W3L1 Mon menopause Flashcards
What is menopause
- The menopause is the final menstrual period
- Average age of menopause around 51-52 years (age range 48-55 years)
- Defined retrospectively after 12 months of absent periods
Stages of manopause
Peri-menopause, menopause transition, Climacteric
* The period when ovarian function declines, cycles are irregular and menopausal symptoms appear
* Begins mid to late 40s, ends one year after menopause
Post menopause
* The whole lifetime after menopause
* No periods, no ovulations, steroid hormones low, cannot conceive
Early menopause
* 40-45 years, 5-8% of women
Premature ovarian insufficiency (POI), premature menopause
* Menopause prior to 40 years old, 2% of women (Mishra et al., 2017 Human Reprod)
* May have intermittent ovarian activity, pregnancy rate 5-50% in lifetime
Changes in age of menopause
-Increased life expectancy from ~42 to ~85 in 100 yrs, with 95% women now reaching menopause
* Factors regulating the age at natural menopause are poorly understood/controversial
* Genetic factors – are important
* Cigarette smoking - Menopause is 1-2 yrs earlier
* Surgical history - Hysterectomy may reduce the age at menopause by around 3-4 yrs
* Ethnicity
* High BMI
* Age at Menarche (<12yrs old)?
* Nulliparity
* Not influenced by Oral contraceptive pill
Age related decline in ovarian follicle numbers
Term 1-2 million follicles
Puberty 300 000-400 000
37 years 100 000, then rapid loss
Peri-menopausal threshold <1000 follicles?
Also decline in quality
Peri-menopause Aetiology
Ovarian primordial follicles decrease with age with an accelerated rate of loss from 37 years
* Follicles become progressively more resistant to stimulation by gonadotrophins
* Follicles that do develop may not secrete sufficient oestradiol (E2) and progesterone (P4) to produce regular menstruation- erratic/short cycle (follicular phase)
* Decrease in oestrogen (and progesterone), follicular –ve feedback reduced – multiple ovulation – twinning risk
* Irregular anovulatory cycles lead to prolonged unopposed oestrogen
* May lead to endometrial hyperplasia and cancer risk
Peri-menopause endocrine changes
- Decreased ovarian inhibin B, AMH from the ovarian granulosa cells
- Gradual rise in FSH
- Fluctuations in oestradiol and progesterone
- No substantial changes in androgen levels
- Sex steroid levels fluctuate markedly on a daily basis
- Measuring sex steroids is not useful when a woman of normal menopausal age develops symptoms
Menopause characteristics
- Decline in oocyte quantity and quality in the years preceding
- Loss of ovarian follicular activity at menopause
- Very low oestrogen (and progesterone)
- Increased FSH/LH levels
- Cessation of menstruation
- Cessation/reduction of sexual drive
Menopause ovarian and endocrine changes
- Ovarian primordial follicle stores are exhausted by atresia and ovulation
- Ovulation will not occur after menopause, but this is retrospective
- Therefore use contraception until no periods for one year, as ovulation may occur right up until last period, though less frequently
- Oestradiol declines following menopause- lack of negative feedback
FSH >40 u/l
LH >30-40 u/l - Androstenedione is still produced by the ovary and adrenal gland and is converted in peripheral tissues to oestrone (E1) = low levels
- Androgens gradually decline during reproductive life but no dramatic change after menopause
Aetiology of Premature Menopause/ Premature Ovarian Insufficiency (POI) <40yrs
Idiopathic (> 70% of cases) Spontaneous POI
Rare causes: Galactosaemia
Auto-immune Addison’s disease, thyroid abnormalities
Genetic: Turner’s syndrome, Fragile X syndrome
Iatrogenic: Surgery/chemo/radiotherapy (8-19% of women under 40)
Premature Menopause/
Premature Ovarian Insufficiency (POI) Diagnosis
- No periods for 4 months before age 40
- FSH levels greater than 40mIU/ml on 2 occasions at least 1 month apart (never rely on one of level); day 2-6 if cycling
- Exclusion of all other causes of absent periods, chromosome test
Management of POI
- NO CURE
- Actually still need contraception: lifetime chance of ever conceiving 5-10%
- HRT/contraception until around 50 years- because ↑ mortality due to osteoporosis and cardiovascular issues
- For young women/girls- monitoring key is susceptible
- If chemo/surgical – move ovary out of the way (experimental)
- Ovarian cryopreservation
- Superovulation- egg freezing or IVF
- Egg Donation
Oestrogen-related consequences of Menopause incidence
20-40% of women have menopausal symptoms requiring treatment
Oestrogen-related consequences of Menopause short-term problem
- vasomotor symptoms (hot flushes, night sweats, formication- skin thin and dry)
- urogenital symptoms (vaginal dryness, atrophic vaginitis, dyspareunia, dysuria, frequency)
- sleep disturbance
- reduced libido
- depression, anxiety, labile mood
- memory loss, fatigue (may be due to other not sleeping etc)
Oestrogen-related consequences of Menopause medium and long-term problem
- Bone loss and osteoporosis
- Weight gain - change in body form (pear to apple), ↓sensitivity of tissues to insulin (hyperglycaemia)
- Cardiovascular disease – increase blood cholesterol, renin (angiotensin II) linked to hypertension
Hot Flushes: oestrogen related consequences
- Most common symptom- occurs in ~ 80% of women
- Mechanisms not known- hypothalamus thermoregulation
- Last 4 min on average (1 to > 10 times a day)
- Up to 30-50% resolve after 3 to 12mths
- Up to 40% may continue to have significant symptoms up to 10 years after menopause
- Increased with smoking, alcohol, surgical menopause, caffeine, weight
- Main reason why women request treatment
- Oestrogen: most effective treatment, 80% reduction
- Meditation, relaxation to reduce anxiety
