Pharmacology of Gonadal Hormones 1

Question 1

Describe the process of regulation for androgen secretion in males.

Answer 1

See image.

Question 2

Describe the structure, secretion pattern, and mechanism of action for GnRH in males.

Answer 2

• Structure - decapeptide
• Secretion
  
  • from hypothalamic nucleus
  • pulsatile
  • 1 pulse/120 min in male
• Mechanism and actions
  
  • GnRH acts through G protein coupled membrane receptors on gonadotropes
  • causes secretion of FSH and LH

Question 3

What causes GnRH receptor desensitization?

Answer 3

• Continuous GnRH secretion
• Receptors are also desensitized by long-acting “superagonists” that are resistant to degradation

Question 4

List the common GnRH analogs.

Answer 4

• Gonadorelin
• Leuprolide
• Cetrorelix

Question 5

Describe the mechanism and pharmacokinetics of gonadorelin.

Answer 5

• Function
  
  • synthetic GnRH
• Pharmacokinetics
  
  • sc or iv administration
  • well absorbed, short half-life
  • administered by pump in a pulsatile manner for sustained stimulatory effect

Question 6

What are the uses of gonadorelin?

Answer 6

• diagnostic
  
  • distinguish whether pituitary unresponsiveness is due to hypothalamic or pituitary failure
  • LH is measured after injection
  • positive response indicates deficiency is hypothalamic, but a long term GnRH deficiency can impair responsiveness
• replacement
  
  • treatment of hypothalamic hypogonadotropic hypogonadism
  • administered by pump

Question 7

What is leuprolide and what are its pharmacokinetics?

Answer 7

• GnRH superagonist
  
  • desensitizes GnRH receptors at the pituitary
  • leads to decreased gonadotropins and androgen
• Pharmacokinetics
  
  • adminstered sc or im
  • depot forms for monthly or longer intervals
  • intranasal agents create a lower bioavailability

Question 8

What are the uses of leuprolide?

Answer 8

• Precocious puberty
  
  • suppress gonadotropins and arrest premature exual maturation
• Metastatic prostate cancer
  
  • same uses and effects as true antagonists such as cetrorelix/ganirelix

Question 9

What is cetrorelix and what are its pharmacokinetics?

Answer 9

• True GnRH receptor antagonists
  
  • ganirelix is another drug in this category
  • decreases gonadotropins, decreasing androgen
• Pharmacokinetics
  
  • administered sc or im once daily
  • good bioavailability

Question 10

What are the uses of cetrorelix?

Answer 10

• Metastatic prostate cancer
  
  • used interchangeably with leuprolide
  • lowers PSA, reduces effects of skeletal metastases and ureteral obstruction
    
    • prolongs survival
  • duration of response is generally 14-20 months

Question 11

What are the adverse effects of GnRH superagonists and antagoinsts?

Answer 11

• Erectile dysfunction
• Antagonists can lead to hypersensitivity reactions
• Superagonists have elicited a syndrome of:
  
  • headache
  • neurologic symptoms
  • pituitary dysfunction
  • thought to be a result of infarction of a pituitary adenoma
• Superagonists produce an initial “flare”
  
  • results in bone pain and urethral obstruction
  • may require anti-androgen treatment

Question 12

Describe the process of female gonadal hromone secretion.

Answer 12

See image.

Question 13

Describe the secretion pattern of GnRH in females.

Answer 13

• Rate is more rapid than the male
  
  • one pulse per 60-90 min
• Rate is slower in luteal phase than in the follicular phase of the cycle

Question 14

What are the uses of Gonadorelin and leuprolide in females?

Answer 14

• Gonadorelin
  
  • used to induce ovulation in the treatment of infertility
• Leuprolide
  
  • suppression of endometriosis and uterine fibroids
  • palliation of breast carcinoma

Question 15

What are side effects of GnRH superagonists specific to the female?

Answer 15

• Vaginal dryness
• Vaginal atrophy
• Bone loss (male and female)