gonads

Question 1

define menopause

Answer 1

permanent cessation of menstuation due to loss of ovarian follicular activity

Question 2

average age of menopause

Answer 2

51 (range from 45-55)

Question 3

define climacteric

Answer 3

transition period to menopause, where periods become irregular

Question 4

2 major symptoms of menopause

Answer 4

hot flushes (head, neck, upper chest), urogenital atrophy and dyspareunia (difficult/painful sexual intercourse)

Question 5

4 other symptoms of menopause

Answer 5

sleep disturbance (most common), depression, decreased libido, joint pain

Question 6

normal hypothalamo-pituitary gonadal axis

Answer 6

hypothalamus -> GnRH -> anterior pituitary -> LH and FSH -> ovaries -> oestradiol and inhibin B -> negative feedback on hypothalamus and pituitary

Question 7

hypothalamo-pituitary gonadal axis: hormonal changes during menopause

Answer 7

hypothalamus -> GnRH -> anterior pituitary -> increased LH and FSH -> ovaries -> reduced release of oestradiol and inhibin B -> reduced negative feedback on hypothalamus and pituitary

Question 8

2 complications of menopause

Answer 8

osteoporosis, cardiovascular risk

Question 9

why does menopause cause osteoporosis, and effect on fracture risk

Answer 9

oestrogen deficiency causing loss of bone matrix; 10-fold increased fracture risk

Question 10

menopause effect on cardiovascular disease risk

Answer 10

protected against CVD before menopause due to oestrogen, but have same risk as men by age of 70

Question 11

how can vasomotor symptoms (hot flushes) be controlled in menopause

Answer 11

hormone replacement therapy (always weigh risk and benefits)

Question 12

hormonal replacement therapy: what does oestrogen promote

Answer 12

endometrial proliferation

Question 13

hormonal replacement therapy: risk of using oestrogen, and why use combined oestrogen and progesterone

Answer 13

endometrial carcinoma, so combined to prevent endometrial hyperplasia

Question 14

what hormone replacement therapy would be prescribed following a hysterectomy

Answer 14

oestogen only as no endometrium as no uterus

Question 15

2 hormone replacement therapy formulations and when given

Answer 15

cyclical: oestrogen everyday and progestogens every 12-14 days; continuous combined

Question 16

hormone replacement therapy formulations: 4 oestrogen preparations (amount, administration and how often)

Answer 16

oral estradiol (1mg), oral conjugated equine oestrogen (0.625 mg), transdermal (patch) oestradiol (50 microgram/day), intravaginal

Question 17

2 pharmacokinetic features of oestradiol

Answer 17

well absorbed but low bioavailability (majority undergoes first pass metabolism) so much higher dose vs transdermal skin patch or ethinyl oestradiol

Question 18

what is estrone sulphate

Answer 18

“conjugated” oestrogen

Question 19

what is ethinyl oestradiol and what does the ethinyl group do

Answer 19

semi-synthetic oestrogen; ethinyl group protects molecule from first pass metabolism

Question 20

besides enteral, how else can more oestrogens be administered

Answer 20

via transdermal skin patches, so require lower dose

Question 21

5 side effects of hormone replacement therapy

Answer 21

breast cancer, coronary heart disease, deep vein thrombosis, stroke, gallstones

Question 22

absolute risk of complications for healthy symptomatic postmenopausal women in 50s taking hormone replacement therapy for 5 years

Answer 22

very low

Question 23

hormone replacement therapy and coronary heart disease: what is important

Answer 23

timing of exposure (mean age in one study was 63 years, not a 50 year old)

Question 24

hormone replacement therapy and coronary heart disease: risk in younger menopausal women, or women < 10 years since menopause, or 50-59 years

Answer 24

no excess risk

Question 25

effect of oestrogen and synthetic progestins on lipid profile and endothelial function

Answer 25

oestrogen has beneficial effects on lipid profile and endothelial function (females have fewer CVD than men), but synthetic progestins negate these effects

Question 26

effects of oestrogen and synthetic progestins in older women (>60) with atherosclerosis, and effect on CVD risk

Answer 26

increased prothrombotic and proinflammatory effects, increasing CVD risk

Question 27

what is tibolone and what actions does it have

Answer 27

synthetic prohormone with oestrogenic, progestogenic and weak androgenic actions

Question 28

effect of tibolone on fracture risk

Answer 28

reduces fracture risk

Question 29

2 risks of using tibolone

Answer 29

increases stroke risk, possibly increases breast cancer risk

Question 30

what is raloxifene

Answer 30

selective oestrogen receptor modulator

Question 31

raloxifene oestrogenic effects in bone

Answer 31

reduces risk of vertebral fractures

Question 32

raloxifene anti-oestrogenic effects in breat and uterus

Answer 32

reduces breast cancer risk

Question 33

2 drawbacks of raloxifene

Answer 33

doesn’t reduce vasomotor symptoms of menopause (must treat with HRT), and increases risk of venous thromboembolism and fatal stroke

Question 34

tamoxifen effect on breast tissue and subsequent use

Answer 34

anti-oestrogenic effect, so used to treat oestrogen-dependent breast tumours and metastatic breast cancers

Question 35

define premature ovarian insufficiency, and % women affected

Answer 35

where menopause occurs before age of 40; occurs in 1% of women

Question 36

4 causes of premature ovarian insufficiency

Answer 36

autoimmune, surgery, chemotherapy, radiation