Administration of Very Low Doses of Estradiol Modulates the LH Response to a GnRH Bolus and the LH and Cortisol Responses to Naloxone Infusion in Patients with Functional Hypothalamic Amenorrhea (FHA): A Pilot Study

Abstract

Background: Functional Hypothalamic Amenorrhea (FHA) is a stress-induced blockade of the reproductive axis. Such impairment is mainly due to altered control of GnRH-induced gonadotropin secretion as well as alterations of other endocrine functions. Methods: Seventeen patients with FHA participated in the study. Basal hormonal profiles and GnRH and Naloxone tests for LH (Luteinizing Hormone) and for LH and cortisol responses, respectively, were performed before and after two weeks of administration of a very low dose of estradiol (2.5 ng two times a day). Results: The treatment improved both gonadotropins, mainly LH. The LH response to the GnRH test improved in terms of the peak amplitude, as evaluated using Instantaneous Secretory Rates (ISR) computation. Moreover, when performing the Naloxone test after the treatment interval, FHA patients showed a quicker LH response and recovery of the cortisol response. Conclusions: Our study supports the relevance of very low dose estradiol priming to promote and restore impaired neuroendocrine function in patients with FHA.