September 3, 2008
By Kat Carney
www.soulcysters.net
J Clin Endocrinol Metab. 2008 Aug 26.
The Impact of Metformin, Oral Contraceptives and Lifestyle Modification, on Polycystic Ovary Syndrome in Obese Adolescent Women in Two Randomized, Placebo-Controlled Clinical Trials.
Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS.
Departments of Obstetrics and Gynecology (KMH, LK, DSG), Cardiology (TC, LK) and Psychiatry (KD), University of Rochester Medical Center, Rochester, NY 14642.
Context: Polycystic ovary syndrome (PCOS) presents in adolescence and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear.
Conclusions: In these preliminary trials both lifestyle modification and oral contraceptives significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and oral contraceptive, reduces central adiposity, reduces total testosterone and increases HDL, but does not enhance overall weight reduction.
Objective: We investigated the effects of metformin, oral contraceptive and/or lifestyle modification in obese adolescent women with PCOS.
Design: Two randomized, placebo-controlled small clinical trials Patients and Participants: 79 obese adolescent women with PCOS
Interventions: In the Single Treatment Trial, subjects were randomized to metformin, placebo, a lifestyle modification program or oral contraceptive. In the Combined Treatment Trial, all subjects received lifestyle modification and oral contraceptive (OC) and were randomized to metformin or placebo.
Main outcome measures: Serum concentrations of androgens and lipids.
Results: Lifestyle modification alone resulted in a 59% reduction in free androgen index (FAI) with a 122% increase in sex hormone binding globulin (SHBG). OC resulted in significant decrease in total testosterone (44%) and FAI (86%), but also resulted in an increase in C-reactive protein (CRP) (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%).
PMID: 18728175 [PubMed - as supplied by publisher]
http://www.soulcysters.net/metformin-reduces-visceral-fat-but-does-not-enhance-weight-reduction-256476/
August 8, 2008
WEB MD on CBSNEWS.COM
Aug. 8, 2008
Drug Treatment And Intrauterine Insemination May Not Work When Used Separately
Two common infertility treatments do not improve fertility, according to a study conducted in the U.K.
Researchers compared drug treatment to induce ovulation with no treatment; they also compared intrauterine insemination — in which the sperm are placed inside the uterus to facilitate fertilization — with no treatment. They only studied couples with unexplained infertility, only one of many reasons for failing to conceive.
“What we found is that neither of these popular and commonly used treatments offered a higher birth rate than no treatment at all,” says Siladitya Bhattacharya, MD, a professor of reproductive medicine at the
University of Aberdeen in Scotland and the study’s lead author. “What we’ve shown is that neither of these first-line treatments is better than [the couples] trying themselves.”
The rate of live births was 17% for the no-treatment group, 14% for the medication group, and 23% for the insemination group. “There were no significant differences between them,” Bhattacharya tells WebMD.
But U.S. fertility experts who reviewed the study for WebMD say the findings probably have little relevance for infertile couples with unexplained infertility in the U.S. because the two infertility treatments — each compared singly to no treatment in the U.K. study — are typically used in combination here. The dose of medication used in the U.K. study is also much lower than what is typically prescribed in the U.S.
Infertility Treatments Fall Short
Bhattacharya and his colleagues recruited 580 infertile women, average age 32, from five hospitals in Scotland, randomly assigning them to one of three groups:
* The medication group took a 50 milligram oral dose of Clomid. If that overstimulated the ovaries, the dose was dropped to 25 milligrams. They were given advice about the best times to have intercourse.
* In the intrauterine insemination group, women monitored their hormone levels and when they were ideal, the sperm were placed inside the uterus to facilitate fertilization.
* The no-treatment group was given general advice about the need to have intercourse regularly during the six-month study.
All the women had been trying unsuccessfully to become pregnant naturally for at least two years. All had unexplained infertility, a condition in which doctors are unable to find any abnormalities after doing tests such as semen analysis, evaluating the fallopian tubes, or ovulation. About one in seven couples are infertile, with about one-quarter of those experiencing unexplained infertility, according to the researchers.
Comparing Infertility Treatments
At the study’s end, 32 women (17%) in the no-treatment group had given birth, compared to 26 (14%) in the medication group and 43 (23%) in the insemination group.
More women who got either the insemination or the medication found the process more acceptable than those who got no treatment, the researchers found.
Bhattacharya believes his team is the first to compare the treatments in this way. “Most people have compared treatment A with treatment B.”
“Although it may seem a bit counterintuitive, this is the one area of medicine where doing nothing could be as effective as going for any of these treatments,” he says.
The researchers write that the findings challenge current practice in the U.K., with recommendations now favoring what they found ineffective — insemination without stimulation by a medication and lower doses of the ovulation-inducing medication to decrease the risk of multiple pregnancies.
The study is published in Online First at bmj.com.
Infertility Treatments: Second Opinion
In an editorial accompanying the study, experts from the Assisted Conception Unit at Guy’s and St. Thomas’ Hospital NHS Foundation Trust in London write that treatment should be individualized, taking into account the woman’s age, the duration of infertility, and other factors.
While U.S. experts point out that they generally use ovarian stimulation and intrauterine insemination in combination, the editorial authors point to a study, published in The Lancet in 2006, that questions the benefit of even the combination treatment compared with no treatment.
They conclude that the generally higher-tech option, in vitro fertilization — in which eggs and sperm are fertilized in the lab, and then the embryo is implanted in the uterus — may be the most cost-effective option.
Treatment approaches differ in the U.K. and U.S., says Donna Session, MD, chief of the division of reproductive endocrinology and fertility and associate professor of obstetrics and gynecology at Emory University School of Medicine in Atlanta. “In the U.S., generally higher doses [of Clomid] are used, typically 100 milligrams a day.” And medication and insemination are typically combined.
“If anything, the take-home point from this study is, in the group where they did insemination alone — without any fertility drug — there wasn’t a significant increase in pregnancy,” she tells WebMD. “Just doing insemination alone is probably not going to really increase a person’s chance of pregnancy.”
Individualizing treatment recommendations is important, she says, taking into account a woman’s age and other factors such as “ovarian reserve” testing to evaluate the quality of the ovaries and how likely a woman is to become pregnant.
“If you have a patient with good results on the ovarian reserve testing, then expectant management [no treatment] might be something the patient might desire,” she says.
The results particularly don’t apply to U.S. women if they are treated by a fertility specialist, says Tracey Telles, MD, chief of reproductive endocrinology and infertility at the Kaiser Permanente Diablo Service Area in Walnut Creek, Calif. “In the United States, the indication of unexplained infertility is definitely managed more aggressively than it was in this study.”
But the less aggressive, less expensive fertility treatments are worth a try in some women, says Mousa Shamonki, MD, director of in vitro fertilization and assisted reproduction at the University of California Los Angeles Medical Center. For unexplained infertility, the lower-tech options include those evaluated in the U.K. study and also injections of hormones combined with intrauterine insemination, he says.
For other types of fertility problems — other than unexplained infertility — Clomid alone may work, Shamonki says. “Clomid works well for women who aren’t ovulating [regularly],” he says, such as women with polycystic ovary syndrome. PCOS is a leading cause of female infertility. Insemination alone may work for couples who have mild male-factor infertility or who have a history of cervical surgery, he says.
If none work, IVF techniques can be tried, he says; if couples are running out of time, they may opt to get more aggressive more quickly.
Psychologically, couples can find waiting frustrating, says Michael Diamond, MD, professor of obstetrics and gynecology at Wayne State University, Detroit. “Usually after a year of trying and not succeeding, the last thing a couple wants to hear is ‘Go home and try again.’”
By Kathleen Doheny
Reviewed by Louise Chang
http://www.cbsnews.com/stories/2008/08/08/health/webmd/main4332030.shtml
August 7, 2008
The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 8 3124-3127
The Endocrine Society
Nicholas A. Cataldo, Huiman X. Barnhart, Richard S. Legro, Evan R. Myers, William D. Schlaff, Bruce R. Carr, Michael P. Diamond, Sandra A. Carson, Michael P. Steinkampf, Christos Coutifaris, Peter G. McGovern, Gabriella Gosman, John E. Nestler, Linda C. Giudice for the Reproductive Medicine Network1
Context: When used for ovulation induction, higher doses of clomiphene may lead to antiestrogenic side effects that reduce fecundity. It has been suggested that metformin in combination with clomiphene can restore ovulation to some clomiphene-resistant anovulators with polycystic ovary syndrome (PCOS).
Objective: Our objective was to determine if cotreatment with extended-release metformin (metformin XR) can lower the threshold dose of clomiphene needed to induce ovulation in women with PCOS.
Design: A secondary analysis of data from the National Institute of Child Health and Human Development Cooperative Multicenter Reproductive Medicine Network prospective, double-blind, placebo-controlled multicenter clinical trial, Pregnancy in Polycystic Ovary Syndrome, was performed.
Setting: Study volunteers at multiple academic medical centers were included.
Participants: Women with PCOS and elevated serum testosterone who were randomized to clomiphene alone or with metformin (n = 209 in each group) were included in the study.
Interventions: Clomiphene citrate, 50 mg daily for 5 d, was increased to 100 and 150 mg in subsequent cycles if ovulation was not achieved; half also received metformin XR, 1000 mg twice daily. Treatment was for up to 30 wk or six cycles, or until first pregnancy.
Main Outcome Measures: Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1–2 wk.
Results: The overall prevalence of at least one ovulation after clomiphene was 75 and 83% (P = 0.04) for the clomiphene-only and clomiphene plus metformin groups, respectively. Using available data from 314 ovulators, the frequency distribution of the lowest clomiphene dose (50, 100, or 150 mg daily) resulting in ovulation was indistinguishable between the two treatment groups.
Conclusion: Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.
http://jcem.endojournals.org/cgi/content/abstract/93/8/3124
Stanford University School of Medicine (N.A.C., L.C.G.), Stanford, California 94305; Duke University School of Medicine (H.X.B., E.R.M.), Durham, North Carolina 27701; Pennsylvania State University School of Medicine (R.S.L.), Hershey, Pennsylvania 17033; University of Colorado (W.D.S.), Denver, Colorado 80218; University of Texas Southwestern Medical Center (B.R.C.), Dallas, Texas 75235; Wayne State University (M.P.D.), Detroit, Michigan 48202; Baylor College of Medicine (S.A.C.), Houston, Texas 77030; University of Alabama at Birmingham (M.P.S.), Birmingham, Alabama 35294; University of Pennsylvania School of Medicine (C.C.), Philadelphia, Pennsylvania 19104; University of Medicine and Dentistry of New Jersey (P.G.M.), Newark, New Jersey 07101-1709; University of Pittsburgh (G.G.), Pittsburgh, Pennsylvania 15260; and Department of Medicine (J.E.N.), Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0565
Address all correspondence and requests for reprints to: Richard S. Legro, M.D., Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033. E-mail: RSL1@psu.edu.
July 11, 2008
The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 7 2670-2678
Karen Elkind-Hirsch, Ory Marrioneaux, Madhu Bhushan, Denise Vernor and Rajat Bhushan
Woman’s Health Research Institute (K.E.-H.), Woman’s Hospital, and Metabolic Center of Louisiana Research Foundation (O.M., M.B., D.V., R.B.), Baton Rouge, Louisiana 70815
Context: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Weight loss and use of insulin-lowering drugs have been shown to improve both reproductive and metabolic aspects of PCOS.
Objective: We evaluated exenatide (EX) and metformin (MET), alone and in combination (COM), on menstrual cyclicity, hormonal parameters, metabolic profiles, and inflammatory markers in overweight, insulin-resistant women with PCOS.
Design, Setting, and Participants: Sixty overweight oligoovulatory women with PCOS (body mass index > 27; 18–40 yr) were randomized to one of three treatment groups: MET [1000 mg twice daily (BID)], EX (10 µg BID), or COM (MET 1000 mg BID, EX 10 µg BID) for 24 wk. The primary outcome was menstrual frequency; secondary outcome measures included changes in ovulation rate, insulin action, anthropometric measures, androgen levels, and inflammatory markers.
Results: Forty-two (70%) patients completed the study. COM therapy was superior to EX or MET monotherapy in improving menstrual cyclicity, ovulation rate, free androgen index, and insulin sensitivity measures and reducing weight and abdominal fat. Both EX arms were more effective in promoting weight loss than MET (P = 0.003).
Conclusions: COM appears better than either EX or MET alone on menstrual cycle frequency and hormonal and metabolic derangements. A marked decrease in central adiposity could partly explain the improvements in reproductive function, insulin-glucose parameters, and adiponectin observed in these overweight women with PCOS treated with COM therapy. Larger trials of longer duration are warranted to assess the long-term efficacy and safety of combined EX-MET therapy in overweight women with PCOS.
http://jcem.endojournals.org/cgi/content/abstract/93/7/2670
