sex hormones 3-4 Flashcards
1
Q
What HRT for women with hysterectomy or mirena in situ?
A
oestrogen only
2
Q
What is mirena in situ?
A
LNG-IUS
3
Q
What is endometrial ablation?
A
operation to remove the lining of the womb which is performed for very heavy periods
4
Q
HRT for women with endometrial ablation
A
progesterone
in case any part of the endometrium is left
5
Q
What determines whether HRT will lead to bleeding?
A
the way progesterone is taken along with oestrogen
6
Q
When is progesterone used for HRT?
A
progesterone taken for 10-14 days a month
a bleed occurs in the days following similar to a menstrual cycle
-> ‘cyclical’ or ‘sequential’ HRT
7
Q
What is continuous combined HRT?
A
continuous progestogen given with oestrogen to avoid bleeding
8
Q
What does continuous combined HRT reduce?
A
reduces the risk of endometrial cancer more than sequential HRT
9
Q
What is sequential/cyclical HRT?
A
progesterone taken for 10-14 dyas a month to give a withfrawal bleed
10
Q
What HRT is given when a woman is post menopausal?
A
continuous combined HRT
11
Q
bleeding when progestogen taken 10-14 days a month
A
monthly bleeding
12
Q
bleeding when progestogen taken for 14 days every 13 weeks
A
bleed every 3 months
13
Q
bleeding when progestogen taken continuously
A
no bleed
14
Q
risks with HRT
A
CVD
stroke
venous thromboembolism (DVT/PE)
15
Q
altrenative for HRT in breast cancer
A
clonidine
16
Q
What can be used for hot flushes?
A
antidepressants (unlicenced in UK)
-> SSRIs
17
Q
What is tibolone?
A
prodrug with weak oestrogenic, progestrogenic and androgenic activity
predominantly oestrogenic effects
in breast tissue is inhibits the enzyme responsible for activation of its metabolites
18
Q
Common side effect of tibolone?
A
breast tenderness
19
Q
How does tibolone work in the endometrium?
A
activates progestrogen and androgen receptors without the stimulation of endometrium bleeding
20
Q
What effects does tibolone have?
A
prevents post menopausal bone loss
reduction of post menopausal symptoms
21
Q
When should tibolone not be given?
A
women who are within 12mths of their last period
22
Q
What class does Raloxifene belong to?
A
SERM - selective oestrogen receptor modulator
23
Q
What does raloxifene bine to?
A
both types of oestrogen receptors
- ER alpha (partial agonist)
- ER beta (antagonist)
24
Q
What activity doesraloxifene have on bone and lipids?
A
oestrogenic activity
reduces LDL levels
25
What activity does raloxifene have on breast and uterine receptors?
anti-oestrogenic activity
26
Effcets of raloxifene
increases BMD
| no effect on post menopausal symptoms
27
side effects of raloxifene
hot flushes
| leg cramps
27
side effects of raloxifene
hot flushes
| leg cramps
28
What does raloxifene reduce?
- 75% reduction in risk of oestrogen positive breast cancer in post manopausal women
- 40% reduction in risk of vertebral fractures
29
What types of # does raloxifene decrease the risk of?
only vertebral fractures
30
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
31
risks with raloxifene
increases risk of venous thromboembolism especially during first 4 months
32
% of women postmenopausal by age of 54
80%
33
What is raised in postmanopausal women?
FSH
34
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
35
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
36
Why does progestogen not need to be given locally?
local doses of oestrogen don't affect the endometrium
37
How long are local applications taken for and why?
long term
| symptoms return when treatment is stopped
38
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)
```
39
treatment for vasomotor symptoms for women who can't use HRT
```
paroxetine
fluoxetine
citalopram
venlafaxine
clonidine
```
40
treatment for vaginal dryness for women who can't use HRT
vaginal lubricant or moisturiser
41
treatment for psychological symptoms for women who can't use HRT
self help groups
psychotherapy
counselling
antidepressants
42
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
43
When is measurement of estradiol/progesterone/testosterone useful?
in diagnosing other causes of amenorrhoea like PCOS
44
What is used to induce labour?
oxytocin as a slow IV infusion
45
When is oxytocin given IM/IV?
prevention and treatment of uterine atomy (failure of uterus to contract) and postpartum haemorrhage
46
another name for vasopressin
ADH
47
What can overstimulation of vasopressin lead to?
pulmonary oedema
fluid overload
water intoxication
48
What prostaglandins affect the female reproductive system?
misoprostol
gemeprost
dinoprostone
carboprost
49
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
50
What do tocolytics do?
stop uterine contractions, postpone delivery and allow time to administer corticosteroids (betametasone) to promote lung maturity in the baby
51
examples of tocolytics
atosibal
beta 2 receptor agonists
CCBs (unlicenced)
COX inhibitors (unlincnced)
52
How does atosiban work?
blocks the effects of oxytocin on myometrium
53
beta 2 adrenoreceptor agonists used as tocolytics
salbutamol
| terbutaline sulfate
54
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
55
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
56
COX inhibitor used as a tocolytic and its MOA
Indometacin
reduces PG production and dec uterine contractions
(unlinenced)
57
examples of ovulation induction agents
clomiphene and tamoxifene
58
What types of drugs are ovulation induction agents?
oestrogen receptor antagonists
59
How do ovulation induction agents work?
prevent negative feedback of oestrogen causing increased secretion of FSH and LH
60
clomiphene use and dose
used tor sub-fertility
taken once a day for 5 days starting within 5 days of menstruation
61
risks with clomiphene
multiple ovulations can occur
| risk of multiple pregnancy
62
What can tamoxifene be used for?
- sub-fertility agent
| - adjuvant (enhances treatment) in oestrogen dependent tumours (breast cancer)
63
dose of tamoxifen for sub-fertilty
taken once a day on days 2, 3, 4 and 5 of the cycle
64
side effects with tamoxifen when used as an adjuvant in breast cancer
hot flushes
| vaginal bleeding
65
ovulation induction agent for obese, insulin resistant women with PCOS
metformin
66
example of an ovulation suppression agent
Danazol
67
MOA of Danazol
inhibits pitrutary gonadotrophin release
reduces ovarian function
producing atrophy of endometrium
blocks O and P recepotors - some androgenic acticity
68
When should Danazol be avoided?
durign pregnancy
-> virilisation of the foetus (development of male characteristics)
69
side effects of Danazol
acne
hirsutism
voice changes
70
What is used to treat benign prostatic hyperlpasia?
alpha blockers
and
5alpha nhibitors
71
treatment of overactive bladder
M3 receptor antagonists
and
beta 3 receptor agaonits
72
What is used to treat prostate cancer?
anti-androgens
| GnRH analogues
73
treatment for erictile dysfunction
PDE5 inhibitors
and
alprodastil
74
What is BPH?
enlargement of the prostate gland
75
What does BPH lead to?
poor stream
hesistancy
nocturia
76
examples of alpha1 adrenoreceptor blockers
alfuzosin
prazosin
tamsulosin
77
How do alpha1 adrenoreceptor blockers work in general?
relax SM and improve urinary flow
78
cautions for alpha1 adrenoreceptor blockers
patients already taking other anti-hypertensive medications
79
side effects of alpha1 adrenoreceptor blockers
tachycardia
palpitations
dizziness
retrograde ejactulation
80
Examples of 5 alpha reductase inhibitors
dutasteride and finasteride
81
What does 5 alpha reductase do?
converts testosterone into active metabolite dihydrotestosterone which activates the androgen receptor
82
How do 5 alpha reductase inhibitors work - dutasteride and finasteride?
dutasteride - blocks both isoforms of 5alpha reductase
| finasteride - blocks isoform 1 of 5alpha reductase
83
What do 5 alpha reductase inhibitors do to the prostate?
can shrink it by 20%
84
What 5 alpha reductase inhibitor is used if the prostate is siginficantly large?
combination product containing dutasteride (500mcg) and tamsulosin (400mcg)
85
examples of anticholinergic agents to treat overactive bladder
oxybutinin
solifenacin
tolterodine
86
How do anticholinergic agents work?
```
block the muscarinic acetylcholine receptor
especially M2 (predominant in the detrusor muscle) and M3 (micturition)
```
87
side effects of anticholinergic agents
```
dry mouth
blurred vision
constipation
drowsiness
prolong the QT interval (solifenacin)
```
88
contraindications for anticholinergic agents
renal failure
closed angle glaucoma
hepatic dysfunction
89
What is used to treat over active bladder in patients where antimuscarinic drugs are ineffective/contraindicated?
beta1 adrenoceptor agonsit - mirabegron
90
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
91
side effects of beta3 adrenoceptor agonists
```
arrhythmias
constipation
diarrhoea
dizziness
headaches
increased risk of infection
nausea
```
92
examples of antiandrogens to treat prostate cancer
steroidal - cyproterone acetate
| non-steroidal - flutamide and bicalutamide
93
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
94
side effect/monitoring for cyproterone
can cause liver toxicity
| monitoring of liver function
95
side effects of antiandrogens
```
all:
- liver toxicity
- breast tenderness
- gynacomastia
- erectile dysfunction
- depression
non-steroidal:
- GI upset
- hepatic dysfunction
```
96
What is erictile dysfunction?
the inability to maintain and achieve an erection for satisfactory intercourse
97
What can ED be a precursor of?
CAD
diabetes
hypertension
98
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
99
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
```
100
physical examination of ED
```
weight
waist circumference
HR
BP
genitalia - hypogonadism, Peyronie's
digital rectal examination - if symptoms of enlarged prostate
```
101
lab investigations for ED
serum lipid levels
fasting glucose levels (10yr CV risk)
serum free testosterone
102
referral options for ED
urology
endocrimology
cardiology
mental health services
103
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
104
When should ED be referred to endocrinology?
if hypogonasiam is suspected (abnormal testosterone)
105
When should ED be referred to cardiology?
man has CVD that makes sexual activity unsafe
| contraindicated PDE-5 inhibitor use
106
When should ED be referred to mental health services?
underlying psychogenic cause suspected
107
goal for ED treament
enable the individual to enjoy satisfactory sexual experience
108
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)
109
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
110
formulations of testosterone for hormone replacement therapy
- long acting T injection (every 3mths)
| - transdermal T gel (applied daily)
111
How to treat male with ED and 1st time presentation?
1. screen for T
2. T normal - PDE5 inhibitors
3. T low (<12nmol/L) - T therapy
112
How to treat man with ED and failure of PDE5i, no previous T testing?
1. screen for T
2. T normal - combination (T + PDE5i)
3. T low - alternative therapies (injections, intraurethral...)
113
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)
114
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
115
MOA of PDE-5i
inhibit phosphodiesterase 5 which is responsible for the breakdown of cGMP
116
What does cGMP do in an erection?
cGMP relaxes the SM and increases blood flow to the corups cavernosum
117
Dose of PDE-5i?
8 doses of PDE-5i with sexual stimulation at maximum
118
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
119
sildenafil - half life, time taken and side effects
t1/2 = 4hrs
taken 30mins - 4hrs before sexual activity
headache
flushing
blurred vision
dyspepsia
120
tadalafil - half life, time taken and side effects
t1/2 = 17.5hrs
taken 12hrs before
headache, dydpepsia, back pain, myalgia
121
svardenafil - half life, time taken and side effects
t1/2 = 4hrs
taken 1hr before
headache, flushing, flu syndrome, rhinitis
122
PDE-5i and potent P450 CYP3A4 inhibitors
dose of PDE-5i needs to be lowered
123
contraindications for PDE-5i
nitrates
124
cautions for PDE-5i
patients who take alpha-blockers for hypertension or BPH
-> risk of hypotension and dizziness
125
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)
```
126
intracavernous (base of penis) injection therapy for ED
second line
| topical alprostadil taken with substanses that can penetrate the skin
127
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
128
penile prosthesis
third line
| pts who don't want/no response/can't continue medical therapy/external device
