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Flashcards in Gonadal Hormones Deck (46)
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1

Ethinyl Estradiol
Mestranol (pro-drug converted to ^)

Synthetic Estrogens

2

Main effects of estrogen 

  • Female Maturation
    • 2° sex characteristics
  • Endometrial proliferation
  • Metabolic
  • Protein Synthesis
    • Increase in hepatic production of binding proteins eg. SHBG
  • Vasculature
    • Increase production of NO and prostacyclin
  • Fluid Balance: Na+ and H20 retention
  • Other Effects
    • Reproductive Function
    • Sexual Behavior
    • GI Tract

3

describe Estrogen use in Postmenopausal Hormonal Therapy

  • Decreases risk of osteoporosis (does not treat osteoporosis)
  • Reestablishes feedback on hypothalamic control of NE secretion, leading to decreased frequency of hot flashes
  • Reverses postmenopausal atrophy of the vulva, vagina, urethra, and trigone of the bladder

4

describe other clinical uses' of estrogen 

  • Primary hypogonadism
    • Progestin added after first uterine bleeding
  • Treatment of androgen-dependent prostate cancer
  • OCPs
  • Menstrual abnormalities

5

List minor AEs of estrogen

  • Uterine bleeding
  • Nausea
  • Breast tenderness
  • Melasma
  • Peripheral edema

6

List moderate/severe AEs of estrogen

  • ↑ risk of endometrial cancer
    • offset by combining estrogen with progestin
  • ↑ migraine frequency 
  • Cholestasis and gallbladder disease
  • HTN
  • Thromboembolism
  • Depression

7

estrogen contraindications

Cytochrome inducers → reduction in efficacy

8

Selective Estrogen Receptor Modulators

Tamoxifen Raloxifene Clomiphene

9

Tamoxifen MOA

Antagonist @ breast

Agonist everywhere else (endometrium, liver, bone)

10

Raloxifene MOA

Antagonist @ uterus & breast

Agonist in bone (inhibits resorption)

11

Clomiphene MOA

Antagonist @ hypothalamus - prevents feedback inhibition, increasing estrogen

12

Tamoxifen clinical use

hormone-responsive breast cancer

13

Raloxifene clinical use 

 

Prevention of hormone-responsive breast cancer

Prevention and treatment of osteoporosis in postmenopausal women (agonist @bone) 

14

Clomiphene clinical use 

Treatment of infertility associated with anovulatory cycles (eg. PCOS)

15

Compare tamoxifen and raloxifene AEs

Endometrial hyperplasia (increased risk of cancer) with tamoxifen, no risk with raloxifene 

  • Hot flashes and nausea
  • Thromboembolism
  • Raloxifene: leg cramps 

16

Clomiphene AEs 

  • Hot flashes, nausea, vomiting, weight gain, breast tenderness
  • Ovarian hyperstimulation
  • Multiple simultaneous pregnancies (10%)
  • Visual disturbances

17

SERD

Fulvestrant

18

Fulvestrant MOA

bind to estrogen receptors → degrades receptor and downregulation

19

Fulvestrant clinical use 

Adjuvant treatment of hormone-receptor + metastatic breast cancer resistant to first-line tamoxifen therapy

20

Fulvestrant AEs

  • Hot flashes
  • Arthralgias
  • Myalgias

21

Aromatase Inhibitors 

Anastrozole, Letrozole (non-steroidal, reversible)

Exemestrane (steroidal, irreversible)

22

AI clinical use 

adjuvant chemotherapy in ER+ breast cancer

23

AI AEs

  • Hot flashes
  • Nausea
  • Fatigue
  • Alopecia
  • Dermatitis

24

Synthetic Progestins

  • Medroxyprogesterone
  • Norgestrol
  • Norethindrone
  • Norgestimate
  • Desogestreol
  • Drospirenone

25

Progestins MOA

enter cell & bind progesterone receptors → lipid-receptor complex binds to a progesterone response element (PRE) and activates gene expression

26

Main effects of Progestins 

  • prevents endometrial hyperplasia by decreasing growth and increasing vascularization of endometrium
  • Thickening of cervical mucus - inhibits movement of sperm
  • ↑ body temperature
  • Maintenance of pregnancy

27

Progestin clinical use 

  • OCPs, HRT
  • endometrial cancer
  • abnormal uterine bleeding
  • infertility
  • dx test of estrogen secretion

28

Progestin AEs

  • Uterine bleeding
  • Weight gain, Insulin resistance
  • Depression, headache
  • Changes in libido
  • Thromboembolic events (rare)
  • Decrease HDL levels (androgenic progestins)

29

Antiprogestin 

Mifepristone - competitive inhibitor at progesterone receptor and cortisol antagonist 

 

30

Mifepristone clinical use and AEs

  • Used in combination with misoprostol as abortifacient
  • AE: vomiting, diarrhea, abdominal/pelvic pain, uterine bleeding