This Article Full Text Full Text (PDF) All Versions of this Article: 91/4/1561    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brundu, B. Articles by Berga, S. L. Search for Related Content PubMed PubMed Citation Articles by Brundu, B. Articles by Berga, S. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROCORTISONE Related Collections Adrenal and Hypertension Female Endocrinology Neuroendocrinology and Pituitary

Increased Cortisol in the Cerebrospinal Fluid of Women with Functional Hypothalamic Amenorrhea

Department of Gynecology and Obstetrics, Emory University School of Medicine (T.L.L., S.L.B.), Atlanta, Georgia 30322; Department of Anesthesiology (L.J.A.) and Departments of Psychiatry, Cell Biology, and Physiology (J.L.C.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260; Division of Reproductive Sciences, Oregon National Primate Research Center (J.L.C.), Beaverton, Oregon 97006; and Department of Gynecology and Obstetrics IRCCS San Matteo (B.B.), University of Pavia, 65-27100 Pavia, Italy

Address all correspondence and requests for reprints to: Sarah L. Berga, M.D., Department of Gynecology and Obstetrics, Emory University School of Medicine, 1639 Pierce Drive, 4208-WMB, Atlanta, Georgia 30322. E-mail: sberga{at}emory.edu.

Context: The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated.

Objective: We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW).

Design: The study is a cross-sectional comparison.

Setting: The study was set in a general clinical research center at an academic medical center.

Participants: Fifteen women with FHA who were of normal body weight and 14 EW participated.

Intervention: Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF.

Main Outcome Measures: Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures.

Results: CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound.

Conclusions: The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

This article has been cited by other articles:

				S. L. Berga Stress and Reprodution: A Tale of False Dichotomy? Endocrinology, March 1, 2008; 149(3): 867 - 868. [Full Text] [PDF]

				N. R Vulliemoz, E. Xiao, L. Xia-Zhang, J. Rivier, and M. Ferin Astressin B, a Nonselective Corticotropin-Releasing Hormone Receptor Antagonist, Prevents the Inhibitory Effect of Ghrelin on Luteinizing Hormone Pulse Frequency in the Ovariectomized Rhesus Monkey Endocrinology, March 1, 2008; 149(3): 869 - 874. [Abstract] [Full Text] [PDF]