News stories about a clinical trial in 2002 prompted many postmenopausal women to avoid hormone replacement therapy out of fear they would develop breast cancer.
The study also touched off a controversy among researchers about whether the presentation of the trial results was accurate or misleading.
Now the clinical trial’s principal investigator is contending that the researchers who did the study misrepresented some of the findings and failed to follow standard scientific-research protocol.
The question this raises once again is whether hormone replacement therapy is safe, or not.
In his article, “The evidence base for HRT: what can we believe?,” Professor Robert D. Langer argues that a small group of the study’s investigators “hijacked” the data. One of his accusations is that the group incorrectly reported that the study was cut short because of higher risks of women developing breast cancer and heart attacks from the hormonal treatment.
The serious allegations against some of the investigators in the Women’s Health Initiative (WHI; NCT00000611) suggest that the study reporting violated guidelines on how trial data should be presented.
“This new study raises questions about due process surrounding the data evaluation, writing, author approval and publication of the original WHI paper,” Rodney Baber, professor and editor in chief of the Climacteric, the journal that published Langer’s article, said in an accompanying editorial. Baber’s piece had the telling title, “What is scientific truth?”
The initial publication of the WHI trial results in 2002 contended that the risks of hormone replacement treatment outweighed the benefits. News releases summarizing the findings quoted the investigators as claiming a 26 percent increased risk of invasive breast cancer in women treated with hormone replacement for postmenopausal symptoms. The risks of such women developing heart disease and stroke were even higher, according to the news releases.
Most women who have considered such treatment are aware of the arguments the publication made against it. Baber said in his editorial that news stories about the trial investigators’ findings prompted many women to stop the treatment. Even more avoided starting it on the advice physicians, he said.
A commentary in the New England Journal of Medicine in 2016 reignited the debate about the safety of hormone treatment. Two of the WHI investigators maintained that the original claims were misunderstood, and did not apply to younger postmenopausal women. Young women with severe symptoms continued to decide against the treatment on the basis of the original publication, however.
Langer’s article makes accusations that go far beyond a misunderstanding. He said the initial trial report was written by a small group on the investigator team who kept their findings and conclusions from the others until publication.
He also contended that the group submitted the article for publication under the names of those from whom they kept the report secret.
The report misrepresented the trial findings, and made claims that were not supported by the data when viewed according to the study protocol, Langer added. In a clinical trial, a pre-established protocol should be followed, not only when performing the study, but also when analyzing the data — particularly main study outcomes.
The trial was designed to compare the effectiveness of the treatment in young and old postmenopausal women. But the report generalized findings in older to younger women, twisting the logic of the study in a scientifically inappropriate manner, Langer contended.
This not only led to women suffering sometimes severe symptoms they could have been avoided, he said, but also experiencing a higher rate of hip fractures, heart attacks, and other conditions that hormone replacement has been shown to prevent.
“Other WHI investigators may hold different views, but this study points to the need for reappraisal and potential change in our overall understanding of the relationship between HRT use and risk,” Baber said in a press release.
“All clinicians constantly reappraise treatment modalities and look at the balance of risk, but now is time for us to recognize that hormone therapy prescribed to healthy postmenopausal women within 10 years of their last menstrual period, is an effective intervention, and for most women benefits outweigh risks,” said Mary Ann Lumsden, professor and president of the International Menopuse Society (IMS).
“It can help avoid the many symptoms women suffer during this transitional period of their lives. We welcome the release of this paper, which reinforces the advice provided in our evidence-based IMS Recommendations on HRT,” she added.
It is unclear why Langer waited until now to release his assessment.