Estrogens and Progestins Flashcards
What are the two cells in the female that produce estrogen?
Theca and granulosa cells
What are the enzymes that are needed to convert cholesterol to estrogen?
3 beta HSD
17 hydroxylase
17, 20 hydroxylase
What is the enzyme that converts androstenedione to testosterone?
17 beta HSD
What is the enzyme that converts androstenedione or testosterone to estrone/estradiol?
Aromatase
What is the function of estrogen on the endometrium?
Proliferation
What are the metabolic effects of estrogen?
Decrease LDL, increase HDL, and increase Triglycerides
What is the effect of estrogen on bones?
Antiresorptive
What is the effect of estrogen on the liver?
Increase plasma proteins
What is the effect of estrogen on the blood?
Increased expression of coagulation factors, decreased antithrombin
What is the effect of estrogen in the menstrual cycle?
Key regulator during follicular phase
What is the role of estrogen in the HPA axis?
Feedback regulation for steroidogenesis and ovulation
What is the role of progesterone in the HPA axis?
Feedback regulation for steroidogenesis and ovulation
What is the effect of progesterone on the endometrium? Uterine contractions?
Causes endometrial differentiation, and preparation for implantation
Decreases uterine contractions
What is the effect of progesterone the cervical glands?
Increases cervical mucus viscosity
What is the effect of progesterone in the menstrual cycle?
Key regulator during the luteal phase
What cells does LH bind to? What does this cause?
Theca cells to increase Testosterone and androstenedione
What cells does FSH bind to? What does this cause? What enzyme is present in these cells?
Granulosa cells to increase estrone and estradiol
Aromatase
When do estrogen and progesterone exert a negative feedback? Positive?
Negative = most of the time Positive = mid ovarian cycle (around day 14)
What causes the surge in LH mid cycle?
Surge in estrogen
What causes the release of the ova from the mature follicle?
Surge is estrogen
What maintains the LH levels late in menstruation?
Corpus luteum
What happens during the follicular phase of the menstrual cycle? (2)
High frequency, low amplitude LH secretion
Estrogen rises
Endometrial proliferation
What happens during the luteal phase of the menstrual cycle? (2)
- Rise in estrogens and progesterone
- Endometrial differentiation under control of progesterone
Which hormone controls endometrial proliferation, and which controls the maintenance/secretory phase?
Proliferation = estrogen
Maintenance/secretory phase = progesterone
What happens to estrogen levels in the luteal phase of menstruation?
Progesterone levels rise
Estrogen levels fall from their peak, but remain elevated
What is the MOA of most steroids?
Bind to intracellular receptor, that then migrates into the nucleus
What is the effect of progesterone on lipid and glucose levels? Estrogen?
Progesterone = Increases LDL and fat deposition, Increases fasting Glucose levels
Estrogen = decrease LDL, increase HDL, increase fats
What is the steroid that causes insulin intolerance?
Progesterone
What is the effect of progesterone on prostaglandin production in the uterus? Why is this significant?
Decreases, which helps maintain the relaxed state of the uterus
What are the three primary natural steroids?
Estradiol
Estrone
Estriol
What are the two primary synthetic estrogens?
Ethinyl estradiol
Mestranol
What is the primary nonsteroidal synthetic estrogen?
Diethylstilbestrol
Natural steroid, synthetic steroid, or nonsteroidal synthetic: Estradiol
Natural
Natural steroid, synthetic steroid, or nonsteroidal synthetic: ethinyl estradiol
Synthetic
Natural steroid, synthetic steroid, or nonsteroidal synthetic: Estrone
Natural
Natural steroid, synthetic steroid, or nonsteroidal synthetic: estriol
Natural
Natural steroid, synthetic steroid, or nonsteroidal synthetic: Mestranol
Synthetic
Natural steroid, synthetic steroid, or nonsteroidal synthetic: diethylstilbestrol (DES)
Nonsteroidal synthetic
What is the benefit of ethinyl estradiol over regular estrogen?
Markedly increased half-life, and much lower dose needed
What is conjugated equine estrogens (Premarin) used for?
Hormone replacement therapy
Why is exogenous estrogen used in menopause?
Maintain bone density
Suppress hot flashes
Suppress urogenital atrophy
What are the four major side effects of exogenous estrogen use over the long term? When do these present?
- CHD
- Stroke
- PE
- Invasive breast CA
Present years later
What are the two protective effects of exogenous estrogen?
Decreases colorectal cancer and hip fractures
What is the way estrogen works as a contraceptive?
Suppresses ovulation via negative feedback pressure on HPG axis
How does estrogen work in treating acne? (2)
- Suppress steroidogenesis
- Increases SHBG production by the liver, thereby decreasing testosterone concentrations
What determines if a birth control pill increases or decreases acne?
More progesterone component usually means more acne
What are the usual side effects of estrogen?
breast tenderness
endometrial hyperplasia
Increased blood coagulation
What causes the increased migraine risk with exogenous estrogen use?
May indicate altered blood flow
What causes the increased risk of cholestasis with exogenous estrogen use?
Changes secretion of cholesterol into bile
What likely mediates the increased risk of developing breast CA with birth control?
Progestin, not estrogen
What is the one clear example where you can administer estrogen alone without concern of endometrial hyperplasia and cancer?
If they’ve had a hysterectomy
What is the MOA of estrogen causing cancer?
Trophic effect of hormones and ROS production during metabolism
How does estrogen increase blood coagulation?
Decreases antithrombin
Increases factors II VII IX and X
How does estrogen cause bloating?
Loss of intravascular fluid
What are the two major parent steroids of progesterone?
Progesterone itself
19-nortestosterone
What is the progestin that is derived from progesterone?
Medroxyprogesterone acetate
What are the progestins that are derived from 19-nortestosterone?
Norethindrone, norgestrel and other nor compounds
What is Medroxyprogesterone acetate (MPA) usually used for?
Commonly combined with estrogen for HRT
What is norethindrone usually used for?
Combinational or progestin only hormone contraception
What is norgestrel usually used for?
Combinational or progestin only hormone contraception
True or false: you never give estrogen alone for birth control
True
What is the MOA of progestins as a contraceptive?
Inhibits HPA axis (80% of the time)
Increases cervical mucous viscosity
Progestins are only effective at inhibiting the HPA axis about 80% of the time, yet are more effective than estrogen alone for contraception. Why are they still very effective as a contraceptive (and not because they’re usually combined with estrogen)
Because they increase cervical mucous viscosity.
What is the MOA of using progestins to treat dysmenorrhea?
Decreases endometrial mass and decreases prostaglandin production
What is the MOA of using progestins to treat endometriosis?
Decreases endometrial proliferation by regulating ER expression and stimulating differentiation of endometrial cells
Why are progestins used in HRT?
Decreases the risk of endometrial hyperplasia caused by estrogens
How does progesterone decrease the pain associated with uterine contractions?
Decrease prostaglandin production
