Normalization of hyperinsulinemia by chronic opioid receptor blockade in hyperandrogenemic women  Dijana Hadžiomerović, M.D., Bernhard Rabenbauer, M.D., Ludwig Wildt, M.D.  Fertility and Sterility  Volume 86, Issue 3, Pages 651-657 (September 2006) DOI: 10.1016/j.fertnstert.2006.01.039 Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Serum concentration (mean ± SD) of LH/FSH, T, free T (fT), sex hormone-binding globulin (SHBG), and DHEAS (left ordinate) and free androgen index (FAI) (right ordinate) in 39 women with hyperandrogenemia and hyperinsulinemia at baseline and after the administration of naltrexone (50 mg/d) for ≥3 weeks. The women were studied before and during naltrexone treatment. *P<.05; **P<.01; ***P<.001 (t-test for paired samples) for comparison with baseline values in the same group. Hadzžiomerović. Opioid blockade and hyperandrogenemia. Fertil Steril 2006. Fertility and Sterility 2006 86, 651-657DOI: (10.1016/j.fertnstert.2006.01.039) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 Body mass index in 39 hyperandrogenemic, hyperinsulinemic patients with three different levels of severity of hyperinsulinemia (A = slight; B = moderate; C = severe hyperinsulinemia) before and during naltrexone treatment. Data are expressed as the mean ± SD. None of the three groups shows a significant change in body mass index. Hadzžiomerović. Opioid blockade and hyperandrogenemia. Fertil Steril 2006. Fertility and Sterility 2006 86, 651-657DOI: (10.1016/j.fertnstert.2006.01.039) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Area under the curve (AUC) of insulin concentration before and after 3–9 weeks of naltrexone treatment for each patient. The levels of insulin were significantly lower (P<.01, t-test for paired samples) when compared to baseline values in all 39 hyperinsulinemic, hyperandrogenemic women. Hadzžiomerović. Opioid blockade and hyperandrogenemia. Fertil Steril 2006. Fertility and Sterility 2006 86, 651-657DOI: (10.1016/j.fertnstert.2006.01.039) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 4 Area under the curve (AUC) of glucose, insulin, and C-peptide concentrations after 75-g glucose load in hyperandrogenemic women before (•) and during (○) the naltrexone treatment. Data are expressed as mean ± SD. When OGTT was repeated during naltrexone administration, the increase in glucose concentrations was not different from that observed before treatment. The levels of insulin were strikingly lower (P<.01, t-test for paired samples) when compared to baseline values. The increase in C-peptide concentrations was influenced to a much lesser extent than that of insulin. Hadzžiomerović. Opioid blockade and hyperandrogenemia. Fertil Steril 2006. Fertility and Sterility 2006 86, 651-657DOI: (10.1016/j.fertnstert.2006.01.039) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions