FA Reproductive

Question 1

Leuprolide Mechanism

Answer 1

GnRH analog with agonist properties when used in pulsatile fashion; antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary → ↓ FSH/LH).

Question 2

Leuprolide Use

Answer 2

Infertility (pulsatile), prostate cancer (continuous - use with flutamide), precocious puberty (continuous).

Question 3

Leuprolide Toxicity

Answer 3

Antiandrogen, nausea, vomiting.

Question 4

Estrogens

Answer 4

Ethinyl estradiol, DES, mestranol

Question 5

Estrogen Mechanism

Answer 5

Bind estrogen receptors

Question 6

Estrogen Use

Answer 6

Hypogonadism or ovarian failure, menstrual abnormalities, HRT in postmenopausal women; use in men with androgen-dependent prostate cancer.

Question 7

Estrogen Toxicity

Answer 7

↑ risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, ↑ risk of thrombi. Contraindications - ER + breast cancer, history of DVTs.

Question 8

Selective estrogen receptor modulators (SERMs)

Answer 8

Clomiphene, Tamoxifen, Raloxifene

Question 9

Clomiphene Mechanism

Answer 9

Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulates ovulation.

Question 10

Clomiphene Use

Answer 10

Treatment of infertility due to anovulation (e.g., PCOS).

Question 11

Clomiphene Toxicity

Answer 11

May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances.

Question 12

Tamoxifen Mechanism

Answer 12

Antagonist on breast tissue; agonist at uterus, bone.

Question 13

Tamoxifen Use

Answer 13

Primarily used to treat and prevent recurrence of ER + breast cancer.

Question 14

Tamoxifen Toxicity

Answer 14

Associated with endometrial cancer, thromboembolic events.

Question 15

Raloxifene Mechanism

Answer 15

Agonist on bone; antagonist at uterus.

Question 16

Raloxifene Use

Answer 16

↓ resorption of bone → used to treat osteoporosis.

Question 17

Raloxifene Toxicity

Answer 17

↑ risk of thromboembolic events

Question 18

Anastrozole, Exemestane Mechanism

Answer 18

Aromatase inhibitors used in postmenopausal women with breast cancer

Question 19

Anastrozole, Exemestane Use

Answer 19

Used in postmenopausal women with breast cancer

Question 20

Hormone Replacement Therapy Use

Answer 20

Used for relief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and osteoporosis (↑ estrogen, ↓ osteoclast activity).

Question 21

Hormone Replacement Therapy TOxicity

Answer 21

Unopposed estrogen replacement therapy (ERT) ↑ the risk of endometrial cancer, so progesterone is added. Possible increased cardiovascular risk.

Question 22

Progestin Mechanism

Answer 22

Bind progesterone receptors, ↓ growth and ↑ vascularization of endometrium.

Question 23

Progestin Use

Answer 23

Used in oral contraceptives and in the treatment of endometrial cancer and abnormal uterine bleeding.

Question 24

Mifepristone (RU-486) Mechanism

Answer 24

Competitive inhibitor of progestins at progesterone receptors.

Question 25

Mifepristone (RU-486) Use

Answer 25

Termination of pregnancy. Administered with misoprostol (PGE1)

Question 26

Mifepristone (RU-486) Toxicity

Answer 26

Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.

Question 27

Oral Contraception

Answer 27

Synthetic progestins, estrogen

Question 28

Oral Contraception Mechanism

Answer 28

Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge → no LH surge → no ovulation. Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus. Progestins also inhibit endometrial proliferation, thus making endometrium less suitable for the implantation of an embryo.

Question 29

Oral Contraception Toxicity

Answer 29

Contraindications - smokers > 35 years old (↑ risk of cardiovascular events), patients with history of thromboembolism and stroke or history of estrogen-dependent tumor.

Question 30

Terbutaline Mechanism

Answer 30

β2-agonist that relaxes the uterus

Question 31

Terbutaline Use

Answer 31

Used to ↓ contraction frequency in women during labor.

Question 32

Danazol Mechanism

Answer 32

Synthetic androgen that acts as partial agonist at androgen receptors.

Question 33

Danazol Use

Answer 33

Endometriosis and hereditary angioedema.

Question 34

Danazol Toxicity

Answer 34

Weight gain, edema, acne, hirsutism, masculinization, ↓ HDL levels, hepatotoxicity.

Question 35

Testosterone, Methyltestosterone Mechanism

Answer 35

Agonist at androgen receptors.

Question 36

Testosterone, Methyltestosterone Use

Answer 36

Treats hypogonadism and promotes development of 2° sex characteristics; stimulation of anabolism to promote recovery after burn or injury.

Question 37

Testosterone, Methyltestosterone Toxicity

Answer 37

Causes masculinization in females; ↓ intratesticular testosterone in males by inhibiting release of LH (via negative feedback) → gonadal atrophy. Premature closure of epiphyseal plates. ↑ LDL, ↓ HDL.

Question 38

Antiandrogens

Answer 38

Finasteride, flutamide, ketoconazole, spironolactone

Question 39

Finasteride Mechanism

Answer 39

5α-reductase inhibitor (↓ conversion of testosterone to DHT).

Question 40

Finasteride Use

Answer 40

Useful in BPH. Also promotes hair growth - used to treat male-pattern baldness.

Question 41

Flutamide Mechanism

Answer 41

A nonsteroidal competitive inhibitor of androgens at the testosterone receptor.

Question 42

Flutamide Use

Answer 42

Used in prostate carcinoma.

Question 43

Ketoconazole Mechanism [Antiandrogen]

Answer 43

Inhibits steroid synthesis (inhibits 17,20-desmolase).

Question 44

Spironolactone Mechanism [Antiandrogen]

Answer 44

Inhibits steroid binding, 17α-hydroxylase, and 17,20-desmolase.

Question 45

Ketoconazole, Spironolactone Toxicity [Antiandrogen]

Answer 45

Gynecomastia and amenorrhea.

Question 46

Ketoconazole Use [Antiandrogen]

Answer 46

Treatment of polycystic ovarian syndrome to prevent hirsutism.

Question 47

Spironolactone Use [Antiandrogen]

Answer 47

Treatment of polycystic ovarian syndrome to prevent hirsutism.

Question 48

Tamsulosin Mechanism

Answer 48

α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α1A,D receptors (found on prostate) vs. vascular α1B receptors.

Question 49

Sildenafil, Vardenafil Mechanism

Answer 49

Inhibit phosphodiesterase 5, causing ↑ cGMP, smooth muscle relaxation in the corpus cavernosum, ↑ blood flow, and penile erection.

Question 50

Sildenafil, Vardenafil Use

Answer 50

Treatment of erectile dysfunction.

Question 51

Sildenafil, Vardenafil Toxicity

Answer 51

Headache, flushing, dyspepsia, impaired blue-green color vision. Risk of life-threatening hypotension in patients taking nitrates.