Functional Hypothalamic Amenorrhea as Stress Induced Defensive System

Since the activity of the reproductive axis is quite complex and modulated and/or affected by several neurotransmitters, neuromodulators and hormones, it is easy to understand that minimal changes of the equilibrium of few of these substances might induce changes of the reproductive axis leading to the amenorrheic condition. Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It might be considered strange, but such negative hypothalamic response to stress is nothing else than a defensive system. In primate females and in human females in particular, an adaptive mechanism during stress is represented by the reduction of reproductive axis activity, blocking a function that is not essential to survive. Some intermediate steps, such as poly- or oligo-menorrhea can anticipate the occurrence of the amenorrheic condition, which is the last and worst stage of this clinical adaptive response to stress.