THE ROUTE OF ADMINISTRATION INFLUENCES THE EFFECT OF ESTROGEN ON INSULIN SENSITIVITY IN POSTMENOPAUSAL WOMEN

Objective: To determine the effect of transdermal estrogen on insulin sensitivity in postmenopausal women and to compare this effect with ch anges observed with oral conjugated equine estrogens. Design: Fourteen postmenopausal women were randomized to receive a transdermal E(2) pa tch, 0.1 mg, for 25 days each month (n = 7) or transdermal E(2) with a dded medroxyprogesterone acetate (MPA), 10 mg, from days 16 to 25 each month (n = 7). An insulin tolerance test (ITT) was performed at basel ine and between days 23 and 25 during the 2nd month of treatment to as sess insulin sensitivity. Values for the disappearance of glucose (K-i tt) were calculated and compared with values obtained from women recei ving 1.25 mg of oral equine estrogens (n = 8). Setting: University Cli nical Research Center. Patients: Healthy postmenopausal women not rece iving hormonal replacement. Intervention: Insulin tolerance tests befo re and after treatment. Main Outcome Measure: Disappearance of glucose and insulin (K-itt) before and after treatment. Results: Women receiv ing transdermal E(2) alone demonstrated improved insulin sensitivity. The K-itt glucose values increased by 13.2%, compared with a 23.9% dec rease in K-itt values observed with 1.25 mg of conjugated equine estro gen. The group treated with transdermal E(2) and MPA had a reduction i n insulin sensitivity. Insulin clearance was enhanced only with transd ermal estrogen and was significantly delayed (blunted clearance) with the addition of MPA to transdermal E(2) and with oral estrogen. Conclu sion: We previously demonstrated a bimodal effect of oral equine estro gens on insulin sensitivity with an improvement occurring with the low er dose of 0.625 mg but with a deterioration with the dose of 1.25 mg. Here we suggest that this effect may be related to a first-pass hepat ic-portal effect in that transdermal E(2) (0.1 mg), which may be equat ed more closely with the larger dose of oral estrogen (1.25 mg), impro ved insulin sensitivity. Progestin, however, appeared to attenuate the beneficial effects of transdermal estrogen and may alter the clearanc e of insulin.