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Last Updated: Oct 11, 2012 - 10:22:56 PM
Research Article
Endocrinology Channel

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Latest Research : Endocrinology

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Clomiphene better than Metforminin for treating infertility in PCOS

Feb 8, 2007 - 7:08:05 AM , Reviewed by: Dr. Sanjukta Acharya
"With this study, my colleagues and I recommend and support the use of clomiphene alone and NOT in combination with Metformin as a first-line therapy for infertility in women with PCOS," said Christos Coutifaris, MD, PhD, Director of the Division of Reproductive Endocrinology and Infertility and the principal investigator from Penn. "These results emphasize the need to test any new application rigorously, no matter how promising it may seem initially."

Key Points of this article
Polycystic ovarian syndrome is associated with insulin resistance which metformin helps to decrease.
Metformin is used in PCOS to improve hirsutism, normalize menstrual cycles and help induce ovulation.
Though both metformin and clomiphene induce ovulation, the chances of pregnancy are lower with the former.
 
[RxPG] Metformin, a drug used to treat diabetes and once thought to have great promise in overcoming the infertility associated with polycystic ovary syndrome (PCOS), is less effective than the standard fertility drug treatment, clomiphene, according to researchers from the University of Pennsylvania School of Medicine and the National Institutes of Health Reproductive Medicine research network. This is the largest, most comprehensive effort yet to compare the two drugs in helping PCOS patients achieve successful pregnancy. The findings appear in the February 8th, 2007 issue of the New England Journal of Medicine.

"With this study, my colleagues and I recommend and support the use of clomiphene alone and NOT in combination with Metformin as a first-line therapy for infertility in women with PCOS," said Christos Coutifaris, MD, PhD, Director of the Division of Reproductive Endocrinology and Infertility and the principal investigator from Penn. "These results emphasize the need to test any new application rigorously, no matter how promising it may seem initially."

According to the study authors, women who took metformin ovulated more that the women who were given the standard treatment. Similarly, women in the combination therapy group ovulated more frequently than did the women in either the clomiphene-alone or the metformin-alone groups. However, as the current study revealed, an increase in ovulation did not result in more successful pregnancies and deliveries for either the metformin alone, or combination group.

"The bottom line here is that ovulation does not necessarily result in a successful pregnancy," said Coutifaris "The results suggest that an ovulation due to clomiphene is two times as likely to result in pregnancy compared to an ovulation caused by metformin."

PCOS affects seven to eight percent of women in the United States and may be the most common cause of female infertility. With PCOS, an excess of male hormones interfere with ovulation and cause the ovaries to enlarge and fill with cysts.

Women with PCOS frequently experience insulin resistance, a pre-diabetic condition in which higher-than-normal amounts of insulin are required to allow glucose to enter tissues. Earlier studies had shown that drugs such as metformin – which make the body more sensitive to insulin – could increase ovulation in PCOS patients. Similarly, several smaller studies had suggested that metformin, alone or when taken together with the drug clomiphene, could result in greater fertility rates for PCOS patients than could clomiphene alone. Clomiphene fosters ovulation by stimulating the release of hormones needed for ovulation to occur.

To conduct the study, the researchers randomly assigned 626 infertile women with PCOS to one of three groups. The first group received clomiphene and a placebo. The second group received metformin and a placebo, and the third group received both metformin and clomiphene. The women took the medication for up to six months. The researchers tested the women's levels of the hormone progesterone to gauge when the women were ovulating.

The researchers found that fewer women in the metformin only group had given birth than had women in either of the clomiphene groups. In the metformin only group, 15 out of 208 women had given birth, or 7.2 percent. In the clomiphene only group, 47 out of 209 women had given birth, or 22.5 percent. In the combined clomiphene-metformin group, 56 out of 209 women had given birth (26.8 percent). The difference in the number of births between the clomiphene only group and the combined clomiphene-metformin group was not statistically significant. The researchers also found that, compared to the other women in the study, obese women were less likely to conceive during the course of the study and less likely to ovulate in response to metformin.

The study authors also noted that while metformin alone did not improve the chances for pregnancy, it was useful for lowering the high blood testosterone levels that occur with PCOS.




Publication: New England Journal of Medicine

Funding information and declaration of competing interests: This study was funded by the National Institute of Child Health and Human Development and the National Center for Research Resources.

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 About Dr. Sanjukta Acharya
This news story has been reviewed by Dr. Sanjukta Acharya before its publication on RxPG News website. Dr. Sanjukta Acharya, MBBS is the chief editor for RxPG News website. She oversees all the medical news submissions and manages the medicine section of the website. She has a special interest in diabetes and endocrinology.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
 Additional information about the news article
PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #3 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals, all of which have received numerous national patient-care honors [Hospital of the University of Pennsylvania; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

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