Hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism | |
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Other names | Secondary hypogonadism |
Hypogonadotropic hypogonadism (HH), is due to problems with either the
Types
There are two subtypes of HH, congenital HH (CHH) and acquired HH (AHH).
Pathogenesis
CHH is a type of HH resulting from the abnormal migration of GnRH neurons during embryonic development. GnRH neurons are derived from the
CHH is a genetically heterogenous disorder with cases reported as being X-linked, recessive and autosomally inherited.[5] 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.[5]
Acquired hypogonadotropic hypogonadism (AHH) is a postnatal onset of a GnRH releasing disorder and/or pituitary gonadotroph cell disorder.[3] There are many causes of AHH, mostly due to structural or functional abnormalities involving the HPG axis such as
Diagnosis
The clinical presentation of HH depend on the time of onset as well as the severity of the defect.[5] Diagnostic tests to measure GnRH levels are difficult. This is because GnRH is confined within hypophyseal portal system and has a short half-life of 2–4 minutes.[4] GnRH levels are thus checked indirectly via LH and FSH levels which will be totally or partially absent in HH. Exogenous GnRH can be used as a diagnostic tool. If the patient has hypothalamic GnRH deficiency, LH and FSH will gradually appear in response to the exogenous GnRH but in pituitary cases of HH, a minimal response will be generated.[8] Typically, CHH is diagnosed in adolescence due to a lack of pubertal development, but it can be possible to diagnose in male neonates. Clinical presentations of CHH involve an absence of puberty by 18 years of age, poorly developed secondary sexual characteristics, or infertility.[5]
In men with CHH, serum levels of inhibin B are typically very low as inhibin B is a marker of Sertoli cell number.[3] For females, CHH is most commonly revealed by
Management
The goal for HH therapy is to induce pubertal development, sexual function, fertility, bone health, and psychological wellbeing.[3] Testosterone therapy for males and estradiol therapy for females is used to improve genital development, develop secondary sexual characteristics, allow for the growth and closure of the epiphyseal plate, as well as improving sexual function.[5] This therapy does not restore fertility as gonadotropins are required for spermatogenesis and folliculogenesis. If fertility is desired, pulsatile GnRH therapy or gonadotropin therapy is necessary.[5]
Gonadotropin therapy involves the use of human chorionic gonadotropin (hCG) and FSH. In the male, hCG stimulates Leydig cells to produce testosterone so that plasma and testicular levels increase. With the increased levels of testosterone, sexual activity, libido and overall wellbeing should improve.[1] Administration of FSH is required to induce spermatogenesis by acting on Sertoli cells. FSH is required for maintaining the production of high numbers of good quality sperm. Gonadotropin therapy in HH men usually is able to generate enough sperm for fertility to occur, however sperm count is still lower than normal.[1]
In the female, the goal for gonadotropin therapy is to obtain ovulation. This is obtained with FSH treatment followed by hCG or LH to trigger ovulation. FSH will stimulate granulosa cells for follicular maturation while LH will act on luteal cells to produce steroids aiding follicular maturation and preparing the endometrium for pregnancy.[citation needed]
For
In up to 10–20% of cases, patients can exhibit sustained fertility and steroid production after therapy, resulting in hypogonadotropic hypogonadism reversal. The mechanism for this reversal is unknown but there is believed to be some
See also
- Androgens and estrogens
- GnRH and gonadotropins (FSH and LH)
- Hypergonadotropic hypogonadism
- Hypothalamic–pituitary–gonadal axis
- Isolated hypogonadotropic hypogonadism