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.
Highlights
Secondary amenorrhea is a common condition that is characterized by the lack of a menstrual cycle for at least 3 months and can be related to several clinical situations [1,2,3,4,5]
The restoration of a normal response to the gonadotropin-releasing hormone (GnRH) stimulating test [16,17]. These findings suggest that the administration of a weak estrogen, like estriol, modulates the neuroendocrine control of the hypothalamus–pituitary unit since it permits a spontaneous increase in GnRH-induced LH synthesis and release in hypogonadotropic patients with Functional Hypothalamic Amenorrhea (FHA)
The GnRH bolus induced an LH response that had a greater amplitude after the treatment interval (Figure 2)
Summary
Secondary amenorrhea is a common condition that is characterized by the lack of a menstrual cycle for at least 3 months and can be related to several clinical situations [1,2,3,4,5]. FHA is quite a complex clinical situation, since it is characterized by a constellation of neuroendocrine impairments [1,2,3,4,6,7,8] that all lead to the failure of reproductive ability due to the presence of reduced or very low LH plasma levels, and almost no changes of FSH, with abnormal pulsatile release [10,11]. 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. 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)
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