1. Clinical uses of gonadotropins and GnRH agonists and antagonists Ashwath V.
GnRH or Gonadotropin releasing hormone is the main regulator of the synthesis and
release of gonadotropins. This hormone is part of the hypothalamic-pituitary-gonadal axis and
the release of GnRH is controlled by the levels of gonadotropins and sex hormones such as
estrogen through a negative feedback system. GnRH is produced in the hypothalamus. However,
it is very important to note that the release of GnRH is pulsatile, this pulsation of GnRH
stimulates the production of FSH and LH in the anterior pituitary gland. The functions of LH and
FSH will be discussed later. Agonists and antagonists of GnRH can be used in the clinical
environment to treat certain diseases.
GnRH agonists have therapeutic and diagnostic value in the clinical environment. Using
GnRH depots (quick acting) can be of great value to help in making a diagnostic differential
between GnRH-dependent and GnRH-independent precocious puberty. This is determined by
monitoring the plasma LH concentration before and two hours after the subcutaneous injection
of GnRH. GnRH agonists such as Leuprolide can be administered in a pulsatile manner to help
treat infertility as this increases the gonadotropin levels. A continuous administration of GnRH,
however, will induce suppression of gonadotropins. This response can be taken advantage of in
the case of certain hormone responsive cancers such as prostate or breast cancer. Additionally,
certain steroid-responsive conditions such as endometriosis, priapism and precocious puberty can
be suppressed via GnRH agonists. In ovarian stimulation for in vitro fertilization, GnRH agonists
can be administered to prevent LH surges and resultantly ovulation.
GnRH antagonists have much more limited function as compared to agonists. An
example of a GnRH antagonist is Ganirelix. Its only clinical use at the moment is in ovarian
stimulation for in vitro fertilization. As many follicles have to mature in a single cycle, early LH
surges, which cause ovulation, must be prevented and this is where GnRH antagonists carry out
their function.
Gonadotropins themselves also have clinical function. The gonadotropins are made up of
luteinizing hormone (LH), follicle stimulating hormone (FSH) and human chorionic
gonadotropin (hCG). Both LH and FSH are essential in males and females for stimulating germ
cell growth and maturation, and these hormones are essential for reproduction. Human chorionic

2. gonadotropin is different as it is released from the placenta, therefore it is only secreted in
pregnant women. Furthermore, hCG can also be found in the urine. Therefore, pregnancy tests
work by detecting hCG in urine (positive if hCG is found in the urine). Recombinant FSH
(follitropin alpha) is commonly used in fertility clinics in ovarian stimulation, in order to develop
multiple follicles in one cycle and it is used in in vitro fertilization as well. Likewise,
recombinant LH is used for follicle maturation, however, it is not used for ovulation induction as
hCG has similar activity and longer half-life. HCG administration in males causes a testosterone
level increase, therefore Leydig cell function can be estimated. This is in case of males that are
suspected to have primary hypogonadism. A lowered testosterone level after hCG administration
points to Leydig cell failure, whereas a normal testosterone level points to a hypothalamic or
pituitary disorder.
The therapeutic uses of gonadotropins are very important in the clinical environment. As
mentioned before, hCG administration in males leads to stimulation of testosterone and FSH and
LH causes germ cell growth and maturation. Therefore, these hormones can be used to treat
infertility in males, this is assuming that the situation is not primary but secondary
hypogonadism. Another common use for gonadotropins is in case of Cryptochoridism. Therapy
includes administration of hCG to stimulate the descent of the testes to its correct anatomical
location. Gonadotropins and GnRH agonists and antagonists are invaluable tools of
pharmacology and medicine that can be used to treat various conditions, their importance is
greatly appreciated.
Sources
Parker, Keith L., and Bernard P. Schimmer. "Introduction To Endocrinology: The
Hypothalamic-Pituitary Axis." Goodman & Gilman's: The Pharmacological Basis of
Therapeutics, 12e. Eds. Laurence L. Brunton, et al. New York, NY: McGraw-Hill, 2011.
AccessMedicine. Web.
Pharmacology of sex hormones, reproduction seminar.