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
What do we use as markers for declining fertility?
- ovarian volume (proxy for no. of follicles)
- AMH
- Response to ovarian stimulation (antral follicle count)
- useful for family planning
Which hormone first decreases during a woman’s reproductive life?
AMH
Which hormone is no longer produced after the menopause?
Progesterone
Which symptom is not associate with the menopause?
Urinary incontinence
How can you manage hot flushes?
- vaso-motor symptoms respond well to oestrogen
- 60%-80% reduction in hot flush severity and frequency dependent on dose
- oestrogen should be used at lowest poss dose for least time - women with a uterus should also be given P to avoid endometrial hyperplasia and cancer
- SSRIs can be prescribed, but not licensed
How can you manage urogenital symptoms?
- Moistures and lubricants
- Topical oestrogen
How can you manage low mood?
- HRT
- CBT
- SSRI (if diagnosed with depression)
How can you manage low libido?
Testosterone patches
How can you manage premature ovarian insufficiency?
Combine HRT until natural age of menopause for bone protection, unless contraindicated
What things do you have to think about when prescribing HRT?
- Oestrogen 80% efficacy at reducing hot flushes, lower doses 60% efficacy - worth starting with low dose
- Patient centred - woman should be clear about indication, risks, benefits and have a review plan
- Consider individual risks (slim non-smoking woman different from obese smoking woman)
- Always use P for 13 days for woman with uterus
- Need contraception if less than 1 year amenorrhoea
- Start with low doses to minimise unwanted effects
- risks are low for SHORT term
What are 7 absolute contraindications for prescribing HRT?
- abnormal vaginal bleeding
- breast lump
- pregnancy
- DVT
- liver disease
- endometrial cancer
- breast cancer
What are some unwanted effects of HRT?
- Progestagenic side effects - skin changes, bloating, anxiety, aches, pains, weight gain, depression, breast tenderness, acne
- Unwanted periods
What are some alternative treatments to HRT?
- SSRIs
- St John’s wort
- Tibolone
- Clonidine
- Gabapentine
- Black Cohosh
According to the Women’s health initiative study, does HRT prevent chronic disease?
- Oestrogen alone in women with a uterus showed no overall benefit or hazard, however it showed a significant increased risk of stroke events
- There were 19 excess adverse events per 10,000 women after 5 years use of combined HRT compared to non-users, although no increases in mortality
What are weaknesses of the HRT study?
- Mostly postmenopausal participants, who had a high prevalence of CV risk factors
- Didnt have sufficient power to examine outcomes in younger women specifically, and there is no certainty about what results would be for perimenopausal women
What are the current views on HRT and venous thromboembolism?
- Increased risk from oral and high dose transdermal
- No increase from transdermal.
- Consider transdermal for women with BMI>30 at an increased risk
What are the current views on HRT and osteoporosis?
- Effective in treating it, however only when taking i, so would need to continue to do so into 80s.
- Risks outweigh benefits
What are the current views on HRT and CV disease?
Increased risk of nonfatal MI, strokes, pulmonary embolus and DVT
What are the current views on HRT and cancers?
- Combined HRT increase risk of breast cancer while taking it, but reduces when stop. Oestrogen alone has little/no risk
- Oestrogen only increases endometrial hyperplasia risk. Combined reduces risk of endometrial cancer
- Non-significant risk increase in ovarian cancer
- Decreased risk of colorectal cancer
What are the current views on HRT and alzheimers?
No benefit
What are the current views on HRT and urinary incontinence?
- Combined HRT significantly increases risk and worsens existing symptoms
What are the current views on HRT and quality of life?
No improvement
