Evidence of a distinct derangement of opioid tone in hyperinsulinemic patients with polycystic ovarian syndrome: relationship with insulin and luteinizing hormone secretion.
Recent data indicate that an altered opioid tone could be involved in the LH hypersecretion and metabolic alterations seen in polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the presence of a common mechanism of action of opioids on altered insulin and gonadotropin release in patients suffering from PCOS. Twenty-eight women affected by PCOS and 8 normal ovulatory women were studied; an oral glucose tolerance test (OGTT) and GnRH tests were performed during the follicular phase before and after 6 weeks of naltrexone treatment (50 mg/day, orally). Plasma levels of sex hormone-binding globulin and steroids were assayed in the basal samples, whereas FSH and LH were analyzed during the GnRH stimulus. Insulin and glucose were assayed by the OGTT. Based on the insulinemic response to OGTT, 17 women were classified as hyperinsulinemic and 11 as normoinsulinemic. No difference in glucose and hormone plasma concentrations was observed before and after naltrexone treatment in both groups. Only basal sex hormone-binding globulin values were higher in normoinsulinemic compared to hyperinsulinemic subjects. Administration of the opioid antagonist significantly reduced the insulin response to OGTT only in the hyperinsulinemic group. No difference were found in the LH increment after the GnRH stimulus in both group of patients before treatment; on the contrary, naltrexone administration reduced the LH response to GnRH in hyperinsulinemic women but failed to be effective in normoinsulinemic subjects. Only 5 patients showed no concordance of drug-induced changes in insulin and LH secretion. In control subjects, naltrexone failed to have any effect on insulin or LH secretion. These data support the involvement of endogenous opioids in the regulation of insulin and LH secretion in a specific group of PCOS patients exhibiting an exaggerated insulin response to OGTT.
Lanzone
A
A
Department of Obstetrics and Gynecology, Catholic University of Sacred Hearth, Rome, Italy.
Fulghesu
A M
AM
Cucinelli
F
F
Ciampelli
M
M
Caruso
A
A
Mancuso
S
S
D000328:Adult; D004723:Endorphins / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications* / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007986:Luteinizing Hormone / Q000378:metabolism*; D009271:Naltrexone / Q000627:therapeutic use; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D004723:Endorphins; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D009271:Naltrexone; D007986:Luteinizing Hormone