CHH is a type of<unk>  resulting from the abnormal migration of GnRH neurons during embryonic development. GnRH neurons are derived from the olfactory placode and migrate into the central nervous system (CNS) during embryonic development. Embryonic migration can be affected by several gene mutations including but not limited to, KAL1, fibroblast growth factor (FGF8), sex determining region Y-Box 10 (SOX10), GNRHR, GNRH1 and KISS1R . Kallmann syndrome results in a loss of smell (anosmia) and is associated with KAL1 mutations. The KAL1 gene encodes anosmin-1, an extracellular adhesion molecule that plays a role in GnRH neuronal migration and adhesion. Mutated KAL1 genes leads to ill GnRH neuronal migration as well as olfactory neuron disorder causing anosmia and non-functional GnRH releasing neurons. Mutations of KAL1 are mostly nucleotide insertion or deletion causing frame shifts in the translation of anosmin-1 resulting in a faulty protein. Inactivating mutations in the genes encoding GNRH1 or its receptor will result in the failure of the HPG axis and give rise to normosmic CHH. Inactivating mutations of KISS1 or KISS1R causes normosmic CHH in humans This is because KISS1 is the mediator for the feedback loop in the HPG axis allowing low levels of sex steroid to stimulate GnRH secretion from the hypothalamus. CHH is a genetically heterogenous disorder with cases reported as being X-linked, recessive and autosomally inherited. The prevalence has been estimated to be 1/4000 to 1/10000 in males and 2 to 5 times less frequent in females. The prevalence difference between male and females is unknown, and is likely to be underreported for females. Acquired<unk>  (AHH) is a postnatal onset of a GnRH releasing disorder and/or pituitary gonadotroph cell disorder. There are many causes of AHH, mostly due to structural or functional abnormalities involving the HPG axis such as sarcoidosis, lymphocytic hypophysitis, pituitary adenomas, craniopharyngiomas and other CNS tumours. Most of these patients have multiple pituitary hormone deficiencies. Hyperprolactinaemia is the most common cause of AHH. It is a well-established cause of infertility in both male and female mammals. Prolactin inhibits GnRH neurons and therefore inhibits the subsequent release of LH, FSH and sex steroids. The mechanism of prolactin induced inhibition of GnRH release is poorly understood. It is suspected that the prolactin receptor is expressed on a small subset of GnRH neurons in mice and thus has a direct inhibitory effect on GnRH release. There is evidence to suggest indirect inhibition of GnRH neurons mediated by other neurotransmitters such as dopamine, opioid, neuropeptide Y and γ-aminobutyric acid. Drug usage of glucocorticoids and opioid analgesics in high dosages can lead to the inhibition of GnRH synthesis. Opioid receptors reside in the hypothalamus and when bound to opioids they decrease the normal pulsatile secretion of GnRH and therefore result in<unk> . Chronic treatment with supraphysiological doses of glucocorticoids results in a marked decrease in testosterone without an increase of LH levels, suggestive of a central mechanism of induced<unk> .
Hypogonadotropic hypogonadism
Hypergonadotropic hypogonadism
Late-onset hypogonadism
Isolated hypogonadotropic hypogonadism
Polyorchidism
Hypergonadotropic hypergonadism
Microorchidism
Dual-role transvestism