Menopause Flashcards
Define menopausal transition
Period of time from changes in menstrual pattern to menopause
Define menopause
The permanent cessation of menstruation due to loss of ovarian follicular function (diagnosed after amenorrhoea for 12 months)
Define perimenopause
No consistent definition. A period of changing ovarian function which precedes the menopause by 2-8 yrs
Define premature ovarian failure
menopause younger than 40
Name 7 symptoms of the menopause
- mood swings
- dry vagina
- Impaired fertility
- Hot flushes
- Disturbed sleep
- Reduced cycle length due to reduced follicular phase
- Irregular periods with episodes of amennorhoea
Why does menopause occur?
- Reduced number of primordial follicles
- Decline in umber of granulosa cells per follicle and functionality
- Impaired oocyte development
- Granulosa cell dysfunction
Why does the number of primordial follicles reduce?
- Genetics
- Apoptosis - decline in granulosa cell survival factors
- Oxidative damage via free radicals
- decreased blood flow - hypoxia
- reduced AMH
Why is there a decline in granulosa cells per follicle?
- Higher rate of apoptosis and decreased proliferation
In what ways does the functionality of granulosa cells reduce?
- Reduced secretory capacity of inhibin A and B, survival factors, oestrogen and progesterone
What is the consequence of the reduced functionality of granulosa cells?
- Survival factors normally prevent cells from entering apoptosis (IGF-1, epidermal GF and progesterone)
- Inhibin A and B suppress FSH secretion - reduced inhibins allows FSH to rise
- High FSH gives a fourfold increased rate of apoptosis in granulosa
When are inhibin A and B produced?
- Inhibin A is produced in the luteal phase by granulosa of dominant follicle and CL - declines as number of cycles reduces
- Inhibin B is produced by granulosa cells in small antral follicles in follicular phase
Why does oocyte development become impaired? And what is its effect?
- as a consequence of impaired production of GFs/Survival factors from granulosa
- increased aneuploidy
- increased oocyte abnormality impair follicle recruitment
- Causes anovulatory cycles and increased miscarriage rate.
What are the consequences of granulosa cell dysfuncion in terms of menstrual cycle
- Shortened cycle (early menstrual transition) - less inhibin B > higher FSH in follicular phase, earlier oestrogen production and LH surge
- Delayed/absent ovulation (late MT) - oestrogen production rises earlier, but may not reach the threshold for GnRH surge, so ovulation doesnt occur or is late. Also fewer FSH receptors in granulosa, so fewer follicles to recruit, so no inhibin A, and FSH rises
- Heavier periods - 2/3 months amenorrhoea, constant oestrogen production which isnt enough for menstruation, but is enough for endometrium development, leads to erratic shedding
- Breast tenderness
- Hot flushes - decreased oestrogen levels leads to a disturbance in serotonin levels. This resets thermoregulatory nucleus and leads to heat loss
What changes in hormones are there as a result of menopause?
- AMH levels decline ~10-15 years before menopause
- Inhibin B decline ~2 years before
- FSH levels are variable each cycle but increase towards menopause
- LH increases close to menopause itself
- Oestrogen levels fall due to ovarian supplies falling (although some produced from fat supplies)
- Adrenal and ovarian androgen levels decline with age (from 20s) but not related to menopause
- No P production after menopause - not ovulating so no CL
Why is there variability in the age of menopause
- Smoking
- ethnicity (south asia is slightly earlier than europe)
- maternal age at menopause
- Several candidate genes
- Surgery / chemo
