Lecture 18 - The Menstrual Cycle Flashcards
Menstrual Cycle
Menstrual cycle –regulated by fluctuating levels of sex hormones
Humans are nearly unique in having a menstrual cycle
Some apes and monkeys
Other species of mammals have estrous cycles
Menstrus = shedding of the lining
Cycle basics
Low E and P mean no negative feedback therefore increased GnRH
GnRH stimulates FSH and LH during menstruation
Starts maturation of ova
Estrogen and progesterone
2 phases:
Follicular is when oocyte into ovum
Luteal following release of ovum
P comes from corp luteum
Corpus luteum degrades
Progesterone decline instigates menstruation
E2 and P: neg. feedback for HPG
Exception to this…
Sex drive
E causes sex drive, not e and p as in rodents. P suppresses it. In rodents, E & P are close together, in humans when P arrives ovulation has occurred so no longer useful to have sex
Hypothalamic Parts
GnRH Neurons
In the medial preoptic area (MPOA)
GnRH acts on anterior pituitary
FSH and LH release
Stimulate ovum which produces E2 and P
There are neurons in the arcuate nucleus which contribute to negative feedback of GnRH neurons
FOLLICULAR PHASE
Between days 1 and 14 (interindividual variations)
late follicular phase = proliferative phase
ends with ovulation
Main hormone: estradiol
STEP ONE
GnRH will stimulate pituitary as P and E2 drop during menstruation
Goes into portal veins and then FSH and LH are released
FSH + LH rise
Stimulate oocytes into ova
STEP TWO
Step Two
Granulose cells around follicles proliferate
-increase FSH and LH receptors
Follicles start producing estrogen
- LH – acts on theca cells to produce T
- FSH activates aromatase to make E2
STEP 3
As estradiol increases negative feedback on the pituitary and hypothalamus
-Lower GnRH, FSH and LH levels
EVENTUALLY, ONE FOLLICLE GAINS DOMINANCE
More than one primordial follicle becomes a primary follicle. More than one of these keeps growing BUT
Near the end of follicular phase FSH is low due to inhibition by estrogen.
Only the follicle with the most FSH ad LH receptors can bind enough FSH to grow
Other follicles atrophy (atretic)
Selects for the most developed follicle
The role of gonadotrophins in the follicular phase
Look at how gonadotropins (FSH and LH) stimulate follicle development
How does this differ in Invitro fertilization
In vitro uses external FSH FSH sufficient for follicle growth No LH (blocked GnRH) but still as large as during typical cycle
LH is needed only to make E, not to develop the follicle
In IVF have extended FSH because exogenous administration
Many follicles mature (fewer atretic)
When admin hCG multiple mature follicles for fertilization
Usually hCG is released after fertilization and is important to maintain it. In IVF we administer from harvesting until implantation to give the maximum chance of pregnancy
Regimes usually skip LH as this is not needed (though some add it at the end just so it can do whatever it does)
STEP FOUR
The dominant follicle continues to secrete increasing estradiol
E2 reaches threshold
Causes LH spike (FSH too)
Ovulation
Basal body temp is higher at LH surge and this can be used to monitor for ovulation (0.3 degrees higher)
Ovulation
Ovulation: The release of a mature ovum (egg) from the ovary
It varies in the individual, but typically occurs on days 11 to 16 of the menstrual cycle.
How does the LH surge occur???
If E2 negative feedback on LH and FSH how does this spike in LH occur?
E2 threshold: once achieved E2 has positive feedback NOT negative
High levels stimulate different set of neurons….
GnRH Neurons
Gonadotrophin Releasing Hormone (GnRH) neurons in hypothalamus
Increase in the MPOA during puberty
Maintained throughout reproductive period
HPG axis
GnRH FSH+LH E2+P/T
What stimulates the GnRH system?
Start of GnRH Pulsatility: UNKNOWN!!!
(1) HPG axis activated at puberty
- Kisspeptin input from Arcuate
(2) GABA inhibits Kisspeptin in juvenile
Lack of Kisspeptin = no GnRH
(3) Late juvenile: glutamate stimulates Kisspeptin
Kisspeptin commences pulsatile GnRH
(4) Late puberty: females preoptic Kisspeptin
E2 activates these MPOA kisspeptin neurons for LH
This is not in the arcuate nucleus, it is its own thing in the MPOA
These give off excitation and activate the HPG axis causing the LH surge
Positive Feedback and the Luteal Surge
Hypothalamus: axons of kisspeptin neurons from arcuate nucleus form synapses with MPOA GnRH neurons
Estrogens negative feedback on arcuate kisspeptin neurons
Reduce GnRH to reduce HPG axis
Just before ovulation: estrogen reaches threshold
- positive feedback on MPOA kisspeptin neurons
- GnRH peak to induce LH peak
The luteal surge causes estrogen peak
-Follicle bursts, releasing the egg into oviduct
The Organizational-Activational Hypothesis
If females get androgens = masculanization
No ovulation, no sex behavior
When you masculinize a female, you are masculinizing LH production, like in men it it all about negative feedback sensitive, pulsatile release
in women LH surge
The change in masculinization is a lack of kisspeptin neurons in the PreOpticArea
Eg in CAH, polycist cos no LH surge therefore eventually cysts
Anovulation
Anovulatory cycle = literally an absence of ovulation
Most often due to hormonal imbalance
-Polycystic ovarian syndrome (PCOS)
Can also occur due to stress, sudden weight loss, excessive exercise or drugs
THE LUTEAL PHASE
Occurs after ovulation
-11-16 days
-Much more stable as this is fertilized ova takes 11 days to implant so cannot run late or early
-‘Begins with the formation of the corpus luteum – progesterone!!
Ends with either:
a) luteolysis
b) pregnancy
The Corpus Luteum
Comes from what was around the ova
The corpus luteum continues to grow for some time, secreting progesterone and some estrogen
Progesterone makes the endometrial lining ready for implantation of an embryo
Estrogen helps make the cervical mucous ‘fertile’
Progesterone and estrogens keep FSH and LH levels low: negative feedback
Luteolysis
Without FSH and LH the corpus luteum atrophies – luteolysis
Result of atrophy: drop in progesterone and estrogen
If pregnant progesterone remains high
Menstruation occurs + increase in FSH and LH to re-start the cycle
Fertilization and the start of pregnancy
High progesterone and moderate amounts of estrogen thickened endometrium for zygote
Zone pellucida around egg
Acrosome of sperm binds to pellucida
First to fuse with ovum membrane
Implantation of egg: human chorionic gonadotropin (hCG)
Measured by pregnancy tests
hCG prevents luteolysis so corpus luteum maintains progesterone until placenta can take over
Sperm and egg
Drills through zona peluza, digesting it
When it releases DNA, a cascade of Ca2+ hardens the shell so only one sperm fertilizes it
hCG production surges immediately after fertilization
At 12 weeks, makes placenta
hCG decreases
Placenta exists which keeps progesterone going
Highest risk for pregnancy before this point therefore told not to tell people you are pregnant before
HCG causes nausea so when it goes away on the 2nd trimester, so does this
Other hormones involved in pregnancy
Prolactin
necessary for lactation and some maternal behaviours
Increases steadily throughout pregnancy
Produces breast milk
Estradiol
Levels high across pregnancy, and rise only at the end
Augment effects of oxytocin which instigates labour
Menstruation
Monthly bleeding, “menses”
Shedding of the endometrium because E2+P reach threshold low
Menstruation lasts anywhere between 2-7 days
The average loss of blood is 35ml during menstruation (range 10-80ml)
Is not a lot, just a shot at a bar
Premenstrual syndrome (PMS)
A set of physical and psychological symptoms before the onset of menstruation
Symptoms of PMS are cyclic - begin up to 7 days before menstruation
End with menstruation
Spectrum disorder: Ranging from mild to severe
Premenstrual dysphoric disorder (PMDD) is most severe
Recognized in the DSM V now
PMDD only in 2-5% of women – must be severe to reach diagnostic criteria
Breast Tenderness Headaches Fatigue Bloating Skin Blemishes Muscle Aches Cramping
Appetite Changes Mood Swings Irritability Crying Spells Depression Sleep Disorders Anxiety
80% experience some symptoms
20-30% experience moderate to symptoms
2-5% experience most severe variant, PMDD
PMS research: Study One
Two groups of women at same points in their cycle
Group 1: 6-7 days away from their period
Group 2: 7-12 days away from their period
6-7 days away reported worse PMS symptoms
Maybe this is because they were looking for them
Might be all psychological (according to feminist prof)
PMDD research: Study Two
GnRH antagonists to eliminate menstrual cycle in PMDD
10 out of 18 women showed improvement
Estradiol and progesterone given to the 10 that showed improvement
PMDD symptoms reappeared after this treatment
The same study was done on women who do not have PMDD
After E2+P treatment they did not experience the PMDD symptoms
Hormone levels in both groups of women were equalized
Only women who had PMDD experienced PMDD symptoms with hormone
Hypothesis:
Hormone sensitive women (more receptors or different distribution of receptors/subtypes)
Not hormone levels but the sensitivity to the hormones
Similar to role of testosterone in male sexual behaviour
PMDD: a modern phenomenon
Before contraceptives women were lactating or pregnant while in reproductive years
PMS more a byproduct of modern civilization
Similar arguments about changes in brain following pregnancy
Similar argument about our next topic which is menopause
A state that women rarely experienced from an evolutionary perspective….
