Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism

Paola Villa; Domenico Valle; Antonio Mancini; Laura De Marinis; Virginia Pavone; Anna Maria Fulghesu; Salvatore Mancuso; Antonio Lanzone

doi:10.1016/s0015-0282(98)00405-1

Reproductive Endocrinology Neuroendocrinology

Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism

Villa P, Valle D, Mancini A, De Marinis L, Pavone V, Fulghesu AM, Mancuso S, Lanzone A

Published January 1999 Fertility and Sterility, 71(1), 115-121

DOI 10.1016/s0015-0282(98)00405-1 PMID 9935127

RRM Academy Synopsis

Naltrexone improved growth hormone response in lean women with PCOS

A 1999 controlled study in Rome found that naltrexone improved the growth hormone response in lean women with PCOS. Obese women with PCOS showed no improvement. The study compared 22 women with polycystic ovary syndrome (PCOS) with 14 healthy women of similar age and weight.

Key Findings

The study enrolled 22 women with PCOS (12 lean, 10 obese) and 14 healthy, normally ovulating controls (7 lean, 7 obese), all given naltrexone for 4 to 5 weeks.
The growth hormone response to GHRH rose significantly in lean women with PCOS. Obese women with PCOS showed no modification after naltrexone.
In lean normoinsulinemic women with PCOS, the growth hormone response rose significantly (P <.02) while the insulin area under the curve was unaffected.
In hyperinsulinemic women with PCOS, naltrexone reduced the insulin area under the curve in obese (P <.01) and lean (P <.04) subgroups. Growth hormone rose only in the lean subgroup (P <.05).
Naltrexone did not change gonadotropin or steroid levels in any group, and the study observed no significant change in body mass index or glucose tolerance.

Interpretation

This controlled clinical study tested 22 women with PCOS, now also called PMOS (Polyendocrine Metabolic Ovarian Syndrome), before and after naltrexone. Fourteen matched controls took part. The women split into 12 lean and 10 obese, and into 14 hyperinsulinemic and 8 normoinsulinemic. Outcomes were hormone responses to standard tests. The authors suggest opioids play a role, because long-term opioid blockade improved growth hormone secretion in lean and normoinsulinemic women. Obesity and high insulin may add to the impaired response, which naltrexone did not overcome. They state that the mechanism of the changes is not clearly established. They call for further studies of the effect on the endocrine and reproductive features of the syndrome.

RRM Context

PCOS involves metabolic and hormonal disturbances beyond the ovary. The study links one of them, a blunted growth hormone response, to body weight and insulin level. Restorative reproductive medicine looks for the underlying drivers in each woman. The subgroup results show how women with one diagnosis can differ. The authors also cite earlier work connecting growth hormone to gonadal function.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To investigate the involvement of opioid tone, obesity, and hyperinsulinemia in GH secretion in women with polycystic ovary syndrome (PCOS).

Design

Controlled clinical study.

Setting

Catholic University of Sacred Heart School of Medicine in Rome, Italy.

Patients

Twenty-two patients with PCOS and 14 healthy, normally ovulating volunteers, matched for age and body mass index.

Interventions

Patients underwent a GH-releasing hormone (GHRH) test and an oral glucose tolerance test before and after 4-5 weeks of treatment with 50 mg/d of naltrexone.

Main Outcome Measures

Serum concentrations of GH, insulin, glucose, steroids, and gonadotropins, as well as the GH area under the curve (AUC-GH) and the insulin area under the curve (AUC-I), were measured before and after naltrexone treatment.

Results

In patients with PCOS, the administration of naltrexone increased the GH response to the GHRH test without interfering with the insulin response to the oral glucose tolerance test. However, the GH response to the GHRH test was improved significantly only in lean patients with PCOS, whereas obese patients with PCOS did not show any improvement in GH secretion. In obese control subjects, the treatment reduced plasma basal insulin concentrations and increased the AUC-GH, whereas in lean control subjects, the treatment reduced the GHRH-induced response. In normoinsulinemic patients with PCOS, the GH response to the GHRH test increased significantly after treatment, whereas the AUC-I was not affected. In hyperinsulinemic patients with PCOS, treatment with naltrexone significantly reduced the AUC-I, whereas the AUC-GH increased only in lean hyperinsulinemic patients with PCOS.

Conclusions

Naltrexone treatment improves GHRH-induced GH secretion in patients with PCOS. However, this GH response is heterogeneously represented in relation to both obesity and hyperinsulinism.

Topics

Reproductive Endocrinology Neuroendocrinology Opioid Peptides

Reproductive Endocrinology › Neuroendocrinology › Opioid Peptides

Paola Villa, Domenico Valle, Antonio Mancini, Laura De Marinis, Virginia Pavone, Anna Maria Fulghesu, Salvatore Mancuso, Antonio Lanzone

P Villa, D Valle, A Mancini, L Marinis, V Pavone, A Fulghesu, S Mancuso, A Lanzone

PMID 9935127 9935127 DOI 10.1016/s0015-0282(98)00405-1 10.1016/s0015-0282(98)00405-1 Villa et al. 1999, Villa 1999

Keywords

Adult, Area Under Curve, Female, Glucose Tolerance Test, Human Growth Hormone/blood, Humans, Hyperinsulinism/blood, Insulin/blood, Naltrexone/pharmacology, Narcotic Antagonists/pharmacology, Obesity/blood, Polycystic Ovary Syndrome/blood, Insulin, Narcotic Antagonists, Human Growth Hormone, Naltrexone

Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism

Naltrexone improved growth hormone response in lean women with PCOS

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords