low dose steroids
To the person who posted on the wonders of low dose steroids: please
document. I have looked into the mostly very bad side effects of steroids,
and from what I gather, even low doses that were previously touted as safe
arent. One person I know had to have a cataract operation from steroid use
for only two weeks, her pulmonologist told her it was very low dose, and
nevertheless…
The link you provide is to an AIDS journal of people experimenting with
various things (like us here). Just because they post about it does not
mean it works, or will be harmless.
Where are the real studies?
Vera
May 17th, 2007 at 5:00 am
Low dose steroids and their safety :
A meta study, ie a study of all the relevant studies in the literature :
Low-dose glucocorticoids have low toxicity risk in most patients
Janis Kelly
Mar 10, 2006
Coimbra, Portugal - The low doses of glucocorticoids (GCs) used by
many rheumatoid-arthritis (RA) patients are generally safe and should
not require specific monitoring except in patients with other risk
factors, such as osteoporosis, according to Dr Jose-Antonio P Da Silva
and colleagues at Hospitais da Universidade, Coimbra, Portugal [1]. Da
Silva led a panel of experts who reviewed the literature on the
adverse effects of long-term, low-dose GCs (<10-mg prednisone
equivalents/day) and the toxicity data from randomized controlled
trials of GCs in RA.
Their report is published in the March 2006 issue of the Annals of the
Rheumatic Diseases.
"Common beliefs about risks of adverse effects of low-dose GC use in
RA are not evidence-based and are probably overestimated," Da Silva
told rheumawire. "We found a surprising lack of methodologically sound
studies addressing the toxicity of low-dose glucocorticoids in RA.
This is an important issue, as studies have shown that GCs inhibit
radiological joint damage in RA."
Review included RCT data, review papers, and textbooks
We found a surprising lack of methodologically sound studies
addressing the toxicity of low-dose glucocorticoids in RA. This is an
important issue, as studies have shown that GCs inhibit radiological
joint damage in RA.
Da Silva headed a working party of rheumatologists, endocrinologists,
and representatives from most groups that have conducted randomized
clinical trials of glucocorticoids in RA. Noting that "the proportion
of patients treated with GCs by practicing physicians every day is
clearly in excess of the usually conservative recommendations in
textbooks and review papers," the panel set out to examine both the
literature (textbooks and review papers) on adverse effects of
long-term, low-dose GCs and toxicity data from randomized controlled
trials of GCs in RA.
Toxicity data from four major clinical trials were analyzed and are
the basis for the major study conclusions. These were the Arthritis
and Rheumatism Council Low-Dose Glucocorticoid Study [2], the German
low-dose prednisolone study conducted by Wassenberg et al [3], the
Utrecht study by van Everdingen et al [4], and the WOSERACT study by
Capell et al [5]. Toxicity data from a large number of other trials
with different methodologies also were summarized and incorporated
into the review.
The authors’ main conclusion is that any definitive connection between
low-dose GCs and most adverse effects is "elusive" and far from
certain, given the toxicity data.
"Concerns about low-dose GC toxicity seem to be based on reported
adverse effects of higher-dose regimens," Da Silva said. "A second
cause of overestimation of GC toxicity could be bias by indication,
especially since patients with more severe disease activity and with
complications of the inflammatory disease are often treated with GCs.
Active and severe disease might be, in itself, a risk factor for
adverse effects of drugs, including GCs. Third, the disease itself may
be responsible for complications that could be erroneously attributed
to the GC medication. Osteoporosis might be a good example of that.
Severe RA itself is a major cause of osteoporosis, and it is even
possible that the suppression of the disease with low-dose GCs might
suppress RA-related osteoporosis more than the small amount of
glucocorticoid-induced osteoporosis."
Da Silva said that the review points up the need for more research on
the frequency and types of adverse effects associated with low-dose
GCs, especially over long-term use.
The authors conclude, "The evidence on which to support clear
recommendations about toxicity of low-dose GCs is surprisingly weak.
The literature and the recent trial results suggest that routine
toxicity monitoring for patients receiving low-dose GCs is not
currently justifiable or cost-effective based on existing evidence."
However, they also point out that patients with additional risk
factors such as osteoporosis, obesity, hypertension, or a family
history of diabetes or glaucoma should be monitored for GC-related
adverse effects.
—————————————————————-
Low-Dose Prednisone Therapy for Patients with Early Active Rheumatoid
Arthritis: Clinical Efficacy, Disease-Modifying Properties, and Side
Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
right arrow Amalia A. van Everdingen, MD; Johannes W.G. Jacobs, MD,
PhD; Dirk R. Siewertsz van Reesema, MD; and Johannes W.J. Bijlsma, MD, PhD
1 January 2002
Background: Oral glucocorticoids combined with disease-modifying
antirheumatic drugs are beneficial and retard radiologic joint damage
in rheumatoid arthritis.
Objective: To investigate the clinical efficacy, disease-modifying
properties, and side effects of low-dose glucocorticoids as
monotherapy for previously untreated patients with early active
rheumatoid arthritis.
Design: 2-year randomized, double-blind, placebo-controlled clinical
trial.
Setting: 2 outpatient rheumatology clinics.
Patients: 81 patients with early active rheumatoid arthritis who had
not been treated with disease-modifying antirheumatic drugs.
Intervention: 41 patients were assigned to 10 mg of oral prednisone
per day, and 40 were assigned to placebo. Nonsteroidal
anti-inflammatory drugs were allowed in both groups. After 6 months,
sulfasalazine (2 g/d) could be prescribed as rescue medication.
Measurements: Clinical variables were assessed at baseline and every 3
months; radiologic studies were performed every 6 months. Adverse
effects were documented every 3 months.
Results: In the first 6 months, the prednisone group showed more
clinical improvement than the placebo group. This effect was not seen
after 6 months except in grip strength and the 28-joint score for
tenderness. Use of additional therapies was significantly less common
in the prednisone group, particularly in the first 6 months. More than
65% of those who completed the study were not taking sulfasalazine.
After month 6, radiologic scores showed significantly less progression
in the prednisone group than in the placebo group. No clinically
relevant adverse effects were observed, except for a higher incidence
of osteoporotic fractures in the prednisone group.
Conclusions: Prednisone, 10 mg/d, provides clinical benefit,
particularly in the first 6 months, and substantially inhibits
progression of radiologic joint damage in patients with early active
rheumatoid arthritis and no previous treatment with disease-modifying
antirheumatic drugs. Because of their limited disease-modifying
effects, glucocorticoids should be combined with disease-modifying
antirheumatic drugs in patients with rheumatoid arthritis.
———————————————————–
Cortisone: A Problem in Pharmaceutical Marketing
William McK. Jefferies, M.D. (Retired)
When cortisone was first reported to produce dramatic beneficial
effects in patients with rheumatoid arthritis in 1949(1), its use was
welcomed as a major advance in medical therapy. The fact that it was a
normal hormone, the only hormone that is absolutely essential for
life, and that it also produced similar dramatic beneficial effects in
patients with other autoimmune disorders, in those with chronic
allergic disorders, and in those with many other illnesses, resulted
in its discoverers being awarded the Nobel Prize. Yet within a few
years patients receiving cortisone or its derivatives had developed so
many serious and sometimes fatal side effects that these medications
developed a reputation for being dangerous drugs whose use should be
limited to patients with serious illnesses that could not be helped by
any other treatment. Meanwhile it became evident that cortisone must
be converted to hydrocortisone before having its characteristic
physiologic effects and chemists pointed out that cortisol was a more
proper term for hydrocortisone, thus adding to the confusion of most
physicians and patients.
When serious side effects developed in patients receiving the large
dosages of cortisone or hydrocortisone (cortisol) that were thought to
be necessary for therapeutic effects, derivatives such as prednisone
or triamcinolone were introduced, but except for less tendency to
produce retention of salt and water (edema), the derivatives often
produced any or all of the undesirable side effects of excessive
amounts of the normal hormone. Hence cortisone and cortisol developed
a reputation for being dangerous drugs whose use should be confined to
patients with serious, life-threatening illnesses that would not
improve with any other treatment.
Having trained at the Massachusetts General Hospital under Dr. Fuller
Albright, a pioneer in the study of adrenocortical function, I was
developing an endocrine clinic and research laboratory at Western
Reserve University Hospitals in Cleveland, Ohio and I saw every
patient admitted for treatment with cortisone or its derivatives for
the first two years that these medications were available. In 1955 I
wrote a review article summarizing the problems that existed at that
time that was published in the New England Journal of Medicine
entitled, "The Present Status of ACTH, Cortisone and Related Steroids
in Clinical Medicine" (2). During this time I determined that the
duration of effect of a single dose of cortisol was approximately 8
hours and that normal human adrenals produced the equivalent of 35 to
40 mg of cortisol daily when taken as tablets by mouth 4 times daily,
before meals and at bedtime in the absence of unusual stress.
Meanwhile I also began to work in an infertility clinic associated
with Western Reserve University and found that many of its women
patients had evidence of mild disorders of adrenal function that
improved when they were given small, subreplacement dosages of
cortisone or cortisol (3). During the next twenty years over 200
babies were born to women with mild disorders of ovarian function who
took safe, physiologic dosages of cortisone or cortisol not only in
order to get pregnant but also throughout their pregnancies to protect
against miscarriages, without any evidence or harm to either mothers
or babies (4). These dosages therefore appeared to be restoring normal
function rather than impairing it.
Some of these women reported that while taking the small, safe dosages
of cortisone or cortisol their symptoms of allergies, or unexplained
chronic fatigue (the chronic fatigue syndrome), or autoimmune
disorders such as rheumatoid arthritis or chronic thyroiditis, also
improved. These beneficial effects of safe, physiologic dosages of
cortisone or cortisol were reported at the annual meeting of the
American College of Physicians in New York City in April, 1966, and in
a paper published in the Archives of Internal Medicine in 1967 (5),
but by that time patents on the normal hormones, cortisone and
cortisol, had expired. Pharmaceutical laws require that when a new use
is found for a medication, it must receive all of the relevant tests
for its safety, including therapeutic trials, before the new use can
be advertised. Because such studies are expensive, pharmaceutical
companies have little incentive for performing them when they no
longer have the protection for their investment that is provided by a
patent. Hence pharmaceutical companies apparently could not even
mention in their package inserts or advertisements any of these
potential new uses of safe dosages of the normal hormone, cortisol!
Further reports of the beneficial effects of safe dosages of cortisone
or cortisol were published in endocrine journals and conference
proceedings in the 1960’s and 1970’s, but these were received
skeptically by most physicians when no ads or promotional efforts by
the pharmaceutical companies marketing the hormones appeared.
I, like most other physicians, did not realize the cause of this
problem, so I thought it might be helped by my writing a book
reviewing the cortisone story and describing the beneficial effects of
safe, physiologic dosages of cortisone or cortisol that had been
observed. In 1981, therefore, Safe Uses of Cortisone was published by
the Charles C. Thomas Company, a reputable medical publisher that had
published much of the earlier work on cortisone and its derivatives.
This book also received little attention until a few patients with
chronic allergies and their physicians found that this therapeutic
approach was both safe and effective. During the past five years, when
it has become evident that the hypothalamus-pituitary-adrenal (HPA)
axis plays a major role in immunity and in the response to stress,
there has been a return to considering the possibility that autoimmune
disorders, especially rheumatoid arthritis, and chronic allergic
disorders might be related to mild adrenocortical deficiency, either
primary in the adrenal glands or secondary to deficient stimulation by
adrenocorticotropic hormone (ACTH) from the pituitary gland. An update
on Safe Uses of Cortisone entitled Safe Uses of Cortisol has therefore
recently been published, reviewing these developments and the evidence
that mild adrenocortical deficiency, a diagnosis that is not mentioned
in medical textbooks, is very probably a factor in the development of
many, if not all, allergic disorders and autoimmune disorders, and
describing a safe treatment of these disorders with physiologic
dosages of cortisol (6). Hopefully this book will help to clarify this
confusing situation. Cortisol is a normal hormone, the only hormone
that is absolutely essential for life, so it must be safe in proper
physiologic amounts!
These developments have therefore revealed a serious problem in our
pharmaceutical laws that will hopefully be corrected. If a cure for
cancer were found tomorrow in a medication whose patent had expired,
especially one that had developed a bad reputation like cortisone, it
might be extremely difficult to get anyone to pay any attention to it!
References
1. Hench PS, Kendall EC, Slocumb CH, Polley HF. The effects of a
hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone:
Compound E) and of pituitary adrenocorticotropic hormone on rheumatoid
arthritis; preliminary report. Proc Staff Meet Mayo Clin 1949, 24:181-97.
2. Jefferies, W.McK. The present status of ACTH, cortisone and related
steroids in clinical medicine. New Eng J Med 1955, 253:441-6.
3. Jefferies, W.McK. Glucocorticoids and Ovulation. In Greenblatt,
R.B.(Ed): Ovulation. Philadelphia, Lippincott,1966. pp 62-74.
4. Jefferies, W.McK. Safe Uses of Cortisol (second edition) Charles
C.Thomas, Springfield, 1996, p.86.
5. Jefferies, W.McK. Low dosage glucocorticoid therapy. Arch Intern
Med 1967, 119:265-78.
6. Jefferies, W.McK. Safe Uses of Cortisol (second edition) Charles
C.Thomas, Springfield, 1996, Chapters 4 through 11.
————————————————–
This article was published in the journal Medical Hypotheses
in March 2003Summary For nearly three decades, the author has
treated
multiple serious diseases of cats and dogs by correcting an
unrecognized
endocrine-immune imbalance originating with a deficiency or
defect of
cortisol. The cortisol abnormality creates a domino effect on
feedback
loops involving the hypothalamus-pituitary-adrenal axis. In
this scenario
estrogen becomes elevated, thyroid hormone becomes bound, and
B and T
cells become deregulated. Diseases with this aberration as a
primary etiological
component range from allergies and strange behavior to severe
cases of
autoimmunity and cancer. Successful treatment and control,
even in critical
cases, have been consistently achieved with a long-term
physiologic (not
pharmacologic) replacement with cortisone along with thyroid
hormone (in
dogs). The treatment represents a major healing modality for
many seemingly
unrelated chronic diseases of animals. In humans, this
endocrine-immune
dysfunction appears to exist and, as in veterinary medicine,
has been
overlooked by researchers and clinicians. Testing and
treatment patterned
after the animal model may offer significant clinical benefits
for challenging
human afflictions.