••• Chapter 56^ GnRH and GnRH Analogs^561
❍ What is the effect of high progesterone levels on the release of GnRH?
Progesterone inhibits GnRH pulses at the level of the hypothalamus, and also antagonizes pituitary response to
GnRH by interfering with estrogen action.
❍ What is the effect of low progesterone on GnRH pulsatile release?
Low progesterone enhances the LH response to GnRH at the pituitary level, and allows the FSH midcycle surge.
❍ What are the two phases of GnRH therapy?
Agonist phase.
Antagonist phase.
❍ What are the three primary positive actions of GnRH on gonadotropins?
Synthesis and storage.
Self-priming so that gonadotropins are ready for direct secretion.
Immediate release.
❍ What are the FDA-approved indications of GnRH agonist therapy?
Endometriosis.
Anemia (preoperatively with iron therapy for uterine leiomyomas).
Central precocious puberty.
❍ What are the non-FDA-labeled indications of GnRH agonist therapy?
Hirsutism.
Induction of amenorrhea in special clinical situations (eg, in thrombocytopenic patients and prior to bone marrow
transplant).
Breast cancer.
Ovarian cancer.
IVF.
Premenstrual dysphoric disorder.
Leiomyoma.
❍ What is the FDA-approved medication given with GnRH agonists as “add-back” therapy?
Norethindrone 5 mg daily.
❍ What other medications have been given clinically as “add-back”?
Low-dose estrogen with low-dose progestin.
❍ What benefit does low-dose estrogen treatment have compared with higher dose estrogen when treating
endometriosis in pelvic pain patients with add-back therapy?
Less pelvic pain and higher continuation rate of treatment.
❍ When can add-back therapy begin in relationship to GnRH analogues?
At the same time.