Estrogens and androgens Flashcards
Estradiol
most potent estrogen produced and secreted by ovaries, principle estrogen in premenopausal women
estrone
metabolite of estradiol, 1/3 istrogenic potency, primary circulating estrogen after menopause
Estriol
another metabolite of estradiol, significantly less potent, present during pregnancy, principle estrogen produced by placenta
ADRs of estrogen
nausea and breast tenderness
How should estrogen therapy be used for intact uterus?
progesterone in combo with estrogen
How should estrogen therapy be used for hysterectomy?
estrogen alone, progesterone may alter the beneficial effects of estrogen on lipid parameters
what are the SERMS
tamoxifen, raloxifene (Evista), Clomiphene (Clomid)
MOA of SERMS
interact with estrogen receptors but have different effects depending on the tissue, selective agonism or antagonism according to tissue type
Clinical use of tamoxifen
palliative treatment of metastatic breast cancer in postmenopausal women, some breast tumors regress with treatment
ADRs of tamoxifen
nausea, hot flashes, endometrial hyperplasia, and malignancy
Raloxifene (evista) use
prophylaxis of br ca in high risk women, prevention and tx of osteoporosis in postmenopausal women, decreases bone resorption and bone turnover, little to no effect on endometrial tissue, decrease total and LDL cholesterol
Adrs of raloxifene
hot flashes, leg cramps, increase of deep venous thrombosis and pulmonary embolism
Clomiphene use
tx of infertilit associated with anovulatory cycles, interferes w/ negative feedback of estrogens on hypothalamus, inc secretion of GnRH and gonadotropins leading to stimulation of ovulation
ADRs of clomiphene
dose related nausea, HA, hot flashes, visual disturbances, ovarian enlargement
progesterone produced in response to
LH in females and males
where is progesterone produced?
in females it is secreted by corpus luteum during luteal phase an dbby placenta, in males it is secreted by testes
What does progesterone do
promotes development of secretory endometrium, accommodates implantation of newly forming embryo
What is the major clinical use of progesterone
contraception and treatment of hormonal deficiencies, and control of dysfunctional uterine bleeding, treatment of dysmenorrhea and management of endometriosis and infertility
Progesterone ADRs
HA, depression, wt gain, changes in libido, some can cause increase in LDH cholesterol- acne, and hirsutism
What is medroxyprogesterone adr
increased risk of osteoporosis, so take with calcium and only use 2 years
Contraceptive MOA
for estrogens- negative feedback on release of LH/FSH, consistent levels prevent LH spike and ovulation; progestin- make cervical mucus less permeable, makes implantation more difficult
Progestin only contaceptives
are less effective, but preferred when estrogen use is not desired, still prevents LH spike, used for breastfeeding women, history of clots and >35 and smokers
How often is injectable progestin given
every 3 months
What can injectable progestin cause
wt gain, and amenorrhea, can delay fertility for several months
Advantages of progestin implants
offers long term contraception, effects reversible when removed, nearly as reliable as sterilization
Complications with contraceptives
increased risk of DVT, increased MI and stroke, inc BP
Advantages of contraceptives
regulation, decreased flow, improved acne, can stabilize moods, dec unplanned pregnancy
ADRs of contraceptives
breakthrough bleeding, imbalance in estrogen and progestin components, nausea/vomiting, wt gain, breast tenderness, fluid retention, depression
androgens
steroids with anabolic and masculinizing effects in both males and females, testosterone is the most important
what is testosterone synthesized by?
leydig cells in testes of the male, thecal cells in the ovary of the female, adrenal gland of both sexes
What are androgens required for?
normal maturation of male, sperm production, increased synthesis of muscle proteins and hemoglobin, dec bone resorption
Schematic of testosterone secretion
secreted by Leydig cells controlled by GnRH from hypothalamus, stimulates anterior pituitary to secrete FSH/LH, LH stimulates steroidogenesis in Leydig cells, FSH causes spermatogenesis
Therapeutic uses of androgens?
males with inadequate androgen secretion, tx male senile osteoporosis and chronic wasting associated with HIV or CA, adjunct therapy in severe burns, ALS, speed recovery from surgery or chronic debilitating diseases
Clinical uses of androgens?
endometriosis- inhibits release of LH/FSH, and antiestrogenic activity, unapproved for increase muscle mass, strength, and endurance
ADR of danazol
wt gain, acne, decreased breast size, deepening voice, increased libido, increased hair growth
PO testosterone
inactivated by 1st pass, but alkylation of 17a position works- oxandrolone (oxandrin)
Testosterone available?
patches, gels, buccal tabs- androderm, androgel, testim, striant, fortesa
ADRs of testosterone in children?
abnormal sexual maturation and growth disturbances
Other ADRs of androgens
increased LDL, dec HDL, fluid retention, premature coronary heary disease
Antiandrogen options
finasteride (proscar), and dutasteride (avodart)
When are antiandrogens used
for tx BPH, also male pattern baldness
dosage of antiandrogens
Finasteride- 5 mg PO, Dutasteride (.5mg PO)
