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ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement.
J Clin Endocrinol Metab 2012; 97(6):1887-96JC

Abstract

CONTEXT

During conditions of ovarian suppression, women with premenstrual dysphoria (PMD) experience abnormal behavioral responses to physiological levels of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation frequently accompanies depression, and ovarian steroids regulate HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We hypothesized that women with PMD would show abnormalities of HPA axis function analogous to those reported in depressive illness, and that ovarian steroids would differentially regulate HPA axis function in women with PMD compared with asymptomatic controls (AC).

OBJECTIVE

Our objective was to characterize the HPA axis response to physiological levels of estradiol and progesterone in women with PMD and AC.

DESIGN AND SETTING

We conducted an open-label trial of the GnRH agonist depot Lupron with ovarian steroid replacement administered in a double-blind crossover design in an outpatient clinic.

PARTICIPANTS

Forty-three women (18 with prospectively confirmed PMD and 25 AC) participated.

INTERVENTIONS

Women received Lupron for 6 months. After 3 months of hypogonadism, women received 5 wk each of estradiol (100-μg patch daily) or progesterone (suppositories 200 mg twice daily). During each condition, combined dexamethasone-suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were performed.

MAIN OUTCOME MEASURES

Plasma cortisol and ACTH levels were evaluated.

RESULTS

HPA axis function was similar in PMD compared with AC. In all, progesterone significantly increased the secretion of cortisol compared with estradiol [area under the curve (t(74) = 3.1; P < 0.01)] and urinary free cortisol (t(74) = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under the curve (t(74) = 2.4; P < 0.05)].

CONCLUSIONS

HPA axis regulation is normal in PMD, suggesting that the pathophysiology of PMD differs from major depression. As observed previously, progesterone but not estradiol up-regulates HPA axis function in women.

Authors+Show Affiliations

Section on Behavioral Endocrinology, National Institute of Mental Health, Bethesda, Maryland 20892-1277, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Controlled Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22466349

Citation

Lee, Ellen E., et al. "ACTH and Cortisol Response to Dex/CRH Testing in Women With and Without Premenstrual Dysphoria During GnRH Agonist-induced Hypogonadism and Ovarian Steroid Replacement." The Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 6, 2012, pp. 1887-96.
Lee EE, Nieman LK, Martinez PE, et al. ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement. J Clin Endocrinol Metab. 2012;97(6):1887-96.
Lee, E. E., Nieman, L. K., Martinez, P. E., Harsh, V. L., Rubinow, D. R., & Schmidt, P. J. (2012). ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement. The Journal of Clinical Endocrinology and Metabolism, 97(6), pp. 1887-96. doi:10.1210/jc.2011-3451.
Lee EE, et al. ACTH and Cortisol Response to Dex/CRH Testing in Women With and Without Premenstrual Dysphoria During GnRH Agonist-induced Hypogonadism and Ovarian Steroid Replacement. J Clin Endocrinol Metab. 2012;97(6):1887-96. PubMed PMID: 22466349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement. AU - Lee,Ellen E, AU - Nieman,Lynnette K, AU - Martinez,Pedro E, AU - Harsh,Veronica L, AU - Rubinow,David R, AU - Schmidt,Peter J, Y1 - 2012/03/30/ PY - 2012/4/3/entrez PY - 2012/4/3/pubmed PY - 2012/8/16/medline SP - 1887 EP - 96 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 97 IS - 6 N2 - CONTEXT: During conditions of ovarian suppression, women with premenstrual dysphoria (PMD) experience abnormal behavioral responses to physiological levels of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation frequently accompanies depression, and ovarian steroids regulate HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We hypothesized that women with PMD would show abnormalities of HPA axis function analogous to those reported in depressive illness, and that ovarian steroids would differentially regulate HPA axis function in women with PMD compared with asymptomatic controls (AC). OBJECTIVE: Our objective was to characterize the HPA axis response to physiological levels of estradiol and progesterone in women with PMD and AC. DESIGN AND SETTING: We conducted an open-label trial of the GnRH agonist depot Lupron with ovarian steroid replacement administered in a double-blind crossover design in an outpatient clinic. PARTICIPANTS: Forty-three women (18 with prospectively confirmed PMD and 25 AC) participated. INTERVENTIONS: Women received Lupron for 6 months. After 3 months of hypogonadism, women received 5 wk each of estradiol (100-μg patch daily) or progesterone (suppositories 200 mg twice daily). During each condition, combined dexamethasone-suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were performed. MAIN OUTCOME MEASURES: Plasma cortisol and ACTH levels were evaluated. RESULTS: HPA axis function was similar in PMD compared with AC. In all, progesterone significantly increased the secretion of cortisol compared with estradiol [area under the curve (t(74) = 3.1; P < 0.01)] and urinary free cortisol (t(74) = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under the curve (t(74) = 2.4; P < 0.05)]. CONCLUSIONS: HPA axis regulation is normal in PMD, suggesting that the pathophysiology of PMD differs from major depression. As observed previously, progesterone but not estradiol up-regulates HPA axis function in women. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/22466349/ACTH_and_cortisol_response_to_Dex/CRH_testing_in_women_with_and_without_premenstrual_dysphoria_during_GnRH_agonist_induced_hypogonadism_and_ovarian_steroid_replacement_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2011-3451 DB - PRIME DP - Unbound Medicine ER -