menopause HRT and oral contraceptives Flashcards
define menopause *
permenannt cessation of menstruation
loss of follicular ovarian activity
average age of 51 (45-55) can be older than 55 `
define climacteric *
transition period - have irregular periods until you stopm
what are the symptoms of menopause *
hot flushes (head, upper chest, neck)
urogenital atrophy and dyspareunia (painful sex)
sleep disturbance
depression
decreased libido
joint pain
symptoms diminish or disappear with time - very troublesome for the first few years
describe the changes to the hormonal axis during menopause *
there is less prodduction off oestradiol and inhibin B
therefore less -ve feedback on pit and hyp = increase in LH and FSH
what are the complications of menopause*
osteoporosis - because of oestrogen deficiency, lose bone matrix = thin bones = 10 fold increased risk of fractures
CVD - women protected against CVD before menopause, have the same risk as men by aged 70 - men have a higher risk than women before this
describe the treatment for menopause *
HRT to control vasomotor symptoms (hot flushes) - may be a small risk of breast cancer, way +ve and -ve, hot flushes can be dehibilitating
need to give oestrogen and progesterone - combined (unless have hysterectomy)
why do you need to give combined oestrogen and progesterone *
oestrogen causes endometrial proliferation, therefore tehre is a risk of endometrial cancer
so give progesterone to ensure shedding of uterus lining = reduced risk of cancer
progesterone not needed when have hysterectomy - no uterus to get cancer
describe the formulations of HRT *
cyclical - oestrogen every day nand progesterone for the last 14 days of the cycle
or continuous combined
oral
transdermal
transvaginal
what are the differnt oestrogen formulations *
oral oestradiol
oestriol
oral conjugated equine oestradiol (from horse urine)
transdermal patch or gel oestradiol
intravaginal
describe the pharmacokinetics of oestrogen *
it is well absorbed
low bioavailabilty orally because of 1st pass metabolism
estrone sulfate is conjugated oestragen
ethinyl estradiol is a semi-synthetic oestogen - ethinyl gp protectc it form 1st pass metabolism so the dose needed is much smaller
most oestrogens can be given transdermally
side effects of oestrogen HRT *
Breast cancer
Coronary heart disease
Deep vein thrombosis
stroke
gall stones
the absolute risk for healthy symptomatic post menopausal women in 50s, with <10yrs since menopause, for 5 yrs is very low
there is a small increase in risk for older women taking HR
What are the effects of taking combined oestrogen and progesterone *
oestrogen - beneficial effects on lipid profiles and endothelial function (explains why wome have less heart disease than men)
synthetic progestins - negate these effects of oestrogen so taking it with oestrogen in young women is bad (incraese risk of CHD)
women over 60 with atherosclerosis are suseptible to the prothrombotic and proinflammatory effects of oestrogen = invraesed risk of heart disease
describe tibolone, benefits and risks *
synthetic prohormone - oestrogenic, progestogenic andd weak androgenic actions
reduces fracture risk
however there is an increased risk of stroke and maybe breast cancer
describe raloxifene *
selective oestrogen receptor modulator - SERM
bind to oestrogen receptor
has an anobolic oestrogenic effect in bone- reduce risk of vertebral fractures - used for treatment and prevention of post menopausal osteoporosis
anti-oestrogenic effect in breast and uterus - reduced breast cancer risk
doesn’t reduce vasomotor symptoms - ie doesnt help hot flushes
risk of raloxifene *
incraese risk of VTE (venous thrombosis) and fatal stroke
what is premature ovarian insufficiency, what are the causes *
menopause occuring before the age of 40
in 1% of women
causes - autoimmune, iatrogenic (surgery, chemo, radiation)
what are the main components of the combined oral contraceptive pill *
oestrogen (ethinyl oestradial - protected from 1st pass metabolism)
progesterone (levonorgesterel or norethisterone)
describe the mechanism of action for combined contraceptive pill *
oestrgen and progesterone cause -ve feedback at hypothalamus and pit
progesterone thickens cervical mucus - more difficult for sperm to penetrate
oestrogen upregulates progesterone receptors
oestrogen counteracts the androgenic effects of synthetic progesterone
take for 21 days or 12 weeks, stop for 7 days
why would you guve a progesterone only contraceptive *
when oestrogens are contraindicated - because progesterone would negate the effect of oestrogen.
for smokers - already have CHD risk
>35yrs
migrane with aura
histrory of thrombosis
before major surgery
during lactation
describe how the pharmacokinetics of progesterone affects its administration*
short half life - must be given at the same time everyday
short action of duration
long acting preparations may be given via an intrauterine system
it is poorly absorbed and rapidly metabolised by the liver
can be given IM as a depot preparation
a variety of orally active synthetic versions available e.g. norethisterone.
describe post-coital contraception *
copper intrauterine contraceptive device - got to exclude pregnancy 1st, affects sperm viability and function, effectiveness not reduced in overweight /obese women, work for up to 5 days after intercourse
levonorgesteral - give within 72 hours, better effects asap
ulipristal - up to 120 hrs after intercourse - anti-progestin actvity, delays ovulation by up to 5 days, impairs implantation
may cause nausea or vomiting
describe tamoxifen *
Anti-oestrogenic on breast tissue
Used to treat oestrogen-dependent breast tumours and metastatic breast cancers
what are the unwanted effects of oestrogen *
Nausea
Headache
Increased weight (water retention and fat deposition)
Cardiovascular
Breast tenderness or swellling
Endometrium cancer
how is a progesterone only contraception administered *
Long acting preparations may be given by deep intramuscular injection (e.g. medroxyprogesterone acetate/Depot-Provera) or via an intra-uterine system
Oral (‘POP’) preparations
what is the difference between the pill and hRT *
same thing - just given for different reasons
HRT - replace the hormones that are meant to be there
contraceptive pill - additional hormones = overstim of kisspeptin neurons - supress axis - dont have LH surge or FSH
what is the maximum age that you can give HRT *
51
is oral testosterone the best form to replace physiological testosterone in people with hypogonadism 8
no
is secondary amenorrhoea associated with low oestrogen levels 8
yes
what is norethhristerone a derivitive of *
testosterone
can you give progesterone IM *
yes
side effects of the combined oral contraceptive pill *
headache
nausea
breast tenderness/swelling
increased weight
increased bp
mood swings
increased risk of blot clots and breast cancer
reproductive action of oestrogen *
stimulate proliferation of endometrium
trigger LH surge in ovulation
vagina secretions
in breast stimulate growth of ductile system
decreases sebaceous gland secretion
main action of progesterone *
stimulates secretory activity in endometrium and cervix so fertilised egg can implant
