To the Editor:
We have read with great interest the well-designed study by Lindholm et al. (1) and we would like to comment on the potential relationship between weight reduction and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) treated with sibutramine.
Lindholm et al., in a double-blind, randomized, parallel-group clinical trial, reported a significant weight reduction after 6 months of treatment with sibutramine, 15 mg daily, in obese PCOS women. The authors reported no influence in fasting glucose and insulin levels, as well as in all indices of IR.
A recent study (2) noted an even greater weight reduction (-15.4±1.1 versus -7.8±5.1Kg) in obese PCOS women with similar body mass index (BMI) within the same time period treated with a smaller daily dose of sibutramine (10 mg). We have also noted a restoration of glucose tolerance in our PCOS women with abnormal OGTT, a reduction in area under the curve for glucose and an improvement in insulin sensitivity.
We would like to comment on the observed differences in the improvement of IR in these two studies. The improvement of IR with sibutramine in our study might be due to the greater weight reduction in our PCOS patients. Thus, in our study, a 5–14% reduction in body weight with sibutramine did not affect insulin sensitivity, whereas a beneficial effect was observed after a greater than 15% reduction of the initial body weight. Based on this observation we could speculate that there is a critical weight loss, which seems to be over 15%, in order to observe a significant improvement of IR.
In a smaller sample of patients, Sabuncu, et al. (3) also reported significant weight reduction and an improvement of insulin sensitivity with sibutramine treatment, similar to that observed in our study.
The improvement of IR with sibutramine is similar to that observed with orlistat treatment in obese PCOS women, where it also appears to be related to significant weight reduction (4). The amelioration of IR in these studies could not be totally explained by weight loss. Central obesity and the amount of visceral fat is associated with IR in obese patients; still the mechanisms for insulin sensitivity improvement with sibutramine treatment in PCOS women should be explored in future studies.
In conclusion, evidence is accumulating that sibutramine treatment in obese PCOS women leads to a significant weight reduction and to an improvement of insulin sensitivity.
Neoklis A. Georgopoulos, MD, PhD Ilias Katsikis, MD, PhD Dimos Florakis, MD Evanthia Diamanti-Kandarakis, MD, PhD Dimitrios Panidis, MD, PhD. Department of Obstetrics and Gynecology
Aristotle University of Thessaloniki Thessaloniki, Greece References
1. Lindholm A, Bizo M , Bjorn I, Woner-Hanssen P, Eliasson M, Larsson A, et al. Effect of sibutramine on weight reduction in women with polycystic ovary syndrome:a randomized, double-blind, placebo-controlled trial. Fertil Steril 2008; 89: 1221-1228.
2. Florakis D, Diamanti-Kandarakis E, Katsikis I, Nassis GP, Karkanaki A, Georgopoulos N, Panidis D. Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic features in overweight and obese women with polycystic ovary syndrome: a randomized, 24-week study. Int J Obes 2008; 32:692–699.
3. Sabuncu T, Harma M, Harma M, Nazligul Y, Kilic F. Sibutramine has a positive effect on clinical and metabolic parameters in obese patients with polycystic ovary syndrome. Fertil Steril 2003; 80: 1199–1204.
4. Panidis D, Farmakiotis D, Rousso D, Kourtis A, Katsikis I, Krassas G. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil Steril 2008; 89:899-906.
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2008.12.083