Therapeutic Agents That Act by Altering Hormone Control Mechanisms

Question 1

Which are the Therapeutic Agents That Act by Altering Hormone Control Mechanisms?

Answer 1

● Danazol (Danocrine®)

● Clomiphene citrate (Clomid®)

● Tamoxifen (Nolvadex®) Toremifene(Fareston®) Fulvestrant (Faslodex®)

● Aromatase Inhibitors:
Anastrozole (Arimidex®) Letrozole (Femara®) Examestane (Aromasin®)

● GnRH & Analogs:

• Leuprolide
• Nafarelin
• Gosselin
• Histrelin

● GnRH Antagonists:

• Cetrorelix (Cetrolix®)
• Ganirelix
• Degarelix

● Bromocriptine mesylate (Parlodel®)

Question 2

What are the characteristics of Danazol (Danocrine®)?

Answer 2

● Weak progestin and weak androgen (partial agonist)
● MOA = Acts directly on ovary to prevent synthesis of
estrogen & progest. by inhibiting certain CYP450s
● Treatment of fibrocystic breast disease (prevent
synthesis of estrogen)
● Treatment of endometriosis (although this
indication has been widely replaced by the use of
GnRH agonists (continuous mode of administration)
● S.E. = due to androgenic agonist effects: reduction
in breast size, thickening of skin with increased oiliness, hair growth, deepening of voice

Question 3

What are the characteristics of Clomiphene citrate (Clomid®)?

Answer 3

● Adverse effects = hot flashes (due to hypothalamic
block); breast tenderness & heavy menses (due to
too much estrogen later in cycle)
● Caution: Visual symptoms : blurred or double
vision, floaters, light sensitivity, scotoma

Question 4

What are the characteristics of Tamoxifen (Nolvadex®) Toremifene(Fareston®) Fulvestrant (Faslodex®)

Answer 4

● Tamoxifen - a drug of choice for tx of breast cancer
● Think of Tamoxifen as a SERM which is an
antagonist at estrogen receptors in the breast, but a partial agonist at estrogen receptors in the endometrium and bone
● Used for treatment of breast cancers that are estrogen receptor-positive
● Fulvestrant = pure estrogen receptor antagonist;
used in tamoxifen-resistant patients

Question 5

What are the characteristics of Anastrozole (Arimidex®) Letrozole (Femara®) Examestane (Aromasin®)

Answer 5

● Anastrozole and Letrozole = competitive, reversible inhibitors of aromatase (the enzyme that converts testosterone to estradiol)
● Examestane = irreversible aromatase inhibitor
● All 3 used in treating breast cancer in pts resistant
to tamoxifen

Question 6

What are the characteristics of GnRH & Analogs:
Leuprolide 
Nafarelin 
Gosrelin 
Histrelin

Answer 6

● Agonists!! at GnRH receptors
● Intermittent = stimulate FSH / LH release (IV or SC)
o Gonadorelin - used to treat infertility caused by hypothalamic hypogonadism) – program pump to admin.
● Continuous = inhibit FSH / LH release (use long-acting analogs or depot formulations)
o Leuprolide, Gosrelin: treat prostate cancer
▪ In men = increase in serum
testosterone levels for about 1-2 weeks; can precipitate pain in men with bone metastases or prostate “flare-up”
▪ In women = get hot flashes/sweats
o Suppress endogenous FSH/LH release and give exogenous FSH/LH to correct
timing for fertilization

Question 7

What are the characteristics of GnRH Antagonists:
Cetrorelix (Cetrolix®)
Ganirelix
Degarelix

Answer 7

● Pure GnRH receptor antagonist
● MOA: bind to pituitary GnRH receptors to
competitively inhibit FSH / LH release
● Used for In-vitro fertilization (prevents LH surge and
premature ovulation), Endometriosis, Uterine fibroids

Question 8

What are the characteristics of Bromocriptine mesylate (Parlodel®)?

Answer 8

● Selective D-2 agonist (mimic effects of dopamine) → inhibits prolactin release from anterior pituitary
● Used for treatment of hyperprolactemia, Parkinson’s disease
● Caution: increased risk of stroke in post-partum women who do not want to lactate