Pharmacology: Hormonal treatment in non malignancy gynaecological conditions Flashcards
What is the danger of unopposed oestrogen?
proliferation of uterine endometrium
premenopausal: irregular bleeding
postmenopause: endometrial hyperplasia when used alone as HRT
Which situation can you used oestrogen alone?
HRT when the woman has undergone hysterectomy
In reproductive years what is the most potent endogenous estrogen?
17-beta-estradiol E2
estrone E1
Both made from ovaries
Estriol E3 is least protent and made from metabolism of E1
After menopause what it the premodinant oestrogen?
E1 as oestrogen secretion stops
Peripheral aromatisation of androstenedione in adipose tissue.
Overweight women have 2 x more E1/E2
In orally administered oestrogen what does the addition of ethinyl group E2 do? (Ethinyl estradiol)
Prevents inactivation and enables efficient gut absorption
What type of drug is clomiphene citrate?
Selective oestrogen receptor modulator
Acts centrally blocking negative feedback of oestrogen to induce FSH
What type of drugs is tamoxifen? What are its effects in different parts of the body?
Selective oestrogen receptor modulator
Oestrogen antagonist in breast
Agonist in skeleton + CV system
Causes endometrial hyperplasia/adenocarcionoma
Where is progesterone chiefly produced?
Corpus luteum, small amount from adrenal cortex
1mg/day pre-ovulation
20-30mg luteal phase
pregnancy the placenta
effects of progesterone?
increases viscoivty of cervical mucus
promotes glandular development of breast
increases body temp
induction of decidual developement
Where is progesterone metabolism?
Liver, excreted in bile, little enterohepatic circulation
Which progesterones are made from 21-carbons?
Medroxyprogesterone acetate (Depot) Dydrogesterone
Potential benefits of 21-carbon progesterones?
Less androgenic
Which drugs are made from 19 carbon derived for noreithisterone?
Noreithisterone
Levonrgestrel
Properities of 19 carbon progesterones
Androgenic properties
What drugs is drospirenone?
C17 chemically related to spironolactone
Antimineral coticoid and antiandrogenic
Why is continuous or cyclic progesterone important in HRT
Protect the endometrium,
Common SE of progesterones
Weight gain Acne Fluid retention Headache breast tenderness
C19: more androgen acne & hirsutism
What limits the use of danazol?
Androgen effects: hirsutism, voice change, oedema
How do GnRH antagonist work?
Block GnRH binding to pituitary gland → noFSH/LH
How do GnRH agonist work?
Non-pulsaltive administration leads to down regulation of GnRH receptors
What happens when first administrating GnRH agonist?
Surge - 2 weeks patients symptoms will worsen
SE GnRH agonist
Menopause like symptoms flushes night sweater insomnia decreased labido headache mood swing vaginal dryness change in breast size acne muscle pain poor mood
fall in bone density
to prevent give oestrogen add back therapy
Which oral medication POP COCP or danazol works best for mennorhagia
Danazol but limited use due to SE profile
Oral medications vs IUS for mennorhaiga
LNG-IUS appears more efficient
fewer SE
Are COCP effective for dysmenorrhoea
Evidence is week
How is COCP used in endometriosis?
Long term cycle use 3 monthly
What other medical Tx can be used for endometrisis
IUD
Danazol - limited use
GnRH analogues with add back therapy
In HRT what is the recommend duration of progesterone to protect the endometrium
12-14 days
What route can you give oestrogen
Oral Transdermal Vaginal cream Pesseries/rings subcut impact
SE HRT
VTE
gall bladder disease
stroke
BC
What symptom of the menopause can progesterone alone treat?
hot flushes
What is tibolone?
Synthetic steroid that has oestrogen and progesterone and androgenic effects. Can be used as an alternative HRT.
