Oral contraceptives, menopause and HRT

Question 1

oestradiol as a hormone/drug

Answer 1

• well absorbed

- low bioavailability (due to first pass metabolism)

Question 2

what are the 3 forms of oestrogen contraceptive?

Answer 2

1) oestrogen sulphate (conjugated oestrogen)
2) estriol
3) ethinyl oestradiol (ethinyl group protects the molecule from first pass metabolism)

Question 3

what are the consequences of a lack of oestrogen?

Answer 3

increased chance of osteoporosis and fracture

Question 4

what other problems does oestrogen contribute to?

Answer 4

breast growth --> cancer
CVS problems (when there is low oestrogen)

Question 5

how is progesterone as a hormone/drug?

Answer 5

• poorly absorbed
• rapidly metabolised in the liver
• given IM
• oral therapy e.g. norethisterone

Question 6

what does Combined Oral Contraceptive consist of?

Answer 6

oestrogen (ethinyl oestradiol)

progestogen (levonorgestrel or norethisterone)

Question 7

what is the effect of using the COC?

Answer 7

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

Question 8

what is the treatment plan of COC?

Answer 8

taken for 21 days, then stop for 7 days, then start again

Question 9

what are the unwanted effects of oestrogens?

Answer 9

• nausea
• headache
• increased weight (water retention and fat deposition)
• CVS problems
• breast cancer
• endometrial proliferation

Question 10

when is progesterone-only contraceptive given?

Answer 10

when using oestrogen in contraindicated e.g in smoker, CVS problems, history of thrombosis

Question 11

examples of emergency contraception (post-coital pill)

Answer 11

• 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

Question 12

what is menopause?

Answer 12

permanent cessation of menstruation

leads to loss of ovarian follicular activity

Question 13

what is the average age of menopause?

Answer 13

51 (45-55)

Question 14

what is the climacteric?

Answer 14

period of transition from predictable ovarian function through the postmenopausal years

Question 15

what is premature ovarian insufficiency?

Answer 15

menopause before the age of 40

1% in women

Question 16

what are the causes of POI?

Answer 16

autoimmune
secondary to surgery
chemo or radiation

Question 17

what are the hormone levels in menopause?

Answer 17

high GnRH
high FSH and LH
low follicle

Question 18

what are the menopause symptoms?

Answer 18

• hot flushes
• sleep disturbance
• depression
• decreased libido
• urogenital atrophy
• joint pain

Question 19

what are the complications of menopause?

Answer 19

-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

Question 20

what is the treatment of menopause?

Answer 20

HRT- combined to prevent endometrial hyperplasia , reduce risk of cancer

Question 21

how is HRT administered?

Answer 21

oral, transdermal, transvaginal

• oral oestradiol
• oral conjugated equine oestrogen

cyclical (E given everyday, P every 12-14 days)
continuous

Question 22

what are the risks of HRT?

Answer 22

• breast cancer
• VTE
• stroke
• gallstones

however very low absolute risk for postmenopausal women <50
older women have a much more increased risk

Question 23

what is the treatment of menopause?: drugs

Answer 23

tibolone (synthetic prohormone)
raloxifene (SERM, agonist)
tamoxifen (SERM, antagonist)

Question 24

what is tibolone? what are the associated risks?

Answer 24

oestrogenic, progestognenic and weak androgenic actions

increased risk of stroke
possible increase in risk of breast cancer

Question 25

HRT, when is oestrogen-only treatment used?

Answer 25

- for women with hysterectomies i.e. have no endometrium | - post-menopausal (don't want further kids)

Question 26

what is raloxifene?

Answer 26

selective oestrogen receptor modulator tissue selective: - oestrogenic in bone - anti-oestrogenic in breast and uterus used to treat and prevent postmenopausal osteoporosis

Question 27

which risks are prevented and which are increased by raloxifene?

Answer 27

risk of vertebral fractures and breast cancer reduced risk of fatal stroke, VTE increased does not affect vasomotor symptoms

Question 28

what is tamoxifen?

Answer 28

SERM, anti-cancer drug - anti-oestrogenic in breast - BUT oestrogenic in uterus used to treat oestrogen-dependent breast tumours and metastatic breast cancers

Question 29

what are the phases of the ovarian cycle?

Answer 29

follicular ovulatory luteal

Question 30

what are the phases of the endometrial cycle?

Answer 30

menstruation proliferative secretory

Question 31

what are the main stages of follicle growth?

Answer 31

primordial follicle Graffian follicle corpus luteum many follicles present some mature only one ovulates

Question 32

what is the pre-antral follicle?

Answer 32

ovum surround by cells

Question 33

what is the early antral follicle?

Answer 33

ovum with granulosa and thecal cells antral filled space becomes the late antral

Question 34

what will the dominant follicle release and what effect does this have before ovulation?

Answer 34

secretes oestrogen | this lowers LH (before LH surge) and causes the other follicles to undergo atresia

Question 35

at what stage of the endometrial cycle does the dominant follicle release oestrogen?

Answer 35

proliferative phase

Question 36

where is aromatase found in the ovary? what is the function?

Answer 36

in granulosa cells (oestrogen producer) convert androgens created by thecal cells into oestrogen

Question 37

what is the role of cervical crypts?

Answer 37

produce mucus to create a less hostile environment for sperm

Question 38

what effect does high oestrogen have on basal temperature?

Answer 38

decreases | progesterones do the opposite

Question 39

what stimulates follicle maturation?

Answer 39

FSH

Question 40

what are the target sites for oestrogen?

Answer 40

- bone - muscle - endometrial growth - glands and breast

Question 41

what is the corpus luteum?

Answer 41

a hormone-secreting structure formed after the ovum has been expelled, it is degraded after a few days if no pregnancy

Question 42

what is menopause?

Answer 42

permanent cessation of mensturation | loss of ovarian follicular activity

Question 43

simply, what are the complications of menopause?

Answer 43

CVD and osteoporosis

Question 44

why is HRT used in menopause?

Answer 44

to control the vasomotor symptoms e.g. hot flushes nb SERMs have no effect on these symptoms

Question 45

what is combined in HRT to prevent endometrial hyperplasia?

Answer 45

oestrogen and progesterone

Question 46

when is oestrogen given alone in HRT?

Answer 46

only in hysterectomy (no endometrium for unnecessary proliferation)

Question 47

how is HRT administered (frequencies)?

Answer 47

cyclical oestrogen every day progesterone evert 12-14 days

Question 48

what is a benefit of tibolone?

Answer 48

reduced fracture risk

Question 49

what are the risks with using raloxifene?

Answer 49

increases risk of DVT/ | fatal stroke

Question 50

what are these drugs oestrogenic in? - raloxifene - tamoxifen

Answer 50

- raloxifene: in bone (not breast or uterus) | - tamoxifen: in endometrium/uterus and bone

Question 51

where is raloxifene anti-oestrogenic?

Answer 51

breast and uterus

Question 52

what sort of cancers should tamoxifen be used for given its oestrogenic effects in the uterus?

Answer 52

for oestrogen- DEPENDENT breast tumours/ metastatic breast cancers it is anti-oestrogenic in the breast by antagonism

Question 53

what effect does the combined contraceptive have on ovulation?

Answer 53

suppresses ovulation by negative feedback on hypo-pit

Question 54

what effect does progesterone have when used in contraceptive?

Answer 54

thickens cervical mucus to make a hostile environment for the sperm