sex hormones 3-4 Flashcards
What HRT for women with hysterectomy or mirena in situ?
oestrogen only
What is mirena in situ?
LNG-IUS
What is endometrial ablation?
operation to remove the lining of the womb which is performed for very heavy periods
HRT for women with endometrial ablation
progesterone
in case any part of the endometrium is left
What determines whether HRT will lead to bleeding?
the way progesterone is taken along with oestrogen
When is progesterone used for HRT?
progesterone taken for 10-14 days a month
a bleed occurs in the days following similar to a menstrual cycle
-> ‘cyclical’ or ‘sequential’ HRT
What is continuous combined HRT?
continuous progestogen given with oestrogen to avoid bleeding
What does continuous combined HRT reduce?
reduces the risk of endometrial cancer more than sequential HRT
What is sequential/cyclical HRT?
progesterone taken for 10-14 dyas a month to give a withfrawal bleed
What HRT is given when a woman is post menopausal?
continuous combined HRT
bleeding when progestogen taken 10-14 days a month
monthly bleeding
bleeding when progestogen taken for 14 days every 13 weeks
bleed every 3 months
bleeding when progestogen taken continuously
no bleed
risks with HRT
CVD
stroke
venous thromboembolism (DVT/PE)
altrenative for HRT in breast cancer
clonidine
What can be used for hot flushes?
antidepressants (unlicenced in UK)
-> SSRIs
What is tibolone?
prodrug with weak oestrogenic, progestrogenic and androgenic activity
predominantly oestrogenic effects
in breast tissue is inhibits the enzyme responsible for activation of its metabolites
Common side effect of tibolone?
breast tenderness
How does tibolone work in the endometrium?
activates progestrogen and androgen receptors without the stimulation of endometrium bleeding
What effects does tibolone have?
prevents post menopausal bone loss
reduction of post menopausal symptoms
When should tibolone not be given?
women who are within 12mths of their last period
What class does Raloxifene belong to?
SERM - selective oestrogen receptor modulator
What does raloxifene bine to?
both types of oestrogen receptors
- ER alpha (partial agonist)
- ER beta (antagonist)
What activity doesraloxifene have on bone and lipids?
oestrogenic activity
reduces LDL levels
What activity does raloxifene have on breast and uterine receptors?
anti-oestrogenic activity
Effcets of raloxifene
increases BMD
no effect on post menopausal symptoms
side effects of raloxifene
hot flushes
leg cramps
side effects of raloxifene
hot flushes
leg cramps
What does raloxifene reduce?
- 75% reduction in risk of oestrogen positive breast cancer in post manopausal women
- 40% reduction in risk of vertebral fractures
What types of # does raloxifene decrease the risk of?
only vertebral fractures
When is raloxifene given to women with vertebral fragility # ?
if they can’t take a BP
or
had fragility # after at least 1yr of treatment with a BP
risks with raloxifene
increases risk of venous thromboembolism especially during first 4 months
% of women postmenopausal by age of 54
80%
What is raised in postmanopausal women?
FSH
What can be used in women who can’t take HRT for symptoms of dry vagina or urinary problems?
oestrogens given locally to the vagina in the form of a low dose cream, pessary, tablet or ring
-> raise local hormone levels but don’t affect whole body
What type of oestrogens are given for ocal application to the vagina?
low doses of natural oestrogens (not synthetic)
- oestriol or oestradiol
- synthetic can enter the bloodstream from the vagina
Why does progestogen not need to be given locally?
local doses of oestrogen don’t affect the endometrium
How long are local applications taken for and why?
long term
symptoms return when treatment is stopped
short term side effects with HRT
breast tenderness leg cramps nausea irritability depression irregular bleeding/spotting (continuous HRT, not serious, if heavy/>6mths consult GP)
treatment for vasomotor symptoms for women who can’t use HRT
paroxetine fluoxetine citalopram venlafaxine clonidine
treatment for vaginal dryness for women who can’t use HRT
vaginal lubricant or moisturiser
treatment for psychological symptoms for women who can’t use HRT
self help groups
psychotherapy
counselling
antidepressants
Why is FSH not measured to diagnose menopause?
- normal results don’t exclude menopause
- inc conc suggests ovarian failure
- inc conc doesn’t indicate an inability to conceive
When is measurement of estradiol/progesterone/testosterone useful?
in diagnosing other causes of amenorrhoea like PCOS
What is used to induce labour?
oxytocin as a slow IV infusion
When is oxytocin given IM/IV?
prevention and treatment of uterine atomy (failure of uterus to contract) and postpartum haemorrhage
another name for vasopressin
ADH
What can overstimulation of vasopressin lead to?
pulmonary oedema
fluid overload
water intoxication
What prostaglandins affect the female reproductive system?
misoprostol
gemeprost
dinoprostone
carboprost
What do PGs do in the female reproductive system?
stimulate contractions of the myometrium to induce medical termination of pregnancy after pre-treatment
OR
prime the cervix before surgical termination of pregnancy
OR
cervical priming in induction of labour
OR treatment post partum
What do tocolytics do?
stop uterine contractions, postpone delivery and allow time to administer corticosteroids (betametasone) to promote lung maturity in the baby
examples of tocolytics
atosibal
beta 2 receptor agonists
CCBs (unlicenced)
COX inhibitors (unlincnced)
How does atosiban work?
blocks the effects of oxytocin on myometrium
beta 2 adrenoreceptor agonists used as tocolytics
salbutamol
terbutaline sulfate
How do beta 2 adrenoreceptor agonists work as tocolytics?
bind to beta 2 receptors on myometrial cell membrane
activtaes adenyl cyclase
leads to inc levels of cAMP and dec intracellular Ca
leading to relaxation of uterus
CCB used as a tocolytic and MOA
nifedipine
dec contractility of uterus by inhibiting entry of Ca into cells through slow Ca channels in the cell membrane
-> not licenced in UK
COX inhibitor used as a tocolytic and its MOA
Indometacin
reduces PG production and dec uterine contractions
(unlinenced)
examples of ovulation induction agents
clomiphene and tamoxifene
What types of drugs are ovulation induction agents?
oestrogen receptor antagonists
How do ovulation induction agents work?
prevent negative feedback of oestrogen causing increased secretion of FSH and LH
clomiphene use and dose
used tor sub-fertility
taken once a day for 5 days starting within 5 days of menstruation
risks with clomiphene
multiple ovulations can occur
risk of multiple pregnancy
What can tamoxifene be used for?
- sub-fertility agent
- adjuvant (enhances treatment) in oestrogen dependent tumours (breast cancer)
dose of tamoxifen for sub-fertilty
taken once a day on days 2, 3, 4 and 5 of the cycle
side effects with tamoxifen when used as an adjuvant in breast cancer
hot flushes
vaginal bleeding
ovulation induction agent for obese, insulin resistant women with PCOS
metformin
example of an ovulation suppression agent
Danazol
MOA of Danazol
inhibits pitrutary gonadotrophin release
reduces ovarian function
producing atrophy of endometrium
blocks O and P recepotors - some androgenic acticity
When should Danazol be avoided?
durign pregnancy
-> virilisation of the foetus (development of male characteristics)
side effects of Danazol
acne
hirsutism
voice changes
What is used to treat benign prostatic hyperlpasia?
alpha blockers
and
5alpha nhibitors
treatment of overactive bladder
M3 receptor antagonists
and
beta 3 receptor agaonits
What is used to treat prostate cancer?
anti-androgens
GnRH analogues
treatment for erictile dysfunction
PDE5 inhibitors
and
alprodastil
What is BPH?
enlargement of the prostate gland
What does BPH lead to?
poor stream
hesistancy
nocturia
examples of alpha1 adrenoreceptor blockers
alfuzosin
prazosin
tamsulosin
How do alpha1 adrenoreceptor blockers work in general?
relax SM and improve urinary flow
cautions for alpha1 adrenoreceptor blockers
patients already taking other anti-hypertensive medications
side effects of alpha1 adrenoreceptor blockers
tachycardia
palpitations
dizziness
retrograde ejactulation
Examples of 5 alpha reductase inhibitors
dutasteride and finasteride
What does 5 alpha reductase do?
converts testosterone into active metabolite dihydrotestosterone which activates the androgen receptor
How do 5 alpha reductase inhibitors work - dutasteride and finasteride?
dutasteride - blocks both isoforms of 5alpha reductase
finasteride - blocks isoform 1 of 5alpha reductase
What do 5 alpha reductase inhibitors do to the prostate?
can shrink it by 20%
What 5 alpha reductase inhibitor is used if the prostate is siginficantly large?
combination product containing dutasteride (500mcg) and tamsulosin (400mcg)
examples of anticholinergic agents to treat overactive bladder
oxybutinin
solifenacin
tolterodine
How do anticholinergic agents work?
block the muscarinic acetylcholine receptor especially M2 (predominant in the detrusor muscle) and M3 (micturition)
side effects of anticholinergic agents
dry mouth blurred vision constipation drowsiness prolong the QT interval (solifenacin)
contraindications for anticholinergic agents
renal failure
closed angle glaucoma
hepatic dysfunction
What is used to treat over active bladder in patients where antimuscarinic drugs are ineffective/contraindicated?
beta1 adrenoceptor agonsit - mirabegron
How do beta1 adrenocrptos agonists work?
cause relaxation of the bladder smooth muscle
stimulation of the beta3 adrenoceptors in the bladder increases mean voided volume per micturition and decreases the frequency of non-voiding conractions
side effects of beta3 adrenoceptor agonists
arrhythmias constipation diarrhoea dizziness headaches increased risk of infection nausea
examples of antiandrogens to treat prostate cancer
steroidal - cyproterone acetate
non-steroidal - flutamide and bicalutamide
How do anti-androgens work?
competitively bind to androgen receptor and suppress the androgen mediated gene expression
cyproterone acts on androgen receptors in the pituitary suppressing LH dependant production of androgens
side effect/monitoring for cyproterone
can cause liver toxicity
monitoring of liver function
side effects of antiandrogens
all: - liver toxicity - breast tenderness - gynacomastia - erectile dysfunction - depression non-steroidal: - GI upset - hepatic dysfunction
What is erictile dysfunction?
the inability to maintain and achieve an erection for satisfactory intercourse
What can ED be a precursor of?
CAD
diabetes
hypertension
disorders that can cause ED
vasculogenic - CVD, hpt, hyperlipidaemia, DM, smoking
neurogenic - MS, Parkinsons, tumours, stroke
anatomical - Peyronie’s disease
hormonal - hypogonadism, hyperthyroidism, hypothyroidism, Cushing’s
drugs - diuretics, antihypertensives, antidepressants, cytotoxics, alcohol
psychological - repationship problems, mental health
assessment of ED
sexual Hx - duration medical/psychiatric/surgical Hx relationship status, Hx of previous partners/relationships sexual orientation/gender identity alcohol, smoking, illicut drugs questionnaires - IIEF, SHIM
physical examination of ED
weight waist circumference HR BP genitalia - hypogonadism, Peyronie's digital rectal examination - if symptoms of enlarged prostate
lab investigations for ED
serum lipid levels
fasting glucose levels (10yr CV risk)
serum free testosterone
referral options for ED
urology
endocrimology
cardiology
mental health services
When to refer ED to urology?
young men always had ED
Hx of trauma to genital area/pelvis/spine
abnormality of penis/testicles
mo response to max dose of 2+ PDE-5 inhibitors
When should ED be referred to endocrinology?
if hypogonasiam is suspected (abnormal testosterone)
When should ED be referred to cardiology?
man has CVD that makes sexual activity unsafe
contraindicated PDE-5 inhibitor use
When should ED be referred to mental health services?
underlying psychogenic cause suspected
goal for ED treament
enable the individual to enjoy satisfactory sexual experience
curable casues of ED
hormonal
post traumatic ateriogenic (young pt)
drug induced - cause sedation, affect CV fxn, affect endocrine, cause hyperprolactinaemia
partners sexual problem
radial prostectomy (removal of prostate gland and surrounding tissues)
testosterone replacement therapy for hypogonadism
- > cause of hypogonadism before starting
- > assess pt before starting testosterone and monitor during
6 month trial of testosterone replacement therapy is serum testosterone < 12 nmol/L
formulations of testosterone for hormone replacement therapy
- long acting T injection (every 3mths)
- transdermal T gel (applied daily)
How to treat male with ED and 1st time presentation?
- screen for T
- T normal - PDE5 inhibitors
- T low (<12nmol/L) - T therapy
How to treat man with ED and failure of PDE5i, no previous T testing?
- screen for T
- T normal - combination (T + PDE5i)
- T low - alternative therapies (injections, intraurethral…)
What life style problems can be changed for ED treatment?
psychosocial issues
adverse eideeffects of non-prescription drugs
influence of co-morbidities (inc partner’s)
normal erection
- sexual stimulation causes nitric oxide to increase
- increased by L-arginine
- catalysed by nNOS and eNOS
- nitric oxide causes vasodilation of arterioles and accumulation of blood
- nitric oxide activated guanylate cyclase
- this causes increased cGMP
- cGMP increases cGK -> erection
- PDE-5 breaks down cGMP
MOA of PDE-5i
inhibit phosphodiesterase 5 which is responsible for the breakdown of cGMP
What does cGMP do in an erection?
cGMP relaxes the SM and increases blood flow to the corups cavernosum
Dose of PDE-5i?
8 doses of PDE-5i with sexual stimulation at maximum
counselling for PDE-5i
drugs do not cause a chemical erection
still need sexual stimulation to cause intial release od nitric oxide which stimulates the synthesis of cGMP
sildenafil - half life, time taken and side effects
t1/2 = 4hrs
taken 30mins - 4hrs before sexual activity
headache
flushing
blurred vision
dyspepsia
tadalafil - half life, time taken and side effects
t1/2 = 17.5hrs
taken 12hrs before
headache, dydpepsia, back pain, myalgia
svardenafil - half life, time taken and side effects
t1/2 = 4hrs
taken 1hr before
headache, flushing, flu syndrome, rhinitis
PDE-5i and potent P450 CYP3A4 inhibitors
dose of PDE-5i needs to be lowered
contraindications for PDE-5i
nitrates
cautions for PDE-5i
patients who take alpha-blockers for hypertension or BPH
-> risk of hypotension and dizziness
vanuum erection device
first line treatment used regardless of ED aetiology satisfaction 35-84% ligher LT use than injections ADR - bruising, local pain, failure of ejactulation, skin necrosis (rare)
intracavernous (base of penis) injection therapy for ED
second line
topical alprostadil taken with substanses that can penetrate the skin
alprostadil (intracavernous injection therapy)
stable form of PGE1
powerful vasodilator
effective for psychogenic and neuropathic ED
increases inflow and reduces venous outlfow by contracting the corporal SM that occlused the draining venules
penile prosthesis
third line
pts who don’t want/no response/can’t continue medical therapy/external device
