesity can aggravate PCOS. It is thought that fatty tissues produce excess estrogen which can affect the brain and result in insufficient secretion of FSH. Insufficient FSH prevents ovulation and may worsen PCOS. Diet and exercise can help maintain a normal body weight. For some women with PCOS, the obesity develops at the time of puberty.

Insulin abnormalities and diabetes - PCOS is also associated with abnormal blood insulin levels, the hormone that regulates blood sugar levels. These abnormalities may include:

Hyperinsulinemia (excess production of insulin)
Insulin resistance (poor response of body tissues to insulin)
Impaired glucose tolerance (a condition of borderline diabetes mellitus)
Type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus, a condition characterized by elevated blood sugar levels)

Insulin resistance and hyperinsulinemia can occur in both normal-weight and overweight women with PCOS. By age 40, up to 35 percent of obese women with PCOS develop impaired glucose tolerance, and up to 10 percent of obese women with PCOS develop type 2 diabetes. These rates are much higher than expected for normal women at this young age.

Impaired glucose tolerance and diabetes are usually detected by blood tests. Often a fasting blood test is sufficient, but sometimes a glucose tolerance test is needed. Weight loss, exercise, and drugs can help normalize blood sugar levels.

Heart disease and hypertension- The presence of both obesity and insulin resistance might increase a woman's risk for coronary artery disease, which is the narrowing of the arteries that supply blood to the heart. Both weight loss and treatment of insulin abnormalities can decrease this risk.

Uterine cancer - Irregular menstrual periods and the absence of ovulation cause women to produce the hormone estrogen, but not the hormone progesterone. Without progesterone, which causes the endometrium to shed each month as a menstrual period, there is a hormonal imbalance. This promotes persistent growth of the endometrium (the lining of the uterus). Eventually, this can lead to endometrial hyperplasia or cancer. Treatment with oral contraceptives or intermittent progesterone-like drugs can promote normal menstrual bleeding and lessen overgrowth of the endometrium.

Sleep apnea - Sleep apnea has been reported to occur in up to 30 percent of women with PCOS. This is a disorder characterized by excessive snoring at night with brief spells where breathing stops (apnea). Patients with this problem experience fatigue and daytime sleepiness.

Hirsutism - Hirsutism is the excess growth of coarse dark hair in a predominantly male pattern. Women affected by PCOS commonly experience hirsutism due to increased levels of the male hormones called androgens. The longer a woman with PCOS goes untreated the more severe her hirsutism will become.

Infertility- Lack of ovulation or infrequent ovulation results in difficulty in getting pregnant.

Most of these above mentioned effects can be anticipated and thus prevented or promptly treated before they pose significant health problems.

PCOS and Infertility

Women with PCOS generally have irregular, infrequent, or even absent ovulation. Without ovulation there is no egg or ovum that is available for fertilization. Also, due to the abnormal hormone levels, the endometrium, or inside lining of the uterus, does not develop normally in women with PCOS. Therefore, even if a rare ovulation was to occur and the egg was fertilized, the endometrium may not be properly developed to allow for the attachment and growth of the embryo.

The good news is that this problem with ovulation be fixed with medications. These include ovulation induction agents, insulin sensitizing drugs and Gonadotropins. Individual needs and response to therapy will usually determine the appropriate medication. It is important to know that these options work best for women who are not obese. Even a modest amount of weight loss may improve the effectiveness of the medications.

Medications called ovulation induction agents, such as clomiphene citrate stimulate the ovaries to release one or more eggs. Clomiphene is simple to use and relatively cost- effective. Clomiphene citrate interacts with the brain, causes an increase in FSH secretion and works well to trigger ovulation in about 80 percent of women with PCOS. About 50 percent of these women will actually become pregnant. Approximately 10 percent of the pregnancies are twins while triplets or more are rare. In women taking clomiphene, ovulation can be confirmed by blood and urine tests or by measurement of body temperature. If the original dose of clomiphene does not trigger ovulation, a higher dose may help.

Several studies have shown that the insulin-sensitizing drug, metformin, increases the effectiveness of clomiphene in producing ovulation. However, it is unknown if this drug is safe during pregnancy, and is stopped once the woman is pregnant.

Gonadotropin therapy is a second, more aggressive medical treatment for PCOS-related infertility. If Clomiphene does not work within approximately six cycles, gonadotropins namely, Leutinizing hormone (LH) and Follicle Stimulating Hormone (FSH) may be used. This medication is more expensive and has a higher incidence of side effects such as hyperstimulation of the ovaries and multiple pregnancies. FSH is used without LH for women with PCOS, and is given as a daily injection under the skin for 7 to 10 days. These drugs trigger ovulation in almost all women with PCOS and can lead to pregnancy in approximately 60 percent.

Surgery is an option in rare situations. In very rare cases, ovulation is not achieved with medications and ovarian surgery may be necessary to stimulate ovulation. This surgery is usually performed via the laparoscope.

If the above mentioned treatments are not successful in producing a normal pregnancy, then the use of the assisted reproductive technologies (ART), such as in vitro fertilization, can be attempted.

In conclusion, a diagnosis of PCOS suggests that you are likely to have some difficulty becoming pregnant. However, with help from your physician, pregnancy should be an option for most patients with PCOS.

There appears to be a higher rate of miscarriage, gestational diabetes, pregnancy-induced high blood pressure, and premature delivery in women with PCOS. Preliminary studies also suggest that metformin might reduce the risk of early pregnancy loss and the development of gestational diabetes mellitus (diabetes during pregnancy) in women with PCOS, while pregnant. Researchers are also looking at how the drug lowers male hormone levels and limits weight gain in women who are obese when they get pregnant. It is not yet known if Metformin usage is safe during pregnancy, since the drug crosses the placenta.

Treatment of PCOS

There is no cure for PCOS, but it is manageable with medications, diet, and exercise. Adequate treatment can help prevent serious long-term risk factors. The treatment is relatively simple and based upon the goals of the patient. Some patients may be concerned primarily with fertility, while others may be more concerned about menstrual cycle regulation, hirsutism or acne. Regardless of the primary goal, patients are advised to report all symptoms to their physician as specifically as possible.

Below are general descriptions of treatments used for PCOS:

Birth control pills: For women who don't want to become pregnant, birth control pills can regulate menstrual cycles, reduce male hormone levels, and help to clear acne. However, the birth control pill does not cure PCOS. The menstrual cycle will become abnormal again if the pill is stopped. A pill that only has progesterone can also regulate the menstrual cycle and prevent endometrial problems. But progesterone alone does not help reduce acne and hair growth. Birth control pills are not recommended for women who smoke and are over the age of 35 years.
Diabetes Medications: The medicine, Metformin, also called Glucophage, which is used to treat type 2 diabetes, also helps with PCOS symptoms. Metformin affects the way insulin regulates glucose and decreases the testosterone production. Abnormal hair growth will slow down and ovulation may return after a few months of use. These medications will not cause a person to become diabetic.
Fertility Medications: The main fertility problem for women with PCOS is the lack of ovulation. Even so, a sperm analysis should be performed and the tubes checked to make sure they are open before fertility medications are used. Clomiphene (pills) and Gonadotropins (shots) can be used to stimulate the ovary to ovulate. If medications do not succeed in achieving a pregnancy, In vitro Fertilization (IVF) is sometimes recommended. Metformin can be taken with fertility medications and helps to make PCOS women ovulate on lower doses of medication.
Medication for increased hair growth or extra male hormones: If a woman is not trying to get pregnant there are some other medicines that may reduce hair growth. Spironolactone is a blood pressure medicine that has been shown to decrease the male hormone's effect on hair. Propecia, a medicine taken by men for hair loss, is another medication that blocks this effect. Both of these medicines can affect the development of a male fetus and should not be taken if pregnancy is possible. Other non-medical treatments such as electrolysis or laser hair removal are effective at getting rid of hair. A woman with PCOS can also take hormonal treatment to keep new hair from growing.
Surgery: Although it is not recommended as the first course of treatment, surgery called ovarian drilling is available to induce ovulation. It is an option in very rare cases. A very small incision IS made above or below the navel, and a small instrument that acts like a telescope is inserted into the abdomen. This is called laparoscopy. The doctor then punctures the ovary with a small needle carrying an electric current to destroy a small portion of the ovary. This procedure carries a risk of developing scar tissue on the ovary. This surgery can lower male hormone levels and help with ovulation. But these effects may only last a few months. This treatment doesn't help with increased hair growth and loss of scalp hair.
Weight Loss: Maintaining a healthy weight is another way women can help manage PCOS. Since obesity is common with PCOS, a healthy diet and physical activity help maintain a healthy weight, which will help the body lower glucose levels, use insulin more efficiently, and may help restore a normal period. Even loss of 10% of her body weight can help make a woman's cycle more regular.

In summary, PCOS is a fairly common, defined syndrome for which no cure exists. Treatment of the symptoms can help reduce risks of future health problems. Today, several drugs and lifestyle modifications can help control the signs and symptoms of PCOS. Medical and surgical treatment can also help women who want to become pregnant, but are having difficulty conceiving. Treatment is individualized and depends on each woman's symptoms, reproductive goals, and presence of other medical conditions. In some women, symptoms of PCOS may be minor and simply annoying, and treatment may seem unnecessary. However, untreated PCOS may increase a woman's risk of other health problems over time. Women with PCOS should take an active role in their medical care by learning as much as they can about the condition and by working with their physician to develop the best treatment plan. Dealing with PCOS can be emotionally difficult. Discussing all concerns with a physician and exploring the medical and cosmetic treatments available to treat PCOS as soon as possible is of vital importance. In the News Dr. Pinto is privileged to be selected by his peers as one of the Best doctors in Dallas, 2005 "Best Doctors in Dallas" D Magazine, October 2005 Recent Publications IVF-immature oocyte Letrozole and PCOS Leydig cell tumor Sperm freezing.