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Modulation of higher-primate adrenal androgen secretion with estrogen-alone or estrogen-plus-progesterone intervention

Conley, Alan J. BVSc, PhD1; Stanczyk, Frank Z. PhD2; Morrison, John H. PhD3; Borowicz, Pawel PhD4; Benirschke, Kurt MD5; Gee, Nancy A. BAS6,7; Lasley, Bill L. PhD6,7

doi: 10.1097/gme.0b013e318273a070
Original Articles

Objective Circulating adrenal steroids rise during the menopausal transition in most middle-aged women and may contribute to differences in between-women symptoms and ultimate health outcomes. However, the mechanisms for this shift in adrenal steroid production in middle-aged women are not known. This study aims to determine whether hormone therapy (HT) for 1 year can modulate adrenal androgen production.

Methods Younger (9.8 [0.4] years, n = 20) and older (22.7 [0.4] years, n = 37) female laboratory macaques were ovariectomized, and each group was treated with different regimens of HT for up to 1 year. Changes in adrenal histology and circulating adrenal androgens were monitored after estrogen-alone (E) or estrogen plus progesterone (E + P) treatment, and these changes were compared with the same measures in similarly aged animals given vehicle.

Results Zona reticularis area, serum dehydroepiandrosterone (DHEA), and serum dehydroepiandrosterone sulfate (DHEAS) were higher in younger vehicle-treated animals compared with older vehicle-treated animals (P < 0.02). Both E and E + P treatments decreased circulating DHEAS in the younger group (P < 0.05). Although E treatment also decreased DHEAS in the older group, this was not statistically significant. In contrast, E + P treatment in the older group resulted in a rise in DHEAS over vehicle, which was significantly higher than the results of E treatment (P < 0.01). Circulating concentrations of DHEA exhibited similar trends, but these changes did not reach statistical significance.

Conclusions These data demonstrate that intervention with ovarian steroids can modulate adrenal androgen production in female higher primates and that both animal age and type of HT regimen determine adrenal response.

From the 1Department of Population Health and Reproduction, School of Veterinary Medicine, University of California at Davis, Davis, CA; 2Department of Obstetrics and Gynecology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; 3Department of Neuroscience, Mount Sinai School of Medicine, New York, NY; 4Department of Animal and Range Sciences, North Dakota State University, Fargo, ND; 5Department Pathology, School of Medicine, University of California at San Diego, San Diego, CA; and 6Center for Health and the Environment, University of California at Davis, Davis, CA; and 7California National Primate Research Center, University of California at Davis, Davis, CA.

Received May 28, 2012; revised and accepted September 10, 2012.

Funding/support: This study was funded, in part, by grant P51 RR00169, the base grant of the California National Primate Center, and grant P01 AG01675-06A1 (to J.H.M.).

Financial disclosure/conflicts of interest: J.H.M. has received royalties from Chemicon, Pharmingen, and Zymed, and has served as academic lecturer at University of Pennsylvania, Cornell University, and University of Pittsburgh.

Address correspondence to: Bill L. Lasley, PhD, Center for Health and the Environment, University of California at Davis, 1 Shields Avenue, Davis, CA 95616. E-mail:

© 2013 by The North American Menopause Society.