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Adrenocortical Effects of Oral Estrogens and Soy Isoflavones in Female Monkeys

Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040

Address all correspondence and requests for reprints to: Charles E. Wood, D.V.M., Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1040. E-mail: chwood{at}wfubmc.edu.

The goal of this study was to evaluate the long-term adrenocortical effects of premenopausal oral contraceptives (OC) and postmenopausal conjugated equine estrogens (CEE) and soy isoflavones in a female cynomolgus monkey model. Half of the animals received a triphasic OC for a period of 26 months, after which all monkeys were ovariectomized and randomized to one of three diet groups for 36 months: 1) isoflavone-depleted soy protein (control) (n = 54); 2) soy protein with isoflavones (129 mg/d equivalent) (SPI+) (n = 56); or 3) isoflavone-depleted soy protein with CEE (0.625 mg/d equivalent) (n = 59). In the premenopausal phase, OC treatment resulted in significantly higher cortisol (F) and lower dehydroepiandrosterone sulfate, androstenedione, and testosterone relative to intact controls. In the postmenopausal phase, CEE treatment resulted in significantly higher basal F and lower dehydroepiandrosterone sulfate, androstenedione, and testosterone when compared with control and SPI+ diets. Serum F and androgens in the SPI+ group did not differ significantly from the control group. The SPI+ group had significantly lower adrenal weight than either control or CEE groups, and this effect was localized primarily to the zona fasciculata region of the adrenal cortex. These findings suggest that long-term estrogen treatment may contribute to an androgen-deficient and hypercortisolemic state.

This work was supported, in part, by Program Project Grant HL-45666 from the NIH/National Heart, Lung, and Blood Institute, Bethesda, Maryland (to J.R.K.), by the NIH/National Center for Complementary and Alternative Medicine R01-AT00639 (to J.M.C.), and by the NIH/National Center for Research Resources T32 RR 07009 (to C.E.W.).

Abbreviations: A4, Androstenedione; BMI, body mass index; BW, body weight; CEE, conjugated equine estrogen(s); DHEA-S, dehydroepiandrosterone sulfate; E2, 17ß-estradiol; ER, estrogen receptor(s); F, cortisol; H&E, hematoxylin and eosin; OC, oral contraceptive(s); SPI–, soy protein depleted of isoflavones; SPI+, soy protein with isoflavones; T, testosterone.

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