Gonadal Hormones and Inhibitors Flashcards
what happens when there is release of CRH
- anterior pituitary releases ACTH, MSH, beta-endorphine
- which cause a release of mineralcorticoids, glucocorticoids, and sex hormones
basically ACTH causes release of hormones from adrenal gland
what happens with increased dopamine
increased dopamine –> decreased prolactin –> increased GnRH –> increased spermatogenesis and ovulation
stimulus that causes an increase in GHRH
- increased exercise and sleep
- decreased somatostatin and glucose
what is general mechanism of gonadal hormones - estrogen, progesterone, and androgens
- they bind to their cytosolic receptor
- the hormone-receptor complex (HRC) then travels into the nucleus
- in nucleus, it is activated –> transcription of the steroid hormone regulated genes
what occurs in 17 alpha hydroxylase deficiency and symptoms it leads to
(17 years olds are salty they can’t have sex)
- increase in aldosterone –> high BP and low K+
- decrease in androgens and cortisol –> cryptochordism and indistinct genitalia in males while females lack secondary sexual characteristics
how do you treat males and females with 17 alpha hydroxylase deficiency
males: anti hypertensives, androgens, and glucocorticoids
females: anti hypertensives, estrogen
what occurs in 21 hydroxylase deficiency and what symptoms it leads to
(21 year olds can only have sex)
- increase in androgens –> over masculinization and pseudo-hermaphroditism in females
- decrease in cortisol and aldosterone –> low BP, high K, high renin activity, and volume depletion
how do you treat 21 hydroxylase deficiency
fluids and salt repletion and give cortisol to decrease ACTH
what occurs in 11 beta hydroxylase deficiency and what symptoms manifest
(11 beta is similar to 21 alpha)
- increase in androgens –> over masculinazation
- decrease in cortisol and aldosterone but increase in 11-deoxycorticosterone –> high BP because of the 11-deoxycorticosterone (how it differs from 21 hydroxylase deficiency)
how do you treat 11 beta hydroxylase deficiency
anti hypertensives and estrogen
what are the main estrogen synthesized within the body
estrone
estradiol (not seen after menopause)
estriol (seen in pregnancy)
what are the estrogen that can administered
CEMD
Conjugated estrogen
Ethinyl estradiol
Mestranol
Diethylstilbestrol
what is mestranol and its importance
prodrug converted –> ethinyl estradiol (seen in some contraceptives) –> increases bioavailability and half life, decreases FSH and LH via feedback
what metabolizes estrogen and the importance
CYP450 metabolizes estrogen –> if given an inducer, it can decrease the effect of contraceptives since estrogen seen in contraceptives
clinical uses of estrogen
- long acting ones used in female hypogonadism
- oral contraceptives together with progestins
- postmenopausal HRT –> decrease hot flashes, prevent bone loss and fracture, decrease urogenital atrophy
- dysmenorrhea, uterine bleeding, prostate cancer, and acne
adverse effects of estrogen
- thromboembolism
- breast cancer
- endometrial hyperplasia and cancer (unless progestins added as well)
adverse effect seen using estrogen diethylstilbestrol during pregnancy
if pregnant with female child –> infertility and vaginal cancer
contraindications of estrogens
- Thromboembolism
- Breast and Endometrial cancer
- Pregnancy
- Liver Disease
what are the SERMs (selective estrogen receptor modulator) and mechanism
RoTTC
Raloxifene
Tamoxifen
Toremifene
Clomiphene
they exhibit agonist behavior in some tissues and antagonist in others
mechanism of tamoxifen and what it is used for
- estrogen receptor antagonist in breast and agonist in bone and endometrium
- used to treat breast cancer or for prophylaxis in high risk patients
adverse effects of tamoxifen
- risk of endometrial cancer
- hot flashes (antagonist)
- thrombosis (agonist)
mechanism and uses of Toremifene and Raloxifene
-Toremifene: treatment and prophylaxis of breast cancer
- Raloxifene: estrogen antagonist in breast and agonist in bone and no effect in endometrium
- prophylaxis against breast cancer
- prevention of post menopausal osteoporosis
estrogen antagonist in all tissue and its use
fulvestrant: treatment of breast cancer in tamoxifen resistant patients
adverse effect of fulvestrant
hot flushes, pain at injection site, headache
what are the aromatase inhibitors and their exact mechanism
inhibits conversion of androgens to estrogen
Anastrozole - reversible
Letrozole - reversible
Exemestane - irreversible aromatase inhibitor
use of aromatase inhibitors (name them) and their adverse effects
anastrozole, letrozole, exemestane
- used in treatment of estrogen dependent breast cancer
- AE: hot flushes, decreased bone mineral density
mechanism and use of clomiphene
- fertility drug used in tx of anovulatory infertility
- estrogen antagonist in hypothalamus and anterior pituitary –> prevents feedback inhibition of GnRH release by hypothalamus –> continued release of GnRH from hypothalamus –> increased LH and FSH from pituitary –> ovulation
adverse effect of Clomiphene
- Ovarian hyper stimulation leading to enlargement of ovary
- Multiple pregnancy
what are the progestins
PMNNNDD
Progesterone Medroxyprogesterone Norgestrel Norethindrone Norgestimate Desogestrel Drospirenone
what is the anti progestin
Mifepristone
what are the newer progestins that lack androgenic and antiestrogenic effects
MNNND
Medroxyprogesterone Norgestrel Norethindrone Norgestimate Desogestrel
mechanism of drospirenone
spironolactone derivative used as an oral contraceptive and antagonizes aldosterone effect –> used in females for acne
AE for long term use of progestins
HAD WAGE
- HDL high, low LDL, and hypertension
- Androgenic - hirsutism and acne
- Depression
- Weight gain
- Anti estrogenic - blocks lipid change
- Glucose intolerance
- Edema and acne
mechanism of mifeprostone
competitive inhibitor of progesterone AND glucocorticoid receptor
use of mifeprostone
- morning after drug abortifacient
- with prostaglandins, increases myometrial contraction
AE of mifeprostone
Excessive bleeding
GI effects: anorexia, abdominal pain etc
