Gonadal Hormones Flashcards
What are the natural estrogens?
- Estrone (E1)
- Estradiol (E2)
- Estriol (E3)
Synthetic Estrogens MOA
- Ethinyl Estradiol
- Mestranol (pro-drug converted to ethinyl estradiol)
MOA: bind estrogen receptor > homone-receptor complex > cell nucleus > changes in gene expression
Main effects of estrogens
- Development of female secondary sex characteristics
- Endometrial proliferation
- Metabolic effect
- Decrease resorption of bone
- Incrase HDL and decrease LDL
- Increase risk of thromboembolic events
- Increase heaptic production of binding proteins (SHBG)
- Vasculate by increase NO and prostacyclin
- Retain Na+ and H2O
What are the clinical uses of estrogens?
- Postmenopausal Hormonal Thearpy: decrease risk of osteoporosis, reestablish feedback on hypothalmic control, reverse postmenopausal atrophy
- Primary Hypogonadism
- Treatment of Androgen-Dependent Prostate Cancer
- Oral Contraceptives
- Menstraul abnormalities
Selective Estrogen Receptor Modulators (SERMS) MOA, Uses
- Tamoxifen - antagonist breast tissue, agonist non breast tissue (female reproductive tract); prevention/Tx of hormon responsive breast CA
- Raloxifene - antagonist uterus/breast tissue, agonist bone; prevention of homone responsive breast CA and prevention/Tx osteoprosis
- Clomiphene - antagonist hypothalamus; Tx infertility associated with anovulatory cycles
MOA: bind estrongen receptor but can be agonist/antagonist
Selective Estrogen Receptor Degraders/Downregulators (SERDs) MOA, Uses
- Fulvestrant
MOA: bind estrogen receptors and cause to be degrades and thus downregulated in all tissues
Uses: adjuvant Tx of hormone-receptor psoitive metastatic breast CA that is resistant to first line antiestrogen (tamoxifen) therapy
Aromatase Inhibitors MOA, Uses
- Anastrozole (non-steroidal) competitive reversible
- Letrozole (non-steroidal) competitive reversible
- Exemestrane (steroidal) irreversible inhibitor
MOA: inhibit peripheral conversion of andgrogens to estrogen
Uses: adjuvant chemotherapy in estrogen receptor positive breast CA
What is the nautral and synthetic progestins?
Natural
- Progesterone
Synthetic
- Medroxyprogesterone
- Norgestrol
- Norethindrone
- Norgestimate
- Desogestreol
- Drospirenone
Progestins MOA, main effects, uses?
MOA: enter cell and bind progestin receptors > lipid-receptor complex binds progesterone response elements (PRE) > gene expression
ME: Decrease growth and increased vasculature of endometrium; thickening of cervical mucus; associated with increased body temperature, maintenance of pregnancy
Uses: oral contraceptives, endometrial CA, abnomral uterine bleeding, hormone replacement therapy, infertility, diagnostic test of estrogen secretion
Antiprogestins MOA, Uses, AE
- Mifepristone
MOA: competitive inhibitor at progesterone receptor
Uses: used in combination with misoprostol as abortifacient
AE: N/V/D, abdominal/pelvic pain, and uterine bleeding
Androgens MOA, main effects
- Testosterone
- Methyltestosterone
- Danazol
MOA: in skin, prostate, seminal vesicles, and epididymis testosterone is converted to 5alpha-dihydrotestosterone(DHT) by 5alpha-reductase and binds to intracellular androgen receptor
ME: male maturation, sexual function, metabolic
Uses of androgens
Testosterone and Methyltestosterone
- Males with hypogonadism
- Chronic wasting pts with HIV or CA
- Stimulate anabolism to promote recover after burns/injuries
- Increase lean body mass
Danazol (also has anti-estrogen activity)
- Endometriosis
- Fibrocystic breast disease
Anti-Androgens
Androgen Receptor Antagonists
- Flutamide
- Spironolactone
5alpha-reductase Inhibitor
- Finasteride
Steroid Synthesis Inhibitor
- Ketoconazole
Flutamide MOA, uses, AE
MOA: non-steroidal competitive inhibitor at androgen receptors
Uses: prostate CA
AE: mild gynecomastia, hot flashes, reversible hepatotoxicity
Spironolactone MOA, Uses, AE
MOA: mineralcorticoid receptor and androgen receptor antagonist
Uses: reduction of androgenic symptoms due to PCOS (hirsutism), aldosteronism, diuretic
AE: gynecomastia, amenorrhea, hyperkalemia
