Female menstrual cycle Flashcards
Dr. Pond
Where does the development of female gametes occur?
Follicles
(starting during the prenatal development of the female)
millions of primordial follicles are formed
only 400-500 are released during reproductive years
Types of Follicles
Follicle development
-Primordial follicle
-Primary follicle
-Graafian follicle (mature follicle)
-Corpus luteum
What is the difference between the Primordial and Primary follicle?
Primordial follicle: one layer of squamous-like follicle cells surrounding the oocyte
Primary follicle: one or more layer of cuboidal cells surround the oocyte
After 1 week of maturation, which hormone is secreted by the dominant follicle
Estrogen
Which hormone drives the development of the follicles?
GnRH -> FSH (follicle-stimulating hormone)
Function of estrogen at day 7
Negative feedback
inhibition of GnRH release -> low FSH
-so other the follicles lose hormonal support and degenrate (atresia)
Function of estrogen at day 14
Positive feedback
stimulates GnRH release -> causing a surge in FSH/LH release
What is the function of LH at day 14
after the surge of FSH/LH
LH causes the follicle to rupture -> OVULATION
the ruptured follicle becomes the Corpus luteum
What is the function of the Corpus luteum?
It secretes estrogen, progesterone, and inhibin
-> inhibits GnRH and FSH/LH release -> thereby preventing the maturation of new follicles since FSH is needed for maturation
What triggers the restart of the menstrual cycle?
The corpus luteum degenerates if fertilization doesn’t occurs -> levels of estrogen, progesterone and inhibin decrease
-> No negative feedback on GnRH
What is the effect of estrogen on the endometrium?
it causes the endometrium to become proliferative (the cells divide, it becomes thick)
What is the effect of progesterone on the endometrium?
-opposes the proliferative effect of estrogen, so the endometrium doesn’t grow too much
-causes the endometrium to become secretory (providing nutrition)
What happens if a signal for pregnancy is received?
release of hCG (until the 1st trimester)
-> prevents degradation of the corpus luteum
-> continued release of
estrogen (endometrium stays proliferative, negative feedback on GnRH)
progesterone: opposes estrogen and keeps the endometrium secretory
Which form of estrogen is mainly produced by the ovary?
Estradiol (E2)
What are the hepatic effects of estrogen in the liver?
-increased synthesis of clotting factor
-increased synthesis of angiotensin I -> increase in blood pressure
caused by the reabsorption of conjugated metabolites of estradiol (enterohepatic circulation), especially when estrogens are taken orally
Estrogen effects in puberty
-Development of vagina, uterus, uterine tubes
-Secondary sex characteristics:
growth of breasts, closing of the epiphysis of long bones, axillary and pubic hair, distribution of body fat, hyperpigmentation of skin (areolae, genitals)
Other Estrogen effects in puberty
-Uterine: hyperplasia of endometrium, watery cervical mucus
-Skeleton: normal skeletal development, antiresorptive (opposes bone breakdown)
-Cardiovascular system: function of blood vessels
-triglycerides and lipoproteins: elevate HDL, decrease LDL and cholesterol
-Liver: increase CBG,
TBG, SHBG, increase clotting factors,
angiotensinogen
-Blood coagulation
-CNS: cognition and memory, mood
- colon, urogenital tract, eyes
Which subtype of estrogen is Estrogen-receptor selective?
Estetrol
Nuclear ER-alpha - agonist
Membrane ER-alpha antagonist
What are SERMs?
-Selective estrogen receptor modulators (bind to estrogen receptors)
-Inhibit ER activity in some tissues/ increase it in others
Tamoxifen and cancer
when Tamoxifen binds to the receptor it does not cause a change in the shape of the receptor -> the receptor is not able to bind to coactivators
Effects and use of Tamoxifen
-Antagonist in the breast (used in breast cancer)
-Agonist in uterus and bone
-Reduced risk of atherosclerosis
-black box warning: uterine malignancies and clot risk
Effects and use of Raloxifen
-Antagonist in breast
-Similar to tamoxifen, but no detectable agonist activity in uterus
-Similar effects as estradiol on lipids and bone
-Used for postmenopausal osteoporosis
-Breast cancer prophylaxis
-ADE: clot risk
Effects and use of Clomiphene
-Partial agonist in hypothalamus/pituitary
-Long-term binding of ER (weeks) results in
downregulation in ERs -> no negative feedback -> GnRH release -> FSH/LH release
How do Progesterone antagonists work?
-Progesterone is needed for pregnancy (keeps endometrium secretory)
-Progesterone antagonists block progesterone receptors
-can terminate pregnancies in the first 7 weeks (95% of women)
-used with prostaglandins (stimulates contractions which helps with the shedding)
-ADE: delayed ovulation in the following cycle, prolonged bleeding
MOA of combination pills
-negative feedback to pituitary -> low level of FSH/LH -> inhibit OVULATION
-change in cervical mucus (progesterone makes it more sticky and harder to penetrate)
-uterine endometrium (it doesn’t become thick and secretory, bc levels of estrogen and progesterone are kept low due to negative feedback)
-> can be helpful for women having heavy bleeding due to too much estrogen -> too thick endometrium -> heavy bleeding
motility and secretion in uterine tubes (due to low levels of progesterone)
How does Progestin alone work?
prevention of pregnancy
-inhibit ovulation (only 85%) during follicular phase
-increase viscosity in cervical mucus
-atrophic (decrease) uterine endometrium
-decrease motility and secretion in uterine tubes
Which contraceptive might be appropriate for breastfeeding patients?
Only progesterone
because estrogen may suppress lactation
Which contraceptive might be appropriate for patients who struggle with acne?
-progesterone without androgenic effect
-progesterone with estrogen (estrogen opposes the androgenic effects of progesterone)
What are the severe ADE of contraceptives?
-Thromboembolism: 3x risk (estrogen)
-MI
-stroke (estrogen)
-cholestatic jaundice (progestin)
-depression
-cancer
How does the drug Phexxi work?
-contraceptive vaginal gel (lactic acid, citric acid, potassium bitartrate)
-makes the pH in the vagina acidic so that sperm won’t survive
-ADE: burning sensation, UTI, dysuria, vaginal pain
