What is Leuprolide (and Histerelin, Geserelin)?
A GnRH analog with agonist properties when used in pulsatile fashion and antagonist properties when used in continuous fashion via negative feedback on the production of FSH and LH
What are the clinical use of estrogens such as ethinyl estradiol, 17B-estradiol, etc.?
hypogonadism or ovarian failure, menstrual abnormalities
hormone replacement therapy in postmenopausal women
men with androgen-dependent prostate cancer
What are the AEs of estrogen therapy?
risk of endometrial cancer and thrombus formation (do not use for ER+ breast cancer or with a hx of TE)
What are some selective estrogen receptor modulators?
Clomiphene, Tamoxifen, and Raloxifene
How does Clomiphene work?
It is an antagonist at estrogen receptors in the hypothalamus and prevents normal feedback inhibition of GnRH resulting in increased release of LH and FSH from the pitutiary, which stimulates ovulation
What is Clomiphene used for?
to treat infertility due to anovulation (e.g. PCOS)
What are the AEs of Clomiphene?
may cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual problems
How does Tamoxifen work?
Agonist at bone and antagonist at breat tissue which can be used to treated and prevent recurrence of ER/PR+ breast cancer
What is the advantage of Raloxifene over Tamoxifen?
It is also an antagonist at the uterus so there is no increased risk of endometrial cancer as in the case of tamoxifen.
This is primarily used to treat osteoporosis in postmenopausal women
What are some aromatase inhibitors?
Anastrozole, letrozole, and exemestane
these can be used to prevent peripheral conversion of testosterone to estrogen for use in ER+ breast cancer in postmenopausal women
What is hormone replacement therapy used for?
relief of menopausal symtpoms (hot flashes, vaginal atrophy), and for prevention of osteoporosis (not tx)
Note that in women with a uterus, progesterone is typically added to prevent endometrial cancer risk from unopposed estrogen causing proliferation
What are some Progestins?
Levonorgestrel, medroxyprogesterone, etonogestrel, megestrol, and more
What are the uses of antiprogestins like mifepristone and ulipristal that act as competitive inhibitors of progestins at progesterone receptors?
They can terminate pregnancy or be used as emergency contraception
How does combined (estrogen AND progestins) contraception work?
estrogens and progestin downregulate LH/FSH and thus prevent estrogen surge leading to no ovulation. Progestins also cause thickening of cervical mucus, thereby limiting the access of sperm to the uterus AND inhibit endometrial proliferation, making the endometrium less suitable for implantation of a blastocyst
How does a copper intrauterine device work?
It produces a local inflammatory rxn toxic to sperm and ova, preventing fertilization and implantation (no hormones used)
This is the MOST effective emergency contraception
What are the AEs of a copper intrauterine device?
heavier and longer menses, dysmenorrhea AND
risk of PID with insertion
What are terbutaline and ritodrine used for?
These are B2-agonists that relax the uterus to decreased contraction frequency in women during labor
What is Danazol?
a synthetic androgen that acts as a partial agonist at androgen receptors in treatment of endometriosis or HANE
What are the AEs of Danazol?
weigh gain, edema, acne, hirsutism in women, manculinization
What are some PDE-5 inhibitors for use in erectile dysfunction? How do they work?
Sidenafil, verdenafil, tadalfil
These work by preventing the breakdown of cGMP to sustain the smooth msucle response to NO and maintain erection longer
What PDE-5 inhibitor cna be used in tx of BPH?
What are the AEs of PDE-5 inhibitors?
"hot and sweaty" but then Headache, Heartburn, and Hypotension
DO NOT take with nitrates
What is minoxidil?
a direct arteriolar vasdilator