Reproductive

Question 1

Leuprolide (mechanism, use [5])?

Answer 1

Mechanism:

• GnRH analog
• Agonist when used pulsatile
• Antagonist when used continuously (down regulates GnRH receptors in pituitary → ↓ FSH/LH

Use:

• Uterine fibroids
• Endometriosis
• Precocious puberty
• Prostate cancer
• Infertility (agonist)

Question 2

Estrogens agonists (names, mechanism, use [3])?

Answer 2

Names: Ethinyl estradiol, DES, Mestranol
Mechanism: Agonist at estrogen receptors
Use:
- Hypogonadism or Ovarian failure
- Hormone replacement therapy in postmenopausal women
- Men with androgen-dependent prostate cancer

Question 3

Ethinyl estradiol, DES, Mestranol (adverse effects [4], contraindications [2])?

Answer 3

AEs:

• Increased risk of endometrial cancer
• Bleeding in postmenopausal women
• Clear cell adenocarcinoma of vagina in females exposed to DES in utero
• Prothrombotic

Contraindications:

• ER + breast cancer
• History of DVTs

Question 4

Selective Estrogen Receptor Modulators (SERMs)?

Answer 4

Clomiphene, Tamoxifen, Raloxifene

Question 5

Clomiphene (mechanism, use, adverse effects [4])

Answer 5

Mechanism:
Estrogen receptor antagonist at hypothalamus → Prevents normal feedback inhibition → ↑ LH and FSH release → Stimulates ovulation

Use:
Infertility due to anovulation (PCOS)

AEs:

• Hot flashes
• Ovarian enlargement
• Multiple simultaneous pregnancies
• Visual disturbances

Question 6

Tamoxifen (mechanism, use, adverse effects)

Answer 6

Mechanism:
Estrogen receptor antagonist at breast; agonist at bone and uterus

Use:
Prevents recurrence of and treats ER/PR + breast cancer

AEs:
↑ risk of thromboembolic events and endometrial cancer

Question 7

Raloxifene (mechanism, use, adverse effects)

Answer 7

Mechanism:
Estrogen receptor antagonist at breast and uterus; agonist at bone

Use:
Treats osteoporosis

AEs:
↑ risk of thromboembolic events but no increased risk of endometrial cancer (vs. tamoxifen)

Question 8

Aromatase inhibitors (names)

Answer 8

Anastrozole, letrozole, exemastane

Question 9

Anastrozole, letrozole, exemastane (mechanism and use)?

Answer 9

Mechanism: Inhibit peripheral conversion of androgens to estrogen
Use: ER + breast cancer in postmenopausal women

Question 10

Hormone replacement therapy (all)?

Answer 10

• Relief/prevention of menopausal symptoms (hot flashes, vaginal atrophy)
• Osteoporosis (since ↑ estrogen causes ↓ osteoclast activity)

Note: Unopposed estrogen replacement therapy ↑ risk of endometrial cancer so progesterone added.

Question 11

Anastrozole (class)?

Answer 11

Aromatase inhibitor

Question 12

Letrozole (class)?

Answer 12

Aromatase inhibitor

Question 13

Exemastane (class)?

Answer 13

Aromatase inhibitor

Question 14

Levonorgestrel (class)?

Answer 14

Progestin

* -gest-

Question 15

Medroxyprogesterone (class)?

Answer 15

Progestin

* -gest-

Question 16

Etonogestrel (class)?

Answer 16

Progestin

* -gest-

Question 17

Norethindrone (class)?

Answer 17

Progestin

* Nor ethinyl!!!

Question 18

Megestrol (class)?

Answer 18

Progestin

* -gest-

Question 19

Progestins (mechanism, use [3])?

Answer 19

Mechanism:
Bind progesterone receptors → ↓ growth and ↑ vascularization of endometrium + thickens cervical mucus

Use:

• Contraception (pill, IUD, etc.)
• Endometrial cancer
• Abnormal uterine bleeding

Question 20

Progestin challenge?

Answer 20

Give to patient with amenorrhea to determine cause.

Remember, estrogen causes growth of endometrium. It is the giving and removing of progesterone that induces menses.

Suppose you are suspicious of Asherman syndrome. Give progesterone and remove.
- If withdrawal bleeding occurs, you know they don’t have that because they grew a thickened endometrium.

Suppose you are suspicious of anovulation due to low levels of estrogen. Without estrogen, there will be no growth of endometrium.
- If withdrawal bleeding occurs here, you know they have sufficient estrogen on board because they grew a thickened endometrium.

Question 21

Mifepristone (class, mechanism, use)

Answer 21

Class: Antiprogestin (*prissy)
Mechanism: Competitive inhibitor of corpus luteum progestins at progesterone receptor
Use: Termination of pregnancy (mifepristone + misoprostol to ensure detached blastocyst is expelled)

Question 22

Ulipristal (class, mechanism, use)

Answer 22

Class: Antiprogestin (*prissy)
Mechanism: Competitive inhibitor of corpus luteum progestins at progesterone receptor
Use: Emergency contraception

Question 23

Combined contraception (contents, mechanisms [3], contraindications [4])

Answer 23

Contents: Progestins + Ethinyl estradiol (pill, patch, ring)
Mechanism:
- Estrogen and Progestin inhibit LH + FSH and thus prevent estrogen release → no LH surge → no ovulation
- Progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus
- Progestins inhibit endometrial proliferation so endometrium is less suitable for implantation of embryo

Contraindications:

• Smokers > 35 yo (↑ risk of cardiovascular events)
• Patients with ↑ risk of cardiovascular disease
  * History of thromboembolism
  * CAD
  * Stroke
• Migraine
• Breast cancer

Question 24

Copper IUD (mechanism, use [2], adverse effects [3])?

Answer 24

Mechanism:
Produces local inflammation toxic to sperm and ova, preventing fertilization and implantation; hormone free

Use:

• Long-acting reversible contraception
• Most effective emergency contraception

AEs:

• Heavier menses
• Dysmenorrhea
• Risk of PID with insertion

Question 25

Terbutaline (mechanism, use)

Answer 25

Mechanism: Beta-2 agonists that relax the uterus Use: ↓ contraction frequency in women during (premature) labor

Question 26

Ritodrine (mechanism, use)

Answer 26

Mechanism: Beta-2 agonists that relax the uterus Use: ↓ contraction frequency in women during (premature) labor

Question 27

Danazol (mechanism, use [2], adverse effects [7])

Answer 27

Mechanism: Androgen that acts as a partial agonist at androgen receptors Use: Endometriosis and Hereditary angioedema AEs: - Weight gain - Edema - Acne - Hirsutism - Masculinization - ↓ HDL - Hepatotoxicity

Question 28

Testosterone, Methyltestosterone (mechanism, use [2], adverse effects [4])?

Answer 28

Mechanism: Agonist at androgen receptors Use: - Treat hypogonadism to promote development of secondary sex characteristics - Stimulate anabolism to promote recovery from burn or injury AEs: - Masculinization in females - Inhibits release of LH → gonadal atrophy in males + ↓ intratesticular testosterone - Premature closure of epiphyseal plates - ↑ LDL, ↓ HDL

Question 29

Finasteride (class, mechanism, use [2])?

Answer 29

Class: Antiandrogen Mechanism: Inhibits 5α-reductase → ↓ conversion of testosterone to DHT Use: BPH and Male pattern baldness *Old men must have too much DHT on board because they get both of these!

Question 30

Flutamide (class, mechanism, use)?

Answer 30

Class: Antiandrogen Mechanism: Nonsteroidal competitive inhibitor at androgen receptor Use: Prostate carcinoma

Question 31

Ketoconazole (class, mechanism, use, adverse effects [2])?

Answer 31

Class: Antiandrogen Mechanism: Inhibits steroid synthesis by inhibiting 17,20-desmolase Use: Reduces androgenic symptoms in PCOS AEs: Gynecomastia (males); Amenorrhea (females)

Question 32

Spironolactone (class, mechanism [3], use, adverse effects [2])?

Answer 32

``` Class: Antiandrogen Mechanism: - Inhibits steroid binding - Inhibits 17α-hydroxylase - Inhibits 17,20-desmolase Use: Reduces androgenic symptoms in PCOS AEs: Gynecomastia (males); Amenorrhea (females) ```

Question 33

Tamsulosin (mechanism, use)?

Answer 33

Mechanism: Selectively antagonizes α1-A,D receptors on prostate and NOT α1-B receptors on vasculature Use: BPH by inhibiting smooth muscle constriction (of the prostate around the urethra)

Question 34

Sildenafil, Vardenafil, Tadalafil (class, mechanism)? | *Read the whole answer!!!

Answer 34

Class: PDE-5 inhibitors Mechanism: Inhibit PDE-5 breakdown of cGMP → ↑ cGMP → prolonged smooth muscle relaxation via NO → ↑ blood flow to corpus cavernosum of penis + ↓ pulmonary vascular resistance

Question 35

Sildenafil, Vardenafil, Tadalafil (use [3], adverse effects [5])?

Answer 35

``` Use: - Erectile dysfunction - Pulmonary hypertension - BPH (Tadalafil ONLY) AEs: - Headache - Flushing - Dyspepsia - Cyanopia (blue-tinted vision) *Viagra is the little blue pill patients always ask about* - Life-threatening hypotension in patients taking nitrates!!! ``` *Hot and sweaty, but then Headache, Heartburn, and Hypotension

Question 36

Minoxidil (mechanism, use [2])?

Answer 36

Mechanism: Direct arteriolar vasodilator Use: - Androgenetic alopecia - Severe, refractory hypertension