EXAM #5: ESTROGENS & PROGESTINS Flashcards
What regulates steroidogenesis in the ovary?
Gonadotropins (LH and FSH)
What cells are required for estrogen synthesis in the ovary?
Theca and granulosa cells
What is the two-cell hypothesis in steroidogenesis in the ovary?
LH= increased androstenedione synthesis in Theca cells
- andorstenedione is then made into testosterone
FSH= stimulates testosterone–>estradiol conversion in the granulosa cells
How will estrogen and progesterone alter GnRH release?
Negative feedback
When does positive feedback occur with estrogen and progesterone ?
Mid-ovarian cycle i.e. day 14
*Positive feedback= increased LH necessary for ovulation
What are the three phases of the menstrual cycle?
1) Follicular
2) Ovulation
3) Luteal
What happens during the follicular phase of the menstrual cycle?
- ESTROGEN rises
- Endometrial cell proliferation occurs
What happens during ovulation?
Estrogen-mediated positive feedback on LH leads to a LH spike that causes ovulation
What happens during the luteal phase of the menstrual cycle?
- Rise in estrogen and progesterone, but MOSTLY PROGESTERONE
- Progesterone control differentiation of the endometrial lining for implantation
What happens if implantation does not occur during the menstrual cycle?
Steroidogenesis is NOT maintained and endometrial lining is shed
What is the MOA of endogenous steroids to produce a physiologic effect?
Bind intracellular receptors and modulate trascriptional activity
Where do endogenous steroid agonists and antagonists compete?
Steroid binding sites
How do progesterone and estrogen differ in regards to their effect on the endometrium?
Estrogen= proliferation
- Follicular phase
Progesterone= differentiation to prepare for implantation
- Luteal phase
What are the metabolic effects associated with estrogen in regards to lipids, bone, liver, and blood?
Lipids= decrease LDL and increase HDL
Bone= antiresorptive
Liver= increased plasma proteins
Blood= increased coagulation factors and decrease antithrombin i.e. PROCOAGULANT
What are the metabolic effects associated with progesterone in regards to lipid and glucose?
Lipids= increase LDL and fat deposition
Glucose= increased fasting glucose
What effect does progesterone have on uterine contraction?
Progesterone DECREASES uterine contraction
How does progesterone decrease uterine contraction?
1) Decreased prostaglandin production
2) Maintenance of relaxin
What effect does progesterone have on cervical glands?
Increased cervical mucous viscosity
*This impairs the sperm ability to swim
What is the primary natural estrogen?
Estradiol
What is the primary synthetic estrogen? What are these drugs used for?
Ethinyl estradiol
*Also, Mestranol both of which are used for birth control
What is diethylstilbestrol?
Non-steroid synthetic estrogen-mimic
*Not used in clinically practice but important for boards
What advantages are seen with synthetic estrogen vs. endogenous estrogen?
1) Increased half-life
2) Decreased first pass effect
This is advantageous from a compliance standpoint
What are conjugated equine estrogens? How are these used clinically?
Natural water-soluble estrogen sulfates
- Higher dose vs. synthetics
- Used for hormone replacement therapy
What are the clinical indications for estrogen therapy?
1) Hypogonadism
2) Hormone replacement therapy
3) Contraception
4) Acne
Specifically, what are the goals of estrogen used in hormone replacement therapy?
1) Maintain bone density
2) Suppress hot flashes
3) Suppress urogenital atrophy
*Often done in post-menopausal women
What risks are associated with estrogen/hormone replacement therapy?
1) CAD
2) CVA
3) PE
4) Invasive breast cancer
Note that this is seen with 4-5 years of therapy; thus, estrogen is NOT a good choice for long-term HRT
What can hormone/ estrogen replacement be protective against?
1) Colorectal cancer
2) Hip fracture
What is the MOA of estrogen therapy as a means of contraception?
Negative feedback on the HPG axis that prevents the LH surge necessary for ovulation
What is the MOA of estrogen as an acne treatment?
1) Suppress steroidogenesis
2) Increase Sex Hormone Binding Globulin (SHBG) to decrease free testosterone
What are the key adverse effects of estrogen therapy (not HRT)?
1) Breast tenderness
2) Endometrial hyperplasia
3) Increased blood coagulation
Also, nausea, cholestasis, migraines, cancer, and bloating
What is the relationship between combined HRT and cancer?
Increased risk of invasive breast cancer
*May be related to progestin not estrogen
What is the relationship between HRT estrogen monotherapy and cancer?
Increased risk of endometrial cancer
What is the relationship between estrogen contraceptive therapy and cancer?
REDUCED ovarian and endometrial cancer
How can estrogen lead to the development of cancer?
1) Trophic effects of the hormone (proliferation promotion)
2) ROS production during metabolism
What are the two parent steroids for the progestins?
Progesterone and 19-nortestosterone
List the progestins.
- Medroxyprogesterone (MPA)
- Norethindrone
- Norgestrel
What are the clinical uses for progestins
1) Contraceptive agents
2) HRT
3) Dysmenorrhea
4) Endometriosis
How does the efficacy of estrogen and progestins compare in prevention of ovulation? Contraception?
Ovulation= progestins only suppress LH surge/ ovulation 80% of the time
Contraception= equal b/c of effect on cervical mucous
What is the effect of progestins used in HRT with estrogen?
Decreased risk of endometrial hyperplasia
What is the MOA of progestins to treat dysmenorrhea?
- Decreased endometrial mass
- Decreased prostaglandin production/ uterine contraction
What is the MOA of progestins to treat endometriosis?
Decreased endometrial proliferation
In theory, what would happen to the endometrial lining with estrogen only? What is the role of progestin?
Continued growth
*Progestins inhibit growth/ proiferation mediated by estrogen
