Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone

Sex honnones appear to play a role in the regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. The objective was to isolate the effects of estradiol (E-2) on central activation of the HPA axis. We hypothesized that the HPA axis response to corticotropin-releasing hormone (CRH) under dexamethasone (Dex) suppression would be exaggerated in response to chronic ovarian hormone suppression and that physiologic E-2 add-back would mitigate this response. Thirty premenopausal women underwent 20 wk of gonadotropin-releasing hormone agonist therapy (GnRH(AG)) and transderma] E-2 (0.075 mg per day, GnRH(AG), + E-2, n = 15) or placebo (PL) patch (GnRH(AG) + PL, n = 15). Women in the GnRH(AG) + PL and GnRH(AG) + E-2 groups were of similar age (38 (SD 5) yr vs. 36 (SD 7) yr) and body mass index (27 (SD 6) kg/m(2) vs. 27 (SD 6) kg/m(2)). Serum E-2 changed differently between the groups (P = 0.01); it decreased in response to GnRH(AG) + PL (77.9 +/- 17.4 to 23.2 +/- 2.6 pg/ml; P = 0.008) and did not change in response to GnRH(AG) + E-2 (70.6 +/- 12.4 to 105 +/- 30.4 pg/ml; P = 0.36). The incremental area under the curve (AUC(INC)) responses to CRH were different between the groups for total cortisol (P = 0.03) and cortisone (P = 0.04) but not serum adrenocorticotropic hormone (ACTH) (P = 0.28). When examining within-group changes. GnRH(AG) + PL did not alter the HPA axis response to Dex/CRH, but GnRH(AG) + E-2 decreased the AUC(INC) for ACTH (AUC(INC), 1,623 +/- 257 to 1,211 +/- 236 pg/ml center dot min, P = 0.004). cortisone (1.795 +/- 367 to 1.090 +/- 281 ng/ml center dot min, P = 0.009), and total cortisol (7.008 +/- 1.387 to 3,893 +/- 1,090 ng/ml center dot min, P = 0.02). Suppression of ovarian hormones by GnRH(AG) therapy for 20 wk did not exaggerate the HPA axis response to CRH, but physiologic E-2 add-back reduced HPA axis activity compared with preintervention levels.