Editorial

Last week, the continuing saga over the efcacy and

safety of hormone replacement therapy (HRT) in
menopausal women took yet another turn. With its
launch of a handbook entitled Menopause and hormone
replacement, the UK Royal College of Obstetricians and
Gynaecologists issued a press release stating that HRT
should only be used for the short-term relief of
menopausal symptoms. On subsequent questioning,
a College spokesperson suggested that the safety limit
for HRT was 5 years. Predictable newspaper headlines
followed the next day, such as Doctors give HRT veyear limit.
This response led ve members of the study group,
which was convened by the College to review and
debate the current evidence for the handbook, to write
an open letter. We do not accept that the safe use of
HRT should be dened by any arbitrary time limit, but
believe that women with indications for HRT should be
assessed individually by their doctors and prescribed
HRT within the full knowledge of its benets and
risks. This attempt to clarify their position was
welcome. But women and their doctors have been
utterly confused and bewildered by scaremongering
headlines, changing or conicting recommendations,
and the increasingly polarised debates that have
continued for over 5 years.
One of the aims of this latest handbook is to restore a
sense of criticial objectivity by looking at the studies
that have caused so much confusion. It also tries to
arrive at a consensus view for clinical practice and offer
recommendations for further research. These are
laudable goals. They follow the understandable anxiety
caused by results from studies such as the Womens
Health Initiative and the Million Women Study, which
The Lancet published in August, 2003. It is a pity that
relations with the media and communication to the
public were not handled in greater depth. Chapter 28 in
the handbook, Communicating issues on hormone
replacement with women, might have given some
helpful pointers here.
When the Million Women Study was published, the
media picked up the most sensational sounding
statements, such as HRT doubles risk of breast cancer
with no or little concept about what these ndings
meant in terms of absolute risks and without looking
at the studys ndings critically. Concerns about design
www.thelancet.com Vol 364 December 11, 2004

and interpretation, expressed in the correspondence

columns after publication, seldom made it into news
headlines. As an observational study, albeit an
impressively large one, the Million Women Study was
taken to task for selection, ascertainment, and
surveillance bias, all of which might have led to
overestimates of the risk of breast cancer.
In July 2002, the randomised trial from the NIHfunded Womens Health Initiative, which examined
the effect of oestrogen plus progestagen on the
prevention of heart disease and hip fractures in over
16 000 women, was stopped 3 years early on advice
from its data monitoring committee. There was an
increased risk of breast cancer, together with evidence
that risk exceeded overall benet. The increased risk of
breast cancer was estimated to be 126 (95% CI
100159). It did not appear until 4 years into the
study and was higher in those who were on HRT before
enrolment. The study also showed an increased risk of
cardiovascular diseases and venous thromboembolism, and a decreased risk of bone fractures and
colorectal cancers.
The oestrogen-only part of the Womens Health
Initiative in women after hysterectomy was also
stopped early in February this year. It showed no effect
on cardiovascular disease (the primary endpoint), an
increased risk of stroke, and a lower risk of breast
cancer that was not statistically signicant (hazard
ratio 077; 95% CI 059101) compared with placebo.
These WHI studies have the clear advantage of being
randomised trials. However, women enrolled were
considerably older (mean age 63 years, range 5079)
than those in early menopause, most of them (over
90%) had no menopausal symptoms, and a large
proportion were overweight (69%) and had other
additional risk factors. Critics therefore warn that these
ndings are not necessarily generalisable to a wider
population of women who seek HRT for the
unpleasant and sometimes crippling symptoms of
menopause.
Menopausal symptoms, dismissed by some as a
normal phase in life for women to endure, can be
extremely unpleasant, interfering with normal life for
many. Hot ashes occur in up to 70% of women and
can disturb sleep and the ability to work. Urogenital
symptoms and bleeding irregularities are common,

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See JAMA 2002; 288: 32133

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HRT: what are women (and their doctors) to do?

Editorial

often not admitted, and impair sexual function. The

current recommendations to use HRT on an individual
basis in those women with troubling symptoms for
the shortest time possible seem sensible given the
research evidence.
But the HRT story is an all too familiar one in modern
medicine. A new drug is found to be potentially useful
in a large proportion of the population. Hypotheses for
extended use, in the case of HRT to prevent
cardiovascular disease and bone fractures, are
generated from observational studies. Its use is then
heavily promoted beyond the initial indication.
Rigorously conducted randomised studies with long

enough follow-up are scarce or lacking. Harm and risk

are uncovered many years after widespread use.
Further observational studies confound uncertainties
and experts are embroiled in confusing discussions on
the interpretation of weak research. Women and
clinicians who treat them do not know what is best
practice, which can lead to undertreatment or beliefbased approaches.
Women, even if they are beyond child-bearing age,
deserve to be taken more seriously and have a right to
be treated based on appropriately planned and
conducted randomised studies. Anything less is
unacceptable. The Lancet

Landmines and their victims remain priorities

Still Pictures

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2070

5 years have passed since the Ottawa Mine Ban Treaty

became international law. 144 countries have now
signed the agreement; these states have 5 more years
to full their commitment to destroy stockpiled
mines and to clear mines from their territory. To mark
this half-way point, 1300 delegates attended a
summit in Nairobi last week to discuss progress since
Ottawa and to launch a 70-point action plan for the
run up to 2009.
The achievements so far are impressive. According
to one estimate, 20 million stockpiled mines have
been destroyed and 4 million have been cleared
from the ground. Most importantly, the number of
new victims has decreased each year and trade in
the weapons has almost ceased. However, considerable challenges lie ahead, not least because China,
India, South Korea, Pakistan, Russia, and the USA
which between them have stockpiles of more than
180 million antipersonnel minesrefuse to ratify
the treaty.
Indeed, landmines seem to have fallen off the
political agenda, even among the signatories of the
treaty. State leaders were conspicuously absent from
the Nairobi summit and the USA did not even send a
delegate. The loss of high-level support could be very
damaging for the anti-landmine movement, which is
in desperate need of political commitment if it is to
meet the 2009 deadline. Media attention, too, has

diminished. Compared with the 1990s, when Princess

Diana was campaigning so vociferously against
landmines, media interest in the Nairobi event was
slight. This will make it harder for anti-mine
organisations to attract the necessary funds for their
cause. The European Unions executive arm recently
promised 140 million (US$186 million) and the USA
has increased its mine-action budget by 50% to
$70 million per year. But these sums are still tiny
compared with the costs of clearing mines from the
82 countries that are affected by landmines or other
unexploded devices.
Much has been achieved since 1999, and Wolfgang
Petritsch, the summits president, is quietly
condent that the targets for stockpile destruction
and mine clearance will be reached by 2009.
Unfortunately, however, the Ottawa treaty does not
include deadlines for treating the 300 000 people
who have been maimed by landmines. In 2005,
another 20 000 people will be injured by these
devices. Most of these individuals will live in the
poorest areas of the world and will have limited
access to medical care to aid their rehabilitation.
The Ottawa signatories are right to applaud
themselves for their progress, but in their eagerness
to achieve the mine-clearing targets, they must not
forget the people who need their help mostthe
mines innocent victims. The Lancet

www.thelancet.com Vol 364 December 11, 2004