The changes are gradual but no less frustrating. Weight gain, excessive hair growth, acne and a steadily worsening irregularity of menstrual periods surfaces. Fertility, once thought to be a natural process, is impaired. After its formal reports in the medical literature and for decades in modern times, the diagnosis, treatment and health risks of Polycystic Ovarian Syndrome (PCOS) have afflicted patients and perplexed their physicians.

However recent advances in the knowledge of this common syndrome, especially in the area of insulin resistance, have helped everyone involved to better understand the problems PCOS causes and turn to newer, more effective treatments to combat them. It is hoped that this will serve as an overview to our readers and offer them hope that was not available until recently.

Women have most likely been affected by PCOS as a disease for a very long time. However, it wasn't until a French physician reported the appearance of polycystic ovaries in the mid 1800's that brought it to the attention of the medical community. Gradually more reports surfaced including surgical recommendations for treatment, most notably the "wedge resection", in which wedge-shaped portions of the ovaries were removed.

In 1935 Stein and Leventhal, two gynecologists from Chicago, described the symptoms of PCOS (immediately named the Stein-Leventhal Syndrome), and noticed that they disappeared, at least for a while, after the wedge resections were done. These patients were for the most part overweight, infertile, hirsute and had a lack of periods. Since those reports many if not most physicians, until recently, have thought of PCOS in this way.

There are, however, a significant number of patient who are not overweight, or may have one or a few of these symptoms. Finally, in 1990, an NIH consensus conference defined PCOS as the finding of elevated androgens and impaired (irregular) ovulation when the hormonal diseases of congenital adrenal hyperplasia (an inherited enzyme disorder), elevated prolactin, thyroid disease and Cushing's syndrome were excluded. This definition is accepted by most PCOS specialists.

Not all patients have all of the symptoms of PCOS. Hirsutism (90%), menstrual irregularities (90%) and infertility (75%) are the most common. Polycystic ovaries can be seen on ultrasound in many (84%). Excessive weight is commonly seen but not exclusive (50%). Insulin resistance is a rather newly found problem (up to 30%). Insulin resistance can be so serious in some patients that Type 2 (adult-type) diabetes has been found in up to 7% of PCOS patients.

How common is PCOS? Much work has been and continues to be done in this area. The answer may depend on many factors, including how it's diagnosed or who is being diagnosed. If ultrasound is the only way used, over 20% of all women have polycystic ovaries. If only irregular periods are used about 10% have PCOS. Ethnicity plays a major role: Caucasians and African-American women have a 4% incidence, but certain Native American groups have an over 20% incidence. Greek women (9%) and perhaps certain Latino groups have a higher incidence. These facts lead many researchers to suggest that PCOS may be an inherited problem in some women. Insulin resistance appears to be inherited too. Can this be a partial answer?

In an effort to confirm a PCOS diagnosis, and to locate a possible source of the problem, doctors will turn to physical exams, laboratory tests and imaging tests. Women with PCOS and excessive weight tend to have more fat tissue at the waist and upper body. Aside then from the usual weight and height measurements, the waist-hip ratio and body-mass index are excellent tools to evaluate excessive weight.

Common blood tests include androgen levels (testosterone, DHEA-sulfate, 17-hydroxyprogesterone, androstenedione for example). Many women have increased LH (luteinizing hormone) levels compared to FSH (follicle-stimulating hormone), resulting in an elevated LH to FSH ratio. l ultrasound is an increasingly popular test. The ovaries are seen to have a polycystic appearance, a bit enlarged and with collections of small follicle cysts lining the outer edge, just under the surface. This finding is called the "pearl necklace", "string of pearls" or "necklace" sign.

The current opinion of many PCOS researchers is that it is a syndrome with more than one cause. Two have been most often proposed: (1) insulin resistance and (2) some type of abnormality in the way the ovary produces hormones (androgens and estrogens). Insulin resistance is strongly linked to PCOS. In this problem the cells of the body cannot process insulin, to keep the blood sugar normal, very efficiently.

Excessive weight further aggravates the insulin resistance. The body will compensate by making more insulin. The excessive insulin stimulates the ovary to make androgens. Additionally, it's difficult to lose weight when insulin levels are elevated, further compounding the problem. At least one third of patients with PCOS can have insulin resistance. In the second case, some researchers have proposed that a gene defect may force the ovary into making the excessive androgens.

Either way, the androgens will cause follicles, normally trying to mature and ovulate, to stop growing. The follicles collect in the ovary (making it appear polycystic), and eventually degenerate. The androgens also may create excessive hair and/or acne. One area that is much less studied, but may be important, is the effect of stress on PCOS. There have been some older and more recent reports that PCOS patients score higher on anxiety or other psychological testing. Adding stress reduction techniques seems to help with PCOS treatments.

PCOS is a syndrome with both short and long term risks to women. In the short term, it can cause infertility and/or uncontrolled or irregular l bleeding (dysfunctional uterine bleeding) with the possibility of anemia. The infertility results from as obvious a problem as a lack of ovulation to as subtle a problem as sub-optimal ovulation (such as luteal phase defect). Irregular bleeding, spotting or staining, which can plague women for weeks or months, is due to a lack of ovulation which would ordinarily cause a regular monthly shedding of the uterine lining (endometrium).

The endometrium continues to grow in thickness despite the lack of regularity eventually breaks down in a disorderly way. Many of the longer-term risks of PCOS have been known for years, but others are just recently being discovered and studied. Women who have the insulin resistance version will have a much higher risk of Type 2 (adult type) diabetes later in life. These women also have a higher risk for "dyslipidemias": high blood levels of cholesterol or other lipid substances. High blood pressure is more common. For this reason, most PCOS researchers feel that there is a higher rate of heart disease and atherosclerosis in women with PCOS. Cancer of the endometrium is a long-term risk that has been known for decades.

Women with PCOS do make enough estrogen to grow their endometrium (much of it from their body fat) but without regular shedding of the lining it can grow uncontrollably. Without ovulation there is no progesterone (hormone of ovulation) to oppose this effect of the estrogen. After many years this "unopposed estrogen" may lead to a precancerous condition of "hyperplasia", which may eventually lead to cancer. Some studies have suggested that PCOS may be linked to a slightly higher chance of ovarian cancer but more work needs to be done. It was previously thought that PCOS may lead to a higher breast cancer risk but this evidence is not quite solid. One new area of research has looked at the risks for pregnancy complications in women with PCOS once they conceive. Miscarriage rates seem to be higher and may be related to their higher androgen or LH levels. Gestational diabetes risks can run up to 30%, and a recent report has studied a possible PCOS link to pre-eclampsia during pregnancy.

The workup for PCOS should include a thorough physical and pelvic examination, laboratory testing, perhaps imaging studies, and definitely counseling as to the risks and treatment choices (which may be different for individual patients). Of course, excessive weight (women with PCOS tend to gain weight in the upper body and trunk more than in the hips and thighs) excess hair growth and acne are looked for. Noticeable skin problems that are suspicious for insulin resistance are acanthosis nigricans, a brownish, raised skin discoloration in the body folds (neck, armpits, groin) and "skin tags" scattered over the skin. If the woman has a long history of irregular bleeding an endometrial biopsy may need to be performed to check for the above endometrial changes.

Hormonal testing for androgens, LH, FSH and for other hormonal diseases that can mimic PCOS must be drawn. The way to check for insulin resistance is controversial at this point, but a popular test is the fasting glucose:insulin ratio. This test is drawn after an overnight fast and checks the baseline levels of the patient's blood sugar and insulin. A ratio less than 4.5 is a good indicator of insulin resistance. However, this test seems to be only 85% effective. Some doctors may choose to extend the test into a 2 or 3 hour glucose tolerance test (GTT) with insulin levels. This test "stresses the system" to uncover the diagnosis. A fasting lipid profile (cholesterol, LDL, HDL, triglycerides) may be drawn also.

The treatment of PCOS has been noticeably changed in recent years. Medications for insulin resistance,metformin, the "insulin sensitizers", have helped many patients. These medications lower insulin levels; androgen levels drop and menstrual cycles return.

The most studied and prescribed is metformin (Glucophage). It is at least 75% effective in recent studies. Many patients will report some weight loss initially on this drug. Newer sensitizers include pioglitazone (Actos) and rosiglitazone (Avandia). These are less well studied but can provide an alternative to metformin if needed. Troglitazone (Rezulin) has been taken off the market. Side effects, especially of metformin, can include gastrointestinal distress (diarrhea, loose bowels, bloating). Liver and kidney problems are extremely unlikely in a non-diabetic but blood pre-screening and occasional monitoring while taking the medications should be done.

PCOS treatment really does depend on the individual medical circumstances, and wishes, of the patient. If she wants fertility treatment clomiphene citrate (Clomid, Serophene), the oral fertility drug, is usually prescribed. If she is insulin resistant, taking metformin or another insulin sensitizer alone is now becoming an option. Some specialists will even give both drugs together. As a last resort ovarian drilling, a same day surgery laparoscopic procedure that is a new version of the old wedge resection, has been shown to at least temporarily make periods regular.

However, this approach does lead to scarring of the ovaries in at least 20% of women, has not been proven to help against insulin resistance, and many will return to irregular periods eventually. Women who are not currently interested in fertility have many options too. Whether insulin resistant or not, oral contraceptives can regulate bleeding to prevent dysfunctional bleeding and uterine cancer risks, and treat acne. If they are insulin resistant, insulin sensitizers can be given to allow for regular periods and prevent the long-term effects of PCOS. The sensitizers will let ovulation occur so sexually active women must use care to avoid unwanted pregnancies. In fact, some specialists are using oral contraceptives and sensitizers together to prevent this.

Hirsutism can be very well treated with oral contraceptives together with the drug spironolactone, which lowers androgens. Vaniqua, a new prescription cream, looks effective for excessive facial hair. Of course, whether wanting to conceive or not, a great way to treat PCOS is by lifestyle alterations including diet, exercise and stress reduction. Weight loss in women with excessive weight can help their response to medications, or for some may even eliminate the need for them. Low carbohydrate diets can be very useful for weight loss in insulin resistant women.

Exercise is essential for weight loss too and diet and exercise must be used together for the best results. Stress reduction can be accomplished in many ways. "Western" methods like biofeedback have been advocated, as well as "Eastern" methods like meditation, tai chi, chi kung and yoga. Anything to reduce stress that is enjoyable, and therefore can be counted on for long-term use, is advisable. In the complementary medicine area, acupuncture has been shown in some small Mainland Chinese studies (and one from our group that was the first report in North America) to allow ovulation and regular periods to occur. The treatment options for women with PCOS have certainly increased!

The diagnosis of PCOS brings a lot of questions, frustrations and anxiety to many patients. Physicians are not the only source of counseling and information anymore, and patients are fortunate to have support and advocacy groups to turn to. The most well known is the Polycystic Ovarian Syndrome Association, which maintains a chapter in nearly every large city in the U.S. The Philadelphia Chapter has been quite active for several years, and now has monthly meetings at the Center for PCOS at Drexel University (Medical College of Pennsylvania Hospital). The active South Jersey Chapter holds regular meetings too. To contact these groups just log on to their web pages through the PCOSA national web site: www.pcosupport.org.

Through the ongoing efforts and partnership of physicians, researchers and patients, the syndrome of PCOS has and will continue to become less of a mystery. The goals of fertility and good health are now within closer reach for women with PCOS.

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