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

ABSTRACT: Sex hormones appear to play a role in the regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. The objective was to isolate the effects of estradiol (E2) 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 E2 add-back would mitigate this response. Thirty premenopausal women underwent 20 wk of gonadotropin-releasing hormone agonist therapy (GnRHAG) and transdermal E2 (0.075 mg per day, GnRHAG?+ E2, n?= 15) or placebo (PL) patch (GnRHAG?+ PL, n?= 15). Women in the GnRHAG?+ PL and GnRHAG?+ E2 groups were of similar age (38?(SD 5) yr vs. 36?(SD 7) yr) and body mass index (27?(SD 6) kg/m2 vs. 27?(SD 6) kg/m2). Serum E2 changed differently between the groups ( P?= 0.01); it decreased in response to GnRHAG?+ PL (77.9?±?17.4 to 23.2?±?2.6 pg/ml; P?= 0.008) and did not change in response to GnRHAG?+ E2 (70.6?±?12.4 to 105?±?30.4 pg/ml; P?= 0.36). The incremental area under the curve (AUCINC) 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, GnRHAG?+ PL did not alter the HPA axis response to Dex/CRH, but GnRHAG?+ E2 decreased the AUCINC for ACTH (AUCINC, 1,623?± 257 to 1,211?± 236 pg/ml·min, P?= 0.004), cortisone (1,795?±?367 to 1,090?±?281 ng/ml·min, P?= 0.009), and total cortisol (7,008?±?1,387 to 3,893?±?1,090 ng/ml·min, P?= 0.02). Suppression of ovarian hormones by GnRHAG therapy for 20 wk did not exaggerate the HPA axis response to CRH, but physiologic E2 add-back reduced HPA axis activity compared with preintervention levels.

SUBMITTER: Gavin KM 

PROVIDER: S-EPMC6139491 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature