Hypothalamic amenorrhea: clinical perspectives, pathophysiology, and management

The development of functional hypothalamic amenorrhea reflects an individual's response to environmental stressors and life-style variables. In this disorder there are no detectable anatomic abnormalities with respect to the hypothalamic-pituitary-ovarian-endometrial axis. Current evidence suggests that the common underlying defect is a decrease in the activity of the hypothalamic gonadotropin-releasing hormone pulse generator. Of the neuroendocrine factors that appear to regulate gonadotropin-releasing hormone activity, the opiate and dopamine neuronal systems have been implicated as factors that are responsible in part for the decreased secretion of gonadotropin-releasing hormone. Because of the functional nature of this disorder, reactivation of the hypothalamic-pituitary unit would be expected to take place in most women after accommodation to environmental stressors or modification in life-style. For women with persistent anovulation, treatment with estrogen-replacement therapy should be offered. In those desiring fertility, ovulation induction with pulsatile gonadotropin-releasing hormone would be the most effective modality.