223 - Reproductive Pharmacology

Question 1

How do GnRH agonists result in lower estrogen levels?

Answer 1

GnRH agonists given continuously will suppress LH and FSH release, resulting in lower estrogen

Normally, when GnRH stimulates the HPG axis it is secreted in a pulsatile manner

Question 2

In the presentation of prolactinoma, why are men more likely than women to present with visual field abnormalities?

Answer 2

Men are more likely to present when the prolactinoma is large

Women will usually have symptoms (ex: abnormal menses, infertility) before the tumor grows large enough to have a mass effect

Question 3

List 2 agents that can be used for post-menopausal hormone replacement therapy

Answer 3

• Raloxifen (a SERM)
• Premarin
  
  • But this is an estrogen-only; make sure to give progesterone periodically too

Question 4

What is the treatment for prolactinoma?

Answer 4

Dopamine agonist

• Bromocriptine
• Cabergolin

Cabergoline is generally well tolerated, but not well studied in women trying to conceive

Question 5

Describe the gonadotropin therapy regimen used to retrieve oocytes in IVF

Answer 5

1. Give injectable FSH
   This rescuse ALL of the follicles that are developing, rather than just the one that usually becomes dominant
2. Give GnRH agonist (continuously) or antagonist
   But why? Don’t we want hormones so that the follicle can mature?
   Yes, but we need to inhibit the LH surge - this would cause the eggs to pop off. A continuous GnRH agonist or a GnRH antagonist will inhibit the LH surge, allowing all of the follicles to mature in the ovary
3. Eventually, give HCG to stimulate final matruation of the many follicles
   HCG has the same effect as LH, but LH is not commercially available - this causes the final maturation of the follicles, which can be collected

Question 6

What is the goal of pharmacologic fertility treatment of PCOS?

Which types of medications can accomplish this goal?

(Which part of the pathway are we trying to augment or inhibit?)

Answer 6

Goal: increase FSH stimulation to the ovary

• SERMs
  
  • Tamoxifen
  • Clomiphene
• Aromatase inhibitors
  
  • Letrozole
• Insulin sensitizers
  
  • Metformin

Question 7

Why is testosterone sometimes referred to as a pro-hormone?

Answer 7

Must be converted to something else to have an effect

• Estrogen (via aromatase)
• DHT (via 5-alpha reductase)

Thank you @Vineeth Thirunavu!

Question 8

What medications can be used to treat PCOS if the patient does NOT want to become pregnant?

What are some reasons to treat PCOS if the pt does not want to become pregnant?

Answer 8

Hormonal birth control

• Meroxyprogesterone acetate (aka depo-provera)
  
  • Progesterone only injection; organizes lining, induces menstruation
• Combination oral birth control

Reasons to treat

• Prevent unopposed estorgen stimulation of the endometrium
  
  • This can lead to endometrial cancer!
• Reduce acne and hirsutism
  
  • Giving hormones -> suppress GnRH -> inhibits LH/FSH, which gets rid of the abnormal ratio contributing to PCOS

Question 9

List 4 indications for 5-alpha reductase inhibitors

Answer 9

• Prostate cancer
• BPH
• Male-pattern baldness
• Hirsuitism

5-alpha reductase turns testosterone into the more potent DHEA

Inhibiting 5-alpha reductase -> decreased androgen effects