Fisiopatología de la disfunción gonadal en la Amenorrea Hipotalámica funcional (AHF) y su relación con la activación del eje hipotálamo-hipófiso-adrenal

functional hypothalamic amenorrhea (fha) is a secondary process to an adaptive response in women with inadequate diets and modified body composition. this process triggers hormonal reactions in the hypothalamus for preservation of metabolic homeostasis. it involves a "central circuit" made up of a network of hypothalamic hormones interrelated with a "peripheral circuit" made up of leptin and adiponectin, among other adipocytokines, and ghrelin, synthesized in the upper gastrointestinal tract. fat mass reduction in these undernourished women and the resulting decrease in leptin leads to neuropeptide y (npy) synthesis in the hypothalamus. this peptide, through direct or indirect action mediated by crh stimulation, and the activation of the opioid and dopaminergic system block the receptors of the gnrh-synthesizing neurons in the arcuate nucleus to inhibit, and thus disturb, the gonadotropin pulsatile activity. the increase in ghrelin also blocks this activity through a complex mechanism: npy synthesis is stimulated and npy, in turn, inhibits gaba interneurons, thus altering the suppressant action normally exerted by this neurotransmitter on the crh. the increase in serotonin levels activates the limbic-hypothalamic-pituitary-adrenal system, probably indirectly, mediated by desensitization of glucocorticoid receptors of crh immunoreactive neurons, thus inducing secretion. crh concentrations in cerebrospinal fluid, as well as 24-h mean plasma cortisol concentrations are high, and their half-life is prolonged. additionally, there is a decrease in cbg associated with elevated free urinary cortisol levels. basal serum cortisol levels are not suppressed by the administration of dexamethasone and the acth response to crh stimulation is blunted. these findings suggest an alteration of cortisol negative feedback effects on crh-acth secretion. the mechanisms of this resistance to cortisol are not fully elucidated. animal studies suggest that prolonged stress modifies the densit