Reproductive Endocrinology and Infertility
Infertility - Polycystic Ovarian Syndrome (PCO)

Diagnosis of PCO

Women with PCO classically have the triad of irregular menstrual periods (oligomenorrhea), excess facial hair growth (hirsutism) and obesity. The ovaries have a characteristic smooth pearly white appearance when viewed surgically. When viewed sonographically multiple small follicles (cysts) are seen around the perimeter of the ovary in a so called "string of pearl" arrangement. It should be noted, however, that not all women will exhibit all the features of this syndrome. In fact the syndrome is quite heterogeneous and not all the "experts" have been able to agree on what exactly constitutes PCO. In this country women are said to have PCO if they do not have regular ovulation (oligo-ovulation) coupled with hormonal and/or physical signs of excess male hormone production and other causes for these symptoms have been ruled out. The ultrasound appearance of the ovaries is a consequence of the long-term lack of regular ovulation. However, this ultrasound appearance is neither necessary nor sufficient by itself to make the diagnosis. Some women may have normal appearing ovaries on ultrasound and have the other features of PCO. We would consider these women to have PCO. Conversely, women may have none of the other features of PCO yet have the typical PCO appearance to the ovaries on ultrasound. These women would not be classified as having PCO.

The menstrual dysfunction usually manifests itself during the teenage years. These women will have their first period at the expected time, but will never establish regular ovulatory cycles. Sometimes this piece of information is not evident in the patient’s history as she often was given birth control pills to regulate her unpredictable cycles. The birth control pills would mask the menstrual dysfunction, but when the pills are stopped, the irregular periods return. Some patients mistakenly think that the long duration of birth control pill use caused their problem, when in fact the underlying problem existed all along. It should be noted that women who have regular ovulatory menstrual cycles all their life and then develop irregular cycles at age 25 or 30, for example, do not have PCO. They have some other condition causing their menstrual dysfunction. The menstrual dysfunction of PCO has its onset during the early teenage years and persists into adult life.

Not all women with PCO are obese. Although most are, some are of normal weight and some are even of low body weight. Likewise, not all women with PCO will have excess facial hair. Most will, but the appearance of facial hair is determined in part by genetics. Some women are genetically predisposed to manifest either more or less facial hair for any given level of male hormone production. However, all women with PCO will have biochemical evidence of excess male hormone production, usually coming from the ovaries. This is true whether or not they have any physical signs of this excess hormone production.

A new area of interest, and one of intense research, is the issue of insulin resistance and PCO. It has been known for some time that women with PCO are at increased risk for developing adult onset diabetes (also known as type II diabetes) later in life. It is now recognized that many women with PCO who are not yet diabetic have "insulin resistance". This means that their blood sugar is normal, but they have to secrete excess amounts of insulin to keep it in the normal range. High insulin levels can have a detrimental effect on ovulation. It is currently speculated that the high concentration of circulating insulin may be a key factor in explaining why women with PCO do not ovulate.

Treatment of PCO

Treatment of PCO depends on the patient’s desires. If she want to become pregnant then drugs are prescribed to induce ovulation. If she wants to regulate her periods and control facial hair, birth control pills are usually given either alone or in combination with another drug called spironolactone. Spironolactone acts directly on the hair follicle to inhibit growth of new hair. Existing hair will need to be removed by some physical means such as electrolysis. It takes at least 6 months to notice any benefit of medical therapy for facial hair growth. In time, however, patients can decrease or even eliminate their need for electrolysis. Birth control pills obviously preclude pregnancy and spironolactone is contraindicated during pregnancy. Therefore women wanting to become pregnant will have to forego the medical treatment of their facial hair.

If pregnancy is desired ovulation is induced with medication. Clomiphene citrate (trade names Clomid , Serophene) is the first-line drug. Approximately 80% of women with PCO will ovulate when given clomiphene, but only one-half of those that ovulate will get pregnant. The reason(s) why the other one-half do not conceive is not known with certainty. Women who do not ovulate with clomiphene have two options. The traditional approach is to give another class of drugs called "gonadotropins". These drugs are given as either a subcutaneous injection or intramuscular injection (Gonal-F, Follistim, Repronex). Although the subcutaneous route of administration is easier and less painful, there is no evidence that any one of these drugs is better than the other when pregnancy is the endpoint. Close monitoring with frequent vaginal ultrasounds and blood tests is mandatory when taking these drugs. There often is a very fine line between not enough and too much of these drugs. Gonadotropins are potentially very dangerous drugs and should be administered only by physicians with extensive experience in their usage. Gonadotropin therapy is a reasonable option in those women who have not ovulated with clomiphene.

Another treatment for PCO is the use of an "insulin sensitizing" drug. The drug most commonly used is metformin (trade name Glucophage). There are other similar drugs and more are sure to come in the next few years. By lowering insulin levels the ovary appears to be able to ovulate either on its own or in response to clomiphene therapy. Not all PCO patients will respond to this therapy. Ideally, only those patients who have documented insulin resistance should be tried on this drug. However, some research studies have given this drug to all PCO patients, without regard to their insulin levels. Most of the studies to date have not looked at pregnancy as the end point when metformin was given. How metformin will fit in to our overall treatment of PCO related infertility remains to be determined. In our practice we screen PCO patients for insulin resistance and offer metformin therapy to those found to be resistant.