June 14, 2008
GALVESTON, Texas – A discovery by researchers at the University of Texas Medical Branch at Galveston may pave the way for new treatments and therapies for a leading cause of female infertility, polycystic ovary syndrome. The syndrome affects as many as 15 percent of women of childbearing age.
Dr. Ayman Al-Hendy, the senior investigator and UTMB associate professor of gynecology, said, “Upon examination of ovarian samples, we have identified an enzyme, catechol-O-methyl transferase, or COMT, that is elevated in the ovaries of PCOS patients. This gives us a novel therapeutic target for possible treatment of PCOS with COMT inhibitors.”
The increased expression of the COMT enzyme leads to higher levels of a metabolite called 2-methoxy estrogen that inhibits egg development and maturation, which in turn leads to lack of ovulation and infertility.
The researchers have also identified the metabolite 2-hydroxyestrogen as a novel biomarker that is secreted at lower levels in the urine of PCOS patients. This has long been suggested by researchers, but never proven until now. “This may also provide a helpful diagnostic marker for the disease,” Al-Hendy said.
First diagnosed in 1935 as Stein-Leventhal syndrome, the cause of PCOS is still unknown. Approximately 10 to 15 percent of women of childbearing age have the complicated syndrome and, according to Al-Hendy, the numbers are rising because of the obesity epidemic. PCOS affects women of all races and nationalities and is defined as having two of the following symptoms: an irregular period with no ovulation, increased hair growth or increased blood testosterone, or polycystic ovaries on ultrasound.
However, physicians often fail to diagnose PCOS because they are unable to see the connection among the diverse set of symptoms, all of which may present differently in women. Many of the symptoms – acne, obesity, excessive hair growth and irregular menstrual periods – are viewed as unpleasant but unrelated.
Women generally seek medical care for PCOS when faced with one of the following conditions: infertility, period disturbances, obesity, excessive hair growth, or hypertension and diabetes. In fact, more than half of all women with PCOS will have diabetes or pre-diabetes before the age of 40. Those with pre-diabetes have elevated blood glucose levels that are not high enough to be diagnosed as diabetics.
In addition, PCOS can affect more than a woman’s fertility, hormones, heart and appearance. Since women with PCOS do not have normal menstruation cycles, they may be at a higher risk for uterine lining cell changes and endometrial cancer.
Doctors cannot specify a treatment because it is not known where the syndrome originates. Because there is no cure for PCOS, it needs to be managed to prevent future problems. Many women will require a combination of treatments, some of which include birth control pills (to control menstrual cycles and reduce the male hormone testosterone), diabetes medications (to control blood sugar), fertility medications (to stimulate ovulation) and anti-androgen medications (to reduce hair growth and clear acne).
Previously, there was no single, quick test to identify PCOS. “Our work is an important, major step forward in PCOS research,” said Al-Hendy. “Physicians now have a specific diagnostic test for PCOS.” Prior to this research finding, a PCOS diagnosis was made through an examination of symptoms and medical history, as well as hormonal testing and ultrasound. Diagnosis was further complicated because women are not likely to show abnormalities in all three.
Researchers still need to confirm their preliminary results with larger numbers, Al-Hendy cautions. “Further studies are needed to ascertain the role of estrogen metabolism in PCOS before this information can be used in clinical settings.”
Now that researchers have this COMT target, they hope to develop targeted therapies and new treatment possibilities. The FDA has approved two COMT inhibitors, one of which is regularly used in the treatment of Parkinson’s disease. Possible next steps include testing these drugs on women suffering from PCOS.
The medical journal Clinical Endocrinology and Metabolism will publish the researchers’ laboratory findings later this summer. The manuscript is titled, “Reduced Levels of Urinary 2-Hydroxyestrogens in Polycystic Ovary Syndrome.”
In addition to Al-Hendy, co-authors of the study are Sana Salih, Hala Fouad, and Manubai Nagamani of UTMB’s Department of Obstetrics and Gynecology; Xia Xu and Timothy D. Veenstra of the Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick Inc., in Frederick, Md.; and Antoni J. Duleba of Yale University’s Department of Obstetrics and Gynecology.
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