E3: Sex Hormones Flashcards
What kind of drug is Leuprolide?
A long acting agonist of GnRH
What does leuprolide do and when is it used?
- Continuous administration suppresses release of LH and FSH after initial surge
- Used in IVF, endometriosis, precocious puberty, sex steroid dependent cancers, and gender affirmation
What kind of drug is Cetrorelix?
GnRH antagonist
What is cetrorelix used for?
Suppressing LH and FSH, used in the same situations as Leuprolide
What are the main differences between long acting GnRH agonists and antagonists?
- Antagonists suppress gonadotropins in 4-5 days while agonist require 3 weeks
- No initial surge of gonadotropins in antagonist treatment
- When treating prostate cancer with an agonist, need to coadminister with antiandrogen
What are the adverse effects of long acting GnRH antagonist/agonist?
Menopausal symptoms and testicular atrophy
What is Human menopausal Gonadotropin (hMG?used for?
Used as FSH in infertility
What is human chorionic gonadotropin used for?
-Used instead of LH, has the same actions
What are the uses of gonadotropins in men?
LH increases testosterone, FSH induces spermatogenesis
What are the uses of gonadotropins in women?
FSH stimulates ovaries and estrogen production, single dose of LH given to induce ovulation
What are the adverse effects of gonadotropins?
-Ovarian hyperstimulation syndrome
-multiple births
-gynecomastia
-uncomplicated ovarian enlargement
-
What is it called when a patient has sudden ovarian enlargement, increased vascular permeability, rapid accumulation of fluid in the peritoneum, hypovolemia, shock, fever, thromboembolisms, and death?
Ovarian hyperstimulation syndrome
What are the contraindications of gonadotropins?
Sex-steroid dependent cancers
What is the MOA of estrogens?
Nuclear receptors
What is the metabolism of estrogens?
Metabolized by the liver and undergo enterohepatic circulation
What are the uses of estrogens?
-oral contraception, postmenopausal HRT, and stimulating pubertal development in hypogonadic girls
What are the adverse effects of estrogen?
-migraines, thromboembolism, endometrial hyperplasia, nausea, HTN, and gallbladder disease
What are the contraindications of estrogens?
Estrogen dependent neoplasms and thromboembolic disorders
What is the MOA of Tamoxifen?
- Seletive estrogen receptor modulator (SERM)
- Antiestrogen
- Has both antagonist and agonist effects
What is the DOC for palliative and prophylactic treatment of breast cancer in premenopausal women?
Tamoxifen
What are the agonist effects of Tamoxifen?
- Bone: Limits bone loss
- Uterus: many increase risk of uterine cancer
What antiestrogen just does not increase the risk of uterine cancer and is frequently use for osteoporosis?
Raloxifene
What is the MOA of Clomiphene?
- Antiestrogen
- SERM
- Antagonizes negative feedback of estrogen in hypothalamus
What is Clomiphene often used for?
Initial infertility therapy (stimulates LH and FSH)
-Causes multiple pregnancies 5-10% of the time
What are the 3 antiestrogen drugs?
Tamoxifen, raloxifene, and Clomiphene
What is the DOC of breast cancer treatment in postmenopausal women?
Anastrozole
What drug would you use for advanced breast cancer after tamoxifen failure in postmenopausal women?
Anastrozole
What are the adverse effects of anastrozole?
Diarrhea, abdominal pain, nausea, vomiting, hot flashes, and joint pain
What are the contraindications of aromatase inhibitors?
Premenopausal women, category X in pregnancy
What kind of drug is Anastrozole?
Aromatase inhibitor
What are the uses of progestins?
- Contraception
- prevent endometrial hyperplasia in HRT
- Treatment of other problems when estrogens are contraindicated
What are the adverse effects of progestins?
- increased BP
- High doses may reduce plasma HDL levels
- depression and drowsiness
What is the MOA of mifepristone?
-antiprogestin, progesterone/glucocorticoid receptor antagonist
What are the uses of mifepristone?
- terminate pregnancy
- prevents implantation (emergency contraception, but not DOC)
What are the side effects of mifepristone?
Vomiting, diarrhea, abdominal pain, and vaginal bleeding
What kind of drug is drospirenone/ ethinyl estradiol?
Combination oral contraceptive
What is the MOA of combination oral contraceptives?
- Inhibit ovulation
- change cervical mucous
- change endometrium (decrease implantation)
What are the advantages of drospirenone?
- Less water retention, FDA approved for PMDD
- very little anti-androgenic properties
What are progestin only mini pills used for?
Breast feeding when estrogen is contraindicated
What are the side effects of long term contraceptives?
Early: breakthrough bleeding
Later: Amenorrhea
What are the 3 emergency contraceptives?
- Plan B (Levonorgestrel only pill)
- Preven
- Mifepristone
What are the adverse effects of combination oral contraceptives?
- Weight gain, nausea, edema, depression, and breakthrough bleeding
- cardiovascular problems (clots, HTN, migraine, MI/stroke)
- Teratogenesis
What are the benefits of combination oral contraceptives?
- effective contraception
- reduces risk for ovarian and endometrial cancer, ovarian cysts, benign breast disease, ectopic pregnancy, and iron deficiency
What are the absolute contraindications for combination oral contraceptives?
ASCVD, thromboembolic phenomena, estrogen dependent cancers, Cerebrovascular disorders, pregnancy, smokers who are older than 35, and uncontrolled HTN/DM
What are the relative contraindications of combination oral contraceptives?
Liver disease, children who have not yet completed epiphyseal closure, migraine, smoking, and older than 35
What are the possible drug interactions with combination oral contraceptives?
- p450 inducers reduce effectiveness
- ABx can reduce effectiveness
- Contraceptives can decrease effectiveness of anticoagulants, anticonvulsants, TCAs, guanethidine, and, oral hypoglycemic
What happens in menopause?
-reduced ovarian response to gonadotropins, decreased ovarian steroids, and increased gonadotropins
What are the symptoms of menopause?
- Vasomotor problems (HA, palpitations, hot flashes)
- Genito-urinary problems: vaginal dryness, atrophy, and pain
- Osteoporosis
- Heart disease ( increase cholesterol and LDL, decreased HDL)
What are the adverse effects of HRT?
- Endometrial cancer (progestin decreases this risk)
- breast cancer
- CVD
- Gallbladder disease
What are the guidelines for prescribing HRT?
- <10 years after menopause, HRT has more benefits than risks
- > 10 years after menopause, dont use HRT
What are the physiological effects of androgens?
- Virilizing effects (spermatogenesis and sexual development)
- Anabolic effects (increase bone density, amino acid incorporation into muscle, and RBC mass)
- Puberty
What are the uses of testosterone?
-Testicular deficiency, female hypopituitarism, hypoproteinemia of nephrosis, negative nitrogen balance, and female-to-male gender affirming hormonal treatment
What are the side effects of Androgens in men?
Decreased spermatogenesis and may exacerbate prostate cancer
What are the side effects of androgens in women?
Masculinization, pseudohermaphroditism
What are the side effects of androgens for both sexes?
- oily skin/acne
- decreased HDL
- Psychological changes
- baldness
- fluid retention
What two drugs are androgen receptor antagonists?
Flutamide and spironolactone
What kind of drug is flutamide and what is it used for?
- androgen receptor antagonist
- used in prostate cancer with long acting GnRH agonist
What are the uses of spironolactone in hormone replacement?
- hirsutism, PCOS, and PMS in women
- Precocious puberty
What kind of drug is Finasteride?
5 alpha reductase inhibitor
-suppresses male sex accessory organs without affecting libido
What are the uses of finasteride?
BPH and male pattern baldness
What are the side effects of finasteride?
Gynecomastia or impotence
-teratogenic
