Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion.
OBJECTIVE
To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women.


METHODS
We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added.


METHODS
During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment.


RESULTS
Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients.


CONCLUSIONS
Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.
Cucinelli
F
F
Department of Obstetrics and Gynecology, Università Cattolica S. Cuore, Rome, Italy.
Paparella
P
P
Soranna
L
L
Barini
A
A
Cinque
B
B
Mancuso
S
S
Lanzone
A
A
D000279:Administration, Cutaneous; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004394:Dydrogesterone / Q000008:administration & dosage / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011863:Radioimmunoassay; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D004967:Estrogens; D007328:Insulin; D008074:Lipoproteins; D045167:Progesterone Congeners; D014280:Triglycerides; D004394:Dydrogesterone; D002784:Cholesterol; D005947:Glucose