A well-known diet drug may be an effective treatment for women with polycystic ovarian syndrome (PCOS). That's the conclusion of a new study from the UK that tested the drug, orlistat (Xenical, Hoffman LaRoche) against metformin (Glucophage, Glucophage XR, Bristol-Myers Squibb), a diabetes medication that's being evaluated as a therapy for PCOS.1
Medications Compared Head-to-Head
In the small open-label study, Vijay Jayagopal, MD, in the department of Medicine at the University of Hull in the UK and his colleagues tested the outcome of using orlistat in comparison to metformin in a group of 21 obese women who had previously been diagnosed with PCOS.
PCOS, also known as Stein-Leventhal Syndrome or Polycystic Ovary Disease (PCOD), affects up to 10 percent of women, and many don't know they have the disease. PCOS is one of the leading causes of infertility in women. It is characterized by cysts on the ovaries—follicles that have matured, but due to abnormal hormone levels, were never released by the ovary. Symptoms can include irregular or absent periods, numerous ovarian cysts in many cases, high blood pressure, acne, higher insulin levels, insulin resistance, type 2 diabetes, infertility, abnormal hair growth on various areas of the body (hirsutism), thinning of hair on the scalp, and weight problems.2
"We know that metformin is a proven and effective treatment for women with polycystic ovary syndrome," said Andrea Dunaif, MD, president-elect of The Endocrine Society, which sponsors the journal in which this study was published. "This study suggests that weight-loss medications may be an effective treatment option for not only obesity, but also the testosterone excess associated with PCOS."
Dunaif is also a professor of Medicine and chief of the division of Endocrinology at Columbia University in New York City.
Targeting Insulin Resistance
Metformin is not approved as a medication for PCOS, but is often prescribed "off-label" by doctors. It is a insulin-sensitizing medication currently approved for people with type 2 diabetes,3 but is thought to be effective for PCOS because of the insulin resistance that is characteristic of the disease. It is prescribed because it helps lower blood sugar, improves the action of insulin, and may help regulate menstrual cycles and improve fertility for women with PCOS. Still, the medication is considered experimental for this indication.4
Why test a diet drug as possible therapy for this condition? Obesity often accompanies PCOS in women with the disease, and Jaygopal and his team wrote that "even modest weight loss has been shown to increase the frequency of ovulation, improve conception, and reduce testosterone, hyperlipidemia, hyperglycemia, and insulin resistance in women with PCOS."
Analyzing Orlistat's Effect
In the UK study, Jayagopal's group selected each woman at random to receive 120 mg doses of orlistat three times per day or 500 mg of metformin three times a day for a total of three months. Prior to receiving the medications, the patients underwent eight weeks of dietary modification. Each patient had a body mass index (BMI) of "37". Body mass index, a measure of a person's healthy weight in correlation with their height, establishes a threshold of obesity at a score of "30". (People at this level or higher are considered obese.)
Each woman was also screened for weight and blood pressure, and fasting blood samples were taken. The tests were conducted at the start of the study, at the start of dosing, and at the completion of the research. Insulin resistance measurements were also taken.
At the end of the study, both orlistat and metformin caused equivalent reductions in each woman's total testosterone. Abnormal increases in male hormones called androgens play a key role in PCOS, which causes symptoms like abnormal hair growth on the body. Orlistat treatment also produced a nearly 5% reduction in weight, which was more significant than the 1% weight loss achieved in the group of women taking metformin.
Fasting insulin levels or blood lipids (fats) measured in the study were not affected by either drug. However, Jayagopal and his colleagues predicted that the study was not large enough to measure a significant enough difference in either of these two factors.
This study was too small and limited to determine whether either drug improved irregular menstrual cycles or ovulation, the investigators wrote. However, other studies have seen improvements in both of these after weight reduction and insulin-sensitizing drug treatment like metformin, they noted. "Information on the relative efficacy of orlistat and metformin in improving menstrual irregularities and ovulation is clearly important as it may influence an individual's choice of treatment if fertility is desired," the team wrote.
In the end, Jayagopal and his team noted that orlistat is at least as effective as metformin in reducing some PCOS symptoms. "In conclusion, this study has demonstrated the therapeutic potential of orlistat in PCOS by producing weight loss and a reduction in testosterone concentration. The improvement seen after treatment with orlistat was additionally similar to that seen with metformin, reaffirming the potential for orlistat to be a useful adjunct in the treatment of PCOS," they wrote.
1. Jayagopal V, Kilpatrick ES, Holding S, Jennings PE, Atkin SL. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. J Clin Endocrinol Metab 2005 Feb;90(2):729-33. Epub 2004 Nov 9.
2. Polycystic Ovarian Syndrome Association. PCOS 101. Available at: http://www.pcosupport.org/medical/whatis.php#pcos. Accessed April 5, 2005.
3. Mayo Foundation for Medical Education and Research. Polycystic Ovary Syndrome. Available at: http://www.mayoclinic.com/invoke.cfm?objectid=6AF557AF-44E0-4DDD-A998ADE4B75EAB04&dsection=8. Accessed April 5, 2005.
4. Costello MF, Eden JA. A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome. Fertil Steril 2003 Jan;79(1):1-13.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
