menopause HRT and oral contraceptives

Question 1

define menopause *

Answer 1

permenannt cessation of menstruation

loss of follicular ovarian activity

average age of 51 (45-55) can be older than 55 `

Question 2

define climacteric *

Answer 2

transition period - have irregular periods until you stopm

Question 3

what are the symptoms of menopause *

Answer 3

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

Question 4

describe the changes to the hormonal axis during menopause *

Answer 4

there is less prodduction off oestradiol and inhibin B

therefore less -ve feedback on pit and hyp = increase in LH and FSH

Question 5

what are the complications of menopause*

Answer 5

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

Question 6

describe the treatment for menopause *

Answer 6

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)

Question 7

why do you need to give combined oestrogen and progesterone *

Answer 7

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

Question 8

describe the formulations of HRT *

Answer 8

cyclical - oestrogen every day nand progesterone for the last 14 days of the cycle

or continuous combined

oral

transdermal

transvaginal

Question 9

what are the differnt oestrogen formulations *

Answer 9

oral oestradiol

oestriol

oral conjugated equine oestradiol (from horse urine)

transdermal patch or gel oestradiol

intravaginal

Question 10

describe the pharmacokinetics of oestrogen *

Answer 10

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

Question 11

side effects of oestrogen HRT *

Answer 11

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

Question 12

What are the effects of taking combined oestrogen and progesterone *

Answer 12

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

Question 13

describe tibolone, benefits and risks *

Answer 13

synthetic prohormone - oestrogenic, progestogenic andd weak androgenic actions

reduces fracture risk

however there is an increased risk of stroke and maybe breast cancer

Question 14

describe raloxifene *

Answer 14

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

Question 15

risk of raloxifene *

Answer 15

incraese risk of VTE (venous thrombosis) and fatal stroke

Question 16

what is premature ovarian insufficiency, what are the causes *

Answer 16

menopause occuring before the age of 40

in 1% of women

causes - autoimmune, iatrogenic (surgery, chemo, radiation)

Question 17

what are the main components of the combined oral contraceptive pill *

Answer 17

oestrogen (ethinyl oestradial - protected from 1st pass metabolism)

progesterone (levonorgesterel or norethisterone)

Question 18

describe the mechanism of action for combined contraceptive pill *

Answer 18

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

Question 19

why would you guve a progesterone only contraceptive *

Answer 19

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

Question 20

describe how the pharmacokinetics of progesterone affects its administration*

Answer 20

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.

Question 21

describe post-coital contraception *

Answer 21

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

Question 22

describe tamoxifen *

Answer 22

Anti-oestrogenic on breast tissue

Used to treat oestrogen-dependent breast tumours and metastatic breast cancers

Question 23

what are the unwanted effects of oestrogen *

Answer 23

Nausea

Headache

Increased weight (water retention and fat deposition)

Cardiovascular

Breast tenderness or swellling

Endometrium cancer

Question 24

how is a progesterone only contraception administered *

Answer 24

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

Question 25

what is the difference between the pill and hRT *

Answer 25

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

Question 26

what is the maximum age that you can give HRT *

Answer 26

51

Question 27

is oral testosterone the best form to replace physiological testosterone in people with hypogonadism 8

Answer 27

no

Question 28

is secondary amenorrhoea associated with low oestrogen levels 8

Answer 28

yes

Question 29

what is norethhristerone a derivitive of *

Answer 29

testosterone

Question 30

can you give progesterone IM *

Answer 30

yes

Question 31

side effects of the combined oral contraceptive pill *

Answer 31

headache

nausea

breast tenderness/swelling

increased weight

increased bp

mood swings

increased risk of blot clots and breast cancer

Question 32

reproductive action of oestrogen *

Answer 32

stimulate proliferation of endometrium

trigger LH surge in ovulation

vagina secretions

in breast stimulate growth of ductile system

decreases sebaceous gland secretion

Question 33

main action of progesterone *

Answer 33

stimulates secretory activity in endometrium and cervix so fertilised egg can implant