Menopause, ageing, osteoporosis Flashcards
menopause is
iatragenic menopause definition
menopause= the permanent ceasing of menstruation, a part of ageing process for women
usually early 50s. process usually gradual, wax and wane over years
iatragenic menopause= by surgery, radiotherapy, chemo etc. Ovaries removed or stopped from working
perimenopause
menopause/ postmenopausal
premature menopause
perimenopause= from beginning of menopausal symptoms to postmenopause
menopause= no menstrual periods 12 months
premature menopause= menopause before 40
describe the hormonal changes and follicular changes in perimenopause
number and responsiveness ovarian follicles declines over 40
leads to decrease in oestrogen and inhibin secretion, so negative feedback on GnRH and FSH, LH
so FSH and LH levels increase
leftover responsive follicles increase oestrogen in response
so oestrogen production may be erratic, levels fluctuating normal high and low
hormone changes in menopause/ postmenopausal
when no more responsive follicles, negative feedback loop is disrupted. FSH and LH levels stay high, stimulate ovarian stromal cells to synthesise androgens (high FSH is therefore a sign of menopause)
in postmenopause, oestrogen derived from ovarian stroma and adipose tissue, androgens aromatised to oestrogen, but a less active form
what tissues are oestrogen dependent
ovary endometrium breast bone fat blood vessels hair colon (testes)
acute clinical sympotoms of menopause
cessation of menses
vasomotor symptoms- hot flushes, night sweats
mood swings, depression, forgetfulness
headaches
explain hot flushes in menopause
70-90% of women experience
hot flushes= vasodilation in face and neck, lasting 1 to 5 mins with profuse sweating
thought caused by narrowing of hypothalmic thermoregulatory set point
- increasing chance sensitivity to intense heat in response to int and ext environmental triggers
- activates heat loss responses ie vasodilation
medium term symptoms of menopause
urogenital atrophy-
vulval, vaginal, urethral, bladder all oestrogen dependent, loss of leads to thinning of epithelium, atrophies
vagina and vulva- dryness, itching, discomfort
bladder- changes in pH, raised vaginal pH, increased bacterial growth so recurrent UTIs
increased risk urinary incontinence/ urgency/ leakage
Sexual problems-
vaginal dryness may cause painful intercourse. loss of libido.
thinning of skin, brittle nails, generalised pains
long term impact menopause on obesity
prevalence obesity higher in post m than pre
menopause causes increase in total body fat
redistribution of fat from peripheries to trunk
if combine w loss of muscle mass and inactivty- obesity and higher risk diabetes type 2
long term impact menopause cardiovascular
oestrogen is vasoactive so promotes vascular remodelling and elasticity so is able to regulate vasodilation and local inflammation
without oestrogen have more vasoconstriction, inflammation so arterial stiffness. may cause atherosclerosis and hypertension
early menopause incr risk of coronary heart diseas, stroke, death
impact menopause on mood
menopause causes decline in synthesis of NTs eg acetylcholine, serotonin, dopamine
results in lo mood, irritability, insomnia
how is diagnosis of menopause made in over 45s
in women over 45 on clinical symptoms alone,
perimenopause- vasomotor symptoms, irregular periods
menopause- no period 12 months AND not on hormonal contraception
if without uterus, based on vasomotor symptoms
how is diagnosis made in under 45s
other conditions need to be excluded, incl PCOS, hypothalmic. pituitary problems so FSH test (u40s do 2 bloods spaced)
not used in UK but
AMH and antral follicle count on ultrasound indicates
types of oestrogen and progesterone drugs delivered in HRT
oestrogen:
oestradiol
conjugated equine oestrogen
Progesterone:
norethisterone
progesterone
what type of HRT is most likely to cause cancer
oestrogen only has 45% incr risk endometrial cancer
if take prog and oestrgen then reduced to 15%
HRT regimens
oestrogen continuously by itself- only if no uterus as othw 45% incr cancer
continuous combined regimen
sequential combined regimen- prog given sequentially for perimenopausal- 2 weeks on 2 weeks off or 3 months on 2 weeks off, useful to maintainperiods so know when enter menopause
HRT routes
oestrogen:
transdermal (patch/ gel) (local skin irritation)
oral (cost-effecive, acceptable)
vaginal oestrogen- cream, tablets, vaginal rings (for urogenital symptoms)
progesterone:
micronised progesterone
oral derivatives
mirena coil
if HRT not effective for sexual desire, testosterone
benefits vs risks HRT
benefits: vasomotor mood and sleep urogenital atrophy osteoporosis
risks:
breast cancer
stroke, venous thromboembolism
ovarian cancer
HRT re breast cancer
risk greater prog and oestro vs oestro alone
risk increases with duration HRT use
h/e lifestyle factors can increase risk just as much so maybe worhty risk
HRT re venous thromboembolism
increases w age and duration HRT
highest with oral oestrogen
no risk with non-oral oestrogens, or micronised progesterone
obesity, smoking also risks
HRT re cardiovascular disease
has beneficial effect at earlier age
in young postmenopausal, oestrogen alone is cardio protective, reduces risk CHD u60
incr risk CHD if start more than 10 y after menopause
h/e combined HRT increases risk CHD, stroke 2.2 times
shouldn’t be used for cardio protection
contraindications HRT
pregnancy undiagnosed vaginal bleeding active or recent VTE/ heart attack suspected/ active breast or endometrial cancer acute liver disease
alternative therapies in leieu HRT
lifestyle:
exercise, lighter clothing, stress reduction, trigger avoidance (caffeine smoking)
vaginal moisturisers, lube, herbal remedies
how common is premature ovarian insufficiency and what to do about it
in in 100 under 40
1 in 1000 under 30
1 in 10000 under 20
HRT recommended unless contraindicated, until age of natural menopause, to improve physical and psychosocial health
osteoporosis is
osteopenia is
osteoporosis is the loss of bone substance, such that fractures of non-traumatic origin are sustained
BMD 2.5 SDs or more below a normal, healthy control. osteoporosis is a disease of bone remodelling
Osteopenia is 2.5 to 1 SD below normal healthy control
how is BMD measured
bone mineral density is measured with DEXA, dual energy x ray absorptiometry, of lower spine and hips
x ray sent via 2 energy streams. 1 stream absorbed by soft tissues, other denotes total absorption. Subtract soft from total= bone results.
bmd computed over area measured
why is bone remodelling important and what is it a balance of
formation and maintenance of skeleton depends on balance between bone formation (osteoblasts) and bone resorption (osteoclasts)
bone remodelling is essential as removes defective bone and responds to mechanical pressure
define bone modelling vs bone remodelling
bone modelling: responsible for growth and shaping of bones during childhood and adolescence
bone remodelling: responsible for maintaining mechanical integrity of skeleton during adult life
why is menopause a risk factor for osteoporosis
oestrogen usually enables osteoblasts and inhibits osteoclasts.
menopause causes sudden increase in osteoclast activity and accelerates below process
in osteoporotic post menopausal, problem is with osteoBlasts
osteoblasts no longer able to catch up with activity of osteoclasts, causes deficit in BMD
action of oestrogen on osteoblasts
oestrogen has positive effect on osteoblasts
- increases collagen type 1 synthesis
- stimulates growth factor synthesis
- regulates osteoblast proliferation
- stimulates expression of osteoblast differentiation and maturation markers
action of oestrogen on osteoclasts
oestrogen has negative effect in osteoclasts
increases apoptosis of osteoclasts
suppresses osteoclast differentiation
acts on osteoclasts via osteoblasts
how is osteoclast differentiation and maturation usually stimulated
- RANK is receptor on osteoclast precursor cell, is an effector molecule, acts on DNA to stimulate maturation
- RANKL (RANK ligand) is located on osteoblast
- RANKL is stimulated to bind with RANK receptor (by IL1, TNF, Vit D, PTH, PTHrp)
- this promotes osteoclast maturation and differentiation
how does oestrogen interfere with osteoclast maturation and differentiation
- oestrogen promotes synthesis of OPG (osteoprotegerin)
- OPG is a decoy of RANK receptor so RANKL binds with OPG instead of RANK
- prevents osteoclast maturation and so formation of active osteoclasts
why don’t all women get osteoporosis
1 in 3 women do
in both m and w, bone mass deteriorates w age
after 45 starts to diminish, women at accelerated rate
if have a higher bone mass before the decline will be less impacted
peak bone mass is influenced by diet and vitamins and ethnicity- white women and asian women do worse
why can’t we take a blood test for osteoporosis
bone markers don’t appear abnormal as very diluted in blood sample
also remodelling process takes 9 months so may be too early to see
osteoporosis in men
1 in 12 men
higher morbidity and mortality
also assoc with falling oestrogen levels
may see osteoporosis when oestrogen receptor mutation or aromatase mutation
