Neuroendocrine and metabolic aspects of functional hypothalamic amenorrhea

Functional disorders of the hypothalamus are the most common reason for amenorrhea. Psychogenic stress, undernutrition and excessive exercise are frequently associated with functional hypothalamic amenorrhea (FHA). It is a nonorganic endocrine disorder characterized by the impairment of gonadotropin-releasing hormone (GnRH) pulsatile secretion. The incidence of FHA ranges from 15% to 55% of the secondary amenorrheas. This condition is determined by the spectrum of GnRH–luteinizing hormone (LH) disturbances. Patients with the diagnosis of FHA are characterised by low mean frequency of LH pulses, complete absence of LH pulsatility, normal-appearing secretion pattern or higher mean frequency of LH pulses. Many neuropeptides play an essential role in the physiological regulation of GnRH pulsatile secretion and some of them such as corticotropin-releasing hormone (CRH) and kisspeptin may be involved in the pathophysiology of FHA. FHA can be also viewed as important metabolic problem. Hypoestrogenism associated with FHA can be correlated with negative impact on skeletal and cardiovascular system. Patients with FHA are characterized by limited peak bone mass formation and increased risk of osteopenia and osteoporosis. Further studies on the short-term and long-term, cardiovascular and skeletal system consequences of hypoestrogenemia in women with hypothalamic amenorrhea are recommended.