What is the ideal first-line regimen in PCOS patients with obesity?

In the management of women with polycystic ovary syndrome (PCOS) and obesity, rosiglitazone monotherapy or in combination with low-dose metformin plus lifestyle modification should be recommended to those with abnormal lipid profiles, according to the results of a trial.

Meanwhile, metformin, along with lifestyle modification, should be considered as first-line regimen for those with insulin resistance, considering the weight-loss benefits of the drug.

“The recommended first-line therapy for PCOS is lifestyle management. Even a reduction of as little as 5-percent body weight could result in benefits. However, the efficacy of lifestyle management often remains unsatisfactory and unsustainable in clinical practice, so pharmacologic treatment is needed,” the investigators said.

In the study, the investigators randomly assigned 204 obese Chinese women (body mass index [BMI] ≥25 kg/m²) with insulin resistance who fulfilled the Rotterdam criteria of PCOS to one of three treatment groups. Group 1 (n=68) received metformin 1,500 mg, group 2 (n=67) received rosiglitazone 4 mg, and group 3 (n=69) were given metformin 1,000 mg and rosiglitazone 4 mg. Treatment was administered once daily for 6 months and was undertaken with diet and regular exercise lifestyle recommendation.

Following 6 months of intervention, menstrual pattern improved in most participants (p<0.001). There were parallel reductions seen in acne scores, weight, BMI, waist circumference, waist-to-hip ratio and serum testosterone, with no significant between-group differences. [Fertil Steril 2019;doi:10.1016/j.fertnstert.2019.09.011]

The metabolic indexes of insulin, carbohydrates and lipids markedly improved from baseline in each group. However, patients who received 1,500 mg/day of metformin achieved greater reductions in weight, whereas rosiglitazone users showed a more notable decrease in total cholesterol (TC) and triglyceride levels.

“Whether metformin or rosiglitazone is more strongly recommended for PCOS remains controversial,” with data from previous studies having been inconsistent, the investigators noted.

“Few studies have compared the effects of metformin, rosiglitazone, and combined metformin and rosiglitazone therapy. In our study, the combined administration of metformin and rosiglitazone for 6 months was not superior to individual administration for the amelioration of metabolic disturbances, which contrasts with the previous studies,” they said. [Chin Med J 2011;124:714-718; J Endocrinol Invest 2005;28:1003-1008; Am J Obstet Gynecol 2007;196:402-410.e1]

The investigators also pointed out that the risk predictors of cardiovascular disease, such as TC/high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)/HDL ratios, did not significantly differ among the three treatment groups. This suggests that lipid metabolism was similar after 6 months of therapy with different insulin sensitizers.

There were some limitations to the study, including lack of blinding and being conducted at a single centre. “In addition, we did not investigate the recovery of ovulation,” they said.