Gonadal Drugs

Question 1

Does gonadorelin inhibit FSH if it is administered IV every 4 hour and why or why not?

Answer 1

Gonadorelin is an agonist of the GnRH receptor and is used to induce the secretion of the gonadotropins follicle-stimulating hormone and luteinizing hormone from the pituitary gland and to increase sex hormone production by the gonads. It is given as a pulsatile treatment for infertility.

Question 2

Does gonadorelin inhibit FSH if it is administered by continuous infusion?

Answer 2

Yes because desensitization occurs.

Question 3

Does leuprolide (GnRH agonist) inhibit FSH release?

Answer 3

Only if given continuously due to desensitization. Otherwise, when given in pulsatile form, induces secretion of LH and FSH.

Question 4

What is the function of aromatase?

Answer 4

An enzyme involved in the production of estrogen that acts by catalyzing the conversion of testosterone (an androgen) to estradiol (an estrogen). Aromatase is located in estrogen-producing cells in the adrenal glands, ovaries, placenta, testicles, adipose (fat) tissue, and brain.

Question 5

Why does estrogen increase risk of breast and endometrial cancer?

Answer 5

bc estrogen stimulates breast and endometrial proliferation in these cancers

Question 6

What are the bone-preserving mechanisms of estrogen?

Answer 6

decreases bone resorption by increasing apoptosis and decreasing RANKL in octeoclasts, decreases bone remodeling by apoptosis of osteocytes, and maintains bone formation by decreasing apoptosis, oxidative stress, and NF-kb activity in osteoblasts

Question 7

Why do OCPs and hormone replacement therapy (menopause) increase thromboembolism risk?

Answer 7

bc they induce an increase in clotting factors, Decrease Antithrombin, Decrease plasminogen activator, and increase platelet aggregation

Question 8

What is the most deadly complication of diethylstilbestrol?

Answer 8

DES used by pregnant woman can cause clear cell adenocarcinoma of vagina and cervix in her female offspring.

Question 9

What are the side effects of estrogen?

Answer 9

Hepatic adenoma, Thromboembolism, stroke
Breast cancer (prolonged use), Endometrial cancer (progestin added to reduce this risk)

Question 10

What are the contraindications of estrogen?

Answer 10

Breast cancer, Endometrial cancer, Pregnancy, Liver disease, History of thromboembolic disorders, and Heavy smokers (highlighted red)

Question 11

What are the differences between tamoxifen, raloxifene, and fulvestrant?

Answer 11

Tamoxifen and raloxifene are SERMs. Tamoxifen is an estrogen partial agonist in uterus, bone, liver, and pituitary and antagonsit in the blood vessels and breast. Used in treating ER+ breast cancer and with Trastumuab in HER 2 Neu+ breast cancer. Raloxifene is an estrogen partial agonist in bone and CVS and antagonist in endometrium and breast. It has a distinct DNA target, raloxifene response element, and is used in treating osteoporosis in post menopausal women. Fulvestrant is a Selective estrogen receptor down regulator (SERDs) and inhibits ER dimerization causing ER alpha and beta receptors to degrade. Used in metastatic breast cancer unresponsive to tamoxifen.

Question 12

Clomiphene chief use is for infertility due to failure of ovulation (max no.of cycles is six ). It is also tried in male infertility due to oligospermia.
What is the mechanism of clomiphene in infertility treatment?

Answer 12

GnRH agonist that induces Gn secretion – only in intact hypothalamic-pituitary axis. Increases LH/FSH levels with each secretory pulse. Follicular maturation enhanced

Question 13

What are the side effects and increased risk of clomiphene?

Answer 13

Ovarian hyperstimulation syndrome (OHSS), Multifetal gestations, Hot flushes, Headaches & blurred vision. Increased risk of ovarian /endometrial cancer (≥12cycles)

Question 14

What is the mechanism of anastrozole and letrozole?

Answer 14

Reversible inhibition of aromatization causing near total estrogen deprivation

Question 15

What is the mechanism of Exemestane?

Answer 15

irreversible aromatase inhibitor causing near total estrogen deprivation

Question 16

What are the mechanisms of danazol?

Answer 16

Partial agonist at progesterone, androgen and glucocorticoid receptors. Inhibits LH and FSH surge.
Direct inhibition of gonadal function + inhibit steroidogenic enzymes ⇛ Endometrial atrophy ⇛ amenorrhoea (inhibits all steroid enzymes including 21B hydroxylase)

Question 17

Why is an androgen abuser infertile and what can be done to prevent it?

Answer 17

Exogenous androgen inhibits FSH and LH.
Leydig cells synthesize less androgen.
Sertoli cells then reduce synthesis of androgen binding protein causing less secretion into the lumen, where normally a high local level of androgen is maintained.
Seminiferous tubules degenerate and there is no sperm. This is prevented by transdermal androgen patches applied to scrotum

Question 18

Why can α blockers (tamsulosin, prazosin) be used for prostate hypertrophy? *****

Answer 18

Relaxes bladder muscles / urethra during the dynamic component of BPH (urine flow) to increase urine outpit (tamsulosin usually used for BPH while prazosin tends to be used in high BP)

Question 19

What is the MOA of mifepristone?

Answer 19

Partial agonist & competitive antagonist at progesterone receptor. Attenuates midcycle Gn surge from pituitary causing Delay in follicular development and Delay/failure of ovulation. Blocks progesterone support to endometrium. Induces menstruation.

Question 20

When is Diethylstilbestrol used?

Answer 20

DES is only used in prostate cancer and “morning after” contraceptive.