••• Chapter 56^ GnRH and GnRH Analogs^565
❍ What are the disadvantages of using GnRH antagonists?
Cost, lack of potency, and undesirable effects due to histamine release.
❍ GnRH analogs currently in the use have half- lives ranging (in hours).
1.5 to 6 hours.
❍ After binding GnRH, the GnRH receptor peptide complexes do what?
They migrate toward each other, then internalize, then are degraded and recycled to the cell surface.
❍ GnRH acts on its cell surface receptor on the gonadotrope to increase the release of LH and FSH by which
mechanisms?
Mobilization of calcium from internal sources.
Calcium influx to intracellular sites from the extracellular space.
Calmodulin binding within the cell.
❍ GnRH acts on its cell surface receptor on the gonadotrope to increase the synthesis of LH and FSH by
which mechanism?
Activation of protein kinases to achieve cytosolic protein phosphorylation.
❍ Can hirsutism be treated with GnRH on a long-term basis?
Yes. If add-back therapy is used.
❍ Are there differences in the isoforms of LH produced by the pituitary during GnRH treatment?
Yes. There is a large decrease in biologically active LH compared with total immunoreactive LH and thus the ratio
of bioactive to total LH is greatly reduced.
❍ What is one of the rare risks of GnRH therapy for submucous myoma?
There is a small risk (2%) that heavy vaginal bleeding will occur usually 5 to 10 weeks later, due to hemorrhage
from degenerating submucous myomata.
❍ What effect does treatment with GnRH have on menstrual bleeding?
At least 70% of women will achieve amenorrhea; however, some women will have light intermittent bleeding or
frequent spotting.
❍ What is the major disadvantage of starting GnRH treatment in the follicular phase of the cycle?
There is a greater tendency for a “flare effect” and a longer delay prior to downregulation.
❍ What is the major disadvantage of starting GnRH treatment in the late luteal phase of the cycle?
The patient may have an early pregnancy and GnRH is contraindicated in pregnancy.