Native apoptotic features of the analogues make them good

Native GnRH is an essential diagnostic tool in
reproductive pathology such as hypogonadism.

During this, there is decreased gonadal steroids as a result of compromised
gonadal function. Primary hypogonadism is caused by damaged gonads, causing circulating
sex steroids to be low. Secondary hypogonadism is an impairment at the
hypothalamic-pituitary level. To distinguish between the two, native GnRH is administered
and circulating LH and FSH levels are measure at regular 15 minute intervals
for an hour.  If circulating
gonadotrophins are high and levels of steroids are low there is a problem with
the gonads, when LH is high there should be androgen presence within
circulation. On the other hand, if circulating FSH and LH were low and sex
steroid are low this could indicate a problem with the pituitary receptors;
however, this can be hard to distinguish with delayed puberty. (Delemarre-van
de Waal, 2004)

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GnRH AGONIST

Agonist are used to treat a
wide range of hormone related pathology. Furthermore, the anti-proliferative
and apoptotic features of the analogues make them good drugs for cancers in the
reproductive tract, such as prostate cancer. Alongside this, they can prevent
activity of growth factors which decreases the synthesis of growth factors and
expression of GnRH receptors. Though it is commonly used in reproductive
cancers due to its action on hormones it can often lead to hormone
insensitivity. (Lopez de Maturana et al., 2008) Commonly used in Precocious
puberty is the agonist Leuprolide
which takes action at the pituitary and effectively shuts down the axis, with
80-100 times the potency of original GnRH. (Chrisp and Sorkin, 1991)

Precocious puberty is the
onset of sexual maturation before the accepted normal low of age, eight years
for girls and nine for boys. These changes take place due to the premature
activation of the HPG axis. (Mul and Hughes, 2008) When untreated can
cause short stature, higher body-mass index (BMI) and physical maturation
before psychological maturation.  Definite
diagnosis will follow once there is evidence of elevated gonadotrophins or
gonadal steroids in circulation. (Berbero?lu, 2009) Suppression of the
active HPG axis is needed to prevent further maturation, therefore GnRH
analogues are used to downregulate and dull receptors. Leuprolide is
administered subcutaneously or intramuscularly which causes a continuous GnRH
stimulation, instead of pulsatile, therefore desensitizing the receptor and
effectively preventing the secretion of FSH and LH. (Mul and Hughes, 2008)
Girls may experience a withdrawal bleed after the first administration of the
drug due to the flare effect of agonists.  (Mul and Hughes, 2008) Once pubertal age is
reached the child may be taken off the treatment and the HPG axis will
recommence at normal. (Berbero?lu, 2009) Typical side effects include hot
flashes, mood swings, allergic reactions, headaches, asthmatic symptoms and
pain at site of injection. (Pubchem.ncbi.nlm.nih.gov, 2018)

            Agonists
have been in use for the treatment of precocious puberty for the past two
decades and have presented good evidence that pubertal maturation continued
sufficiently with the cessation of treatment; however, this data is mainly in
relation to females.  (Mul and Hughes,
2008) Due to their high potency and long half-life, they have the greatest
anti-fertility effects. (Padula, 2005) A study of 26 precocious puberty
patients, 20 females and six males, where females had onset of puberty at age
4.7 and the males at the age of 6.2. Comparing patients treated with a GnRH agonist
and had reached maximal height with patients that had not undergone treatment.

Looking at results, the median height of female patients that underwent
treatment after the age of five was greater by 4.9cm than those that did not
undergo treatment. Whereas female patients that underwent treatment before the
age of five had 6.5cm more that those that took treatment after the age of
five. In male patients, the difference in height was greater, the disparity in
mean height between treated and untreated was 10.7cm. (Paul et al., 1995) A
secondary study, consisting of 58 females and eight males treated with a slow
releasing GnRH agonist Triptorelin
and compared to an older study of untreated patients, it presented that with
treatment there was a greater 4.8cm difference in height for females and an
8.3cm difference in males. (Carel et al., 1999) This may indicate that stopping
the onset of puberty before as early as possible will yield the best response. One
can interpret that the long-term treatment of precocious puberty patients at a
younger age leads to better height outcomes for both genders. Males have a
greater height restoration than females, however it can be argued that males
reach a greater height than females and therefore will have a higher mean
height. It can be concluded from the ratio of participants that females are
more prone to precious puberty than their male counterpart. Though the study
proves that the agonist allows children to attain their adult height, BMI
changes directly affect the quality of health of an individual. Alternative
studies done show that agonists have no effect on the BMI of the girls (Yang et
al., 2017) This can be seen as controversial due to the fact that it does not completely
treat the individual but instead suppresses it till appropriate.

 

GnRH ANTAGONIST

The use of GnRH
analogues is common in hormone dependent cancers. The prostate gland of males
located under the bladder and in front of the rectum, is the most common place
for cancer amongst men. (Attard et al., 2015) This can cause pain when
urinating, blood in urine and pelvic pain. Known risks are to be age, race and
family history. Prostate growth, maintenance and activity requires the presence
of androgens. Unlike other reproductive organs the prostate continues to grow
with the help of androgens,