Menopause

Question 1

What are the four theories around why we have Menopause?

Answer 1

1. Blessings of Modern Life
   
   • Most animals reproduce as long as they live
   • We live longer now, this wasn’t an issue in the past!
   • Fixed # follicles
2. Senescence
   
   • Deterioration of reprod. precesses with age
   • Protects aging women from hazards of childbirth.
3. Group Selection***
   
   • Menopause protects the human genepool against birth defects due to the age-related increase in chromosomal abnormalities
   • Only confirmed theory!!
4. Good-mother/grandmother
   
   • Pause from reproduction to provide extended maternal care of offspring

1,2 and 3 may just be an incidental finding

Question 2

How was the timing of Menopause determined?

What signifies the end of a woman’s reproductive life?

Answer 2

• Under intense evolutionary pressure, consequence of the ovaries running out of follicles
• Occurs between 50 and 52 yrs (45-55)
• End of Reproductive Life: last epsidoe of natural menstrual bleeding men- month, pauo- to stop
• Atresia and ovulation (only ~400 follicles) lead to exhaustion of follicular reserve

Question 3

POF and EM?

Answer 3

Premature Ovarian Failure: ovarian failure <40yrs

• Affects 1% of women and 0.1% by age 30yr
• Increasing issue as women delay childbearing

Early Menopause: 40-45yr

Question 4

The age of menopause can be correlated with the age of _____ by a ____year gap

Answer 4

The age of menopause can be correlated with the age of last birth by a 10 year gap of last time of fertility.

This shows us that is a woman gets menopause at 48 she was probably infertile at 38

Question 5

How do follicle numbers change throughout life?

Answer 5

• peak in fetal development of ~7mill
• Down to 1mill by birth
• steady ddecline to ~400, 000 by puberty
• Menopause: <1000 follicles

Question 6

What’s the ‘popcorn Hypothesis’?

Answer 6

Describes how the quality of follicles also decrease over time, as well as the quantity

• The best follicles go early (20’s)
• As you get close to 40, the ovary “turns up the heat” by increasing the levels of FSH to try get the last few follicle ‘kernels’ to grow and ovulate.
• But as you age the amount of chromsomal abnormalities decrease.

Question 7

When are you ‘most fertile?

Answer 7

Optimal Fertility: 20’s

declines

End of fertility: starts around 40’s

Question 8

University students knowledge quiz

Answer 8

1. Chance of a women getting pregnant from unprotected intercourse around ovulation
   
   • Real answer:
   • Students answer: overestimated fertility by 10-20%
2. Chance of a women getting pregnant via IVF
   
   • Real answer
   • Students answer: overestimated older years by 20-30%, medical students convinced technology could save fertility

Question 9

What influences timing of Menopause

Answer 9

• Independent from race, parity, marital status and age of menarche
• Mothers and daughters have similar menopausal age strong genetic correlation/prediction
• Pourly nourished and/or smoking women have an earlier menopause
  
  • Repro. system the first to shut down
  • smoking is earlier by 1-2 yrs; mainly from atresia of primordial follicles

Question 10

Does ‘male menopause’ exist?

Answer 10

“andropause”

• Thought to affect men 40-55yr
• Due to testosterone decline
• Body changes occur very rapidly: mood change, fatigue, loss of sex drive and physical agility
• Not much strong evidence; and you’d need a really low level to have an effect
  
  • Probably just to sell male products

Question 11

Draw the female reproductive phases leading upto

Answer 11

Pre-menopause: 40 to age of irregular menstrual cycles (~46 yrs)

Menopausal Transition: from start of irregular cycles to menopause (Last menstrual bleed)

Post-menopause: after last menstrual bleed.

Peri-menopause: when all the symptoms and clinical features are noted

Ovarian senescence: as ovary is active for ~1yr after last menstrual bleed.

Question 12

What does STRAW show us.

Answer 12

We can measure the stges of menopause BUT

Its the peri-menopause where we see the clinical symptoms, the longer and more irregular menstrual cycles

Question 13

When do we have irregular menstrual cycles?

Answer 13

At the beginning and end of a womens reproductive life.

• Takes until around 20-30 to begin having regular cycles
• THis gets irregular again ~40yr as cycles begin to length (transitioning into menopause begins)
  
  • Where a follicle begins to grow, nothing happen/goes wrong, undergoes atresia and we have to wait for the next cycle to get another follicle

Question 14

The longer the cycle length, the less like it is ________

Answer 14

The longer the cycle length, the less like it is ovulatory

<40 days: ovulatory

>40 days: not likely to develop and ovulate

Question 15

Older women are more likely to have _______ cycles

Answer 15

Older women are more likely to have anovulatory cycles

26-40 yrs: ~5 % anovulatory

41-50yrs : ~15% anovulatory

Question 16

THe Perimenopausal phase is a time of?

Answer 16

Erratic hormone fluctuations which starts at the begnning of the menopausal transition and continues through to ovarian senescence.

~5-10% of women don’t experiance a transition phase and just abruptly cease menstrual activity

Climacteric: Physical and emotional symptoms associated with the perimenopause

Question 17

Dogma around accelerated decline of events just prior to perimenopause

Answer 17

1. Follicle levels reduce below a critical threshold (~25,000 follicles)
2. Inhibin B levels begin to decline
   
   • Inhibin B is produced by the granulosa cells of primary follicles, and these cells are decreasing along with the follicles
3. ​Release on inhibin negative feedback on FSH
4. FSH levels rise (popcorn hypothesis)
5. Acceleration of last few Follicle loss by:
   
   1. ​Shortened follicular phase
   2. Increased early follicular oestrogen

Question 18

How much does the increased FSH deplete the follicuar pool just prior to perimenoopause?

Answer 18

• Increased FSh stimulates a greater proportion of primordial follicles to enter the growing pool
• Accelerates depletion of primordial reserve from ~20-40/day to ~80/day

Also increases “twinning” as you age because of this!! Two dominant follicles have been able to survive

Question 19

What are feautures of perimenopause?

Answer 19

• Irregular cycles
• Annovulatory cycles comon (bad follicles)
• Gonadotrophs elevated (especially FSH)
  
  • remains high post-menopause
  • clinical indicator
• Oestrogen levels are often high early peri-MP, but then low late peri-MP
• Unpredictable hormone patterns
• Ovulation is still possible
• but Contraception is difficult

Question 20

Answer 20

FSH: loss of negative feedback from inhibin, begins to rise ~7-8 yr prior to menopause. Remains high after (clinical diagnostic indicator)

LH: only rises a little as not affected by inhibin

Estrodial: Produced by granulosa and thecal cells in follicles, high up till 2 years prior to menopause, then comes crashing down

Estrone: relatively unaffected as the adrenal glands are the main producer. This becomes the main sources of oestrogen most menopause

Question 21

Answer 21

Testosterone: loss of libido

Question 22

Post-menopause?

Answer 22

From the last menstrual bleed, this doesn’t truly reflect what’s happening in the ovary.

There’s no simple test to confirm menopause, and it’s usually defined retrospectively.

Woman >45yrs, who’s had amenorrhoea for at least 12 months is highly unlikely to ovulate again, and is probably post-menopausal.

Fluctuations in hormones (esp. oestrogen) can continue >6months

Question 23

Are there any follicles left post-menopause?

Answer 23

Some may be left, but they are non-responsive

(POPCORN HYPOTHESIS)

Question 24

Post-menopausal oestrogen production

Answer 24

• By around 1yr post menopause, the ovary has essentially ceased producing hormones: “ovarian senescence”
• Estrogen produced daily is less then 1/10th what she used to
• Circulating estrodial levels are very low and don’t fluctuate
  
  • Pre-MP: changes 10-fold
  • Post-MP: very little variation
• Main Estrogen source: Oestrone
  
  • still reduced post MP

Question 25

Difference between oestrogen and oestrone?

Answer 25

Oestrogen: from extraglandular production * Three types: **estradiol, estrone and androstenedione** **Estradiol:** produced by the growing follicles * Source of high levels of oestrogen in a reproductive woman **Estrone:** product of this aromatisation, * while some of it is converted to oestrodial, it's the predominant E in the post-menopausal years * What men use, now we have the same levels * In stromal cells of adipose tissue via ***aromatisation of androstenedione*** (secreted froom the adrenal cortex) * **1/10 of biological activity** of oestradial "weakly oestrogenic"

Question 26

The perimenopausal symptions are due to the deprivation of _______ during this time

Answer 26

The perimenopausal symptions are due to the deprivation of **oestrogen** during this time. * These symptoms usually follow the onset of the menopausal transition but they may precede it, and continue for a while post-menopause * ~**10% need medical help** to deal with these symptoms

Question 27

Top three symptoms of Menopause are?

Answer 27

1. Hot Flushes : change in vascular structures 2. Night Sweats: poor sleep quality, anxiety etc 3. Vaginal Dryness Lower breast volume means we can screen older woman better

Question 28

Menopause Treatment is?

Answer 28

Hormone Replacement Therapy Oestrogen treatment will stop or reduce symptoms Adverse riskks not entirely known, so not given forever * Increase breat or uterine cancer, heart disease * Does reeduce osteoporosis Should be given for the smalles amount and only for women with moderate to severe symptoms. LOWEST DOSE AT SHORTEST TIME