HRT: beneficial in some, harmful in others?

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Rheumawire

Feb 13, 2004

HRT: beneficial in some, harmful in others?

Leicester, UK - The primary prevention of chronic diseases alone does

not justify the use of hormone replacement therapy (HRT), according to a

clinical decision analysis on the net harm or benefit of HRT [1]. Women

with menopausal symptoms, however, might benefit, depending on the

severity of symptoms and the reduced quality of life each woman

attributes to them.

" Thus, a decision analysis tailored to an individual woman would be more

appropriate in clinical practice than a population-based approach, " Dr

Cosetta Minelli (University of Leicester, UK) and colleagues write in

the February 14, 2004 issue of the BMJ.

Although it is mainly used to relieve menopausal symptoms, HRT has shown

benefits in preventing osteoporosis and other chronic diseases. However,

recent randomized trials have drawn up a serious side-effect profile of

HRT, especially in terms of breast-cancer and heart-disease risk. In

2002 one arm of the 17 000-patient Women's Heath Initiative (WHI) trial

was stopped early due to an increased risk for breast cancer, coronary

heart disease (CHD), stroke, and pulmonary embolism with combination

therapy, as reported by rheumawire.

Minelli and colleagues argue that, because the WHI did not consider

menopausal symptoms, its results are insufficient to draw up a strategy

for HRT use. " Previous recent work has simply looked at the number of

cases rather than considered the impact on quality of life and

mortality, " coinvestigator Dr Abrams told rheumawire. " Therefore,

it is difficult to say anything about the overall net effect, since the

diseases are very different. "

Based on " best currently available evidence, " including 3 recently

published studies on HRT, the group from Leicester conducted a decision

analysis on the net benefit of 5 years of combined estrogen and

progestin therapy in a hypothetical population of white UK women at the

age of 50. They compared benefitsrelief of symptoms, prevention of hip

fractures, and decreased risk of colorectal and endometrial cancersvs

the risksbreast cancer, CHD, stroke, and pulmonary embolismin women with

and without menopausal symptoms and with different baseline risks for

breast cancer and used quality-of-life-years (QALYs) for the impact of

each outcome.

With all components included, their model identifies a threshold above

which potential harms outweigh the benefits. Data on risk were based on

3 randomized trials, 1 on the long-term effects of HRT published in the

Lancet in 2002 [2] and 2 reports of the HERS II trial in the Journal of

the American Medical Association 2002 on noncardiovascular and

cardiovascular outcomes [3,4]. Relief of symptoms was based on a recent

meta-analysis by the Cochrane Collaboration. The analysis was done

across a range of quality-of-life (QoL) values to " obtain results

tailored to individual women according to their perceived QoL with

symptoms, " the authors explain.

The model showed that, in women free of symptoms, HRT was not justified,

because they derived a net harm from it. In women with menopausal

symptoms, on the other hand, HRT is on average beneficial, with

decreasing benefit with increasing risk of breast cancer.

However, Minelli et al stress that this benefit is highly subjective,

depending on the QoL value attributed to the symptoms. " This value

varies widely owing to the substantial variability in severity of

symptoms and perception of their impact on everyday life reported by

women, " they write. Therefore, the model should be used individually by

each woman rather than provide an " estimate for an average woman. " The

group advocates an individually tailored approach in the decision for or

against HRT. " In fact, 1 of the main conclusions we make, if not the

main 1, is that the decision of whether to take HRT or not has to be

made on an individual basis, taking account of a woman's own

circumstances, eg, impact of menopausal symptoms on QoL and her baseline

risk of breast cancer, " Abrams commented. He pointed out that, although

the application of sophisticated decision analyses is difficult in

practice, their " graphical decision aid " could be of great help. " It

does capture the elements of the fact that different women will have

symptoms that affect their QoL differently and have different inherent

risks of breast cancer. We would suggest they are a promising future

development to enable informed patient decision making, " he stated.

The results of this analysis are contrary to the latest findings of the

WHI, published in March 2003 and reported by rheumawire, which showed

that estrogen plus progestin did not improve health-related quality of

life, even in the youngest women or among those suffering from

menopausal symptoms. The findings do, however, concur with

recommendations by the UK Medicines and Healthcare Products Regulatory

Agency and the FDA. In October 2003 the FDA's Endocrinologic and

Metabolic Drugs Advisory Committee advised that the current labeling for

HRT products for relief of menopausal symptoms and as a second-line drug

for the prevention of osteoporosis in postmenopausal women is still

satisfactory, even in light of the mounting evidence of harm from

further WHI data.

In an editorial in the same issue of the BMJ, Dr Klim McPherson

(Churchill Hospital, Oxford, UK) raises several critical issues in terms

of the future of HRT [5]. He considers Minelli's analysis " essential but

inevitably aggregated and somewhat static. " He also points out that the

risks for breast cancer and heart disease assumed for this study were

too conservative, because a great number of women in the trial did not

complete treatment. Higher risk values, he argued, " would make the

probability of net harm considerably greater for any woman. " Due to the

increasing evidence of harm associated with HRT, he paints a grim

picture of its future use, with physicians being tempted to highlight

its benefits and downplay the risks. Subgroup analysis with patients who

show fewer side effects will also play into this scenario, he said. " The

latest results on coronary heart disease from the Women's Health

Initiative study provide (unsafe) opportunities to cite subgroups for

which the bad effects are not observed, " he writes. " Such claims are

often not plausible, never mind adequate. Reputations (and money) are at

stake. "

McPherson also voices criticism about the efficacy and safety of

so-called " natural remedies " as an alternative to HRT, asking, " Will

adequate research be done to ensure that we avoid another half century

of uncontrolled experimentation on menopausal women? "

Rommelfanger

Sources

1. Minelli C, Abrams KR, Sutton AJ, et al. Benefits and harms associated

with hormone replacement therapy: clinical decision analysis. BMJ 2004;

328:371-375.

2. Beral V, Banks E, Reeves G. Evidence from randomised trials on the

long-term effects of hormone replacement therapy. Lancet 2002 Sep 21;

360(9337):942-4.

3. Hulley S, Furberg C, Barrett-Connor E, et al. Noncardiovascular

disease outcomes during 6.8 years of hormone therapy: Heart and

Estrogen/Progestin Replacement Study Follow-up (HERS II). JAMA 2002 Jul

3; 288(1):58-64.

4. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease

outcomes during 6.8 years of hormone therapy: Heart and

Estrogen/Progestin Replacement Study Follow-up (HERS II). JAMA 2002 Jul

3; 288(1):49-57.

5. McPherson K. Where are we now with hormone replacement therapy? BMJ

2004; 328:357-358.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org