Prescribed exercise in people with fibromyalgia: parallel group randomised controlled trial
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7357.185 (Published 27 July 2002) Cite this as: BMJ 2002;325:185All rapid responses
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Dear Sirs,
I am an expert patient, who has had the misfortune to
have suffered the torture of FMS/CFS for 5 years after
the birth of my second son. The previous six years I
had pain in my hips and was extremely tired from the
birth and my job as full time mum of my first lively,
sleepless son.
I have fully recovered extremely quickly. Less than 6
months of skilful physiotherapy and sports medicine.
I thought you might be interested to know that FMS/CFS
is progressive and therefore preventable. Had I been
treated by a competent physiotherapist or indeed been
referred to a competent physiotherapist within the NHS.
I guess I wasn't, even after the birth of my children,
because of who I am.
I have a physical report by the private physiotherapist
who has given me my life back.
1. An unstable right sacroiliac joint
2. Poor gluteal control in stance phase
3. A dynamic flexion-extension shear at l3
4. Sway back posture
5. Hypomobile anterior hips structures and
thoracolumbar junction
6 Right anterior palpation of C6 reproduced headache.
He goes on to say;- My working hypothesis was based
upon physical findings, which explained the multi focal
pain. The initial injury caused a compensatory internal
rotation of her right leg. Over a period of time, the
altered mechanics and decreased shock absorbency
causes the right sacroiliac joint to become functionally
unstable. The secondary changes include the
hypomobility to the anterior hip and thoracic spine. The
forward sitting head posture can be related to the
thoracic spine stiffness and poor spinal patterns of
movement.
Manual therapy was directed to the stiff, hypomobile
segments, whilst a progressive, functional and tailored
rehab program was implemented to enable Ms Barratt
to move correctly in a pain free fashion.
He goes on to say that I have a well controlled diet and
maintain an adequate level of fitness.
He also says, I see no reason why Ms Barratt should
not have a normal and pain free life with minimal levels
of rehabilitative exercise and care.
As you will see, his physical report acknowledges the
WHO's definition of Fibromyalgia as musculo/skeletal.
I do not believe that FMS is a disease, it is a
mechanical problem, that causes CFS. A senior
clinical physiotherapist, within the musculo/skeletal
rhuematology department at my
local hospital, two years previously gave her analysis,
as 'postural due to stress'. And we all know where this
led me to within the NHS. Had the head of pain clinic
not forgotten to follow up my appointment with him, he
would have sent me to see a psychiatrist!
I am hoping that someday soon, GP's will be educated
and Sports Medicine will be widely available within the
NHS. The combination of physical injury, trauma and
infection for elite athletes, such as Kelly Holmes and
Paula Radcliffe is the cocktail that produces the
various diagnosis's of Athletes Overtraining syndrome,
Underperformance syndrome, Under recovery
syndrome and CFS. Rheumatologists, it seems to
me, suffer from their own professional policies. The
combination of physical injury, trauma and infection
could be used as a model for prevention of FMS/CFS.
How is this going to be done?
I am also a Patient and Public Involvement forum
member for [don't laugh] Camden and Islington Mental
Health and Social Care Trust, however as I have not
told my fellow forum members that I am writing to you, I
do not have this hat on at the moment.
with best regards
Jane Barratt
janebarratt@talktalk.net
Competing interests:
None declared
Competing interests: No competing interests
I apparently have had fibromyalgia for 25-30 years. I have tried MANY
medications. I have tried FOUR exercise programs.
Three of these exercise programs were supervised. Each resulted in
not only a SEVERE "flare up" but a permanent and OVERALL worsening of the
condition. I have only spoken with one person who has had relief from
regular exercise; the exercise is Yoga and she is in the "early stages" of
the illness.
I have spoken to untold numbers of other sufferers who experienced
the same results as I have with exercise programs. One of whom was
formerly an aerobics instructor!
Even without ALL the details of the study I still question the claims
made by the researchers and the misleading interpretation of the results--
the actual statistics of which are rarely mentioned.
Another issue is that the medical community still does not seem to
recognize that fibromyalgia is a progressive illness. There ARE stages.
Over the last 25-30 years I had to progressively lessen my working hours
and responsibilities; despite the fact that I was my sole support and was
a single parent.
The longer this misinformation (that "Exercise Helps Fibromyalgia")
is perpetuated, the long it will be until there is real and actual
progress made in relieving, and possibly curing, its sufferers.
Researchers especially should not have preconcieved notions and go
into a study to "prove" a point. They should be looking for REAL results.
Competing interests:
None declared
Competing interests: No competing interests
Editor—We welcome the prominence given to the article on the use of
exercise therapy in fibromyalgia by Richards and Scott (1), but have some
concerns over the way the results may be interpreted.
The outer cover of the journal featured the picture of a swimming
woman with the underlying headline, “Prescribing exercise for fibromyalgia
- simple, cheap, and effective. We suggest that this is misleading.
Swimming was not part of the exercise programme described in the article
and there is no evidence that swimming is beneficial in this condition.
The actual exercise programme was “an individualised aerobic exercise
programme, mostly walking on treadmills and cycling on exercise bicycles”.
Individualised programmes involving expensive equipment are neither simple
nor cheap.
The use of the term “effective” should be qualified. The primary
outcome measure, change in self rated global impression, although
statistically in favour of the exercise treatment group, resulted in only
35% of those randomised to this intervention being classified as
responders. Also only 19 of the 69 subjects randomised to the exercise
treatment were able to complete more than two-thirds of the twice weekly
classes. In absolute terms this treatment could be described as useful for
some patients but not effective for all.
Regarding the secondary outcome measures: the changes in the
Fibromyalgia Impact Questionnaire (FIQ) showed deterioration in the FIQ at
3 months, a 7% improvement at 6 months and a 4% improvement at 1 year.
These latter 2 results were statistically significant but do not represent
a clinically meaningful improvement.
Details of the existing medications, which participants continued at
entry were not provided. If there was a difference in the medications
being taken by the groups who found the exercise intervention effective,
ineffective or who failed to complete the course, this might mean that the
effectiveness of the exercise was due to support from the drug treatments.
It is therefore inappropriate to isolate the exercise programme as being
responsible alone for the improvement found by some patients.
Despite these reservations we believe that this study does provide
evidence of the benefits of exercise for this difficult to treat
condition, as have several previous studies (2). Fibromyalgia is very
heterogeneous in its severity and for many patients exercise needs to be
incorporated into a multidimensional management programme, as recently
highlighted in the May 2002 edition of the Rheumatic Disease Clinics of
North America entitled the “Rational Management of Fibromyalgia” (3, 4,).
We are concerned that that the way this study was presented may encourage
some doctors to dismiss patients with the words “go and take more
exercise”, without considering the complexity of the problems in those
with severe symptomatology. Exercise is of benefit in most chronic
disorders, but more is not always better. Indeed there are negative
aspects of too much exercise done too soon (5). It is to the credit of the
Richard and Scott study that the intensity of exercise was individualized
each subject and started out a gentle pace.
Kathy Longley, Co-ordinator,
Medical Advisory Board, Fibromyalgia Association UK,
41, Wedmore Park
Southdown
Bath. BA2 1JZ
UK
Robert Bennett, MD, FRCP Professor of Medicine,
Oregon Health & Science University,
Portland, Oregon,
USA
Alan Edwards, Clinical Assistant *
The David Hide Asthma and Allergy Research Centre
St Mary’s Hospital
Newport.
Isle of Wight. PO30 5TG
UK
Norman Farron, Biomedical Scientist
239 Down Road
Portshead
Bristol BS20 8HU
UK
Moira Henderson, Medical Adviser for the Department of Work and
Pensions
Department of Work and Pensions
The Adelphi
1-11 John Adam Street
London. WC2N 6HT
UK
Kim Lawson, Senior Lecturer in Pharmacology
Division of Biomedical Sciences
Sheffield Hallam University
City Campus
Sheffield. S1 1WB
UK
Marcus Vaz, Registered Osteopath
2 Marfleet Close
Lower Earley
Reading
Berks. UK
Members, Medical Advisory Board, Fibromyalgia Association UK.
References
1. Richards SC, Scott DL. Prescribed exercise in people with
fibromyalgia: parallel group randomised controlled trial. BMJ 2002;
325(7357):185.
2. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating
fibromyalgia syndrome (Cochrane Review). Cochrane Database Syst Rev
2002;(3):CD003786.
3. Bennett RM. The rational management of fibromyalgia patients. Rheum Dis
Clin North Am 2002; 28(2):181-99,
4. Littlejohn GO, Walker J. A realistic approach to managing patients with
fibromyalgia. Curr Rheumatol Rep 2002; 4(4):286-292.
5. Jones KD, Clark SR. Individualizing the exercise prescription for
persons with fibromyalgia. Rheum Dis Clin North Am 2002; 28(2):419-436
Competing interests: No competing interests
EDITOR - We read with interest the paper by Richards et al, which
suggests that incremental exercise provides an effective intervention for
fibromyalgia, compared to relaxation strategies.1
Previous studies have suggested that exercise has been found to be an
effective short term strategy for the management of this chronic
condition.2 However, there are concerns over the methodological quality
of some of these studies. Different regimens and duration of intervention
and follow up mean that many of these studies are not directly comparable.
However, the common theme in many of the studies is poor compliance.
What is not clear from the discussion by Richards et al 1 is whether
a warming up programme was used in the exercising group. Also, no mention
is made of whether or not exercise related injuries were sustained during
the 12-week intervention. Warming up is known to reduce muscle stiffness
and may reduce the severity and subsequent symptoms of muscle damage in
healthy subjects. 3
Taurine supplementation and depletion, and prednisolone have been
investigated in animal models in an attempt to limit the oxidative and
mechanical stress, which is thought to lead to muscle fibre damage 4,5 .
Impairment in the action of transport proteins for glucose and lactate has
also been implicated in the increase in muscle stiffness following
unaccustomed exercise.
We believe that it is essential that all physicians prescribing
graded exercise therapy (which may be conducted within National Lottery
funded Healthy Living Centres) should explain the risks and potential side
effects of this treatment. We also feel that compliance with graded
exercise programmes could be improved if we can find suitable treatments
for exercise induced muscle stiffness and soreness. [END]
Simon N Paul, Specialist Registrar in Rheumatology and Rehabilitation
Nick C Harvey, Specialist Registrar in Rheumatology
Richard M Ellis, Consultant in Rheumatology and Rehabilitation
Department of Rheumatology, Salisbury District Hospital, Salisbury,
Wiltshire. SP2 8BJ.
Email : dr.paul@salisbury.nhs.uk
References.
1. Richards S, Scott D L. Prescribed exercise in people with
fibromyalgia: parallel group randomised controlled trial. BMJ 2002; 325:
185-187.
2. Offenbächer M, Stucki G. Physical therapy in the treament of
fibromyalgia. Scand J Rheumatol 2000; 29 Suppl 113:78-85
3. McHugh M. Br J Sports Med 1999:33: 377
4. Dawson Jr R, Biasetti M, Messina S, Dominy J. Amin Acids 2002:22(4):309
-24
5. Jacobs SC, Bootsma AL, Willems PW, Bar PR, Wokke JH. J Neurol
1996:243(5):410-6
Competing interests: No competing interests
Horace Reid speaks about the high attrition rate, which has caused
many people to drop out of the study
All fibromyalgia sufferers talk about having good days followed by bad
days and the very high drop out rates in this paper suggest that forcing a
regime of graded exercise on fibromyalgia sufferers is less effective than
making the exercise appropriate on a day by day basis. This is known as
pacing.
In January 2002 the Department of Health released a report from the
working party for Chronic Fatigue and ME. Which discussed graded exercise
versus pacing. Whilst these conditions are different from fibromyalgia
there are a number of similarities in symptoms.
One key controversy that exists over graded exercise rests on whether the
nature of the treatment is appropriate for the nature of the disease, at
least in some individuals. Existing concerns from voluntary organisations
and some clinicians include the view that patients have a primary disease
process that is not responsive to or could progress with graded exercise,
and that some individuals are already functioning at or very near maximum
levels of activity.
A successful outcome probably depends on the therapy being initially based
on current physical capacity, mutually agreed between the therapist and
patient, and adapted according to the clinical response. Appropriate
education regarding the rationale and cautions of this therapy needs to be
given to potential candidates for graded exercise. Patients who drop out
of therapy need to be followed up swiftly to review the reasons and
reassess their management plan.
Competing interests: No competing interests
Dear editor
While congratulating Richards and Scott for their report on the
effectiveness of a commonly used treatment intervention for fibromyalgia
patients [1]. I feel their paper suffers from the same failing they
identify in other work i.e. the generalisability of results. It is known
that patient with fibromyalgia commonly feature on physiotherapists’
caseloads [2], however, I venture that few fibromyalgia patients in the
NHS have access to personal trainers providing individual exercise
regimes. I submit, therefore, that this limits the extent to which
Richards' and Scott's results can be generalised to the broad population
of fibromyalgia suffers receiving treatment in the NHS. Indeed our own
work has revealed that published trials investigating exercise
intervention in fibromyalgia generally involved more prolonged treatment
intervention than is the case in clinical practice. I respectfully suggest
that future research should focus on pragmatic randomised controlled
trails evaluating what is current practice in the NHS for fibromyalgia
sufferers.
1. Richards SCM, Scott DL. Prescribed exercise in people
fibromyalgia: parallel group randomised controlled trail. BMJ 2002; 325:
185-187.
2. McVeigh J, Archer S, Hurley DA, Baxter GD, Basford JR.
Physiotherapy management of fibromyalgia syndrome: survey of current
practice in Northern Ireland. Physiotherapy 2002; 88: 435-436.
Mr. J McVeigh
Lecturer/Practitioner in physiotherapy
University of Ulster and Royal Group of Hospitals Trust,
Belfast,
Northern Ireland
Competing interests: No competing interests
Trials of graded exercise and cognitive therapy for the
fatigue syndromes have a dreary predictability. The
sample will be small, the investigators will play ducks
and drakes with the inclusion criteria, the outcome
measures will depend on self-report, with insufficient
objective corroboration. There will be a high attrition
rate among the participants, necessitating an
intention-to-treat analysis.[1] There will be no report of
adverse events, despite frequent complaints from
patients.[2] The authors will claim that their therapy is
"effective", meaning anything or nothing. When the
project begins to ship water, blame is subtly transferred
from investigators to participants. Many of these
deficiencies were identified in a recent JAMA systematic
review on CFS trials,[3] despite which a number are
replicated in this King's-inspired paper[4] on the allied
condition of fibromyalgia.
The authors acknowledge "high dropout rates". Less
than 28% of patients attended all the exercise sessions
offered and 16% attended none. A 30% attrition rate
was anticipated, but the flow chart suggests that patient
absence from exercise treatment averaged 55%. When
formulating their protocol, the rheumatologists were
advised by Professor Simon Wessely's associates in
King's College department of Psychological Medicine.
Chronic fatigue syndrome overlaps fibromyalgia, and
70% of patients in this trial satisfied CFS criteria. In
2000 one well-conducted survey found that 12.9% of
CFS patients received major benefit from graded
exercise, but 38.8% found it harmful.[2] Wessely now
admits the limited efficacy of this form of therapy,[5]
though he has yet to confide this insight to the
readership of the BMJ.
The high drop out rates in some CFS trials have been
identified as a phenomenon in its own right. The JAMA
reviewers queried whether dropouts might be attributed
to "adverse effects arising from the intervention". In this
latest paper, the authors say they "did not record any
adverse events in either group". Statistics for those who
felt worse or very much worse were recorded, but are
not published. It is not clear whether drop-out patients
were actively surveyed for evidence of harm. It seems
that dropouts did find that "exercise worsens the
condition."
The authors propose that future trials "confront the
issue of compliance", by subjecting patients to
cognitive behavioural therapy. Possibly this initiative too
was suggested by Professor Wessely's department.
Six months ago, Wessely announced a new era of
amity between patients and physicians, in the
management of CFS.[6] In this context the authors'
choice of words is unfortunate, and the implications are
perturbing.
Many patients did not share the authors' enthusiasm for
graded exercise. Large numbers exited the trial for that
reason, the study suggests.[7] The authors' response
is that in future investigations, therapists should
systematically challenge the individual intelligence and
collective judgement of those patients who choose to
withdraw.
A recent BMJ editorial implied that such an approach
should not be contemplated, especially where CFS
patients are concerned.[8] But Richards & Scott are
oblivious to warning voices, and cognitive behavioural
therapists are to be drafted in. Their role, it appears, will
be to erase the validity of the patients' experience, and
to substitute the comfortable perception that doctor
knows best.
Ah, if only all clinical trials might be conducted this way.
=========
1 cf Prins JB et al, Cognitive behaviour therapy for
chronic fatigue syndrome: a multicentre randomised
controlled trial, Lancet Vol 357 841-47, March 17 2001.
This trial had significantly higher dropout rates in the
CBT group (40%) than in the support group (32%) or
control group (20%). Of 377 eligible patients, 99 (26%)
refused to participate from the beginning.
2 Cooper L, Report on Survey of Local ME Groups, pp
19 & 20. (Action for ME and the ME Association, 2000).
Accessed 21 May 2001 at
http://www.meassociation.org.uk/locgrsur.pdf
3 Whiting P et al, Interventions for the Treatment and
Management of Chronic Fatigue Syndrome - A
Systematic Review, JAMA 2001 Vol. 286, #11, pp.
1360-1368.
4 Richards SCM, Scott DL, Prescribed exercise in
people with fibromyalgia, BMJ 2002;325:185 ( 27 July).
5 GET and CBT are only "modestly effective", he says,
and "not remotely curative"- Wessely S, Chronic Fatigue
Syndrome - Trials and Tribulations, JAMA Vol. 286, #11,
September 19, 2001.
6 Clark C, Wessely S et al, Chronic fatigue syndrome: a
step towards agreement, Lancet Vol 359 no 9301, 12
January 2002.
7 cf "Chronic fatigue syndrome, Clinical practice
guidelines 2002", (Working Group, Royal Australasian
College of Physicians), MJA 6 May 2002 176 (8 Suppl):
S17-S55. - "many studies have significant refusal and
drop-out rates, which may reflect on the acceptability of
the treatment regimens. These factors significantly limit
the generalisability of the findings."
8 "Views of patients are certainly beginning to prevail
with chronic fatigue syndrome" - Smith R, The
discomfort of patient power, BMJ 2002;324:497.
Competing interests: No competing interests
Prescribing exercise for fibromyalgia is a tempting option, and the
BMJ's cover picture offers an example of exercise that surely many would
wish to undertake. There are a few points though that may be worth noting.
Firstly, the study recruited patients diagnosed between January 1997
and June 1998 but when published three years after the study was finished,
it did not offer any data on the follow up period beyond the first year.
Secondly, the authors did not provide any explanation as to why the
comparative benefit of graded exercise is largely limited to the
improvement in the quality of life questionnaire responses and did not
influence McGill pain score, fibromyalgia impact questionnaires or fatigue
severity. I would hesitate to accept an improvement in "tender point"
counts as of much relevance because there is controversy regarding the
nature of these pressure points and the validity of methods used to elicit
them, and of course,mechanical dolorimetry suggests that these patients
have a reduced tolerance of pain at all sites.
Thirdly, given the fact that over two thirds of patients in each of
the arms (48 and 47) fulfilled the full definition of chronic fatigue
syndrome (CFS), I fail to understand why the authors have not provided us
with any data on this important subgroup in terms of their outcome
measures. I am also surprised why the data on fatigue measures in the two
groups were not even presented in the paper given the fact that CFS and
fibromyalgia are considered to be overlap disorders. Was this because
graded exercise (as compared to relaxation) was not particularly effective
for fatigue and the authors were instructed not to give importance to the
fatigue outcome in this study since it would undermine the precriptions of
graded exercise for CFS frequently advocated by the BMJ in the past year?
Fourthly, there is almost an over-reiteration of fibromyalgia as a
"medically unexplained symptom". In reality, fibromyalgia does not
represent a single symptom and authors should have taken note of an
authoratitive text before submitting to this naive paradigm.[1]
Finally, it has been suggested that cognitive behaviour therapy(CBT)
would improve patient's compliance to graded exercise. This is a new and
untested hypothesis. Having done a post-doctoral thesis some time ago on
patient compliance to long term anti-epileptic drug therapy,I have some
reservations in accepting that compliance to "prescriptions" would be
specifically enhanced by CBT over and above other measures.Infact, the
term "compliance" itself is very contentious since it is defined as the
extent to which a patient's behaviour coincides with the doctor's advice.
Thus, the term compliance, even when used in the context of medical
therapy, has been objected to as having overtones of obsolete, arrogant
attitudes, implying obedience to the doctor's orders [2]. The suggested
alternative is adherence.
Whilst no one would question that physical exercise improves quality
of life both in health and diseases in general, recommending graded
exercise as a specific prescription for complex disorders like
fibromyalgia and CFS is a gross oversimplication of science. The BMJ
headlines of graded exercise in fibromyalgia and CFS however keep
reminding me of an old text that I had come across sometime back in an
antique book shop. This book was written by Frenkel who was the medical
superintendent of the Freihoff Sanatorium in Switzerland and one of the
first to recommend extensive physiotherapy for neurologic diseases with
his introduction of exercises for tabetic ataxia in 1890. Frenkel's book
("The treatment of tabetic ataxia by means of systematic exercise")
suggest to me that learning history is as important as precribing
exercises even if we are treating only the "non-diseases".
Last but not the least,I hugely appreciate the efforts of the authors
in researching this difficult area.
References
1. Mense S, Simons DG, Russell IJ. Muscle pain: understanding its
nature, diagnosis and treatment. Philadelphia: Lippincott Williams &
Wilkins 2001.
2. Lawrence DR, Bennet PN. Clinical Pharmacology. Edinburgh:
Churchill Livingstone 1987.
Competing interests: No competing interests
Dear Editor,
I applaud the BMJ not just for publishing Richards and Scott’s paper on
the treatment of Fibromyalgia, but also for putting it on your front
cover.
Fibromyalgia is still seen by some doctors as a non-disease, and many
sufferers are denied adequate treatment and support. Treatment options are
limited, but successive studies have shown that a graded exercise program,
combined with an element of CBT, can greatly reduce disability.
Long-term studies are still lacking, but with the advent of “exercise
prescription” schemes and healthy living centres, there is some hope that
effective interventions may be offered to more of the 1 to 2% of the
population who suffer from this condition.
Our website works with local groups to support sufferers and has been
publishing a self-help exercise guide for some time. We have also been
lobbying the government to achieve a higher profile for the condition, and
more funds for research.
Thank you for raising the profile for Fibromyalgia. We hope that through
your intervention, more doctors will be able to adequately treat and
support their patients in the future.
Yours truly,
Martin Westby
Competing interests: No competing interests
Magnesium repletion, not DHEA, for treatment of fibromyalgia
Selwyn and colleagues describe graded aerobic exercise as a simple,
cheap, effective, and available treatment for fibromyalgia.1 It has been
suggested that because dehydroepiandrosterone (DHEA) levels have been
found to be low in the condition and raised by exercise, DHEA supplements
can be used. However, DHEA supplements may increase the risk of breast
cancer in postmenopausal women.
A reanalysis of nine prospective studies found strong evidence that
in postmenopausal women the levels of the predominant endogenous sex
hormones, oestrogens and androgens, are strongly associated with breast
cancer risk. The risk for breast cancer increased statistically
significantly with increasing concentrations of all sex hormones examined:
total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-
bound estradiol (which comprises free and albumin-bound estradiol),
estrone, estrone sulfate, androstenedione, DHEA, DHEA sulphate, and
testosterone.2
Missmer and colleagues also found higher median levels of plasma
oestrogens and androgens, including DHEA and DHEA sulphate postmenopausal
women with breast cancer than in controls.3 The increased relative risks
(RRs) of ER+/PR+ tumours in women with highest levels of hormones were 3.3
for oestradiol; 2.0 for testosterone; 2.5 for androstenedione; 1.6 (0.9 to
2.7) for DHEA and 2.3 (1.3 to 4.1) for DHEA sulphate. About a third of the
postmenopausal women had no detectable amounts of progesterone or had
plasma levels ranging from 1.5 to 10 ng/dL. In contrast, DHEA levels
ranged from 169 to 536 ng/dL.
Patients with fibromyalgia have significantly lower levels of
magnesium in erythrocytes but not in serum. For a 100 patients the mean
RBC Mg was 1.92 mmol/L compared with 2.3 mmol/L in the reference
population. 4 Low red cell magnesium levels relate to irregular muscle
activity in myothermograms and over-exercise can cause muscle damage
unless magnesium deficiencies are repleted.5 In contrast to steroid
hormones, magnesium supplements are a safe and an essential treatment for
fibromyalgia.
1 Selwyn C M Richards and David L Scott. Prescribed exercise in
people with fibromyalgia: parallel group randomised controlled trial. BMJ
2002; 325: 185
2 The Endogenous Hormones and Breast Cancer Collaborative Group.
Endogenous sex hormones and breast cancer in postmenopausal women:
reanalysis of nine prospective studies. J Natl Cancer Inst 2002; 94: 606-
16.
3 Missmer SA, Eliassen H, Barbiera RL, Hankinson SE. Endogenouis
estrogen, androgen, and progesterone concentrations and breast cancer risk
among postmenopausal women. J Natl Cancer inst 2004:94: 1856 -65.
4 Romano TJ, Stiller JW. Magnesium deficiency in fibromyalgia
syndrome. J Nutr Med 1994; 2: 165-167.
5 Howard JMH. Muscle action, trace elements and related nutrients:
The Myothermogram. In: Chazot G, Abdulla M, Arnaud P, eds. Current trends
in Trace Element Research: Proceedings of International Symposium on Trace
Elements. Paris, 1987, Smith-Gordon, London 1989:79-85.
Competing interests:
None declared
Competing interests: No competing interests