The Effects of Hormonal Replacement Therapy on... : American Journal of Obstetrics and Gynecology (original) (raw)

General Obstetrics And Gynecology

The Effects of Hormonal Replacement Therapy on Insulin Sensitivity in Surgically Postmenopausal Cynomolgus Monkeys (Macaca fascicularis)

William T. Cefalu
Janice D. Wagner
Audrey D. Bell-Farrow
Zhong Q. Wang
Michael R. Adams
Gianna Toffolo
Claudio Cobelli

American Journal of Obstetrics and Gynecology

171

(

)

440

445

August 1994

OBJECTIVE

Our purpose was to evaluate the effect of hormone replacement therapy on insulin resistance in postmenopausal cynomolgus monkeys (Macaca fascicularis).

STUDY DESIGN

We studied 37 surgically postmenopausal cynomolgus monkeys that were fed a moderately atherogenic diet for 12 weeks with either no treatment (control), conjugated equine estrogens, medroxyprogesterone acetate, combination conjugated equine estrogens and medroxyprogesterone acetate, or tamoxifen. Insulin sensitivity and glucose effectiveness were determined by the frequent-sampling intravenous tolerance test by means of the minimal model analysis.

RESULTS

There were no differences in body weight, total plasma cholesterol, or body fat distribution between control and conjugated equine estrogens, medroxyprogesterone acetate, or combination treatment groups. However, compared with control animals (insulin sensitivity = 5.9 +/-1.2 x 10 sup -4 min sup -1 microunits sup -1 ml) or conjugated equine estrogens treatment (6.3 +/-1.1 x 10 sup -4 min sup -1 microunits sup -1 ml) insulin sensitivity was significantly decreased in animals treated with medroxyprogesterone acetate (2.9 +/-0.4 x 10 sup -4 min sup -1 microunits sup -1 ml, p < 0.001) or conjugated equine estrogens and medroxyprogesterone acetate (2.8 +/-0.6 x 10 sup -4 min sup -1 microunits sup -1 ml, p < 0.001). Although insulin sensitivity was shown to be decreased in the tamoxifen-treated animals (insulin sensitivity = 4.6 +/-0.6 x 10 sup -4 min sup -1 microunits sup -1 ml), the difference was not statistically significant compared with the control or conjugated equine estrogens--treated animals. No significant differences were seen for glucose effectiveness comparing control animals (glucose effectiveness = 0.043 +/-0.006 min sup -1) to animals treated with medroxyprogesterone acetate (glucose effectiveness = 0.046 +/-0.009 min sup -1), conjugated equine estrogens and medroxyprogesterone acetate (0.048 +/-0.008 min sup -1) or tamoxifen (0.039 +/-0.006 min sup -1).

CONCLUSION

These results suggest that progestins alone or in combination with estrogens can induce insulin resistance in postmenopausal monkeys while having no effect on plasma lipid concentrations or glucose effectiveness. (AM J OBSTET GYNECOL 1994;171:440-5.)