Time to review all the evidence for HRT Print E-mail
Read below for the BMJ's Commentary "Time to review all the evidence for
hormone replacement therapy": Truly! Feminist researchers have been
screaming this from the rooftops for the past 20-plus years! - Lynette.

BMJ 2005;330:345 (12 February)

Time to review all the evidence for hormone replacement therapy
Fay Crawford,NHS R&D fellow1,Peter Langhorne,professor of stroke care2

1 Tayside Centre for General Practice, MacKenzie Building, Dundee DD2 4BF, 2
Academic Department for Geriatric Medicine, Glasgow Royal Infirmary, Glasgow
G31 2ER
Correspondence to: F Crawford f.crawford{at}chs.dundee.ac.uk

The meta-analysis by Bath and Gray provides evidence that hormone
replacement therapy does not confer any protection against stroke in
postmenopausal women but increases their risk of stroke.1 These observations
add to a rapidly expanding literature on the potential hazards and benefits
of the therapy.2

The women's health initiative trial contributes well over half of the
current trial data, and its findings dominate the meta-analysis. The women's
health initiative trial sought to assess the risks and benefits of three
separate interventions—a low fat diet, hormone replacement therapy, and
calcium supplements—in 64 500 women over a 15 year period.3 Two separate
types of hormone replacement therapy were tested, monotherapy (oestrogen
alone) and dual therapy (oestrogen plus progesterone), in two separate trial
arms recruiting a total of 27 000 women.

In the dual therapy arm of the trial (n = 16 608) an increased risk of
stroke became apparent by the second year, and the trial was ended three
years early. Subgroup analysis indicated an increased risk of ischaemic
strokes in women in all risk categories, not just those judged to be at high
risk. The monotherapy arm (oestrogen alone, for women without a uterus) of
the trial (n = 10 739) was also ended early because of an increase in
non-fatal strokes. Full details from the subgroup analysis of this second
arm are not yet available, and the evaluations of the low fat diet and
calcium supplements are continuing.

What should women and their doctors now conclude about hormone replacement
therapy? Although opinions may vary about whether the female menopause is a
deficiency disease or a rite of passage, several facts seem clear: hormone
replacement therapy can relieve some troublesome menopausal symptoms,4 but
it does have other important health effects, both bad and good.5 The women's
health initiative trial found that therapy did not meaningfully improve
measures of physical and mental function or quality of life,5 but some
effects that women might value—namely perceptions on youthfulness,
attractiveness, and skin tone—have not been adequately studied. Balancing
these factors in individual treatment decisions can be difficult. There is a
clear need for an overarching meta-analysis of all relevant individual
patient data, which can include key baseline participant characteristics,
hormone replacement therapy characteristics, and all relevant outcomes
(including time to event analyses).

In the interim, all women who consult for hormone replacement therapy need
to understand that it can carry an increased risk of ischaemic stroke,
coronary events, venous thrombosis, and possibly breast cancer.2 In order to
minimise these hazards, doctors should recommend hormone replacement therapy
only for severe menopausal symptoms and for the shortest possible time in
women who are fully informed of these risks.
Contributors: FC wrote the first draft of the commentary, and PL revised the
text. Both authors are guarantors.

Funding: FC is funded by the Chief Scientist Office, Scotland.

Competing interests: None declared.


Bath PWM, Gray LJ. Association between hormone replacement therapy and
subsequent stroke: a meta-analysis. BMJ 2005;330: 342-4.[Abstract/Free Full
Grady D. Postmenopausal symptoms—therapy for symptoms only. N Engl J Med
2003;348: 1835-7.[Free Full Text]
Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird
A, et al. Effect of estrogen plus progestin on stroke in post menopausal
women. The women's health initiative: a randomised trial. JAMA 2003;289:
2673-84.[Abstract/Free Full Text]
Hlatky MA, Boothroyd D, Vittinghoff E, Sharp P, Whooley MA for the HERS
Research Group. Quality of life and depressive symptoms in postmenopausal
women after receiving hormone replacement therapy. JAMA 2002;287:
591-7.[Abstract/Free Full Text]
Hays J, Ockene J, Brunner RL, Kotchen JM, Manson JE, Paterson RE, et al.
Effects of estrogen plus progesterone on health related quality of life. N
Engl J Med 2004;384: 1839-54.