Estrogens and Progestins Flashcards
What are the estrogen derivatives used clinically?
Conj. Equine estrogens Diethylstilbestrol estradiol ethinyl estradiol mestranol
What are the clinically used progestins? (progesterone derived)
Medroxyprogesterone acetate (MPA)
What are the clinically used progestins? (19-nor compounds)
.
When does positive feedback occur in the ovarian cycle?
Mid cycle (day 14) induces ovulation
What hormones are involvedin the follicular phase
High F low Amp LH
What steps are involved in the follicular phase
HF/LA LH secretion
Estrogen rises
Endometrial Proliferation
What causes the ovulation phase?
Estrogen induced gonadotropin surge
What steps are involved in the Luteal Phase?
Rise in Estrogen and Progesterone
Endometrial diff under control of progesterone
What is the MOA of Steroids?
Steroids bind to intracellular receptors and mod. transcriptional activity
Ag/Ant compete for steroidbinding sites
Alternative pathways too
What are the metabolic effects of Estrogen?
Dec LDL, Inc HDL, Inc TRGs Keeps bone from being resorbed Inc. coagulation factors dec. antithrombin Increases Plasma Proteins
What are the Metabolic effects of Progesterone?
Inc. LDL, Inc Fat Deposition
Inc. Fasting Glucose
What are the endometrial effects of Estrogen?
Endo. Proliferation
What are the endometrial effects of Progesterone?
Endo Differentiation, prep for implantation, decrease uterine contractions
What are the effects of Estro/Progesterone onthe menstrual cycle?
Estrogen- Reg Follicular Phase
Progesterone- Reg Luteal phase
What are the effects of Progesterone on Uterus smooth muscle?
Decrease uterine contraction
DecProstaglandin
Maintain relaxin secretion
What are the effects of Progesterone on Cervical glands?
Increase cervical mucous Viscosity
What is the reason for chemical modification of estrogen?
Increase the half life by putting ethinyl group on it.
HL = from minutes to 13-27 hrs
What is different about the conjugated equine estrogens? (naturally derived)
Need to give much more bc it is much more readily metabolized
What are the pharmacological uses of estrogens? Hypogonadism
Hypogonadism (promotes dev. of female sex organs)
Development of Ovaries, fallopian tubes, uterus, vagina and breasts
What are the pharmacological uses of estrogens? Hormone Replacement therapy
Maint boneDensity Supress hot flahes Supress Urogenitl atrophy HPG axis Endometrium- Bone- antiresorptive Development- Ov, Fall tubes, Ut, vag, br
What are the Pathophysiology effects of Estrogens?
Inc Risk of: CHD Stroke PE Breast Cancer Dec risk of: Colorectal cancer Hip Fracture
What are the pharmacological uses of estrogens? Contraception
HPG axis: negative feedback activation of axis
Decreased ovulation
What are the pharmacological uses of estrogens? Acne Tx
Supress steroidogenensis
Increase SHBG production by liver and dec. free T conc.
HPG Axis
Liver- increase plasma proteins
What are the adverse effects of Estrogen?
Br Tenderness
Endometrial Hyperplasia
Inc Blood Coagulation
Nausea Cholestasis- Change in cholesterol secretion, bile canaliculi function Migraine Cancer Bloating- loss ofintravascular fluid
What are the cancer risks associated with Hormone Replacement Therpy?
HRT combo: Breast cancer (due to progestin not estrogen)
HRT just estrogen: Endometrial Cancer
Contraceptive: Red risk of ovarian and endometrial Cancer
Cancer Mech: Trophic effects of hormones
Reactive oxy species prod. from met. of drug
What two drugs are often combined for HRT?
Estrogen and Medroxy-Progesterone
What are the clinical uses of Progestins? Contraceptive
Alone or in combination with estrogen (more effetive)
HPG Axis
Cervical Glands
What are the clinical uses of Progestins? HRT
Dec Risk of endometrial hyperplasia
What are the clinical uses of Progestins? Dysmenhorrea
Dec. Endometrial Mass
and dec prostaglandin prod
What are the clinical uses of Progestins? Endometriosis
Dec endometrial proliferation by regulating ER expression and stimulating differentiation of endometrial cells
