Endo 10: HRT, menopause and oral contraceptives Flashcards
Define menopause
- Permanent cessation of menstruation
- Loss of ovarian follicular activity
CLIMACTERIRIC= period of transition
Average age of menopause
51 (45-55)
Complications of menopause (note that these are NOT symptoms!)
Osteoporosis, due to oestrogen deficiency, loss of bone structure and 10X more risk of fracture (oestrogen is an anabolic hormone)
CVD- protected until menopause, after have the same risk as men by age 70
Menopause symptoms
- Hot flushes (head, neck, upper chest)
- Urogenital atrophy & dyspareunia (=painful sexual intercourse )
- Sleep disturbance
- Depression
- Decreased libido
- Joint pain
Diminish with time
What is the problem with only giving oestrogen
What is usually given in HRT
When could oestrogen only be given in HRT
Causes endometrial proliferation
Risk of endometrial carcinoma
HRT: oestrogen and progesterone (reduces endometrial hyperplasia)
Oestrogen only in hysterectomy
Outline the hormonal changes in menopause
Cessation of ovarian function, less oestradiol and inhibin B produced, so less negative feedback on pituitary and hypothalamus so increase GnRH and thus LH and FSH
Where is inhibin B produced
FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH
What is the point of HRT
To control the vasomotor symptoms (flushes)
What will patients usually be given if they have not had a hysterectomy at menopause
Eostrogen and progesterone (to prevent endometrial hyperplasia)….
Remember, in endometrial cycle, oestrogen causes the PROLIFERATIVE stage, and progesterone causes the SECRETORY stage
Differentiate cyclic and continuous combined HRT formulations
Continous combined (both e and p continuously) Cyclic- oestrogen every day and p every 12-14 days
Different oestrogen preparations for HRT
Oral estradiol
Oral conjugated equine oestrogen
Transdermal patch
Intravaginal
patch dose much lower than others
What does ‘conjugated’ oestrogen mean
Oestrogen conjugated to sulphur
What is bioavailability of oestrogen
Low (good absorption but high 1st pass metabolism)
Special feature of ethinyl oestradiol
Ethinyl group protect molecule from first pass metaolsim
ALSO A CONTRACEPTIVE
Side effects of HRT
Think BCD:
Breast cancer
Coronary heart disease
Deep vein thrombosis
Stroke
Gall stones
Risk of taking HRT for 5 years for woman in 50s for CHD
VERY LOW,
Risk increases for women over 60 because they have atherosclerosis already. In these patients…. more CHD events
Be mindful of risk factors still
Differentiate the use of ethinyl oestradiol in contraception vs in menopause
In HRT you are giving bit of oestrogen to reduce symptoms,
In contraception you give to suppress HPG axis so you get less FSH and LH
Outline tibolone
Used for HRT (not contraception)
Tib sounds like fib, and this is a fib as it’s
Not an oestrogen,
It has oestrogenic, progestogenic and androgenic effects
Reduces fracture
Increases stroke (2.2X), possible breast cancer
Outline ramoxifen
It is a SERM
Selective estrogenic receptor modulator….
In bone it is oestrogenic (so increases bone strength)
In breast and uterus anti-oestrogenic so reduces breast cancer risk
But increases stroke risk and VTE
How does tamoxifen work what is it used to treat
Antioestrogenic on breast… used to treat oestrogen dependent breast tumours and metastatic breast cancer
(T for tits, treats breast cancer)
What is premature ovarian insufficiency
Menopause before aged 40…. 1% of women
Causes of premature ovarian insufficiency
Autoimmune
Chemotherapy
Radiation
Surgery
How is combined oral contraceptive given (i.e how do they use)
Take for 21 days stop for 7
What is in combined oral contraceptiopon
Eostrogen (ethinyl oestradiol) and progestogen (levonorgestrel or norethisterone)
Remember that it’s ethinyl oestradiol as this doesn’t undergo extensive first pass metabolism
How do combined oral contraceptives work
SUPPRESS OVULATION:
Giving high oestrogen and progestogens will have negative feedback to reduce FSH and LH release.
Progesterone will also thicken the cervical mucus so less likely for sperm to get to the egg
When to give progestogen only contraceptive and why
When oestrogen contraindicated: smoker, over 35, migraine with aura
Because, even though they are not over 60, they are going to have massively increased risk factors for atherosclerosis already and oestrogen will increase this (it’s pro-inflammatory/prothrombotic in the case of atherosclerosis)
How are progesterone only contraceptives taken
Same time every day (they have short half life, short duration of action)
or
Intrauterine for long acting prep (mirena coil)
What are the conditions for giving copper IUD.
How does it work
Is its effectiveness reduced in overweight or obese women
How long after sexual ntercourse is it effective for
This is emergency contracpetion (POST COITAL)….. intrauterine contraceptive device….
exclude other pregnancy first
it affects sperm viability and function
Effectiveness not reduced in overweight/obese women
5 (up to 7) days after unprotected intercourse
e.g MIRENA
Other than copper IUD, 2 other emergency contraceptives and when to take.
What is the problem with these
Levonorgestrel (within 72 hrs)- progestogen
Ulipristal (up to 120hrs)
Associated with reduced effectiveness in overweight patients
How does ulipristal work
anti-progestin activity?????
Delay ovulation by 5 days
impair implanation
How do the effects of oestrogen differ with age
In younger women ,taking oestrogen in HRT:
- has beneficial effects on lipid profile &endothelial function
Older women above 60 on HRT,
-Already have higher levels of atherosclerosis
-Susceptible to prothrombotic &
proinflammatory effects of oestrogen
For younger women on HRT, why do they not see the beneficial effects of oestrogen when taking HRT
Because of the endometrial hyperplasia associated with HRT, they must it with progestins
The synthetic progestins negate the beneficial effects of oestrogen on CHD
Outline the safety of HRT
Timing of exposure is important
No excess risk in younger menopausal women
Women < 10 years since menopause or 50-59 years: no excess risk
Older women (>60):
Atherosclerosis
Susceptible to prothrombotic &
proinflammatory effects of oestrogen
Just the overall thing about oestrogen and progesterone
FOR HRT:
Don’t want to give oestrogen alone due to endometrial proliferation and cancer
Don’t want to give in over 60s because these already have atherosclerosis and oestrogen will be proinflammatory/pro-thrombotic in this case
In youner women (i.e. 50, or within 10 years of menopause), the atherosclerosis is not so bad. In younger people, oestrogen has positive effects on lipid profile and endothelial function. BUT the progestins negate these effects.
FOR CONTRACEPTION:
Again always give oestrogen with progesterone (combined) due to endometrial cancer risk
In women over 35 who have smoking/overweight etc. they are porbably going to be having higher atherosclerosis so giving oestrogen will be pro-inflammatory/pro-thrombotic in this case.
So you give progesterone only
Note…. in HRT, you are giving small dose of oestrogen (and progesterone to reduce proliferation risk) to reduce symptoms of flushing etc.
In contraception you are giving higher dose oesterogen/progesterone to negatively feedback on the pituitary/hypothalamus to be reducing LH and FSH and prevent pregnancy
