Läkemedelsföretagen tvekar ofta inför att satsa på ny antibiotika för att det inte är tillräckligt lönsamt, men de ska nu ges ekonomiska morötter köpa inderal receptfritt Ofta fås en bättre/snabbare absorption när läkemedel tas på fastande mage men för vissa läkemedel är det önskvärt att minska risken för biverkningar från mag-tarmkanalen genom att läkemedlet tas tillsammans med föda.
Gynaecology.co.uk
Menopause International 2009; 00: 1–2. DOI: 10.1258/mi.2009.009019
Why are physicians reluctant to useestrogens for anything – or do theyprefer ‘PROFOX’?
London PMS and Menopause Clinic, London, UK
Correspondence: Professor John Studd, London PMS & Menopause Clinic, 46 Wimpole Street, London W1G8SD, UK. Email: [email protected]
Estrogens to physicians appear to be as garlic is to Dracula
antidepressants. The depression became cyclical as PMS as
and equally illogical. The reluctance for bone physicians
the periods returned. As they moved into their 40s, the
to use estrogens for low bone density and for psychiatrists
PMS that had never been adequately treated became
to use transdermal estrogens for hormone responsive
worse as the cyclical depression became more continuous
depression is hard to understand and is a matter of great
with fewer good days a month. Being in good mood
concern. This objection is not new as it antedated the
during their pregnancies followed by PND and PMS is the
2002 Women’s Health Initiative (WHI) study and the
clue that hormonal fluctuations are a major part of the
equally suspect Million Women Study by many years;
aetiology of depression in women and most importantly
however, these data are now used for justification for their
that elevation of plasma oestradiol levels will improve the
choice of medication. Even general practitioners formerly
enthusiastic about hormone replacement therapy (HRT)
These women respond to moderately high-dose trans-
have been hobbled by outdated views from advisory
dermal oestradiol at all three stages of their depression;
bodies and will prescribe only for the severest of vaso-
postnatal,4 premenstrual5 and perimenopausal6,7 but all
motor or atrophy symptoms in the lowest dose and the
too often they are neglected or treated with a range of
antidepressants or mood-stabilizing drugs. The younger
It would seem logical that a 50–60-year-old woman
women thus suffer years of dysfunctional depression. It is
with hot flushes, tiredness, depression, loss of libido,
astonishing how often women with a diagnosis of bipolar
pelvic atrophy and low bone density should have estro-
depression become normal when their severe PMS is
gens in a dose appropriate for the pathology, but this is
treated by suppression of ovulation. Psychiatrists are not
not happening. The fortunate few may have such treat-
aware of the effect of estrogens on depression in spite
ment with relief of these symptoms and a substantial
of relevant publications of randomized controlled trials.
decrease in fracture risk as they have a 10–20% increase
Unfortunately, these studies have not been repeated
in bone density after 5–10 years of estrogens. But the
by those most involved in the mental heath of women
majority of these women will either have no treatment
because psychiatrists do not seem to be interested in
or receive antidepressants or bisphosphonates depending
hormonal therapy and the pharmacological companies
on which specialist clinic she is referred to.
have little desire to fund head-to-head studies of
Selective serotonin reuptake inhibitors (SSRIs) of
their profitable inpatent antidepressants against cheap
doubtful value are used for depression and also hot
estrogens. Women therefore suffer from this territorial
flushes regardless of their effects on libido, mental acuity,
memory, general wellbeing, weight gain and the increas-
Are things better with osteoporosis? In June 2009 there
ing problem of long-term dependency. These drugs also
is a major three-day international meeting on osteoporo-
have a deleterious effect on bone density1 even more than
sis in Manchester run by the National Osteoporosis
does depression untreated with SSRIs.2 It is commonplace
Society without a single plenary lecture on the role of
to see depressed perimenopausal women who have a
estrogens. There may be a few free communications but
longstanding history of premenstrual depression (PMS),
there are no hormone companies involved and no interest
postnatal depression (PND) who will say that they were
from the bone physicians or rheumatologists on the
last well without depression many years ago when they
scientific committee, Hence the most effective, cheapest
were last pregnant. They then had many months of
and probably safest long-term treatment will not feature.
PND and was either undiagnosed or treated with
How else will these specialists learn the simple skills of
Menopause International Vol. 00 No. 0 Month 2009
J Studd Why are physicians reluctant to use estrogens for anything
hormone therapy? The programme committee have not
There is no doubt that HRT is effective in reducing the
responded to protests about this omission, which is the
number of osteoporotic fractures but is it safe? The initial
equivalent to failing to discuss angiotensin-converting
2002 WHI study reported an increase in major side-effects
enzyme inhibitors in a meeting on hypertension.
due to wrong patients of the wrong age given the wrong
Not only do estrogens produce a dose-dependent and
dose of an inappropriate continuous estrogen/progesto-
duration-dependent increase in bone density and bone
gen HRT preparation. It is little consolation to stress that
architecture, but the cancellous bone collagen is also
the investigators were informed of this about 15 years ago.
increased,8 leading to increased strength and fracture
However, it is now clear that this preparation caused no
protection. It should be noted that HRT is the only
harm if started within 10 years of the menopause. It is
treatment that has been demonstrated to produce fewer
also re-assuring that hysterectomized patients in this age
hip and vertebral osteoporotic fractures in low-risk
group receiving estrogen alone have a substantial decrease
and mid-risk women. The generalized increase in skin
in heart attacks, breast cancer and deaths,14 although the
and bone collagen that occurs when postmenopusal
study of this age group was discontinued prematurely
women take estrogens is also seen in the intervertebral
without significance being confirmed or otherwise.15
discs. The protective cushion of the discs make up 25%
No convincing explanation has been given.
of the length of the vertebral column but decreases with
The increasing awareness of the safety of HRT on the
age. Estrogens prevent this shrinkage, bisphosphonates
cardiovascular system as featured in a IMS meeting in
January is discussed by Stevenson in an accompanying
My view is that estrogens should be the first choice for
editorial in this edition of Menopause International.16
the prevention and treatment of low bone density in theunder 60s.10 Claus Christianson in a personal communi-
cation goes further believing that they should be the first,second and third choice in this age group. Consideringthe poor efficacy, long-term side effects and cost ofthe non-hormonal preparations, it is hard to disagree. But they may cause vaginal bleeding that seems to be
another garlic moment for physicians as they feel unableto cope with it. The irony is that many bone physicians
1 Williams LJ, Pasco JA, Jacko FN, Henry MJ, Dodd S, Berk M.
who have little knowledge of estrogen therapy would
Depression and bone metabolism. A review. Psychother Psychom2009;78:16–25
regard themselves as endocrinologists.
2 Vestergaard P, Rejnmark L, Mosekinlde J. Anxiiolytics, anti-
Bisphosphonates are now the first-line treatment in
depressants and the risk of fracture. Osteoporos Int 2006;17:807–16
spite of increasing anxiety about osteonecrosis of the
3 Studd J, Panay N. Hormones and depression in women.
jaw,11 mid-shaft femoral fractures and abnormal histo-
4 Gregoire A, Kumar R, Everitt B, Henderson AF, Studd JW.
morphometric changes in the bone.12 There is perhaps a
Transdermal oestrogen treatment of severe postnatal depression.
more serious problem, if that is possible. Oesophageal and
stomach symptoms are so common that 30% of women
5 Watson NR, Studd JW, Savvas M, Garnett T, Baber RJ. Treatment
taking oral bisphosphonates require proton pump
of severe premenstrual syndrome with oestradiol patches and
inhibitor (PPI) therapy for ‘heartburn’. These are the
cyclical oral norethisterone. Lancet 1989;2:730–2
6 Montgomery JC, Appleby L, Brincat M, et al. Effect of oestrogen
drugs that reduce bone density and have been reported
and testosterone implants on psychological disorders in the
to significantly increase osteoporotic hip fractures after
7 Schmidt PJ. Mood, depression, and reproductive hormones in the
Fosamax once weekly now in generic form is inexpen-
menopausal transition. Am J Med 2005;118(Suppl 12B):54–8
8 Khastgir G, Studd JWW, Holland N. Anabolic effect of long-term
sive and therefore being recommended by the National
estrogen replacement on bone collagen in elderly postmeno-
Institute of Clinical Excellence, an organization that
pausal women with osteoporosis. Osteoporos Int 2001;12:465–70
still has not reported on HRT for the prevention and
9 Muscat Baron Y, Brincat M, Galea R, Calleja N. Low intervertebral
treatment of osteoporosis. The other generic preparation
disc height in postmenopausal women with osteoporotic
prescribed frequently to post-menopausal women is
vertebral fractures compared to hormone-treated and untreatedpostmenopausal women and premenopausal women without
Prosac, which is already being used in combination with
fosamax as a post-HRT nightmare, which could be called
10 Studd JW. Estrogens should be first choice in the prevention and
PROFOX (PROzac þ FOsamaX). This substitute for estro-
treatment of osteoporosis in women under the age of 60.
gens would have a deleterious effect on mood, memory,
11 Basu N, Reid DM. Bisphosphonate-associated osteonecrosis of the
libido, upper gastrointestinal symptoms requiring
PPI treatment and more hip fractures with little or no
12 Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast
improvement of the hormone responsive symptoms that
formation and long-term oral bisphosphonate therapy. N Engl
trouble 50–60-year-old women. Moving from Bram Stoker’s
Dracula to Mary Shelley’s monster, we must be beware that
13 Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD.
Use of proton pump inhibitors and risk of osteoporosis-related
this created Frankeinstein drug does not become a feature
of the treatment of middle-aged women. In combination,
14 Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA,
PROFOX will produce more problems in combination than
Black H. Women’s Health Initiative Steering Committee. Effects of
the individual components and either option is less effec-
conjugated equine estrogen in postmenopausal women withhysterectomy: the Women’s Health Initiative randomized
tive in well-selected patients than oestradiol perhaps with
controlled trial. JAMA 2004;291:1701–12
the addition of testosterone and a short monthly course of
15 Studd J. Hysterectomy – a life-saving as well as a life-enhancing
a progestogen in women with a uterus.
Menopause International Vol. 00 No. 0 Month 2009
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Provide volume number in references [9,11].
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