Oral contraceptives, menopause and HRT Flashcards
oestradiol as a hormone/drug
- well absorbed
- low bioavailability (due to first pass metabolism)
what are the 3 forms of oestrogen contraceptive?
1) oestrogen sulphate (conjugated oestrogen)
2) estriol
3) ethinyl oestradiol (ethinyl group protects the molecule from first pass metabolism)
what are the consequences of a lack of oestrogen?
increased chance of osteoporosis and fracture
what other problems does oestrogen contribute to?
breast growth --> cancer CVS problems (when there is low oestrogen)
how is progesterone as a hormone/drug?
- poorly absorbed
- rapidly metabolised in the liver
- given IM
- oral therapy e.g. norethisterone
what does Combined Oral Contraceptive consist of?
oestrogen (ethinyl oestradiol)
progestogen (levonorgestrel or norethisterone)
what is the effect of using the COC?
suppresses ovulation
- feedback of E and P on hypothalamus and pituitary
- P thicken cervical mucus
- E upregulates P receptors
- E counteracts androgenic effect of synthetic P
what is the treatment plan of COC?
taken for 21 days, then stop for 7 days, then start again
what are the unwanted effects of oestrogens?
- nausea
- headache
- increased weight (water retention and fat deposition)
- CVS problems
- breast cancer
- endometrial proliferation
when is progesterone-only contraceptive given?
when using oestrogen in contraindicated e.g in smoker, CVS problems, history of thrombosis
examples of emergency contraception (post-coital pill)
- levonorgestrel: E+P or P only
within 72 hours - copper IUD: affects sperm viability and function
- ulipristal: delays ovulation unto 5 days with anti-progestin activity
within 120 hours
what is menopause?
permanent cessation of menstruation
leads to loss of ovarian follicular activity
what is the average age of menopause?
51 (45-55)
what is the climacteric?
period of transition from predictable ovarian function through the postmenopausal years
what is premature ovarian insufficiency?
menopause before the age of 40
1% in women
what are the causes of POI?
autoimmune
secondary to surgery
chemo or radiation
what are the hormone levels in menopause?
high GnRH
high FSH and LH
low follicle
what are the menopause symptoms?
- hot flushes
- sleep disturbance
- depression
- decreased libido
- urogenital atrophy
- joint pain
what are the complications of menopause?
-osteoporosis:
loss of bone matrix
risk of fracture
loss of bone mass
- CVS
women are protected from CVS disease before menopause but have the same risk as men by age 70
what is the treatment of menopause?
HRT- combined to prevent endometrial hyperplasia , reduce risk of cancer
how is HRT administered?
oral, transdermal, transvaginal
- oral oestradiol
- oral conjugated equine oestrogen
cyclical (E given everyday, P every 12-14 days)
continuous
what are the risks of HRT?
- breast cancer
- VTE
- stroke
- gallstones
however very low absolute risk for postmenopausal women <50
older women have a much more increased risk
what is the treatment of menopause?: drugs
tibolone (synthetic prohormone)
raloxifene (SERM, agonist)
tamoxifen (SERM, antagonist)
what is tibolone? what are the associated risks?
oestrogenic, progestognenic and weak androgenic actions
increased risk of stroke
possible increase in risk of breast cancer
HRT, when is oestrogen-only treatment used?
- for women with hysterectomies i.e. have no endometrium
- post-menopausal (don’t want further kids)
what is raloxifene?
selective oestrogen receptor modulator
tissue selective:
- oestrogenic in bone
- anti-oestrogenic in breast and uterus
used to treat and prevent postmenopausal osteoporosis
which risks are prevented and which are increased by raloxifene?
risk of vertebral fractures and breast cancer reduced
risk of fatal stroke, VTE increased
does not affect vasomotor symptoms
what is tamoxifen?
SERM, anti-cancer drug
- anti-oestrogenic in breast
- BUT oestrogenic in uterus
used to treat oestrogen-dependent breast tumours and metastatic breast cancers
what are the phases of the ovarian cycle?
follicular
ovulatory
luteal
what are the phases of the endometrial cycle?
menstruation
proliferative
secretory
what are the main stages of follicle growth?
primordial follicle
Graffian follicle
corpus luteum
many follicles present
some mature
only one ovulates
what is the pre-antral follicle?
ovum surround by cells
what is the early antral follicle?
ovum with granulosa and thecal cells
antral filled space
becomes the late antral
what will the dominant follicle release and what effect does this have before ovulation?
secretes oestrogen
this lowers LH (before LH surge) and causes the other follicles to undergo atresia
at what stage of the endometrial cycle does the dominant follicle release oestrogen?
proliferative phase
where is aromatase found in the ovary? what is the function?
in granulosa cells (oestrogen producer)
convert androgens created by thecal cells into oestrogen
what is the role of cervical crypts?
produce mucus to create a less hostile environment for sperm
what effect does high oestrogen have on basal temperature?
decreases
progesterones do the opposite
what stimulates follicle maturation?
FSH
what are the target sites for oestrogen?
- bone
- muscle
- endometrial growth
- glands and breast
what is the corpus luteum?
a hormone-secreting structure formed after the ovum has been expelled, it is degraded after a few days if no pregnancy
what is menopause?
permanent cessation of mensturation
loss of ovarian follicular activity
simply, what are the complications of menopause?
CVD and osteoporosis
why is HRT used in menopause?
to control the vasomotor symptoms e.g. hot flushes
nb SERMs have no effect on these symptoms
what is combined in HRT to prevent endometrial hyperplasia?
oestrogen and progesterone
when is oestrogen given alone in HRT?
only in hysterectomy (no endometrium for unnecessary proliferation)
how is HRT administered (frequencies)?
cyclical
oestrogen every day
progesterone evert 12-14 days
what is a benefit of tibolone?
reduced fracture risk
what are the risks with using raloxifene?
increases risk of DVT/
fatal stroke
what are these drugs oestrogenic in?
- raloxifene
- tamoxifen
- raloxifene: in bone (not breast or uterus)
- tamoxifen: in endometrium/uterus and bone
where is raloxifene anti-oestrogenic?
breast and uterus
what sort of cancers should tamoxifen be used for given its oestrogenic effects in the uterus?
for oestrogen- DEPENDENT breast tumours/
metastatic breast cancers
it is anti-oestrogenic in the breast by antagonism
what effect does the combined contraceptive have on ovulation?
suppresses ovulation by negative feedback on hypo-pit
what effect does progesterone have when used in contraceptive?
thickens cervical mucus to make a hostile environment for the sperm
