Reproductive Flashcards
What is the mechanism of Leuprolide?
GnRH analog with agonist properties when used in pulsatile fashion; antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary → ↓ FSH/LH).
What is the clinical use of Leuprolide?
Infertility (pulsatile), prostate cancer (continuous—use with flutamide), uterine fibroids (continuous), precocious puberty (continuous)
What are the toxicities of Leuprolide?
Antiandrogen, nausea, vomiting
What is the mechanism of Estrogens (ethinyl estradiol, DES, mestranol)?
Bind estrogen receptors
What is the clincal use of Estrogens (ethinyl estradiol, DES, mestranol)?
Hypogonadism or ovarian failure, menstrual abnormalities, HRT in postmenopausal women; use in men with androgen-dependent prostate cancer
What are the toxicities of Estrogens (ethinyl estradiol, DES, mestranol)?
↑ 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
Selective estrogen receptor modulators (SERMs) - What are the key features of Clomiphene?
Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulates ovulation. Used to treat infertility due to anovulation (e.g., PCOS). May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances.
Selective estrogen receptor modulators (SERMs) - What are the key features of Tamoxifen?
Antagonist on breast tissue; agonist at uterus, bone; associated with endometrial cancer, thromboembolic events. Primarily used to treat and prevent recurrence of ER + breast cancer.
Selective estrogen receptor modulators (SERMs) - What are the key features of Raloxifene?
Agonist on bone; antagonist at uterus; also ↑ risk of thromboembolic events; ↓ resorption of bone → used to treat osteoporosis.
What are the key features of Hormone Replacement Therapy?
Used for relief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and osteoporosis (↑ estrogen, ↓ osteoclast activity).
Unopposed estrogen replacement therapy (ERT) ↑ the risk of endometrial cancer, so progesterone is added. Possible increased cardiovascular risk.
What are the key features of Anastrozole/exemestane?
Aromatase inhibitors used in postmenopausal women with breast cancer
What is the mechanism of Progestins?
Bind progesterone receptors, ↓ growth and ↑ vascularization of endometrium
What is the clinical use of Progestins?
Used in oral contraceptives and in the treatment of endometrial cancer and abnormal uterine bleeding
What is the mechanism of Mifepristone (RU-486)?
Competitive inhibitor of progestins at progesterone receptors.
What is the clinical use of Mifepristone (RU-486)?
Termination of pregnancy. Administered with misoprostol (PGE1).
What are the toxicities of Mifepristone (RU-486)?
Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.
How to the oral contraceptives, synthetic progestins and estrogen) work?
Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge → no LH surge → no ovulation.
Oral contraception - What are the unique features of progestin as an oral contraceptive?
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.
What are the contraindications of oral contraceptives (synthetic progestins, estrogen)?
Smokers > 35 years old (↑ risk of cardiovascular events), patients with history of thromboembolism and stroke or history of estrogen-dependent tumor
What are the key features of Terbutaline?
β2-agonist that relaxes the uterus; used to ↓ contraction frequency in women during labor.