Weight Loss Promoted By Drug Combination In Polycystic Ovary Syndrome

Women with polycystic ovary syndrome, or PCOS, lost significantly more weight when they took two drugs that are traditionally used to treat diabetes, rather than either drug alone, a study from Slovenia demonstrates. The results were presented at The Endocrine Society's 95th Annual Meeting in San Francisco.

PCOS is the leading cause of infertility among women. In the United States, the disorder affects approximately 5 million women, according to the U.S. Department of Health and Human Services Office of Women's Health. This translates to 1 in 10 to 20 women, overall, who are affected. The disease probably is genetic, although the exact causes are still unknown.

In PCOS, the ovaries produce excessive amounts of male sex hormones, or androgens. The name of the disease derives from small cysts that form on the ovaries, which do not produce enough of the hormone that triggers ovulation. When this occurs, the ovarian follicles, which have filled with fluid in preparation for ovulation, remain as cysts when ovulation fails to take place. In addition to infertility, symptoms include excessive hair growth in areas that usually are relatively hairless; obesity; menstrual irregularity; thinning or balding hair on the scalp; prediabetes or diabetes; and anxiety or depression. Weight loss in these women leads to higher chances of conception, improved pregnancy outcomes and improved metabolic profile.

Treatment varies depending upon the severity of the disease, and includes lifestyle modifications and drug therapy. Some of the same medications that are used to treat diabetes also improve PCOS symptoms. One of these medications, metformin, works by regulating the hormone insulin and by suppressing androgen activity, which, in turn, helps control blood-sugar levels and has beneficial effects on ovarian function. The problem with metformin, however, is that it does not always aid with weight loss.

Because of this, investigators examined different drug combinations to see which ones caused the most weight loss. In addition to metformin, they administered another diabetes medication called liraglutide, both alone and in combination with metformin, to determine which approach led to the greatest amount of weight loss.

They found that patients who took the combined drugs lost 6.5 kilograms (kg), or about 14 pounds, on average, compared to about 4 kg, or almost 9 pounds, on liraglutide alone, and 1 kg, or about 2 pounds, on metformin alone. Furthermore, 22 percent of participants on the combined treatment lost a significant amount of weight, defined as 5 percent or more of their body weight, compared to 16 percent of those on liraglutide. No one in the metformin group achieved this amount of weight loss. In terms of body-mass index and waist circumference, the combined-treatment group saw greater improvements than either of the single-medication groups. For both of these measurements, liraglutide alone outperformed metformin alone.

"The effect of metformin on weight reduction in polycystic ovary syndrome is often unsatisfactory," said study author Mojca Jensterle Sever, MD, PhD, who served as lead author with Andrej Janez, MD, PhD, a fellow consultant at the University Medical Center in Ljubljana, Slovenia. "Short-term combined treatment with liraglutide and metformin appears better than either metformin or liraglutide alone on weight loss and decrease in waist circumference in obese women with PCOS who had been previously poor responders regarding weight reduction on metformin alone."

The main side effect was nausea, which occurred more often with liraglutide than with metformin. The nausea did improve with time, however, and was not associated with weight loss.

Study participants comprised 36 women with PCOS who had lost less than 5 percent of their body weight on a six-month course of metformin preceding the study. Their average age was 31 years. Investigators randomly assigned them to one of three treatment groups for the 12-week study, including metformin alone, liraglutide alone, and both medications.

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Identifying Genetic Markers In Overweight Newborns Could Prevent Obesity In Later Life

Similar genetic variations occur in both overweight newborns and obese adults, a large study finds. The results were presented at The Endocrine Society's 95th Annual Meeting in San Francisco.

"Our data suggest that adult obesity and newborn adiposity share, in part, a common genetic background," said study lead author Reeti Chawla, MD, fellow in pediatric endocrinology at Ann & Robert H. Lurie Children's Hospital of Chicago and the Northwestern University Feinberg School of Medicine, in Chicago, IL. "Allowing earlier identification of high-risk newborns may allow for earlier interventions to take place to possibly prevent obesity later in life. "

Obesity has become an epidemic worldwide. In the United States alone, more than one-third of adults are obese, according to the Centers for Disease Control and Prevention. Excess weight and obesity are related to numerous health problems, including heart disease, type 2 diabetes, stroke and some cancers. Since being obese in childhood increases the risk of adult obesity, medical researchers are interested in identifying early risk factors, or genetic markers, to help predict who is at greater risk for weight gain.

One of these genetic markers is called a single nucleotide polymorphism, or SNP, which is a naturally occurring genetic variant within the general population. In this case, investigators used SNPs related to adult obesity to identify genetic markers associated with higher newborn weight and skinfold thickness.

Investigators were able to identify 144 SNPs associated with birth weight or skinfold thickness. Since some of these 144 SNPs are closely linked and inherited together, they then narrowed the group down to 45 SNPs that are related to higher fat among newborns.

Investigators obtained the genetic data of 4,465 newborns from a large, multi-ethnic study examining the association between maternal blood-sugar levels and risk of poor pregnancy outcome. The study, called the Hyperglycemia and Adverse Pregnancy Outcomes, or HAPO, comprised mothers and infants from diverse ethnic backgrounds, including 1,095 Afro-Caribbean, 1,363 European, 616 Mexican-American and 1,207 of Thai descent.

Chawla said that she and her team now are using the 45 SNPs identified in this study to develop a genetic risk score "to determine whether bearing a large number of these SNPs predicts which newborns are at risk for increased fat at birth and, potentially, obesity later in life."

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The Importance Of A Father's Diet Before Conception

When fathers eat a high-fat diet before conception of offspring, the male offspring have increased body weight after weaning and high body fat in midlife despite eating a low-fat diet, a new study in mice finds. The results were presented at The Endocrine Society's 95th Annual Meeting in San Francisco.

"Many researchers have studied the effects of maternal diet on the risk of obesity in their children. We found that the father's diet also affects the offspring in ways that are inherited," said the study's principal investigator, Felicia V. Nowak, MD, PhD, associate professor of molecular endocrinology at Ohio University in Athens.

The inherited differences in metabolism in the offspring of obese fathers appear to be epigenetic - changes in how genes are expressed that are "not hardwired" into the genes, meaning that they are modifiable by internal and external environmental factors, Nowak said. The cause of these changes was not behavioral because the offspring did not observe what their fathers ate nor did they have access to a high-fat diet, she noted.

In their study, the researchers fed male mice a 13-week diet that was either high fat (45 percent of calories derived from fat) or low fat (10 percent of calories from fat; control mice) but contained the same number of calories. The mice that ate the high-fat food became obese. All mice were mated with females that had received the matched low-fat diet. All their offspring received standard laboratory mouse chow.

The mouse pups underwent testing of their body weight and fat at various ages: 20 days, which was right after weaning and is similar in age to human infants or toddlers, according to Nowak; 6 weeks, which is roughly equivalent to adolescence; 6 months, or young adulthood; and finally 12 months, or older adulthood.

Compared with offspring from control mice, the male offspring of paternal mice with diet-induced obesity had higher body weight starting at 6 weeks of age, and the increased weight was still present at 6 and 12 months, the authors reported. In addition, at 6 months, the male offspring of the obese paternal mice had a higher percentage of total body fat than control offspring did. There were, however, no observed differences in the amount of brown fat, the calorie-burning fat that both rodents and humans have.

Surprisingly, male offspring of the high-fat-fed paternal mice also showed increases in voluntary running at 6 weeks. Female offspring ran more than male offspring at 6 months and 12 months, Nowak said. She said they are studying possible causes for this behavior, which might offset the increased body fat and reduce the offspring's risk of metabolic disease such as diabetes and heart disease.

"Increasing numbers of children and adolescents are affected by obesity," Nowak said. "It is essential that we identify markers for early detection and prediction of obesity and diabetes. This will enable individuals to make healthy lifestyle choices and receive targeted health care interventions to delay or prevent the related disabilities and increase life expectancy."

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