FA Reproductive Flashcards
Leuprolide Mechanism
GnRH analog with agonist properties when used in pulsatile fashion; antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary → ↓ FSH/LH).
Leuprolide Use
Infertility (pulsatile), prostate cancer (continuous - use with flutamide), precocious puberty (continuous).
Leuprolide Toxicity
Antiandrogen, nausea, vomiting.
Estrogens
Ethinyl estradiol, DES, mestranol
Estrogen Mechanism
Bind estrogen receptors
Estrogen Use
Hypogonadism or ovarian failure, menstrual abnormalities, HRT in postmenopausal women; use in men with androgen-dependent prostate cancer.
Estrogen Toxicity
↑ 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)
Clomiphene, Tamoxifen, Raloxifene
Clomiphene Mechanism
Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulates ovulation.
Clomiphene Use
Treatment of infertility due to anovulation (e.g., PCOS).
Clomiphene Toxicity
May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances.
Tamoxifen Mechanism
Antagonist on breast tissue; agonist at uterus, bone.
Tamoxifen Use
Primarily used to treat and prevent recurrence of ER + breast cancer.
Tamoxifen Toxicity
Associated with endometrial cancer, thromboembolic events.
Raloxifene Mechanism
Agonist on bone; antagonist at uterus.
Raloxifene Use
↓ resorption of bone → used to treat osteoporosis.
Raloxifene Toxicity
↑ risk of thromboembolic events
Anastrozole, Exemestane Mechanism
Aromatase inhibitors used in postmenopausal women with breast cancer
Anastrozole, Exemestane Use
Used in postmenopausal women with breast cancer
Hormone Replacement Therapy Use
Used for relief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and osteoporosis (↑ estrogen, ↓ osteoclast activity).
Hormone Replacement Therapy TOxicity
Unopposed estrogen replacement therapy (ERT) ↑ the risk of endometrial cancer, so progesterone is added. Possible increased cardiovascular risk.
Progestin Mechanism
Bind progesterone receptors, ↓ growth and ↑ vascularization of endometrium.
Progestin Use
Used in oral contraceptives and in the treatment of endometrial cancer and abnormal uterine bleeding.
Mifepristone (RU-486) Mechanism
Competitive inhibitor of progestins at progesterone receptors.
Mifepristone (RU-486) Use
Termination of pregnancy. Administered with misoprostol (PGE1)
Mifepristone (RU-486) Toxicity
Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.
Oral Contraception
Synthetic progestins, estrogen
Oral Contraception Mechanism
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.
Oral Contraception Toxicity
Contraindications - smokers > 35 years old (↑ risk of cardiovascular events), patients with history of thromboembolism and stroke or history of estrogen-dependent tumor.
Terbutaline Mechanism
β2-agonist that relaxes the uterus
Terbutaline Use
Used to ↓ contraction frequency in women during labor.
Danazol Mechanism
Synthetic androgen that acts as partial agonist at androgen receptors.
Danazol Use
Endometriosis and hereditary angioedema.
Danazol Toxicity
Weight gain, edema, acne, hirsutism, masculinization, ↓ HDL levels, hepatotoxicity.
Testosterone, Methyltestosterone Mechanism
Agonist at androgen receptors.
Testosterone, Methyltestosterone Use
Treats hypogonadism and promotes development of 2° sex characteristics; stimulation of anabolism to promote recovery after burn or injury.
Testosterone, Methyltestosterone Toxicity
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.
Antiandrogens
Finasteride, flutamide, ketoconazole, spironolactone
Finasteride Mechanism
5α-reductase inhibitor (↓ conversion of testosterone to DHT).
Finasteride Use
Useful in BPH. Also promotes hair growth - used to treat male-pattern baldness.
Flutamide Mechanism
A nonsteroidal competitive inhibitor of androgens at the testosterone receptor.
Flutamide Use
Used in prostate carcinoma.
Ketoconazole Mechanism [Antiandrogen]
Inhibits steroid synthesis (inhibits 17,20-desmolase).
Spironolactone Mechanism [Antiandrogen]
Inhibits steroid binding, 17α-hydroxylase, and 17,20-desmolase.
Ketoconazole, Spironolactone Toxicity [Antiandrogen]
Gynecomastia and amenorrhea.
Ketoconazole Use [Antiandrogen]
Treatment of polycystic ovarian syndrome to prevent hirsutism.
Spironolactone Use [Antiandrogen]
Treatment of polycystic ovarian syndrome to prevent hirsutism.
Tamsulosin Mechanism
α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α1A,D receptors (found on prostate) vs. vascular α1B receptors.
Sildenafil, Vardenafil Mechanism
Inhibit phosphodiesterase 5, causing ↑ cGMP, smooth muscle relaxation in the corpus cavernosum, ↑ blood flow, and penile erection.
Sildenafil, Vardenafil Use
Treatment of erectile dysfunction.
Sildenafil, Vardenafil Toxicity
Headache, flushing, dyspepsia, impaired blue-green color vision. Risk of life-threatening hypotension in patients taking nitrates.
