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Disorders of gonadotropin secretion 

Disorders of gonadotropin secretion
Disorders of gonadotropin secretion

Sarah L. Berga

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date: 23 May 2022

Folliculogenesis and ovulation depend upon adequate gonadotropin stimulation, which in turn requires appropriate gonadotropinreleasing hormone (GnRH) input. There exists a group of related disorders in which GnRH drive to the pituitary is reduced, resulting in secondary diminution of follicle-stimulating hormone (FSH) and luteinizing hormone input to the ovary. Clinically, reduced GnRH drive results in a spectrum of ovarian compromise, ranging from luteal insufficiency to chronic anovulation. Variable menstrual patterns follow, including amenorrhoea, polymenorrhoea, with or without menorrhagia, and oligomenorrhoea, depending on the extent of follicular activity across time. Rarely, there is an organic or congenital cause for reduced GnRH drive, such as a brain tumour, coeliac disease, or migration of an insufficient number of GnRH neurons from the olfactory placode into the hypothalamus during fetal development. Typically, the cause is functional, that is, due to the endocrine consequences of certain psychological or behavioural variables. Anorexia nervosa provides the most dramatic example, but most women who develop functional hypothalamic anovulation do not meet criteria for an eating disorder and do not develop one subsequently. Because of the occult and heterogeneous nature of the behavioural variables that contribute to the genesis of this related group of disorders, a variety of names have been used to describe this syndrome, including exercise amenorrhoea, stress-related or stress-induced anovulation, functional hypothalamic amenorrhoea, functional hypothalamic chronic anovulation, and psychogenic amenorrhoea. Occasionally, psychiatric syndromes other than eating disorders such as depression coexist with functional hypothalamic anovulation, but unlike anorexia nervosa, in which amenorrhoea is almost universal, amenorrhoea is less common in women with bulimia and depression. Despite the multiplicity of names, the pathogenesis of anovulation in these diverse clinical settings is similar. In recognition of their common nature, I have chosen herein to refer to this group of disorders as ‘functional hypothalamic anovulation’ or FHA. As noted above, not all women have reduced gonadotropin secretion to the extent that they become amenorrhoeic or even persistently anovulatory, but most investigations have focused on subjects with the most complete expression of these related disorders, namely, those who are amenorrhoeic due to chronic anovulation. Generally, functional hypothalamic anovulation is considered to be a form of secondary amenorrhoea, but it can present as primary amenorrhoea. The diagnosis of functional hypothalamic anovulation is one of exclusion.

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