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Millions of women with type 2 diabetes and heart disease may beinadequately diagnosed and treated because their symptoms are indications of alittle-understood syndrome, say physicians and researchers.
A study published by researchers at UCLA in the June 2004 issue ofJournal of Endocrinology and Metabolism suggests that polycysticovary syndrome (PCOS), a set of symptoms associated with hormonal imbalance,afflicts 6.6% of premenopausal women and an unknown number of postmenopausalwomen, according to Ricardo Azziz, MD, the study's lead author and chair ofobstetrics and gynecology at UCLA. Other experts estimate that 6 million U.S.women and girls have PCOS, and some believe that baby girls may be born withthe syndrome.
Women suffering from PCOS may have a broad range of symptoms including type2 diabetes and associated insulin resistance, obesity, infertility, andexcessive body and facial hair.
Women with PCOS tend to have higher circulating insulin levels thatstimulate the ovaries to produce increased amounts of testosterone. Thisimbalance of male hormones disrupts menstrual periods and can causeinfertility. More than 50% of PCOS patients are obese and 50% have diabetes byage 40, according to the American Association of Clinical Endocrinologists(AACE).
However, symptoms vary and PCOS is not easy to diagnose. Partly because ofthis, and because many physicians lack knowledge of the syndrome, individualsymptoms may be treated while the syndrome goes unrecognized. "Manywomen struggle with symptoms and complications such as adult acne,infertility, obesity and hirsutism without addressing the underlyingcause," explains Azziz.
If PCOS is not treated, the problems can become even more serious: thesyndrome can lead to coronary calcification in women as young as 35 and fatalheart disease and cancer in women under 50.
Because obesity and type 2 diabetes cases are on the rise—even invery young girls—those who treat PCOS see it as essential thatphysicians in many disciplines—including pediatrics, dermatology, familymedicine, and gynecology—learn to screen for the symptoms of PCOS, makepreliminary diagnoses, and refer patients to specialists, according to RhodaCobin, MD, a New York-based endocrinologist.
Reluctantly, PCOS experts concede that there are fewer than 100, perhapsless than 50 physicians who have some mastery of PCOS in the U.S. As a result,doctors who are stumped, particularly general practitioners working in morerural areas, may not know to whom they should refer their patients.
DEFINING PCOS—HARDER THAN IT LOOKS
Although PCOS was first identified in 1937, its cause has remained elusive,and there is not even universal agreement on a set of symptoms.
"PCOS is a collection of conditions; it lacks a definitiveidentifying test, and so a proper diagnosis depends on consideration of manyfactors. Since an exact definition of PCOS is not universally agreed on, thecriteria for its diagnosis are somewhat amorphous," wrote Howard Zisser,MD, of the Sansum Diabetes Research Institute, with co-authors Darren Salmiand Lois Jovanovic, MD, in the May 2004 issue of Experimental Biology andMedicine.
In 1990, at a National Institutes of Health-sponsored event on PCOS,doctors established a new set of criteria for diagnosing PCOS. These criteriawere revised and expanded again at a PCOS workshop held in Rotterdam, theNetherlands, last year. The workshop was cosponsored by the European Societyfor Human Reproduction and Embryology (ESHRE) and the America Society ofReproductive Medicine (ASRM). The findings were published in the January 2004issue of Fertility and Sterility.
NEW CRITERIA FOR PCOS DIAGNOSIS
But the new criteria established at the 2003 Rotterdam workshop left openas many questions as they answered, according to Robert Schenken, MD, ASRMpresident. "PCOS remains a syndrome, and no constellation of findings orset criteria can exclusively be used for a clinical diagnosis. Further studiesare needed to assess risk levels based on different diagnosticcriteria," he said at the time of the workshop.
Even the syndrome's name is problematic and misleading, experts say."One of the main problems has to do with the name PCOS and thehistorical image of a typical PCOS [patient]: obese and hirsute," Zissersays. "But not all PCOS patients actually have polycystic ovaries. Ifthey did, it would make making the diagnosis much easier."
Polycystic ovaries were defined at the Rotterdam workshop as those found byultrasound to contain 12 or more follicles measuring 2–9 mm in diameteror having an increased volume of 10 ml or more. Cysts form when folliclesmature but do not release eggs.
But by themselves polycystic ovaries are not diagnostic for PCOS. Although90% of PCOS sufferers have polycystic ovaries—often with the cysts linedup on the surface of the ovaries, forming the appearance of a "pearlnecklace"—similar symptoms can also be found in up to 25% of womenwithout PCOS, according to Walter Futterweit, MD, chief of the endocrineclinic at the Mount Sinai Medical Center in New York.
Findings from Rotterdam reinforced some common characteristics of PCOSwhile adding others: obesity, menstrual irregularities, signs of excessandrogynism, and glucose intolerance. But PCOS remains a diagnosis ofexclusion that is made both clinically and with ancillary testing. MonitoringPCOS patients for glucose intolerance and diabetes is critical.
AWARENESS REMAINS LOW
Awareness of PCOS among patients and physicians remains low—a problemthat medical associations including AACE, the Androgen Excess Society (AES),and the American Society of Reproductive Endocrinology (ASRE) have promised toaddress via position papers, workshops, training, and continuing medicaleducation courses. While there is no cure for PCOS, patients are oftenwell-managed by a combination of drug therapy and improved lifestylechanges.
Because they are unaware of PCOS, women who may suffer from PCOS seektreatment for an isolated symptom such as obesity rather than the wholeproblem. In Azziz's study, for example, about 75% of the women with PCOS hadhirsutism, 24% were overweight, and 32% were obese.
As a result, doctors with limited knowledge of PCOS may not see the need totest for it and instead may just recommend a reduced-calorie diet and exercisefor women who are significantly overweight or birth control pills for thehormonal imbalances, for example.
"Doctors will focus on the part of the problem they are knowledgeableabout or specialize in, and then PCOS goes unchecked," says Mark Perloe,MD, a reproductive endocrinologist in Atlanta.
"In fact, women may also have other symptoms [of PCOS] and go toseveral doctors before the syndrome is diagnosed and treated. Many women Itreat [for PCOS] have already seen as many as five doctors or more before theysee me," he adds.
One of the best indicators is insulin resistance. However,insulin-resistance tests—widely used in diagnosis amongendocrinologists—are fraught with problems. In fact, such tests are moreart than science Perloe says.
By treating symptoms, patients may unwittingly hide evidence of PCOS anddelay diagnosis. For example, women with PCOS may get electrolysis treatmentsfrom dermatologists, to permanently rid themselves of excess body and facialhair, thinking of it merely as a cosmetic problem. In eliminating the excesshair, they are also eliminating a symptom that might have otherwise beenuseful for diagnosis, says Azziz.
Patients with PCOS who take birth control pills to treat irregular periodswill also normalize their hormones and make the syndrome harder to detect,adds Futterweit.
Just as important is ruling out other diagnoses, Futterweit says. Theseinclude the absence of other causes of hyperandrogenism: virilizing tumor,hyperprolactinemia, congenital adrenal hyperplasia, and Cushing'ssyndrome.
RESEARCH AND TREATMENT
Researchers and doctors agree that weight loss, exercise, and improved dietare among the most important components of a successful PCOS treatment plan.Weight loss and exercise can help decrease insulin resistance and minimizelipid abnormalities, according to Cobin. "Weight reduction can alsodecrease testosterone, insulin, and luteinizing hormone levels," sheadds.
Metformin is widely prescribed to PCOS patients to increase insulinsensitivity. The drug has also shown promising initial results in women withexcessive body and facial hair, and in helping to regulate menstrual cycles,although its effects on infertility and other symptoms are not yet known.
AACE and other associations have created online member directories thatlist endocrinologists and other specialists with experience treating PCOS. Anactive patient support and medical advocacy group, the Polycystic OvarianSyndrome Association (PCOSA), is also a source of physician and patienteducation resources.
At its annual conference in October, PCOSA is unveiling a campaigncoordinated with AACE to raise awareness of PCOS, presenting a review of themost recent research on the syndrome and releasing information for medicalprofessionals and patients.
For now, experts agree that patients must take an active part in treatingtheir PCOS. Azziz sums it up: "Lose weight, eat less junk food andprocessed carbohydrates, eat fewer sweets, even sweet sugary vegetables likecorn, eat foods with lower glycemic index, exercise, and manage stress."
Footnotes
Polycystic Ovarian Syndrome Association P.O. Box 3403 Englewood, Colo.80111 877-775-PCOSwww.pcosupport.org.
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