Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Fulghesu AM et al., 1995 · Hum Reprod
A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to evaluate the involvement of endogenous opioids in the pathophysiology of the hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist. An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose, insulin and connecting peptide (c-peptide) concentrations were evaluated in all samples. Based on their insulinaemic response to OGTT, patients were classified as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group without affecting the c-peptide incremental area; in the normoinsulinaemic group there was a slight, but not significant, increase in both c-peptide and insulin incremental areas. The two groups showed similar c-peptide incremental areas after naltrexone treatment. There was no significant difference in the c-peptide:insulin incremental areas molar ratio between the two groups; after treatment, a significant increase in this ratio was observed in both groups. When we considered the data as an expression of the fractional hepatic extraction of insulin, we found a lower value for hyperinsulinaemic in comparison with normoinsulinaemic patients (not significant), and a significant (P < 0.01) improvement of this parameter in the hyperinsulinaemic group after naltrexone administration. In conclusion, we suggest that the contribution to hyperinsulinaemia in PCOD patients may be at least in part due to both increased pancreatic secretion and reduced hepatic removal of insulin. Chronic pharmacological inhibition of opioid tone could improve the insulin plasma concentration by acting chiefly on the liver metabolism of insulin in hyperinsulinaemic patients.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Fulghesu AM et al., 1993 · Obstet Gynecol
To evaluate the involvement of endogenous opiates in the pathophysiology of the hyperinsulinism in patients affected by polycystic ovary disease by administering naloxone and naltrexone. We also studied the hormonal status following long-term opioid antagonist administration. Twenty-one women affected by polycystic ovary disease participated in the study. An oral glucose tolerance test (GTT) was performed at baseline and repeated after short-term naloxone infusion and after 6 weeks of naltrexone administration. Plasma glucose and insulin levels were evaluated in all samples. Gonadotropins, sex hormone-binding globulin, and androgen levels were determined initially and after the naltrexone treatment. None of the patients showed any alteration of glucose tolerance. Based on the insulin response to the GTT, the patients were classified as normo- or hyperinsulinemic. Opioid antagonist administration significantly reduced the insulin response to the GTT in hyperinsulinemic patients, without affecting their glycemic levels. In normoinsulinemic patients, glucose plasma levels were increased whereas insulin levels were not modified by the treatments. Gonadotropin and androgen plasma concentrations were not modified after naltrexone administration. This work supports a role for the endogenous opiates in the regulation of exaggerated insulin secretion in patients with polycystic ovary disease. The reduction of insulin secretion failed to demonstrate any hormonal modification in such hyperandrogenized patients.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Hadziomerovic D et al., 2006 · Fertility and Sterility
Evaluation of the effects of naltrexone on hyperinsulinemia and hyperandrogenemia in hyperandrogenemic, hyperinsulinemic women. Controlled clinical study. Department of Gynecologic Endocrinology and Reproductive Medicine, Center of Obstetrics and Gynecology, Medical University of Innsbruck, Austria. PATIENT(S): Thirty-nine hyperandrogenemic, hyperinsulinemic women were studied. INTERVENTION(S): Women were treated with naltrexone (50 mg/d) for >or=3 weeks. MAIN OUTCOME MEASURE(S): Body mass index (BMI), gonadotropin (LH, FSH) and androgen (T, free T, DHEAS) levels, and plasma levels of glucose, insulin, and C-peptide, during a standard 75-g oral glucose tolerance test (OGTT), were determined before and during chronic opiate receptor blockade. RESULT(S): The BMI did not change during therapy. When OGTT was repeated after treatment with naltrexone, glucose levels were not different from those before treatment. Insulin response, however, had dramatically declined. We also observed a significant decrease in the levels of serum androgens. CONCLUSION(S): Hyperinsulinemia associated with hyperandrogenemia can be improved or completely abolished by chronic opiate receptor blockade. This observation suggests that endogenous opiates play a critical role in the process leading to hyperinsulinemia in hyperandrogenemia.
Neuroendocrinology · Opioid Peptides
Lanzone A et al., 1991 · Hum Reprod
In order to test the hypothesis that endogenous opiates are at least partially responsible for hyperinsulinaemia in patients with polycystic ovarian disease (PCOD), the effect of naloxone (an opiate receptor blocker) on the insulin response to oral glucose load (OGTT) was studied in 20 women with PCOD and 17 control subjects at days 5-8 of their follicular phase. After fasting overnight for 10-12 h, each woman received an i.v. bolus injection (2 mg) of naloxone or an equal volume of saline infusion followed by a constant infusion of naloxone or saline solution at a rate of 8 ml/h (1 mg/h of naloxone) for 5 h. OGTT (75 g) was performed 1 h after the bolus injection. The naloxone study was performed 48 h after the saline study. Naloxone did not modify the insulin response to OGTT in either group. When the data were related to the insulin response, in PCOD hyperinsulinaemic patients, naloxone significantly reduced (P less than 0.02) the insulin response to OGTT without any change in glycaemic response curves. In control and PCOD normoinsulinaemic patients, naloxone did not change significantly either the glycaemia or the insulin levels after OGTT. No change of gonadotrophin and steroid secretion was found in any patient receiving naloxone. In conclusion, endogenous opiates may play a significant role in hyperinsulinaemia in PCOD.
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