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PHA223 > sex hormones 3-4 > Flashcards

sex hormones 3-4 Flashcards

1
Q

What HRT for women with hysterectomy or mirena in situ?

A

oestrogen only

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2
Q

What is mirena in situ?

A

LNG-IUS

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3
Q

What is endometrial ablation?

A

operation to remove the lining of the womb which is performed for very heavy periods

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4
Q

HRT for women with endometrial ablation

A

progesterone

in case any part of the endometrium is left

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5
Q

What determines whether HRT will lead to bleeding?

A

the way progesterone is taken along with oestrogen

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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

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7
Q

What is continuous combined HRT?

A

continuous progestogen given with oestrogen to avoid bleeding

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8
Q

What does continuous combined HRT reduce?

A

reduces the risk of endometrial cancer more than sequential HRT

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9
Q

What is sequential/cyclical HRT?

A

progesterone taken for 10-14 dyas a month to give a withfrawal bleed

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10
Q

What HRT is given when a woman is post menopausal?

A

continuous combined HRT

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11
Q

bleeding when progestogen taken 10-14 days a month

A

monthly bleeding

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12
Q

bleeding when progestogen taken for 14 days every 13 weeks

A

bleed every 3 months

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13
Q

bleeding when progestogen taken continuously

A

no bleed

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14
Q

risks with HRT

A

CVD
stroke
venous thromboembolism (DVT/PE)

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15
Q

altrenative for HRT in breast cancer

A

clonidine

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16
Q

What can be used for hot flushes?

A

antidepressants (unlicenced in UK)

-> SSRIs

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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

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18
Q

Common side effect of tibolone?

A

breast tenderness

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19
Q

How does tibolone work in the endometrium?

A

activates progestrogen and androgen receptors without the stimulation of endometrium bleeding

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20
Q

What effects does tibolone have?

A

prevents post menopausal bone loss

reduction of post menopausal symptoms

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21
Q

When should tibolone not be given?

A

women who are within 12mths of their last period

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22
Q

What class does Raloxifene belong to?

A

SERM - selective oestrogen receptor modulator

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23
Q

What does raloxifene bine to?

A

both types of oestrogen receptors

  • ER alpha (partial agonist)
  • ER beta (antagonist)
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24
Q

What activity doesraloxifene have on bone and lipids?

A

oestrogenic activity

reduces LDL levels

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25
Q

What activity does raloxifene have on breast and uterine receptors?

A

anti-oestrogenic activity

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26
Q

Effcets of raloxifene

A

increases BMD

no effect on post menopausal symptoms

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27
Q

side effects of raloxifene

A

hot flushes

leg cramps

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27
Q

side effects of raloxifene

A

hot flushes

leg cramps

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28
Q

What does raloxifene reduce?

A
  • 75% reduction in risk of oestrogen positive breast cancer in post manopausal women
  • 40% reduction in risk of vertebral fractures
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29
Q

What types of # does raloxifene decrease the risk of?

A

only vertebral fractures

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30
Q

When is raloxifene given to women with vertebral fragility # ?

A

if they can’t take a BP
or
had fragility # after at least 1yr of treatment with a BP

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31
Q

risks with raloxifene

A

increases risk of venous thromboembolism especially during first 4 months

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32
Q

% of women postmenopausal by age of 54

A

80%

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33
Q

What is raised in postmanopausal women?

A

FSH

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34
Q

What can be used in women who can’t take HRT for symptoms of dry vagina or urinary problems?

A

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

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35
Q

What type of oestrogens are given for ocal application to the vagina?

A

low doses of natural oestrogens (not synthetic)

  • oestriol or oestradiol
  • synthetic can enter the bloodstream from the vagina
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36
Q

Why does progestogen not need to be given locally?

A

local doses of oestrogen don’t affect the endometrium

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37
Q

How long are local applications taken for and why?

A

long term

symptoms return when treatment is stopped

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38
Q

short term side effects with HRT

A 
breast tenderness
leg cramps
nausea
irritability
depression
irregular bleeding/spotting (continuous HRT, not serious, if heavy/>6mths consult GP)
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39
Q

treatment for vasomotor symptoms for women who can’t use HRT

A 
paroxetine
fluoxetine
citalopram
venlafaxine
clonidine
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40
Q

treatment for vaginal dryness for women who can’t use HRT

A

vaginal lubricant or moisturiser

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41
Q

treatment for psychological symptoms for women who can’t use HRT

A

self help groups
psychotherapy
counselling
antidepressants

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42
Q

Why is FSH not measured to diagnose menopause?

A
  • normal results don’t exclude menopause
  • inc conc suggests ovarian failure
  • inc conc doesn’t indicate an inability to conceive
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43
Q

When is measurement of estradiol/progesterone/testosterone useful?

A

in diagnosing other causes of amenorrhoea like PCOS

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44
Q

What is used to induce labour?

A

oxytocin as a slow IV infusion

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45
Q

When is oxytocin given IM/IV?

A

prevention and treatment of uterine atomy (failure of uterus to contract) and postpartum haemorrhage

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46
Q

another name for vasopressin

A

ADH

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47
Q

What can overstimulation of vasopressin lead to?

A

pulmonary oedema
fluid overload
water intoxication

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48
Q

What prostaglandins affect the female reproductive system?

A

misoprostol
gemeprost
dinoprostone
carboprost

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49
Q

What do PGs do in the female reproductive system?

A

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

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50
Q

What do tocolytics do?

A

stop uterine contractions, postpone delivery and allow time to administer corticosteroids (betametasone) to promote lung maturity in the baby

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51
Q

examples of tocolytics

A

atosibal
beta 2 receptor agonists
CCBs (unlicenced)
COX inhibitors (unlincnced)

52
Q

How does atosiban work?

A

blocks the effects of oxytocin on myometrium

53
Q

beta 2 adrenoreceptor agonists used as tocolytics

A

salbutamol

terbutaline sulfate

54
Q

How do beta 2 adrenoreceptor agonists work as tocolytics?

A

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
Q

CCB used as a tocolytic and MOA

A

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
Q

COX inhibitor used as a tocolytic and its MOA

A

Indometacin
reduces PG production and dec uterine contractions
(unlinenced)

57
Q

examples of ovulation induction agents

A

clomiphene and tamoxifene

58
Q

What types of drugs are ovulation induction agents?

A

oestrogen receptor antagonists

59
Q

How do ovulation induction agents work?

A

prevent negative feedback of oestrogen causing increased secretion of FSH and LH

60
Q

clomiphene use and dose

A

used tor sub-fertility

taken once a day for 5 days starting within 5 days of menstruation

61
Q

risks with clomiphene

A

multiple ovulations can occur

risk of multiple pregnancy

62
Q

What can tamoxifene be used for?

A
  • sub-fertility agent

- adjuvant (enhances treatment) in oestrogen dependent tumours (breast cancer)

63
Q

dose of tamoxifen for sub-fertilty

A

taken once a day on days 2, 3, 4 and 5 of the cycle

64
Q

side effects with tamoxifen when used as an adjuvant in breast cancer

A

hot flushes

vaginal bleeding

65
Q

ovulation induction agent for obese, insulin resistant women with PCOS

A

metformin

66
Q

example of an ovulation suppression agent

A

Danazol

67
Q

MOA of Danazol

A

inhibits pitrutary gonadotrophin release
reduces ovarian function
producing atrophy of endometrium
blocks O and P recepotors - some androgenic acticity

68
Q

When should Danazol be avoided?

A

durign pregnancy

-> virilisation of the foetus (development of male characteristics)

69
Q

side effects of Danazol

A

acne
hirsutism
voice changes

70
Q

What is used to treat benign prostatic hyperlpasia?

A

alpha blockers
and
5alpha nhibitors

71
Q

treatment of overactive bladder

A

M3 receptor antagonists
and
beta 3 receptor agaonits

72
Q

What is used to treat prostate cancer?

A

anti-androgens

GnRH analogues

73
Q

treatment for erictile dysfunction

A

PDE5 inhibitors
and
alprodastil

74
Q

What is BPH?

A

enlargement of the prostate gland

75
Q

What does BPH lead to?

A

poor stream
hesistancy
nocturia

76
Q

examples of alpha1 adrenoreceptor blockers

A

alfuzosin
prazosin
tamsulosin

77
Q

How do alpha1 adrenoreceptor blockers work in general?

A

relax SM and improve urinary flow

78
Q

cautions for alpha1 adrenoreceptor blockers

A

patients already taking other anti-hypertensive medications

79
Q

side effects of alpha1 adrenoreceptor blockers

A

tachycardia
palpitations
dizziness
retrograde ejactulation

80
Q

Examples of 5 alpha reductase inhibitors

A

dutasteride and finasteride

81
Q

What does 5 alpha reductase do?

A

converts testosterone into active metabolite dihydrotestosterone which activates the androgen receptor

82
Q

How do 5 alpha reductase inhibitors work - dutasteride and finasteride?

A

dutasteride - blocks both isoforms of 5alpha reductase

finasteride - blocks isoform 1 of 5alpha reductase

83
Q

What do 5 alpha reductase inhibitors do to the prostate?

A

can shrink it by 20%

84
Q

What 5 alpha reductase inhibitor is used if the prostate is siginficantly large?

A

combination product containing dutasteride (500mcg) and tamsulosin (400mcg)

85
Q

examples of anticholinergic agents to treat overactive bladder

A

oxybutinin
solifenacin
tolterodine

86
Q

How do anticholinergic agents work?

A 
block the muscarinic acetylcholine receptor
especially M2 (predominant in the detrusor muscle) and M3 (micturition)
87
Q

side effects of anticholinergic agents

A 
dry mouth
blurred vision
constipation
drowsiness
prolong the QT interval (solifenacin)
88
Q

contraindications for anticholinergic agents

A

renal failure
closed angle glaucoma
hepatic dysfunction

89
Q

What is used to treat over active bladder in patients where antimuscarinic drugs are ineffective/contraindicated?

A

beta1 adrenoceptor agonsit - mirabegron

90
Q

How do beta1 adrenocrptos agonists work?

A

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
Q

side effects of beta3 adrenoceptor agonists

A 
arrhythmias
constipation
diarrhoea
dizziness
headaches
increased risk of infection
nausea
92
Q

examples of antiandrogens to treat prostate cancer

A

steroidal - cyproterone acetate

non-steroidal - flutamide and bicalutamide

93
Q

How do anti-androgens work?

A

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
Q

side effect/monitoring for cyproterone

A

can cause liver toxicity

monitoring of liver function

95
Q

side effects of antiandrogens

A 
all:
- liver toxicity
- breast tenderness
- gynacomastia
- erectile dysfunction
- depression
non-steroidal:
- GI upset
- hepatic dysfunction
96
Q

What is erictile dysfunction?

A

the inability to maintain and achieve an erection for satisfactory intercourse

97
Q

What can ED be a precursor of?

A

CAD
diabetes
hypertension

98
Q

disorders that can cause ED

A

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
Q

assessment of ED

A 
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
Q

physical examination of ED

A 
weight
waist circumference
HR
BP
genitalia - hypogonadism, Peyronie's
digital rectal examination - if symptoms of enlarged prostate
101
Q

lab investigations for ED

A

serum lipid levels
fasting glucose levels (10yr CV risk)
serum free testosterone

102
Q

referral options for ED

A

urology
endocrimology
cardiology
mental health services

103
Q

When to refer ED to urology?

A

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
Q

When should ED be referred to endocrinology?

A

if hypogonasiam is suspected (abnormal testosterone)

105
Q

When should ED be referred to cardiology?

A

man has CVD that makes sexual activity unsafe

contraindicated PDE-5 inhibitor use

106
Q

When should ED be referred to mental health services?

A

underlying psychogenic cause suspected

107
Q

goal for ED treament

A

enable the individual to enjoy satisfactory sexual experience

108
Q

curable casues of ED

A

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
Q

testosterone replacement therapy for hypogonadism

A
  • > 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
Q

formulations of testosterone for hormone replacement therapy

A
  • long acting T injection (every 3mths)

- transdermal T gel (applied daily)

111
Q

How to treat male with ED and 1st time presentation?

A
  1. screen for T
  2. T normal - PDE5 inhibitors
  3. T low (<12nmol/L) - T therapy
112
Q

How to treat man with ED and failure of PDE5i, no previous T testing?

A
  1. screen for T
  2. T normal - combination (T + PDE5i)
  3. T low - alternative therapies (injections, intraurethral…)
113
Q

What life style problems can be changed for ED treatment?

A

psychosocial issues
adverse eideeffects of non-prescription drugs
influence of co-morbidities (inc partner’s)

114
Q

normal erection

A
  • 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
Q

MOA of PDE-5i

A

inhibit phosphodiesterase 5 which is responsible for the breakdown of cGMP

116
Q

What does cGMP do in an erection?

A

cGMP relaxes the SM and increases blood flow to the corups cavernosum

117
Q

Dose of PDE-5i?

A

8 doses of PDE-5i with sexual stimulation at maximum

118
Q

counselling for PDE-5i

A

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
Q

sildenafil - half life, time taken and side effects

A

t1/2 = 4hrs

taken 30mins - 4hrs before sexual activity

headache
flushing
blurred vision
dyspepsia

120
Q

tadalafil - half life, time taken and side effects

A

t1/2 = 17.5hrs

taken 12hrs before

headache, dydpepsia, back pain, myalgia

121
Q

svardenafil - half life, time taken and side effects

A

t1/2 = 4hrs

taken 1hr before

headache, flushing, flu syndrome, rhinitis

122
Q

PDE-5i and potent P450 CYP3A4 inhibitors

A

dose of PDE-5i needs to be lowered

123
Q

contraindications for PDE-5i

A

nitrates

124
Q

cautions for PDE-5i

A

patients who take alpha-blockers for hypertension or BPH

-> risk of hypotension and dizziness

125
Q

vanuum erection device

A 
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
Q

intracavernous (base of penis) injection therapy for ED

A

second line

topical alprostadil taken with substanses that can penetrate the skin

127
Q

alprostadil (intracavernous injection therapy)

A

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
Q

penile prosthesis

A

third line

pts who don’t want/no response/can’t continue medical therapy/external device

PHA223 (43 decks)

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