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4 SUCCESS OF METFORMIN-PIOGLITAZONE IN RESOLVING ENDOCRINOPATHY AND INSULIN RESISTANCE-HYPERINSULINEMIA IN 40 WOMEN WITH POLYCYSTIC OVARY SYNDROME NOT OPTIMALLY RESPONSIVE TO METFORMIN ALONE.
  1. D. Aregawi,
  2. M. Salehi,
  3. M. Agloria,
  4. M. Winiarska,
  5. L. Sieve,
  6. P. Wang,
  7. C. J. Glueck
  1. Cholesterol Center, Jewish Hospital, Cincinnati, OH

Abstract

In 40 women (36 white, 1 black, 3 other) with polycystic ovary syndrome (PCOS) not optimally responsive to metformin (MET 2.55 g/day) for 1 year, endocrine and menstrual response to MET (2.55 g) with added pioglitazone (PIO 45 mg/day) for 1 year were compared to outcomes on MET alone. Before MET, 35% of women were obese with BMI 30.0 to < 40 and 48% had BMI 40 or higher (severely obese). In the year before MET, the mean ± SD (median) of expected menses was only 23 ± 27% (median 17%), rising to 44 ± 41% (median 33%) after 1 year on MET (p = .002), then rising to 81 ± 30% (median 100%) after 6 months on MET-PIO (p < .0001), 76 ± 33% (median 100%) at 9 months, and 78 ± 35% (median 100%) at 12 months. Before MET, mean ± SD weight was 106 ± 28 kg and median BMI 37.6 kg/m2. After 1 year on MET weight fell (104 ± 28 kg, p = .01) but increased on MET-PIO (106 ± 29 kg, p = .03). On MET for 1 year, median DHEAS fell nonsignificantly (p = .75) from median 224 to 201 μg/dL but then fell to 169 μg/dL on MET-PIO (p = .03). Median sex hormone binding globulin (SHBG) was 25 nmol/L before MET, 20 on MET (p > .1), and rose to 27 on MET-PIO (p < .001). Median fasting serum insulin was 20.2 μU/mL before MET, 20.1 on MET (p > 0.1), but then fell to 13.1 μU/mL on MET-PIO (p < .001). HOMA insulin resistance was 3.90 before MET, 4.76 on MET (p > .1), but then fell to 2.74 on MET-PIO (p < .001). HOMA insulin secretion was 285 before MET, 217 on MET (p > .1), but then fell to 159 on MET-PIO (p < .001). HDL cholesterol, 41 mg/dL before MET, 40 mg/dL on MET (p > .1), rose to 44 mg/dL on MET-PIO (p < .001). In obese and severely obese women with PCOS who do not optimally respond to MET, addition of PIO to MET (despite weight gain) promotes much more regular menses, lowers DHEAS, elevates SHBG, lowers fasting serum insulin, lowers HOMA insulin resistance and HOMA insulin secretion, and elevates HDL cholesterol. Combination of the insulin-sensitizing agents MET and PIO successfully resolves endocrinopathy and insulin resistance-hyperinsulinemia in obese women with PCOS who are not optimally responsive to MET alone.

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