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Diet, exercise boost ovulation in PCOS

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Results will change practice

These findings emphasize the importance of lifestyle intervention in women with PCOS who are trying to have children. This reasonably large study found that diet and exercise offer advantages to women with PCOS, not only in reversing some of the metabolic effects of PCOS, but also in higher ovulation rates and trends toward improved pregnancy rates.

Bradley J. Van Voorhis

It’s also noteworthy that simply putting women on birth control pills alone had some negative effects on glucose metabolism and the risk for metabolic syndrome. So, the other significant message is that it’s probably not wise to simply place women with PCOS on oral contraceptives alone, and oral contraceptive therapy should be done in conjunction with lifestyle interventions.

The findings are practice changing in that they’ll motivate me to always counsel patients with PCOS who are starting oral contraceptives on the potential for adverse effects and the need for dietary control and weight loss. It was surprising to me, the effect of a relatively short course of birth control pills on glucose metabolism and metabolic syndrome.

Dr. Bradley Van Voorhis, professor of medicine and director of the division of reproductive endocrinology and infertility at the University of Iowa, Iowa City, made these comments in an interview. He reported having no financial disclosures.


 

AT 2014 ASRM

References

HONOLULU – Preconception diet and exercise, by themselves or in combination with oral contraceptives, improved ovulation rates, compared with birth control pills alone, in a randomized study of 149 women with polycystic ovary syndrome.

The study randomized women with polycystic ovary syndrome (PCOS) who wanted to conceive to 16 weeks of either oral contraceptive pills; lifestyle modification consisting of increased physical activity, brief behavior modification lessons, a weight-loss medication, and caloric restriction using meal replacements; or a combination of both lifestyle interventions and oral contraceptives. All subjects then received four monitored cycles of ovulation induction with clomiphene.

Dr. Richard S. Legro

Dr. Richard S. Legro

Ovulation rates in the lifestyle intervention group and the combination therapy group were significantly higher (60% and 67%, respectively) than in the oral contraceptives group (46%), Dr. Richard S. Legro and his associates reported in a prize-winning presentation at the 2014 annual meeting of the American Society for Reproductive Medicine.

“Looking at the relative rate of ovulation, there was a 30%-50% improved rate of ovulation if the patient had undergone a preconception lifestyle modification,” compared with oral contraceptives alone, said Dr. Legro, professor of ob.gyn. at Pennsylvania State University in Hershey.

There was a trend toward higher live birth rates in the lifestyle intervention group (26%) and the oral contraceptives group (12%, P = .05), with the live birth rate in the combination group nearing that of the lifestyle intervention group (24%).

Investigators stopped the study before enrolling its goal of 248 women after the two groups with lifestyle intervention separated from the oral contraceptives group and an interim analysis concluded that further data would be unlikely to show a significant difference in results between the two groups employing lifestyle interventions.

Women in the combination therapy group lost 6.5% of body weight on average, compared with a 6.2% loss in the lifestyle interventions group and a 1% loss on oral contraceptives. The weight loss goal was 7% of body weight.

Dr. Legro said he was surprised by marked exacerbation of glucose intolerance in women on oral contraceptives that was ameliorated by lifestyle interventions. After the 16 weeks of preinduction treatment, changes in oral glucose tolerance test areas under the curve showed significant differences between the oral contraceptives group (a mean increase of 24 mg/dL/hour) and the lifestyle modifications group (a decrease of 1 mg/dL per hour) or the combination therapy group (a decrease of 17 mg/dL/hour).

The oral contraceptives group also showed trends toward increased blood pressure and fasting glucose levels plus a significant increase in triglyceride levels. The risk for developing metabolic syndrome during the 16 weeks of treatment more than doubled in the oral contraceptives group, compared with a statistically nonsignificant 20% increased risk in the lifestyle interventions group and a nonsignificant 30% decrease in risk in the combination therapy group, he reported.

The continuous oral contraceptive was ethinyl estradiol 10 mcg/norethindrone acetate 1 mg under the brand name LoEstrin 1/20.

The lifestyle modifications involved meal replacements for all three meals per day using fresh vegetables and fruit for a 500 kcal/day deficit. The goal for physical activity was 150 minutes per week, and the monthly behavioral modification lessons were adapted from the Diabetes Prevention Program. Participants with a body mass index of at least 30 received 5-15 mg/day of the antiobesity drug sibutramine until it was removed from the market, after which obese participants received 60 mg of orlistat with meals.

“Is it worth doing all this?” Dr. Legro asked. To answer that question, he and his associates conducted a post-hoc analysis comparing the results from the lifestyle modifications or combination therapy groups with results from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) study of clomiphene citrate or letrozole for ovulation induction without any pretreatment.

Cumulative ovulation rates were 40%-50% higher in the current study’s groups that included lifestyle interventions than in the PPCOS II study’s clomiphene group. The likelihood of a live birth more than doubled in the current study’s groups that included lifestyle interventions, compared with the PPCOS II clomiphene group.

The lifestyle interventions treatment “is very reproducible. It’s simple. It’s safe, and it’s well tolerated,” he said. “Oral contraceptive pills pretreatment likely offers little benefit versus immediate treatment with ovulation induction.”

One serious adverse event in the current study occurred in the oral contraceptive group, an episode of menorrhagia that sent the patient to an emergency department.

Concurrent lifestyle modification should be recommended for overweight or obese women with PCOS who are taking oral contraceptives, whether or not they are seeking fertility treatment, Dr. Legro said.

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