Gonadal Hormones Flashcards
Which hormones from the anterior pituitary stimulate release of gonadal hormones?
LH and FSH
How does pulsatile release of GnRH compare to non-pulsatile release?
- pulsatile release stimulates release of LH/ FSH
- sustained release inhibits LH/FSH release
What hypothalamic signal stimulates LH/FSH release from the anterior pituitary?
GnRH
What is the effect of FSH?
spermatogenesis or follicular development
What is the effect of LH?
steroidogenesis
- estrogen and progesterone release form the ovaries
- testosterone from the testes
What is special about gonadorelin compared to other GnRH agonists?
gonadorelin has a very short half life and thus replicates the pulsatile release of GnRH that normally stimulates the release of LH and FSH
What are drugs that end in “-relin”?
GnRH agonist
What are drugs that end in “-relix”?
GnRH antagonists
What is the clinical use of depot ganirelix?
- it is a GnRH antagonists used to control prostate cancer
- depot formulations allow for long-term use without frequent hospital visits
What are the primary uses of pulsatile GnRH agonists? Sustained GnRH agonists and antagonists?
pulsatile are used to stimulate gonadotropin release
- female and male infertility
- testing and diagnosis of problems with gonadotrophs in the anterior pituitary
sustained agonists and antagonists inhibit gonadotropin release
- suppress LH surge to control ovarian stimulation
- endometriosis
- uterine fibroids
- prostate cancer and occasionally ovarian cancer
- delay precocious puberty or puberty in transgender adolescents
What are the side effects of GnRH toxicities?
- hypersensitivity reactions
- menopausal-type symptoms in women
- gynecomastia in men
What are urofillotropin and fillotropin?
- FSH from urine of post-menopausal women
- recombinant FSH
How does chorionic gonadotropin compare to menotropins?
- chorionic gonadotropin has far more LH than FSH activity
- menotropins have balanced LH and FSH activity
What is menotropin?
a gonadotropin obtained from menopausal women and thus known as hMH (human menopausal gonadotropin) with equal FSH and LH activity
How does hCG compare to hMH?
hCG has far more LH activity than FSH, while hMG has balanced activity
What are the primary uses of pharmacologic gonadotropins?
- induce ovulation (in those with hypogonadotropism, polycystic ovaries, obesity, etc. or who are using assisted reproductive techniques)
- treat male infertility
What is the risk of using gonadotropins to induce ovulation?
there is a risk for ovarian hyper stimulation syndrome and multiple pregnancies
How are gonadotropins used in the treatment of male infertility? Specifically which drugs are used and what is the time course?
- start with hCG because it is least expensive and then move on to hMG
- often takes 4-6 months before sperm can be detected
Gonadotropins carry what black box warning?
should not be used for the treatment of obesity
What is the primary endogenous estrogen produced by the human ovaries? What other forms are produced?
- estradiol (E2) is produced in the greatest quantity
- estrone (E1) and estriol (E3) to a lesser extent
What is estropipate?
purified crystalline estrone
What benefit do estrogen esters offer compared to endogenous estrogens? What is their limitation?
- they are metabolically-resistant pro hormones with improved bioavailability and longer half life
- but are readily hydrolyzed once in the active form
How are conjugated estrogens produced?
they are equine estrogen sulfate sodium salts blended to a high, standardized potency
What is unique about ethanol estradiol?
- it undergoes extensive hepatic metabolism into active metabolites
- as a result it has excellent oral bioavailability
What is unique about diethylstilbestrol (DES)?
it is an estrogen historically used to prevent pregnancy complications but caused a variety of complications itself, including clear cell carcinoma of the vagina
Those women whose mothers used diethylstilbestrol need to be monitored for what?
clear cell carcinoma of the vagina
What is unique about esterified estrogens?
they are derived from soybeans and yams and consist mostly of estrone and equilin
What is bisphenol A?
an estrogenic compound that leaches from plastics
What is Genistein?
an estrogen that is often contained in herbal treatments for menopause
Through what intracellular cascade do estrogens work?
- they bind intracellular estrogen receptors located in the nucleus
- this complex binds to the estrogen-response element and initiates gene transcription
What are the primary uses for estrogen therapy?
- primary hypogonadism
- hormonal contraception
- ovarian suppression for those with dysmenorrhea, endometriosis, e tc.
- hormone replacement in post-menopausal women
What is endometriosis?
growth of endometrium outside the uterus
Which estrogen therapies have good oral bioavailability?
- ethinyl estradiol
- esterified estrogens
What are the adverse effects of estrogen therapy?
major concerns are proliferation of estrogen-responsive cancers and estrogen’s ability to induce a hypercoagulable state; may also cause:
- nausea
- beast tenderness
- hyperpigmentation
- migraine
- cholestasis and gall bladder disease
- hypertension
Estrogen therapies carry what risk for malignancy?
uterine and breast cancer
Under what circumstances is unopposed estrogen not to be used for replacement therapy? Why? What is used to oppose it?
- postmenopausal women with a uterus
- estrogens stimulate proliferation of the endometrium and can promote cancer
Post-menopausal women with a uterus who wish to undergo estrogen hormone replacement also need to be placed on what drug?
progestins, to decrease uterine proliferation
How are most progestins administered? Which are available for IM?
- most are given orally
- progesterone and medroxyprofesterone acetate are available for IM
What is unique about desogestrol?
it is the cleanest progestin with very few non-progestin affects
What are some common non-progestin effects of progestin agonists?
- estrogenic
- androgenic
- antiestrogenic
- antiandrogenic
- anabolic
- antimineralocorticoid
Through what mechanism do progestins act?
they bind a nuclear receptor and initiate transcription by binding, as a complex, to the progesterone-response element
What are the primary indications for progestins?
- hormonal contraception
- ovarian suppression for dysmenorrhea, endometriosis, etc.
- postmenopausal hormone replacement
What are the most common adverse effects associated with progestins?
- may increase blood pressure
- those with more androgenic effects may decrease plasma HDL
Most hormonal contraceptions use what sort of estrogen and progestin?
- ethanyl estradiol
- norethindrone, L-norgestrel, desogestrel
Through what mechanism does hormonal contraception work?
- it suppresses the FSH/LH surge through negative feedback to inhibit ovulation
- also thickens the cervical mucus and decreases fallopian tube motility
What is the main concern or adverse effect associated with hormonal contraception?
risk of venous thromboembolism
What are the purposes of peri- and post-menopausal hormone therapy?
- decrease hot flashes, vaginal dryness, and other symptoms
- prevent GU atrophy
- prevent osteoporosis
- prevent atherosclerosis
- prevent dementia
What risks are associated with peri- and post-menopausal hormone therapy?
- heart disease, stroke, PE, and DVT
- breast cancer (only when estrogen + progestin is used)
- uterine cancer in those with a uterus receiving unopposed estrogen
- increased triglycerides
How long should post-menopausal hormone replacement last?
use for the shortest period and lowest dose possible to achieve treatment goals
What is the primary use of tamoxifen?
treatment of breast cancer
What are SERMs?
- selective estrogen receptor modulators
- with tissue-specific partial agonist and partial antagonist activity at estrogen receptors
What is the primary use of raloxifene?
treatment of osteoporosis
What is clomiphene? How does it’s action suit it’s clinical use?
- it is a SERM
- it blocks estrogen feedback within the HPG axis
- thereby increasing LH and FSH release to induce ovulation
Which drug’s are used to induce ovulation?
- clomiphene is used first because it is cheaper and easier to use
- then hCG is used
What is the primary use of fulvestrant?
it is an estrogen antagonist used in the treatment of tamoxifen-resistant breast cancer
What mefiprisonte? How is it used clinically?
- a progesterone antagonist
- primarily used as a postcoital contraceptive or abortifacient in combination with misprostol or PGE1
What are aromatase inhibitors?
drugs that block the estrogen production in the periphery
What is danazol?
a derivative of 17a-ethinyl-testosterone with weak progestin, androgen, and glucocorticoid activity used to suppress ovarian function
What are aromatase inhibitors used for?
the treatment of breast cancer
Through what mechanism do androgens effect cellular change?
they bind intracellular receptors and alter gene expression
What are the primary uses of androgens in clinic?
- androgen replacement
- gynecologic disorders like endometriosis
- as anabolic agents after trauma, disease, etc.
- for growth stimulation in boys with delayed puberty
- osteoporosis in men
- aging
What is the downside of using androgens for growth stimulation in boys with delayed puberty?
the androgens can cause premature closure o bone epiphyses
What adverse effects are associated with androgen use?
- acne
- sleep apnea
- gynecomastia through conversion to estradiol
- testicular atrophy and azoospermia through feedback inhibition
- hirsutism
- sodium retension
- hepatic dysfunction, cholestasis, jaundice
- psychological dependence
- aggression and psychosis
What is the primary use of androgen antagonists and androgen suppression?
the treatment of prostate cancer
What is unique about ketoconazole?
it inhibits adrenal and gonadal steroid synthesis, but increases the estrogen to testosterone ratio, contributing to gynecomastia
What are the primary uses of cyproterone?
it is an androgen receptor inhibitor used for hirsutism in women and excessive sexual desire in men
What is spironolactone?
a drug that competes with DHT and aldosterone
