Menstrual Cycle I Flashcards

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1
Q

What is needed for correct menarche to occur?

A

Pulsatile release of both GnRH and gonadotrophins is key in maintaining HPG axis

Continuous release causes cessation

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2
Q

How is length of menstrual cycle measured?

A

The number of days between first day of menstrual bleeding of one cycle to onset of menses of the next cycle

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3
Q

What are the stages of the menstrual cycle?

A
  • menses
  • follicular phase
  • ovulation
  • luteal phase
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4
Q

What is the median duration of menstrual cycle?

A

Median duration of MC is 28 days with most cycles between 25=30 days

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5
Q

How long does menstruation last?

A

Menstruation lasts 3-8 days, written as 7/28 or 5-6/27-32

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6
Q

What is polymenorrhea?

A

MC < 21 days = polymenorrhea

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7
Q

What is oligomenorrhea?

A

MC>35 days=oligomenorrhea

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8
Q

When does the menstrual cycle become expectedly irregular

A

Menstrual cycle typically most irregular around extremes of reproductive life i.e menarche and menopause

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9
Q

Describe the levels of FSH throughout the cycle

A

FSH rise (MF) coinciding with antral follicle recruitment

Peaks with LH surge

Suppressed completely during luteal phase

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10
Q

How do LH levels change during the menstrual cycle?

A

LH rises with an exponential peak (LH surge), suppressed during luteal phase

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11
Q

Why do E2 levels rise?

A

E2 levels rise due to increase in antral follicle no. secreting more oestrogen
Large exponential rise due to dominant follicle selection → LH surge

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12
Q

Which hormone dominates the luteal phase?

A

Progesterone dominates luteal phase as secreted from CL.

Rise due to ovulation and demise due to lack of fertilisation

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13
Q

Which steroids are produced by the ovary?

A

Theca - androgen production

Granulosa - oestrogen production

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14
Q

Why do only granulosa cells produce oestrogen?

A

Aromatase only available in GC

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15
Q

What causes antral follicles to grow?

A

Selective FSH rise causes selection of antral follicles to grow

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16
Q

How does the dominant follicle survive?

A

Growing follicles pump out E2 (-ve) decline in FSH causes DF to survive only

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17
Q

How does DF survive and grow?

A

DF grows exponentially (MF) pumps out lots >300pmol of E2 (+ve) - LH surge

Ovulation of mature oocyte

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18
Q

What happens to remaining follicles (not DF)?

A

Remainder of oocyte converted into CL secreting P > E2 (-ve)

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19
Q

Describe the cyclical nature of mammals

A

All mammals have cyclical ovarian function & the same reproductive system (in terms of HPG axis) to produce a mature egg and the necessary sex steroids

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20
Q

Which mammals undergo menses?

A

Menstrual cycles occur only in humans, primates (apes and monkeys)

Named for regular appearance of menses i.e. shedding of the endometrial lining

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21
Q

What is meant by oestrous cycles?

A

The cyclic appearance of behavioural sexual activity (heat or oestrus)

No menstruation – the endometrium is reabsorbed if fertilization does not occur

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22
Q

Describe the feedback mechanisms of the HPO axis

A

-ve / +ve feedback from E2 & P

But also +ve/-ve feedback from activins and inhibins

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23
Q

Where is inhibin produced?

A

Produced by testis (Sertoli cells) and ovary (Granulosa cells)

24
Q

Describe the structure of inhibin

A

Disulphide-linked protein dimers

Common α-subunit with different β-subunits giving two forms of Inhibin

25
Q

How do inhibins affect FSH secretion?

A

Both forms specifically suppress FSH secretion by pituitary without affecting LH secretion

26
Q

Where are activins found?

A

Isolated Activins from follicular fluid

27
Q

What is the role of activin?

A

stimulate FSH secretion

28
Q

What is follistatin?

A

Another FSH-suppressing protein from follicular fluid

29
Q

How does Follistatin produce its FSH-suppressing efefcts?

A

Binds activin with high affinity » neutralizes FSH-stimulating ability of activin

30
Q

How are inhibis and activins produced?

A

Biosynthesis of inhibins and activins occurs from 3 genes, makes precursor protein:
> from TGFb superfamily

  • a-protein specific for inhibin
  • Ba-protein can form either activin / inhibin
  • Bb-protein can form either activin / inhibin
31
Q

What are the different forms of inhibin?

A

Inhibins take 2 forms depending on β-chain composition

- Inhibin A and Inhibin B

32
Q

What are the various forms of activins?

A

Activins take 3 forms depending on β-chain composition

Activin A (βA-homodimer), 
Activin B (βB-homodimer)
Activin AB (βAβB-heterodimer)
33
Q

Which cells secrete activin / inhibin?

A

Activin and inhibin released by granulosa cells

34
Q

How does activin:inhibin ratio change throughout the menstrual cycle?

A

Ratio of Activin:Inhibin decreases as the cycle progresses

  • Activins = ↑FSH in EFP
  • Inhibins = ↓FSH in LFP
35
Q

What other factor can affect activin activity?

A

Activin activity can be further regulated by how much follistatin is in the follicular fluid - can bind and reduce activity

36
Q

Describe the follicle size in the late follicular phase

A

Late follicular phase corresponds with larger antral follicles

37
Q

What is AMH?

A

Anti-Mullerian Hormone is a glycoprotein and member of the TGFβ superfamily

38
Q

When is AMH expressed in males?

A

In males expressed from week 8 of development; causes regression of Müllerian ducts by a wave of apoptosis

39
Q

Where is AMH secreted in the ovaries?

A

Expressed by ovarian granulosa cells with levels peaking in selectable follicles

(large preantral and small antral follicles) » then decreasing
AMH produced primarily in early antral follicles and then dies off as follicles grow

40
Q

What are the 2 actions of AMH on folliculogenesis?

A
  1. Inhibits transition from primordial → primary follicles

2. Inhibits FSH-dependent cyclical recruitment of follicles

41
Q

What is the evidence that AMH limits primordial-primary follicle transition?

A

Born with resting primordial follicles - slowly activate and grow
k/o AMH = follicle growth

42
Q

How does AMH inhibit FSH-dependent recruitment of follicles?

A

Inhibits FSH-stimulated aromatase and FSH receptor expression → in normal cycle would act to prevent over-recruitment of growing follicles

43
Q

Describe the process of follicular growth of preantral follicles

A

Preantral follicular growth occurs continuously once follicles activated

Grow slow + regulated - reach point where FSH required

↑FSH = desired size follicles continue to grow and enter next stage - smaller cohort chosen

44
Q

Outline the growth of antral follicles and the DF

A

Antral follicles grow
Granulosa cells multiply
Activins activated to enhance stimulation + follicle growth

Follicles grow = E2 production and inhibins resulting in -ve feedback = ↓FSH

⇒ dominant follicle selected as other follicles in cohort die away due to lack of FSH

45
Q

What stimulates dominant follicle selection?

A

Raised FSH present a “window” of opportunity

E2 levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth

46
Q

How does the DF survive the lack of FSH?

A

As FSH falls, LH increases.
Dominant follicle acquires LH receptors on granulosa cells.

Other follicles do not, so they lose their stimulant and die.

47
Q

Which androgens are stimulated by gonadotropins during the menstrual cycle phases?

A

Follicular phase
- FSH drives oestrogen production

Luteal phase
- LH drives progesterone

48
Q

Which receptors are expressed by Granulosa cells?

A

Granulosa have FSHr

Later acquire LHr in mid-follicular phase onwards

49
Q

Which receptors do theca cells express?

A

Theca always has LHr, never FSHr

50
Q

Describe how the levels of inhibin B vary in the menstrual cycle

A

highest in early-mid FP
- (activin: inhibin)

Declines in LFP - small peak at LH surge

Zero in luteal phase

51
Q

Outline the levels of inhibin A in the menstrual cycle

A

Increases in late FP

Highest levels in luteal phase (made by CL) – contributes to inhibition of FSH.

Decline in Inhibin A at end of luteal phase allows for FSH increase

52
Q

What other factors provide energy for mothers during pregnancy?

A

Pregnancy is an energy demanding process for mother - requires input from adipose tissues, insulin etc.

53
Q

How may pathophysiological processes get disrupted during pregnancy?

A

If the mother becomes:
- Anorexic: exercise induced /eating disorders

  • Overweight: insulin resistance
54
Q

Why do changes occur in the reproductive tract during menstrual cycle?

A

Characteristic changes occur in reproductive tract tissues due to varying concentrations of E2 & P in different parts of MC

55
Q

Which areas of the reproductive tract are affected by menstrual cycle hormonal changes?

A

Endometrium
Oviduct/Fallopian tubes
Cervix
Vagina: changes in vaginal epithelial cells