Gonadal Hormones Flashcards
When the primary follicle matures, it secretes
estrogen
Mature follicle releases ovum and then follicle transforms into
Corpus Luteum
Corpus Leuteum secretes
progesterone which is involved in maintenance of the endometrium
Ovarys release what hormones
estrogen and progesterone
Precursor for hormones
cholesterol
Enzyme transforms non aromatic onto aromatic
Aromatase
Main natural estrogen
estradiol
Genistein
Natural compound found in plants such as soy, used OTC , used to support women undergoing menopause. It can activate estrogen receptors similar to Estadiol.
Bisphenol A
Used in plastic bottles. Might have hormonal effects. Could be disruptive in developing fetuses.
Why use synthetic estrogens?
estrogen has low bioavailability when taken orally. Can increase the bioavailability when used as a cream, but it is still low.
Pharmokinetics of estrogens
Binds strongly to sex hormone binding globulin.
Biotransformation in the liver and excretion in bile (can compromise the liver).
Lipophilic , requires proteins for shuttling.
Cytoplasmic receptors, not transmembrane.
Binding estrogen forms complex with receptors, dimerizes then binds to DNA sequence. Different receptors than GCS, but same sequence of events.
Physiological effects of estrogens
Decrease rate of bone resorption
Reduce total plasma cholesterol
Endometrial effects
stimulate production of leptin
structure and function of skin and blood vessels.
Enhance blood coagulability
Maturation
Clinical uses of estrogens
hypogonadism
postmenopausal hormone therapy
hormonal contraceptive
Estrogen side effects
Uterine bleeding
Cancer (slightly enhanced risk of breast cancer, but rare)
Progestins produced by CL and synthesized in
ovary, testis, adrenal cortex, placenta during pregnancy
Progestins are metabolized in the
liver and secreted in the urine as a glucuronide conjugate
Progesterone favors
fat deposition, increased basal insulin levels and promotes glycogen storage
Progesterone competes with
aldosterone and decreases sodium reabsorption
Progesterone increases
body temp (indicator of ovulation)
Synthetic progestins do not
usually support implantation of fertilized egg
1:1 estrogen progesterone ratio
monophonic
bi and tri phasic differs in
hormone levels
continuous progestin therapy aka
mini pills
Use mini pills when
patients don’t respond to estrogen
Estrogens to known
Ethinyl Estradiol
Mestranol
Estradiol Valerate
Progestins to know
norgestrel
desogestrel
norethindrone
Main purpose of combined forms of estrogen and progesterone
prevent LH spike and inhibit ovulation
Progestins mostly effect
endometrium and changes in the uterus
Mini pills do not . . .
inhibit ovulation, but influence changes in the endometrium. Effects are purely on endometrium.
Pharmacologic effects of hormonal contraceptives (1)
depression of ovarian function
hypertrophy of cervix
changes in cervical mucous
stimulation of breasts (risk of breast cancer)
Pharm effects of hormonal contraceptives (2)
change in other hormones regulated to AP
increased pigmentation, changes in serum production
increased coagulation
beneficial changes in lipid profile
change in levels of globulins (more globulins that binds steroids = less bioavailability , only active in their free form)
Adverse effects of estrogens (mild)
nausea, Mastalgia, edema, headache, lack of withdrawal bleeding
Adverse effects of estrogens (moderate)
abnormal bleeding when its not time for the period
vaginal infections
weight gain
acne and hirsutism
amenorrhea
Adverse estrogen effects severe
cancer, depression , vasular disorders
SERMs
selective estrogen receptor modulators (not called antagonist because they inhibit some receptors in some tissues, but activate in other, depends on location.
SERMs to know
tamoxifen
raloxifen
toremifene
clomifene
mifepristone
How does tamoxifen, raloxifen, and toremifene work?
used in patients with breast cancer after mastectomy to prevent metastasis and used in cancer that responds to increase estrogens. Could cause hot flashes, no negative impacts on bone.
How does clomifene work?
blocks only estrogen receptors in the brain. (hypothalamus and Ant pit) blocks the neg feedback , so CNS keeps pumping estrogens . Why use these? In fertility clinics , to stimulate fertilization.
Mifepristone
Antagonist of GCS and MCS, but mainly blocks progesterone receptors. Will be used to induce abortions often used in combinations of drugs that will stimulate uterine contractions, certain prostaglandins may increase uterine contractions.
Androgens are produced in
testes or adrenal glands
Physiological form of Testosterone
Dihydrotestosterone
Taking testosterone may increase estrogens
aromatase does this conversion
Physiological effects of androgens
maturation
replacement therapy
low libido (also used in females)
growth stimulators (AIDS)
Androgen side effects
prostatic hyperplasia
sleep apnea, agressiveness
Acne
masculinizing effects
Drugs that inhibit androgens will be used in treating
prostate cancer or prostate hyperplasia
Dihydrotestosterone may
stimulate balding , so drugs may block this to prevent balding
Inhibits synthesize of steroids way up the pathway
Ketoconazole, spironolactone
Inhibits 5 alpha reductase which converts testosterone to dihydrotestosterone
finasteride and Dutasteride
Directly inhibits receptors of dihydrotestosterone
Flutamide, cyproterone, spironolactone
Combination given for prostate hyperplasia
alpha 1 antagonist and 5 alpha reductase inhibitor
