Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion
F. Cucinelli et al., Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion, EUR J ENDOC, 140(3), 1999, pp. 215-223
Objective: To evaluate the impact on glucose and insulin metabolism of tran
sdermal estrogen patches before and after the addition of cyclic dydrogeste
rone in postmenopausal women.
Design: We studied 21 postmenopausal women seeking treatment for symptomati
c menopause. All patients received transdermal 50 mu g/day estradiol for 24
weeks. lifter 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 sensiti
vity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insuli
n and C-peptide response to OGTT were expressed as area under the curve (AU
C) 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 concentr
ations were assessed at baseline and at 12 and 24 weeks of treatment.
Results: Nine patients proved to be hyperinsulinemic and 12 were normoinsul
inemic. 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 s
ignificant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoi
nsulinemic (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 normoinsuli
nemic patients,
Conclusions: Transdermal estrogen substitution alone and combined with cycl
ical dydrogesterone may ameliorate hyperinsulinemia in a selected populatio
n, of postmenopausal women.