Native GnRH is an essential diagnostic tool inreproductive pathology such as hypogonadism.
During this, there is decreased gonadal steroids as a result of compromisedgonadal function. Primary hypogonadism is caused by damaged gonads, causing circulatingsex steroids to be low. Secondary hypogonadism is an impairment at thehypothalamic-pituitary level. To distinguish between the two, native GnRH is administeredand circulating LH and FSH levels are measure at regular 15 minute intervalsfor an hour. If circulatinggonadotrophins are high and levels of steroids are low there is a problem withthe gonads, when LH is high there should be androgen presence withincirculation.
On the other hand, if circulating FSH and LH were low and sexsteroid are low this could indicate a problem with the pituitary receptors;however, this can be hard to distinguish with delayed puberty. (Delemarre-vande Waal, 2004) GnRH AGONIST Agonist are used to treat awide range of hormone related pathology. Furthermore, the anti-proliferativeand apoptotic features of the analogues make them good drugs for cancers in thereproductive tract, such as prostate cancer. Alongside this, they can preventactivity of growth factors which decreases the synthesis of growth factors andexpression of GnRH receptors. Though it is commonly used in reproductivecancers due to its action on hormones it can often lead to hormoneinsensitivity. (Lopez de Maturana et al., 2008) Commonly used in Precociouspuberty is the agonist Leuprolidewhich takes action at the pituitary and effectively shuts down the axis, with80-100 times the potency of original GnRH. (Chrisp and Sorkin, 1991)Precocious puberty is theonset of sexual maturation before the accepted normal low of age, eight yearsfor girls and nine for boys.
These changes take place due to the prematureactivation of the HPG axis. (Mul and Hughes, 2008) When untreated cancause short stature, higher body-mass index (BMI) and physical maturationbefore psychological maturation. Definitediagnosis will follow once there is evidence of elevated gonadotrophins orgonadal steroids in circulation. (Berbero?lu, 2009) Suppression of theactive HPG axis is needed to prevent further maturation, therefore GnRHanalogues are used to downregulate and dull receptors. Leuprolide isadministered subcutaneously or intramuscularly which causes a continuous GnRHstimulation, instead of pulsatile, therefore desensitizing the receptor andeffectively preventing the secretion of FSH and LH. (Mul and Hughes, 2008)Girls may experience a withdrawal bleed after the first administration of thedrug due to the flare effect of agonists.
(Mul and Hughes, 2008) Once pubertal age isreached the child may be taken off the treatment and the HPG axis willrecommence at normal. (Berbero?lu, 2009) Typical side effects include hotflashes, mood swings, allergic reactions, headaches, asthmatic symptoms andpain at site of injection. (Pubchem.ncbi.nlm.nih.
gov, 2018) Agonistshave been in use for the treatment of precocious puberty for the past twodecades and have presented good evidence that pubertal maturation continuedsufficiently with the cessation of treatment; however, this data is mainly inrelation to females. (Mul and Hughes,2008) Due to their high potency and long half-life, they have the greatestanti-fertility effects. (Padula, 2005) A study of 26 precocious pubertypatients, 20 females and six males, where females had onset of puberty at age4.7 and the males at the age of 6.2. Comparing patients treated with a GnRH agonistand had reached maximal height with patients that had not undergone treatment.
Looking at results, the median height of female patients that underwenttreatment after the age of five was greater by 4.9cm than those that did notundergo treatment. Whereas female patients that underwent treatment before theage of five had 6.5cm more that those that took treatment after the age offive. In male patients, the difference in height was greater, the disparity inmean height between treated and untreated was 10.7cm.
(Paul et al., 1995) Asecondary study, consisting of 58 females and eight males treated with a slowreleasing GnRH agonist Triptorelinand compared to an older study of untreated patients, it presented that withtreatment there was a greater 4.8cm difference in height for females and an8.3cm difference in males. (Carel et al., 1999) This may indicate that stoppingthe onset of puberty before as early as possible will yield the best response. Onecan interpret that the long-term treatment of precocious puberty patients at ayounger age leads to better height outcomes for both genders.
Males have agreater height restoration than females, however it can be argued that malesreach a greater height than females and therefore will have a higher meanheight. It can be concluded from the ratio of participants that females aremore prone to precious puberty than their male counterpart. Though the studyproves that the agonist allows children to attain their adult height, BMIchanges directly affect the quality of health of an individual.
Alternativestudies done show that agonists have no effect on the BMI of the girls (Yang etal., 2017) This can be seen as controversial due to the fact that it does not completelytreat the individual but instead suppresses it till appropriate. GnRH ANTAGONIST The use of GnRHanalogues is common in hormone dependent cancers. The prostate gland of maleslocated under the bladder and in front of the rectum, is the most common placefor cancer amongst men.
(Attard et al., 2015) This can cause pain whenurinating, blood in urine and pelvic pain. Known risks are to be age, race andfamily history. Prostate growth, maintenance and activity requires the presenceof androgens. Unlike other reproductive organs the prostate continues to growwith the help of androgens,