Hi everyone - this was published two years ago in the Journal of the British Menopause Society ( Post-reproductive health), but women are often asking about alternative treatments to HRT if they are unable to take HRT eg due to being genetic high risk. I have put the link in the past but the paper was originally open access ( as they all usually are on first publication) but after a while you have to pay - so the answer is to download any new papers you are interested in! We can't put attachments on our posts on this forum so I have pasted it from the pdf which messes up the layout. Sorry about the format but it would take too long to edit!
I haven't put in all the refs but can do if interested.
The full reference is: Consensus statement for non-hormonal-based treatments for menopausal symptoms. Jane Woyka, Post Reproductive Health 2017, Vol. 23(2) 71–75
Here goes:
"Introduction
This is an update on our consensus paper published in
2014.1 Research of women's views still confirms that the
vast majority of women will look for non-hormonal or
alternative treatments to help manage menopause
symptoms rather than seeking medical help.2 Some
women have medical contraindications to hormonal
therapies and greater experience working with breast
cancer survivors3–5 provides better evidence as to how
best to manage these patients with an individualised
holistic treatment plan.6–8.There are increasing numbers
of women preparing for risk-reducing surgery or
other treatments which will impose a sudden menopause,
many of whom will not be recommended to
take hormonal therapies or who will be recommended
to take hormone replacement therapy (HRT) only to
age 50.9 National Institute of Clinical Excellence
(NICE) quality standard 143 recommends that
women are given information before they have treatment
which will precipitate menopause.10
Recommendations from NICE 2015 guidelines11 and
other international bodies have been incorporated into
this statement. Hot flushes and night sweats are
the most common menopausal symptoms, and there
is evidence they may last for several years, with average
duration of seven years in some studies.12,13
Most alternative therapies are evaluated in respect to
vasomotor symptoms, and some will also have effect on
mood. Placebo effect may be as great as 30–50% in
many studies (and for some, that in itself might be considered
a treatment option).14,15 Much of the most
recent information comes from studies involving
breast cancer survivors.16 Urogenital problems due to
estrogen deficiency are covered in a separate consensus
statement.17
Several non-hormonal therapies have been used for
symptom control, although no treatment is as effective
as estrogen.18,19 Prescribable non-hormonal therapies
that have been tested in randomised placebo controlled
trials and shown to be effective include paroxetine, fluoxetine,
citalopram and escitalopram, venlafaxine,
gabapentin and pregabalin and clonidine. Self-help
options which include isoflavones and soya products,
herbal therapies such as Black Cohosh and St John's
Wort, cognitive behavioural therapy (CBT) with targeted
self-hypnosis, acupuncture and nerve block have
also been used for vasomotor symptom control.7,20,21
Clonidine:alpha adrenergic receptor
agonist/licence class anti-hypertensive
and menopause symptom control
Clonidine is the only non-hormonal drug with a
licenced indication for control of hot flushes in the
UK.22 Clonidine 25 mg is prescribed twice daily for
two weeks increased to a maximum of 50 mg three
times a day. Evidence base is contradictory, although
one study shows significant reduction in the numbers of
hot flushes and improved quality of life compared with
placebo in breast cancer survivors using 100 mg
daily.23–25 Side effects of clonidine are dose related
and at higher doses clonidine causes sleep disturbance
in at least 50% of users. It must be withdrawn gradually
as abrupt cessation can cause rebound hypertension.
22 As an anti-hypertensive, clonidine may not be
suitable for patients with a baseline low blood pressure.
Selective serotonin re-uptake inhibitors
(fluoxetine, paroxetine, citalopram,
sertraline) and the serotonin
noradrenaline re-uptake inhibitor/
selective serotonin re-uptake inhibitors
(SSRI-SNRI) venlafaxine
Historically, selective serotonin re-uptake inhibitors
(SSRI) and SNRIs are recognised and licensed for
their effects on depression and anxiety, but for the purposes
of this review, we are considering the unlicensed
use and effect on vasomotor symptoms.5 NICE guidance
is that SSRIs are not offered first line for vasomotor
symptoms unless HRT is contraindicated.
In the USA, FDA approval was granted in 2015 for
paroxetine for menopausal hot flushes.26 Most studies
compare SSRI or SSRI/SNRI with that of placebo and
some with clonidine or gabapentin but not with each
other.27 Overall, studies demonstrate that venlafaxine
37.5mg titrated up to 150 mg per day, paroxetine 10 mg
daily or citalopram 10 mg–30 mg are the most effective.
28,29 Paroxetine has the best evidence and at 10 mg
is as effective as at higher doses and associated therefore
with a lower incidence of side effects.19,23
Fluoxetine has evidence of efficacy and lower incidence
of side effects.5,27 Sertraline seems least effective
and escitalopram improves flushes and has significant
benefits and improvement in well-being but some
side effects.30–32 Many recent studies are with
venlafaxine which consistently seems effective.5,27,33–35
Desvenlafaxine has also been studied for hot flush control
but is not available in the UK.36
SSRIs and SSRI/ SNRIs induce significant adverse
events (SAEs) such as dry mouth, nausea, constipation
and appetite problems which are directly dose
related.5,27,37 Nausea can be reduced by using a long
acting formulation, using a once daily dose with
food. Reduction in libido is another class effect at
higher doses than those usually used for vasomotor
symptoms.
Some SSRIs inhibit cytochrome P450 activity,7,38
an enzyme involved in tamoxifen metabolism, and consequently,
most guidelines recommend that SSRIs
such as fluoxetine and paroxetine must not be
prescribed concomitantly with tamoxifen.27,39 The
Comite de l'volution des pratiques eneoncoloigie
(CEPO) guidance is less prescriptive in referencing the
Arimidex, Tamoxifen Alone, or in Combination Study
(ATAK), suggesting there is no strong evidence to
avoid.5 We know too that the impact on cytochrome
P450 is dependent on genotype and thus any SSRI may
potentially inhibit tamoxifen efficacy for some
patients.40
Since paroxetine is the SSRI with the best evidence
for efficacy19,23 effective at 10 mg daily, it is the SSRI of
choice for patients not taking tamoxifen and the more
usual 20 mg dose chosen if an antidepressant effect is
also required.
Venlafaxine is the preferred treatment for breast
cancer survivors taking tamoxifen, and at 75 mg,
there is significant reduction in hot flushes with concomitant
improvement in fatigue, mental health and
sleep disturbance.27
Gamma aminobutyric acid: Class
anti-epileptics
Gabapentin at 300mg daily increasing to 300 mg maximum
three times a day or pregabalin 75–150mg twice
daily shows statistically significant improvement in hot
flushes as compared with placebo.5,23,41–43 Dose-dependent
side effects limit compliance, the most common
side effects being somnolence, dizziness, weight gain
and dry mouth.44 Gabapentin may be as effective as
venlafaxine45 but most patients prefer venlafaxine.
There is no evidence of further benefit with gabapentin
given concurrently with anti-depressants.5 Most studies
are of short duration with little evidence on long-term
data. Pregabalin is now licenced for depression.
Isoflavones and soya products
Phytoestrogens can form a large part of dietary intake
in certain ethnic groups and these patients can be
advised to continue what is considered to be normal
levels of dietary intake. Most studies evaluating the
effectiveness of phytoestrogens are of poor quality
and in the very many studies undertaken (181 by
2007) very few natural health products were shown to
reduce hot flush frequency.11,20 Data on phytoestrogen
safety and survival benefits in breast cancer patients
are inconsistent and as they are known to have
estrogenic activities, isoflavones including red clover
are not usually recommended for breast cancer
survivors.5,27,46
Herbal treatments
Some studies show effectiveness of Black Cohosh in hot
flush reduction although less so in breast cancer
patients.5,27 Black Cohosh can be associated with
adverse effects such as constipation, arrhythmia,
weight gain, abdominal cramps.21 Black Cohosh may
potentially interfere with tamoxifen activity and should
be avoided by patients taking tamoxifen.5 NICE 2015
recommended that women with a history of, or at
higher risk of, breast cancer should be advised that
there is some evidence that St John's Wort may have
benefit for vasomotor symptoms but that because of
uncertainty about appropriate doses, persistence of
effect and potential for serious drug interactions that
it should not be recommended.11,47 There are no studies
of more than poor quality evaluating St John's Wort in
non-breast cancer patients and its effect on vasomotor
symptoms may be due to its low dose anti-depressant
activity. If a herbal treatment is chosen, patients should
look for the MHRA traditional herbal remedy (THR)
stamp validating strength and quality.
Behavioural therapies
The North American Menopause Society (NAMS)
Statement in 2015 recommends a CBT approach that
combines relaxation techniques, sleep hygiene and
learning to take positive healthy attitude to a menopause
challenge.21,46 One study found hypnotherapy
as effective as gabapentin in hot flush reduction.48
Supporting clinical studies demonstrated the effect in
reducing women's ratings of their hot flush problems.
Additionally, clinical hypnosis was found to have better
results than a structured attention approach in
post-menopausal breast cancer survivors. CBT is also
recommended as a treatment option for anxiety experienced
during the menopause transition and postmenopause.
A CBT approach which is theory based
can have an impact on both vasomotor symptom perception
and control and reduction in stress and wellbeing,
sleep problems and vasomotor symptomatology.
There are two-way interactions between mood and
vasomotor symptoms with 10% of women more likely
to have depressed mood during menopause. There is a
fact sheet (written by Professor Myra Hunter, Kings
College London) on the Women's Health Concern website
which provides guidance on cognitive behavioural
therapy almost in a self-help format for women to
access directly.49 The recent appreciation of benefit
from behavioural therapies on vasomotor symptoms
perhaps suggests that the mechanism by which SSRIs
work for hot flushes could be as a result of their direct
class effect on mood.
Other treatments
Stellate ganglion block in symptomatic women with a
diagnosis of breast cancer is theoretically a treatment
option but to date there are only six small clinical articles.
50 Electro acupuncture, EA, as compared with
Gabapentin found highest effectiveness in the EA
group and lowest adverse effects.51 Results of studies
of acupuncture are mixed with many showing it to be as
effective as sham acupuncture indicating what must be
a high placebo response.11,21 Further studies are
needed.
Treatments for breast cancer survivors
Most women diagnosed and treated for breast cancer
will live with their cancer, rather than die from it.
A common consensus is to avoid estrogen replacement
therapy for breast cancer survivors. More research is
needed into the safety of possibly using estrogen-based
therapies11 particularly in receptor negative patients
but for the moment most clinical guidelines will consider
estrogen treatment contraindicated.9 Even BrCA
gene carriers who become menopausal following
risk-reducing surgery will be guided to take estrogen
replacement only up to the age of 50.9 There are a variety
of position statements, guidelines and consensuses
for management of vasomotor symptoms in breast
cancer survivors from International and National
Societies on the value and safety of alternatives.
5,11,16,21,27 A meta-analysis of adverse effects in
non-hormonal drugs in breast cancer survivors shows
a much higher level of adverse effects with 81% of
SAEs in one treatment group compared with those on
placebo, low dose therapies and acupuncture.5 The
NAMS Consensus Statement September 2015 looks
for solid evidence of a few therapies that work so as
not to waste patients' time experimenting with things
that really do not work.21 NAMS recommends SSRIs,
SNRIs, gabapentin, pregablin, clonidine, CBT and clinical
hypnosis. The UK guidelines, i.e. NICE CG 23 and
NICE CG 80 indicate that SSRIs, SNRIs and gabapentin
are no better than placebo and that paroxetine and
fluoxetine may reduce the efficacy of tamoxifen.11 For
breast cancer survivors, NICE CG 80 recommends clonidine,
venlafaxine and gabapentin although the NICE
2015 indicates that only St John's Wort may improve
symptoms, although not recommended because of serious
drug interactions.9,11,16
Isoflavones, red clover and Black Cohosh are not
recommended for breast cancer survivors by any of
the international bodies.5,16,21,27
New developments
Treatment with neurokinin 3 receptor agonists shows
promise in a recent small placebo controlled RCT, with
40% reduction in the number, severity and bother/
interference due to vasomotor symptoms. Larger
RCT trials will be underway soon.
Summary practice points
. As clinicians we must be familiar with alternative
therapies, to help inform and guide women as to
which options are most likely to be beneficial to
them.
. Few complementary and alternative treatment
options have proven evidence of effectiveness, but
although many options do not stand up to scrutiny
from a robust and evidence-based perspective there
will be individual women who will benefit from some
of these treatments.
. Placebo effect is not inconsiderable and in menopausal
studies will play a part in individual experience
and reported benefits."
The numbers refer to the references.
Hope this helps
Hurdity x
Author
Topic: Consensus statement for non-hormonal-based treatments for menopausal symptoms (Read 2204 times)