Estrogens and Progestins Flashcards
Hormone domino for estrogen release
At puberty: hypothalamus GnRH –> anterior pituitary FSH/LH –> estrogen from ovaries
Pharm use of estrogens/progestins
for contraception - supression of HPO axis via negative feedback
Physiologic use of estrogens/progestins
Menopausal hormone therapy (MHT)
granular cells secrete
estradiol - allows endometrium to proliferate
leuteal cells secrete
progesterone - early, with estrogen, suppress LH/FSH. later at higher levels, has anti-estrogen effects to halt proliferation of endometrium
clinical use of synthetic GnRH
Test for delayed puberty
Replacement (pulsatile) therapy: male and female infertility or abnormal function of hypothalamus
Continuous administration: prostate cancer, endometriosis, idiopathic precocious puberty
Pulsatile GnRH agonist administration
Increases LH and FSH release from pituitary
Continuous GnRH agonist administration
blocks release of gonadotropins after 3-4 weeks (downregulation of receptors) after an initial rise of gonadotropin release
Continuous GnRH antagonist administration
reduces testosterone levels in one week without initial rise
SIde effects of GnRH
vasodilation, headache, multiple pregnancies, hypoestrogenic SSX. If using continuously, can have “flare symptoms” secondary to surge in testosterone. NO flare symptoms with antagonists
Exogenous FSH MOA
stimulates gametogenesis and follicular development in women and spermatogenesis in men
Exogenous LH MOA
stimulates testosterone production in testicular Leydig cells and (w/FSH) stimulates follicular developement in ovary
Gonadotropin clinical uses
hypogonadism with infertility. FSH used with LH sequentially in women and together in males
Side effects of exogenous gonadotropin use
ovarian enlargement, multiple births, spontaneous abortion, gynecomastia
Human Chorionic Gonadotropin (from urine of preggos) MOA
Stimulates corpus luteum to produce and maintain placenta.
Stmulates Leydig cells to produce testosterone
hCG uses
action similar to LH, some FSH action. For infertility in M and F
hCG Side Effects
H/A, depression, edema, gynecomastia, Ab production
Estrogen MOA
diffuse through PM, enter nucleus and bind estrogen receptor (ERa, ERb) to ultimately initiate gene transcription
Estrogen antagonist MOA
Will enter cells and bind ER, but reduce transcription of genes.
Estrogen Physiologic Effect
Maintain CT structure, alter liver metabolism, enhance blood coagulability, alter plasma lipid composition (cardioprotective)
Estrogen menopausal hormonal therapy - symptomatic TX
Treats the vasomotor symptoms and vulvovaginal/urogenital complaints. Use for a short period of time at lowest possible dose
Non-hormonal therapy for hot flashes is an alternative for women with E+ breast cancer or history of blood clots
:)
Estrogen menopausal hormonal therapy - Prevention of osteoporosis
ONLY for patients at significant risk of osteoporosis. Worry for breast cancer risk, MI, blood clots.
Selective estrogen receptor modulators (SERMs) have less risks
Raloxifene (Evista) SERM
Estrogen like activity on bone (increase mineral density) and liver (decrease LDL and total cholesterol)
Lack agonist activity (growth) in breast and uterine tissue.
Retain risk of clots d/t increase in hepatic clotting factor synthesis
Estrogen menopausal hormonal therapy - prevention of cardiovascular disease
NO LONGER APPROVED FOR HD PREVENTION
Menopausal hormonal replacement therapy Contraindications
undiagnosed vaginal bleeding, acute liver disease, active thrombosis, recent hx of breast or endometrial CA
Exogenous estrogen used in primary hypogonadism for…
~11-13 yo; sexual development, growth, avoid psychological aspects of delayed puberty
Adverse effects of Estrogen use
post-menopausal bleeding, N/V/D, breast tenderness, migraines, HTN
Progesterone is the most important progestin: precursor to estrogens, androgens, adrenocorticoids
:)
Progesterone is synthesized…
in the ovary (corpus luteum), testis, adrenal gland and placenta
Progesterone physiologic effects
Favors fat deposition, promotes liver glycogen storage, increases insulin levels, may compete with aldosterone
Progesterone clinical uses
Oral and implant contraceptives
Menopausal hormone therapy (MUST be added to estrogen in women with a uterus)
Progesterone side effects
mental depression, somnolence, H/A, breast enlargement, weight gain
Hormonal controceptives contain either estrogen plus progestin (COC) or Progestin alone
:)
COC MOA (estrogen and progestin in synergistic)
inhibition of ovulation via supression of FSH and follicle development (estrogen) and prevention of ovulatory surge of LH (progestin)
If nausea, breast tenderness, edema occur…
decrease estrogen in COC
If early/mid-cycle spotting, decreased flow/amenorrhea occur…
Increase estrogen, decrease the progestin dose
If weight gain, hair growth, depression, fatigue, adverse lipid changes…
Decrease Progestin
if excessive bleeding or late cycle spotting occur..
increase progestin and decrease estrogen dose
COC use Contraindicated in
smokers >35 years old, uncontrolled HTN, DM with end organ damage, hx of VTE, hx of breast cancer or migraines with aura
EC: Plan B MOA
altered oviduct motility or endometrial changes. Preventing from implanting
Tamoxifen (Nolvadex) Use
SERM - used for treatment and prevention of breast CA. Induce hot flashes
Raloxifene (Evista) Use
SERM - approved for prevention of breast cancer and prevention/treatment of postmenopausal osteoporosis. Induce hot flashes
Clomiphene (Clomid)
Partial estrogen receptor agonist. Stimulates ovulation
MIfepristone
Antagonist of progesterone receptor, terminate early pregnancy
Medroxyprogesterone (Provera)
Progesterone derivatives with little effect on gonadotropin release
Norethindrone OCP
1st generation. Lower progestin activity than 2nd gen. also have higher risk of unscheduled bleeding
Levonorgestreal/norgestrel OCP
2nd generation. MOre progestin activity than 1st gen, improved libido, acne, hirsutism, dyslipidemia
Desogestrel OCP
3rd generation. May be helpful in those with acne. slightly higher risk of VTE
Drospirenone (Yasmin) OCP
4th Generation. Antimineralocorticoid and antiandrogenic activity, increased risk of VTE
