Reproductive ageing Flashcards
What is ovarian reserve?
Oocytes and Follicles
Process begins in embryonic life
20 weeks gestation - 6-7 million follicles
At birth - 1.5-2 million follicles
At menarche - follicles
Follicular atresia (breakdown) continues throughout life
Follicular loss accelerates when the total number of
follicles is -25,000
When follicles are sufficiently depleted
menopause occurs…
What is the correlation beween ageing and reproduction?
- As age increases, miscarriage rate/ month increases
- Pregnancy rate decreases / month
What are the stages of reproductive ageing workshop (STRAW)?
-Reproductive
- Menopausal transition
- Postmenopause
- FSH levels increase
What are some facts about menopause?
- Average age = 51 years
- Factors impacting menopause:
- Maternal age at menopause
- Tobacco use
- Socio-economic status/education
- Alcohol use
- BMI
- Factors that are unlikely ro impact on age at menopause:
- Oral contraceptive pill use
- Race
- Height
What is the endocrinology of the mestrural cycle?
With rises in FSH, a few follicles are stimulated — FSH then stimulates inhibin (from
granulosa cells) which suppresses production of FSH via —ve feedback
During the follicular phase, oestrogen suppresses production of from the
anterior pituitary gland. When the egg has nearly matured, levels of estradiol
reach a threshold above which they now stimulate production of LH (for ovulation)
These opposite responses of LH to oestrogen may be enabled by the presence of
two different estrogen receptors in the hypothalamus: estrogen receptor alpha,
which is responsible for the negative feedback loop, and estrogen
receptor beta, which is responsible for the positive relationship
During the luteal phase progesterone (from the corpus luteum) inhibits LH/ FSH
making the endometrium receptive to implantation of the blastocyst and
supportive of the early pregnancy; side effect of raising basal body temperature
What are the hormonal changes in the ageinf reproductive system?
1.) Depleted follicle number
2.) Oestrogen ususually regulates LH surge
3.) Inhibin usually inhibits FSH secretion
Both of these decrease
What is the inhibin B ovarian reserve test?
- Can measure the level of Inhibin B
- secreted predominantly during folliculat phase
- May influence folliculogenesis (maturation of ovarian follicle)
- Primarily produced by an FSH-sensitive cohort of antral follicles (mature ovarian follicles)
- In ageing:
- Decrease in inhibin B secretion :
- Number os small antral follicles recruited in each cycle diminshes and consequently insufficient inhibin B is produced to fully lower FSG
- Associated with elevated FSH levels
- Also decreased oocyte quality and fertility potential
What is the anti-mullerian hormone Ovarian reserve test?
Inhibits the development of the
Müllerian ducts (paramesonephric
ducts) in the male embryo to stop ovaries forming
As number of antral follicles decrease with age, Anti-Müllerian hormone (AMH) serum levels also become diminished (undetectable near
menopause)
Represent ovarian quantitative
reserve
Independent of menstrual cycle
phase- so useful diagnostically
What are the fertility changes that occur during peri (transition) menopause?
Fertility and Fecundity Decrease
* Peak fecundity Occurs at 24 y, with a gradual decrease to 35 and a rapid decrease after 35
Ovulatory cycle continues after onset of perimenopause
However, cycle length becomes more variable
* Shortening of follicular phase
* No change in luteal phase
What are the symptoms of perimenopause?
Vasomotor instability (85%)
Sleep disturbances
Mood disturbances
Somatic symptoms:
Fatigue, palpitations, headache, increased migraine,
breast pain and enlargement.
Oligo- -Y Anovulation (ovaries don’t release an oocyte)
heavier or irregular periods
Most effects due to loss of oestrogen
What are hot flushes?
- Sudden onset of reddening of the skin over the head, neck and chest accompanied by a feeling of intense body heat and sometimes concluded by profuse perspiration
- Number 1 complaint to physicians
- Can last for a few secs to several mins
- Rare to recurrent every few minutes
- Most severe at night and during times of stress
- More common among overweight women
- Usually last for shortish periof, i.e.,1-2 years but for 25% of ppl will last for more than 5 years.
What causes menopause?
- Lack of oestrogen leads to a change in the sensitivity of the “set” point in the thermostat, This misinforms the hypothalamus about increased body temperature but the resposne is to dissipate heat
- The message is transmitted by the nervous system’s chemical messengers , including epinephrine, norepinephrine, prostahlandin and serotonin
- Response = elevated HR
- Skin vasodilation to circulate more blood to radiate off the heat
- Sweat hlands release sweat to cool the body off even more.
How to manage hot flushes?
Lower the ambient temperature
Short-term Oestrogen replacement (80-95% reduction)
Alternative therapies
High dose progestins
SSRl’s (Paroxetine, Fluoxetine(+/-))
* SNRI (Velafaxine (+/-))
Gabapentin
Clonidine (adrenergic agnoist)
What are some other key phsyical changes in menopause?
- Psychosomatic
- Vasomotor instability
- Metabolic changes?
- Coronary artery disease?
- Accelerated bone loss?
- Urogenital atrophy?
- Skin changes?
What is the menopausal metabolic syndrome?
Lipids
— Hypertriglyceridemia
- Decrease in HDL Cholesterol
— increase in LDL Cholesterol
Abnormalities in Insulin
* decrease in insulin secretion and elimination
— Insulin resistance
-Hyperinsulinemia
— HRT reduces onset of DM and improves insulin resistance
Other Factors
— Endothelial dysfunction
— increase in visceral fat
— increase in uric acid
- decrease in SHBG
- increase blood pressure
* increase in PAI-I
