Endo III

increase cortisol-binding globulin, increases free cortisol

Estrogen effects on the adrenal gland

promotes bone formation (absence leads to osteoporosis risk), increases efficiency of calcium absorption, promotes calcitonin synthesis

Estrogen effects on the bones

stimulates ductal growth, promotes growth of estrogen positive cancer (endometrial)

Estrogen effects on the breast

improves sleep quality, antidepressant, vasomotor stability (absence leads to hot flashes)

Estrogen effects on the CNS

alteration in composition of bile (increases cholesterol saturation), increase gallstone risk

Estrogen effects on the gallbladder

increased clotting factors (increase blood clot risk), decreased antithrombin III

hematologic effects of estrogen

influence synthesis of hepatic products, increase HDL, increase TG (risk of CV disease), decrease total cholesterol to HDL ratio

Estrogen effects on the liver and serum lipids

fluid retention (risk of CV disease), maintenance of muscle strength, nausea, increased prolactin

Metabolic effects of estrogen

increases free cortisol

Progesterone effects on the adrenal gland

stimulates glandular growth, inhibits proliferation decrease in fibrocystic disease

Progesterone effects on the breast

sedation

Progesterone effects on the CNS

increased hematocrit, increase fibrinolytic activity

Hematologic effects of progesterone

decreased HDL and increase LDL (CV risk), increase ratio of total cholesterol to HDL

Progesterone effects on the liver and serum lipids

glucose intolerance, anabolic weight gain, depression, fatigue, increased appetite

Metabolic effects of progesterone

inhibit release of FSH and LH, female maturation, prepare endometrial lining for implantation, decrease bone resorption, retain Na+ and water, increase TG and HDL, decrease LDL, enhance coagulability

Basic estrogen effects

contraceptives, HRT (post menopausal), female hypogonadism, anti-estrogens for hormone sensitive cancer

Therapeutic uses of estrogen

inhibits release of FSH and LH, prepare and maintain endometrial lining, increase body temperature

Basic progestin effects

contraceptive (monotherapy or with estrogen), HRT (dysmenorrhea, amenorrhea, abnormal uterine bleeding), endometriosis

therapeutic uses for progestins

inhibit the release of LH and FSH

Why do we give estrogen and progesterone for contraceptives

better F

Why are synthetic analogs preferred over main hormones for contraception

ethinyl estradiol, diethylstilbestrol (non-steroidal)

Examples of estrogen derivatives used for contraception

levonorgestrel, medroxyprogesterone (provera can be injected Q14 days), norethinterone, drospirenone

Examples of progestin derivatives used for contraception

Use back up contraceptive (1 month with oral, 2 weeks with injection, concurrent enzyme inducers)

Patient education measures for oral contraceptives

chest pain, SOB, DVT symptoms, severe HA, dizziness, weakness, numbness, breast lumps

What needs to be monitored when on contraceptives

Monophasic (constant ratio), biphasic (ratio changes once), triphasic (ratio changes twice)

What are the different combinations of estrogen and progestin?

mimic normal patterns of estrogen and progestin

What is the purpose behind biphasic and triphasic formulations of OCs?

individualized based on medical hx, prior OC use, hormone related ADRs (try to start simple)

How do you pick a OC?

women unable to take estrogen (CV risk or ADR inolerance)

Progestin only contraceptives are indicated for

mini pill, IM Depo-Provera, hormonal IUD

Examples of progestin only contraceptives

metabolized by CYP450s, excreted in the urine and bile

How are oral contraceptives metabolized and excreted?

Plan B, Next choice (2 doses), Ella (ulipristal acetate (120 hours))

Examples of post-coital contraceptives with only progestin - NOT intended for regular use

Gut bacteria are involved in the metabolism of OCs, antibiotics block the reabsorption

Why are women on estrogen/progestin based contraceptives able to get pregnant after taking antibiotics

Mifepristone (progesterone antagonist) and misoprostol

What combination of drugs can be given within 10 weeks of unwanted pregnancy as a single dose for emergency postcoital contraception because it prevents implantation?

Drospirenone

Which is the only progestin with anti-HTN propety?

inhibits estrodiols negative feedback of LH and FSH (increases ovarian stimulation and ovulation), Agonist in the liver (increase clotting factors)

MOA for the clomiphene (conception drug)

thromboembolic disease hx

C/I for clomiphene

increases afterimages, increase chance of multiple pregnancy

ADRs for clomiphene

Fine for menopausal symptoms (night sweats, hot flashes), assess for osteoprosis prevention, absolutely not for CV prevention

Regarding HRT in post-menopausal women what are the current recommendations

Calcium and vitamin D supplements, weight bearing exercise, Bisphosphonates (1st line)

What is our treatment plan for osteoporosis

Bind and accumulate in the bone (especially spine and hip), inhibits bone reabsorption (must take for YEARS)

MOA for bisphosphonates

take on empty stomach (increases bioavailability), 50% is absorbed by bone the rest is excreted by kidneys, take in upright position (alen/iban/rise-) with a full glass of water

Patient education measures for bisphosphonates

flu-like symptoms, kidney damage, acid reflux/heart burn (alen, iban, rise)

ADRs for bisphosphonates (-dronates)

Zoledronic acid (1/yr infusion)

What can we use to circumvent the acid reflux and heart burn from alen/iban/risedronate?

osteonecrosis of the jaw after dental surgery

ADRs of zoledronic acid

SERM (Selective Estrogen Receptor Modulator)

tissue specific estrogen agonist/antagonist

Tamoxifen, Raloxifene, Bazedoziene/estrogen

Examples of SERMs

antagonist in breast, agonist in bone, uterus, liver

MOA for tamoxifen

antagonist for breast and endometrial tissue, agonist in bone

MOA for Raloxifene

agonist in bone

MOA for Bazedoziene/estrogen

There are different conformations of estrogen receptors and levels of co-activators/co-repressors in various tissues

Explain why in some tissues SERMs acts agonist vs. antagonist

progesterone is down, down regulation of GABAa

Explain the pathophysiology behind post-partum depression

mimics a neuropeptide, allopregnanolone (increase activity of GABAa)

MOA for Zuranolone

drowsiness, dizziness

ADRs for Zuranolone

brexanolone (hella expensive)

Other drugs for PDD

corticotrophs, gonadotrophs, thryotrophs, somatotrophs (GH), lactotrophs (prolactin)

Cells of the anterior pituitary responsible for making hormones

oxytocin

Ejection of milk during breast feeding depends on

dopamine

Prolactin is inhibited by

oxytocin, ADH

Hormones of the posterior pituitary

stimulates uterine contraction (inducing childbirth)

MOA for oxytocin (pitocin)

facilitate delivery of healthy infants, prolonged labor, long pregnancies, pregnancies with associated HTN, therapeutic abortions

Indications for pitocin

misoprostol

What oral synthetic PG E1 analog has been used off label to cause abortions?

risk of uterine rupture, uterine bleeding (monitor mom and fetus)

ADRs of misoprostol

ED, galactorrhea, amenorrhea

Increased secretion of prolactin can result in

Antipsychotics (block dopamine)

What type of medications can lead to hyperprolactinemia

Bromocriptine (LOW bioavailability 7%), pergolide, cabergoline

Dopamine receptor agonist used to treat hyperprolactemia

pergolide, cabergoline

Which dopamine receptor agonist are preferred due to less ADRs

psychosis, hallucinations, HA, N/V, postural HTN, nasal congestion

ADRs for dopamine receptor agonist