Naloxone decreases insulin secretion in hyperinsulinemic postmenopausal women and may positively affect hormone replacement therapy.
OBJECTIVE
To evaluate the influence of the opioid system on glyco-regulation in postmenopausal women before and after hormone replacement therapy (HRT).


METHODS
Prospective nonrandomized clinical study.


METHODS
Academic research environment.


METHODS
Twenty-one healthy normo- or hyperinsulinemic postmenopausal women.


METHODS
Oral glucose tolerance test (OGTT) (saline study), OGTT with IV injection of naloxone (naloxone study), and hyperinsulinemic euglycemic clamp performed before treatment, after 12 weeks of estrogen replacement therapy (ERT), and after 12 additional weeks of estro-progestin combined therapy (i.e., HRT).


METHODS
Glucose, insulin, and c-peptide plasma levels assessed in fasting condition and during the two OGTTs (area under the curve [AUC]). Evaluation of fractional hepatic insulin extraction (FHIE) and peripheral sensitivity to insulin.


RESULTS
At baseline, there is a greater increase of the FHIE and a more significant reduction of the insulin AUC in the hyperinsulinemic patients during the naloxone study compared with the saline study. In these women, ERT enhanced the c-peptide AUC and improved the FHIE; naloxone infusion mainly increased these two parameters. HRT did not induce any further change.


CONCLUSIONS
Endogenous opioid peptides are involved in the modulation of carbohydrate metabolism in menopause in hyperinsulinemic patients more than in other patients. The favorable changes of the glyco-insulinemic metabolism induced by HRT may be partially due to the induction of the opioidergic activity.
Cucinelli
Francesco
F
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Soranna
Liberato
L
Perri
Concetta
C
Romualdi
Daniela
D
Barini
Angela
A
Mancuso
Salvatore
S
Lanzone
Antonio
A
D019540:Area Under Curve; D002096:C-Peptide / Q000097:blood; D004357:Drug Synergism; D015914:Estrogen Replacement Therapy; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000627:therapeutic use*; D000078790:Insulin Secretion; D008875:Middle Aged; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D017698:Postmenopause; D011446:Prospective Studies; D012965:Sodium Chloride / Q000627:therapeutic use
D002096:C-Peptide; D007328:Insulin; D007329:Insulin Antagonists; D009292:Narcotic Antagonists; D009270:Naloxone; D012965:Sodium Chloride