see also pharmacology main index; endometriosis; anti-androgens

• PBS Nafarelin product information (pdf)

• GnRH agonists stimulate release of pituitary gonadotrophins LH and FSH, with consequent initial increase of ovarian and testicular steroidogenesis.
• continuous dosing rather than physiologic pulsatile dosing gradually abolishes the stimulatory effect on the pituitary gland.
• Within three to four weeks, daily administration leads to decreased pituitary gonadotrophin secretion and/or the secretion of gonadotrophins with lowered biological activity with consequent suppression of gonadal steroidogenesis and inhibition of functions and tissues that depend on gonadal steroids for their maintenance.
• ongoing Rx results in a menopause-like state in women and androgen deficiency states in males
• use in males:
  • often used for Rx of metastatic prostate Ca

• the main indication is laparoscopically proven endometriosis in patients with ongoing symptoms and who do not wish to get pregnant.
  • usual dose: 6 month course of nafarelin 400micrograms inhaled daily induced amenorrhoea in approximately 65%, 80% and 90% of patients after 60, 90 and 120 days, respectively.

• controlled down regulation of ovaries prior to in-vitro fertilisation (IVF)
• The purpose of down regulation is to provide a more controlled stimulation for subsequent stimulation and thereby minimise the occurrence of spontaneous ovulation and premature luteinisation.
• 75% of women on nafarelin 400microgram inhaled bd achieve down regulation by 38 days of Rx

• examples of GnRH agonists used:
  • goserelin depo injection every 3 months
  • nafarelin
  • buserelin
  • leuprolide acetate 1mg s/c daily

• undiagnosed abnormal PV bleeding
• pregnancy or those who may become pregnant
• lactation
• known hypersensitivity to GnRH agonists

• These include women with chronic anovulation/ menstrual disturbances due to weight loss, athletic or other forms of hypothalamic amenorrhoea, immobilisation, glucocorticoid usage or a strong family history of osteoporosis.
• prior Rx with GnRH
• these patients should have bone mineral density testing prior to Rx

• patients with rhinitis may need to use a nasal vasoconstrictor 30min prior to dosing to ensure absorption.

• Diagnostic tests of pituitary-gonadal function conducted during the treatment and 4 to 8 weeks after discontinuation of nafarelin therapy may therefore be misleading.

• potential for clinical flare-up of endometriotic symptoms and lesions within the first few weeks of treatment due to the transient rise in oestradiol secretion.
• Transient cyst formation that may accompany GnRH agonist use is more common when GnRH agonists are commenced in the follicular phase of the cycle (flare effect).
• oestrogen-sensitive migraine, epilepsy.
• ovarian hyperstimulation but not usually true ovarian hyperstimulation syndrome:
  • exaggerated follicular response to gonadotrophin stimulation and is triggered by the luteinising agent (ie. hCG administration or a spontaneous LH surge)
  • this causes hypovolaemia, oliguria, ascites, pleural effusions, haemoconcentration, electrolytic disturbances and hepatic dysfunction.

• Functional ovarian cysts have been reported to occur in the first two months of therapy.
• Many, but not all, of these events occurred in patients with polycystic ovarian disease.
• These cystic enlargements may resolve spontaneously, generally within four to six weeks of therapy, but in some cases discontinuation of drug and/ or surgical intervention may be required.

• hot flushes
• change in libido
• vaginal dryness
• headaches
• emotional lability
• acne
• myalgia
• decreased breast size

• after 6 months Rx with nafarelin:
  • vertebral trabecular bone density and total vertebral bone mass, measured by quantitative computed tomography (QCT), decreased by an average of 8.7% and 4.3%, respectively, compared to pretreatment levels.
  • There was partial recovery of bone density in the post-treatment period; the average trabecular bone density and total bone mass were 4.9% and 3.3% less than the pretreatment levels, respectively.

• hypersensitivity reactions (0.2%)
• pulmonary fibrosis
• interstitial pneumonitis