Gonadotropins

Question 1

Gonadorelin

Answer 1

1. GnRH agonist
2. Short acting agonist (pulsed IV to stim FSH and LH prodcution and release). Not available in US.
3. Tx for infertility
   - inducing ovulation in women
   - Dx for hypogonadotropic hypogonadism
   - tx delayed puberty
   - stim spermatogenis in men w/hypogonadotropic hypogonadism.
4. SC inject/pump
5. CI: less likely to cause ovarian hyperstimulation and multiple births than direct administration of LH and FSH.

Question 2

Leuprolide, goserelin, nafarelin

Answer 2

1. Long acting GnRH agonists, used to inhibit HPG axis activity. SC or IM weekly depot injections, Nafarelin is nasal spray.
2. Continuous administration of these long acting GnRH agonists causes an initial surge and then an ultimate inhibition of gonadotropin release.
3. Tx to stop endogenous LH surge when stimulating with exogenous gonadotropins for ART (infertility)
   - Tx in prostate cancer to reduce adrogen production.
   - In women to tx endometriosis and polycystic ovarian disease and uterine leiomyomas.
   - Tx precocious puberty. To provide chemical castration.
4. SE:
   - menopausal symptoms in women with long acting GnRH analongs,
   - ovarian cysts.
   - Testicular atrophy,
   - decreased bone density,
   - hot flashes/sweats/amenorrhea
   - Men w/metastatic prostate tumors, initial rise in testosterone may cuase bone pain and neuralgia so anti-androgen is often administered simultaneously.
   - HA/N, light headedness, swelling at injection site.
5. CI: pregnancy and breast feeding.

Question 3

Cetrorelix, ganirelix

Answer 3

1. GnRH antagonists
2. Cetrorelix is competitive GnRh receptor antagonist. Suppresses LH at lower doses and FSH at higher doses.
3. Suppress endogenous LH and FSH for assisted reproductive technologies (ART). Only 4-5 days of drug therapy are required, compared to 3 weeks for leuprolide.
   - Tx endometriosis and uterine fibroids.
4. SC injection by pt, well tolerated.

Question 4

Human menopausal gonadotropins (hMG) or Menotropins

Answer 4

Contains both FSH and Lh but used as an FSH drug, isolated from urine of post-menopausal women.

Question 5

uFSH

Answer 5

Purified preparation, with only FSH

Question 6

Follitropin alfa and Follitropin Beta

Answer 6

Recombinant human FSH

• more batch to batch consistency no urinary contaminants -
• more expensive
• controversial if more successful in IVF than uFSH or hMG.

Question 7

human Chorionic Gonadotropin (hCG)

Answer 7

1. Typical LH agonist used, extracted from urine of pregnant women.
2. Similar structure to LH and binds to LH receptor
3. Longer half-life than LH, rhCG give SC while hCH is given IM

Question 8

Choriogonadotropin alfa

Answer 8

Recombinant protein

Question 9

Lutropin

Answer 9

Recombinant LH, only approved for use in combination with follitropin alfa.

Question 10

Gonadotropin pharmacology

Answer 10

1. Indications:
   - Pituitary/hypothalamic hypogonadism (HH) w/infertility
   - distinguish btw hypogonadotropic hypogonadism and constitutional delay of puberty.
   - Induce spermatogenesis in HH men.
   - Inc testosterone in men for reasons other than fertility.
   - Infertility in women w/functional ovaries that have not responded to other tx. FSH and LH generally used in sequence.
2. SE:
   - uncomplicated ovarian enlargement
   - may cause ovarian hyperstimulation syndrome
   - risk of multiple births,
   - gynecomastia,
   - HA, depression, edema, precocious puberty.
3. CI: sex steroid-dependent neoplasia, precocious puberty.