sex hormones - oestrogen and HRT Flashcards
1
Q
natural oestrogens or synthetic - which ones have a more appropriate profile for HRT
A
natural
2
Q
natural oestrogens: (3)
A
estradiol, estrone, estriol
3
Q
synthetic oestrogens:
A
ethinylestradiol, mestranol
4
Q
ethinylestradiol - synthetic or natural?
A
synthetic oestrogen
5
Q
mestranol - synthetic or natural?
A
synthetic oestrogen
6
Q
estradiol, estrone, estriol - synthetic or natural?
A
natural oestrogens
7
Q
if long term oestrogen therapy is required in women with a uterus, also add the following to reduce risk of cystic hyperplasia of endometrium (or of endometirotic foci in women who have had hysterectomy) and possible transformation to cancer
A
add progestogen
8
Q
are oestrogens used to suppress lactation and why?
A
no longer used to suppress lactation because of their association with thromboembolism
9
Q
treatment for menopausal women with vaginal atrophy or vasomotor instability
A
HRT with small doses of an oestrogen (together with a progestogen in women with a uterus) is appropriate for alleviating menopausal symptoms such as vaginal atrophy or vasomotor instability
vasomotor instability = edema, abnormal skin color, and temperature differences, and it can contribute to sweating abnormalities
10
Q
what effect does oestrogen given systemically in the perimenopausal and postmenopausal period or tibolone given in the postmenopausal period have on postmenopausal osteoporosis
A
they diminish postmenopausal osteoporosis, but other drugs are preferred
11
Q
treatment of menopausal atrophic vaginitis
A
may respond to short course of topical vaginal oestrogen preparation used for a few weeks and repeated if necessary
12
Q
systemic therapy with an oestrogen or drugs with oestrogen properties alleviates which symptoms?
A
alleviates symptoms of oestrogen deficiency such as vasomotor symptoms
13
Q
what are the characteristics of tibolone and how is tibolone given i.e. what cycle and what progestogen
A
- it combines both oestrogen and progestognenic activity with weak androgenic activity
- given continuously without cyclical progestogen
14
Q
can HRT be given to women with early natural or surgical menopause (before 45 years) and why?
A
yes since they are at high risk of osteoporosis
15
Q
for early menopause, HRT can be given until the approx age of …
A
natural menopause (i.e. until age 50 years)
16
Q
if osteoporosis is the main concern, should you give HRT
A
no consider alternatives
17
Q
When can clonidine be used and what are the drawbacks
A
- can be used to reduce vasomotor symptoms in women who cannot take an oestrogen
- but it can cause unacceptable SE
18
Q
HRT increases the risk of the following….
A
- VTE
- stroke
- endometrial cancer (reduced by progestogen)
- breast cancer
- ovarian cancer
- CHD in women who started combined HRT >10y after menopause
19
Q
for women who started combined HRT >10 years after menopause, there is an increased risk of
A
CHD
20
Q
which cancers does HRT increase the risk of (3)
A
endometrial, breast and ovarian
21
Q
the risk of this cancer with HRT can be reduced by a progestogen
A
endometrial
22
Q
what types of HRT increase the risk of breast cancer after 1 year of use
A
ALL types - systemic (oral or transdermal)
23
Q
increased risk of breast cancer is higher for which types of HRT?
A
combines oestrogen-progestogen HRT (esp continuous HRT preps where both O and P are taken throughout each month)
risk increases with longer duration of HRT
24
Q
What further increases the risk of breast cancer - longer duration of HRT use or age at which HRT is started?
A
longer duration of HRT use
25
Although the risk of breast cancer is lower after stopping HRT than it is during current use, the excess risk persists for...
more than 10 years after stopping compared with women who have never used HRT.
26
do vaginal preparations containing low doses of oestrogen to treat local symptoms also have an effect on breast cancer risk?
not thought to
27
why is radiological detection of breast cancer more difficult with HRT use, esp combined O-P treatment?
can be made more difficult as mammographic density can increase with HRT use especially oestrogen-progestogen combined treatment, but this is not thought to be the case with tibolone.
28
tibolone risk of breast cancer
associated with an increased risk of breast cancer during treatment, although the extent of risk and its persistence after stopping is currently inconclusive.
29
HRT - risk of endometrial cancer depends on...
dose and duration of oestrogen-only HRT
30
in women with a uterus, addition of a progestogen cyclically (for at least 10 days per 28 day cycle) reduces the risk of....
endometrial cancer.
31
if a progestogen is given continuously, this eliminates the risk of endometrial cancer but this must be weighed against..
the increased risk of breast cancer
32
the risk of endometrial cancer in women who HAVE NOT used HRT increases with....
BMI
33
the increased risk of endometrial cancer in users of oestrogen-only HRT or tibolone is more apparent in women who are... (to do with weight)
not overweight
34
is there an increased risk of endometrial cancer with tibolone
yes
35
risk of ovarian cancer with HRT and does this persist
- long term use of combined HRT or oestrogen-only HRT is associated with a small increased risk of ovarian cancer
- this increased risk disappears within a few years of stopping
36
risk of VTE
- increased risk of DVT and PE in pt using combined or oestrogen-only HRT, especially in the first year of use
37
when are HRT users most at risk of VTE
first year of use
38
in women who have predisposing factors of VTE, what should you do
it is prudent to review the need for HRT, as in some cases the risks of HRT may exceed the benefits
39
what further increase the risk of DVT
travel involving prolonged immobility
40
is the risk of VTE lower for transdermal route?
Although the level of risk of thromboembolism associated with non-oral routes of administration of HRT has not been established, it may be lower for the transdermal route compared to the oral route
41
risk of stroke - who is most likely
Risk of stroke increases with age, therefore older women have a greater absolute risk of stroke
42
HRT and stroke risk
Combined HRT or oestrogen-only HRT slightly increases the risk of stroke.
But risk of stroke increases with age regardless so older women have greater absolute risk of stroke
43
Tibolone and risk of stroke
increases the risk of stroke about 2.2 times from the first year of treatment; risk of stroke is age-dependent and therefore the absolute risk of stroke with tibolone increases with age.
44
which drug is associated with a 2.2x increased risk of stroke from the first year of treatment?
tibolone
45
does HRT prevent CHD
no so do not prescribe for this purpose
46
which population is at increased risk of CHD?
women who start combined HRT more than 10 years after menopause
47
choice of HRT for a women with a uterus
- normally requires O with cyclical P for the last 12-14 days of the cycle
- or a prep which involves continuous administration of both O + P
- or a prep which provides both O and P activity in a single prep
48
which preparations are NOT suitable for use in perimenopause or within 12 months of the last menstrual period and why?
continuous combined preparations or tibolone
women who use this may bleed irregularly in early stages of treatment
if bleeding continues endometrial abnormality should be ruled out and consideration given to changing to cyclical HRT
49
what HRT is suitable for continuous use in women without a uterus
oestrogen alone
50
when should progestogen also be considered in addition to oestrogen for women without a uterus
in endometriosis, endometrial foci may remain despite hysterectomy and the addition of a progestogen should be considered in these circumstances.
51
use of oestrogens in elderly pt is potentially inappropriate (STOPP) is prescribed in pt with...
history of breast cancer or venous thromboembolism (increased risk of recurrence)
52
in the elderly, oral oestrogens may be inappropriate if...
prescribed without concurrent progestogen in those with an intact uterus (risk of endometrial cancer).
53
when to stop HRT before major surgery under GA, including orthopaedic and vascular leg surgery, and why ? and when to restart HRT?
predisposing factor for venous thromboembolism and it may be prudent to stop HRT 4–6 weeks before surgery
should be restarted only after full mobilisation
54
what to do if HRT is continued or if discontinuation is not possible (e.g. in non-elective surgery) in surgery
prophylaxis with unfractionated or low molecular weight heparin and graduated compression hosiery is advised.
55
Stop HRT (pending investigation and treatment) if any of the following occur
- sudden severe chest pain (even if not radiating)
- sudden breathlessness (or cough with blood stained sputum)
- unexplained swelling or severe pain in calf of one leg
- severe stomach pain
- serious neurological effects
- hepatitis, jaundice, liver enlargement
- BP >160 systolic or >95 diastolic
- prolonged immobility after surgery or leg injury
- detection of RF which contraindicates treatment
56
if a pt on HRT gets any of the following serious neurological effects they must stop HRT
- unusual severe prolonged headache esp if first time or progressively worse
- sudden partial or complete loss of vision
- sudden disturbance of hearing or other perceptual disorder
- dysphasia (impaired speech)
- bad fainting attack
- collapse
- first unexplained epileptic seizure
- weakness, monitor disturbances
- very marked numbness suddenly affecting once side or one part of body
57
if a patient has the following BP readings they must stop HRT
systolic about 160
diastolic above 95
58
what is ethinylestradiol licensed for
short-term treatment of symptoms of oestrogen deficiency, for osteoporosis prophylaxis if other drugs cannot be used and for the treatment of female hypogonadism and menstrual disorders.
licensed for palliative treatment of prostate cancer
59
what is raloxifene licensed for
treatment and prevention of postmenopausal osteoporosis
60
does raloxifene reduce menopausal vasomotor symptoms
no
61
what are the two main groups of progestogen
progestogen and its analogues
testosterone analogues
62
name the 2 progesterone and its analogues
dydrogesterone and medroxyprogesterone acetate
63
name the two testosterone analogues
norethisterone and norgestrel
64
the newer progestogens desogestrel, norgestimate and gestodene are all derivatives of...
norgesterol which is a testosterone analogue
65
levonorgestrel is the active isomer of ..... and has .... its potency
norgestrel
twice
66
progesterone and its analogues are less ..... than the testosterone derivatives
androgenic
67
what is virilisation
female develops characteristics associated with male hormones (androgens), or when a newborn has characteristics of male hormone exposure at birth
68
do progesterone or dydrogesterone virilisation
no
69
where endometriosis requires drug treatment, it may respond to ........
a progestogen, e.g. norethisterone, administered on a continuous basis
70
although oral progestogens have been used widely for menorrhagia, they are relatively ineffective compared with
tranexamic acid, or particularly where dysmenorrhoea is also a factor, mefenamic acid
71
Why does a progestogen need to be added to long term oestrogen therapy for HRT in women with a uterus, and on what basis is it administered?
to prevent cystic hyperplasia of the endometrium and possible transformation to cancer; it can be added on a cyclical or a continuous basis.
72
this EHC can be used to treat moderate to severe symptoms of uterine fibroids in premenopausal women where surgery and uterine artery embolisation are unsuitable, or have failed
intermittent ulipristal acetate
73
side effect (bleeding) on cyclical HRT where a P is taken for 12-14 days of each 28 day O treatment cycle
usually results in regular withdrawal bleeding towards the end of the progestogen.
74
side effect (bleeding) of continuous combined HRT
commonly produces irregular breakthrough bleeding in the first 4–6 months of treatment. Bleeding beyond 6 months or after a spell of amenorrhoea requires further investigation to exclude serious gynaecological pathology.
75
A woman who is under 50 years and free of all risk factors for venous and arterial disease can use the following to provide both relief of menopausal symptoms and contraception
low-oestrogen combined oral contraceptive pill
recommended that the oral contraceptive be stopped at 50 years of age since there are more suitable alternatives
76
does HRT provide protection and how long is a woman considered potentially fertile for
HRT does not provide contraception and a woman is considered potentially fertile for 2 years after her last menstrual period if she is under 50 years, and for 1 year if she is over 50 years
77
where on the body should HRT patches be applied
clean, dry, unbroken areas of skin on trunk below waist line e.g. thigh, buttock
do not apply on or near breasts
do not apply under elasticated or tight areas of clothing or folds in skin or on skin directly exposed to sunlight
## Footnote
Generally, HRT patches should be applied below the waistline, ideally on the lower abdomen, hips, or buttocks, because these areas provide optimal absorption and minimize the risk of irritation and unwanted side effects. Applying patches above the waistline, particularly near the chest, shoulders, or arms, is not recommended, especially because applying them on or near the breasts may increase the risk of localized side effects.
78
lenzetto how to use
Apply to dry, healthy skin of the inner forearm or alternatively the inner thigh and allow to dry for 2 minutes before covering with clothing
Avoid skin contact with another person (particularly children) or pets and avoid washing the area for at least 1 hour after application.
If a sunscreen is needed, apply at least 1 hour before Lenzetto®.
79
a patient is going on holiday and also uses Lenzetto transdermal spray. she asks you if she can apply suncream at the same time as her sprays
If a sunscreen is needed, apply at least 1 hour before Lenzetto®.
80
how to use oestrogel
Apply gel to clean, dry, intact skin such as arms, shoulders or inner thighs and allow to dry for 5 minutes before covering with clothing.
Not to be applied on or near breasts or on vulval region
Avoid skin contact with another person (particularly male) and avoid other skin products or washing the area for at least 1 hour after application.
81
how to use sandrena
Apply gel to intact areas of skin such as lower trunk or thighs, using right and left sides on alternate days
Wash hands after application
Not to be applied on the breasts or face and avoid contact with eyes
Allow area of application to dry for 5 minutes and do not wash area for at least 1 hour.
82
unlicensed vaginal use of estradiol pessaries or tablets and estring
used for the prophylaxis of recurrent urinary-tract infection in postmenopausal women, but are not licensed for this indication.
83
contraindications of HRT
FHx breast cancer
Hx VTE
oestrogen dependent cancer
recent arterial thromboembolic disease e.g. angina, MI
thrombophilic disorder
undiagnosed vaginal bleeding
untreated endometrial hyperplasia
active arterial thromboembolic disease e.g. angina or MI
84
name an anti-oestrogen
clomifene
85
MOA clomifene
anti oestrogen that induces gonadotrophin release by occupying oestrogen receptors in the hypothalamus, thereby interfering with feedback mechanisms
86
what is clomifene indicated for
female infertility due to ovulatory dysfunction
87
why should clomifene not normally be used for longer than 6 cycles
possible increased risk of ovarian cancer
88
incidence of multiple birth is increased with this drug
clomifene which is used for female infertility due to ovulatory dysfunction
89
what is tibolone indicated for - 2
short term treatment of symptoms of oestrogen deficiency (including women being treated with gonadotropin releasing hormone analogues)
osteoporosis prophylaxis in women at high risk of fractures where other prophylaxis is CI or not tolerated
90
what is raloxifene indicated for - 2
treatment and prevention of postmenopausal osteoporosis
breast cancer (chemoprevention in postmenopausal women at moderate to high risk, specialist supervision !!) - not licensed for this in UK
