to the editor: I have several comments I wish to share regarding the article1 on hip fractures by Dr. Brunner and colleagues. It must be stressed that atypical clinical presentations of hip fractures in elderly patients are common. These patients frequently report vague calf or knee pain resulting in potential for misdiagnosis (especially when the patient recalls or is incapable of recalling any previous trauma). Thorough evaluation and radiographic survey should be aggressively pursued in similar cases.
The authors state, “Although hormone replacement therapy has been used for osteoporosis prevention, recent results from the Women's Health Initiative (WHI) trial2 demonstrated that overall health risks exceeded the benefits of using combined estrogen plus progestin for an average follow-up period of 5.2 years in healthy postmenopausal women in the United States. The WHI findings indicated that the estrogen-progestin combination is not a viable intervention for primary prevention of chronic diseases.”
I disagree. The WHI study2 actually reported that estrogen replacement related beneficial effect on both hip and vertebral fractures. The authors state: “The reductions in clinical vertebral fractures, other osteoporotic fractures, and combined fractures supported the benefit for hip fractures found in this trial.”2 I agree with the authors that the WHI is the first trial with definitive data supporting the ability of postmenopausal hormones to prevent fractures at the hip, vertebrae, and other sites.2 The WHI did not provide sufficient data to support the statement in your article1 that “the estrogen-progestin combination is not a viable intervention for primary prevention of chronic diseases.” Rather, I would respectfully propose that it may not be a viable option for some chronic disease prevention (notably, coronary heart disease), potentially excluding the osteoporosis where there still may be benefits.
in reply: Dr. Brzezny insightfully highlights important findings of the Women's Health Initiative (WHI) trial.1 The WHI trial1 demonstrated that among the study participants, estrogen plus progestin reduced the observed hip and vertebral fracture rates by one third compared with placebo. The reductions in other osteoporotic fractures (23 percent) and total fractures (24 percent) were found to be statistically significant.1 These and other findings1,2 provide convincing data that support the ability of combination hormone therapy to prevent fractures of the hip, vertebrae, and other sites.
However, the WHI trial1 also demonstrated that the overall harm of combination hormone therapy exceeded its overall benefit. The WHI data1 indicated that if 10,000 women received the hormone combination therapy (estrogen plus progestin) for one year, compared with 10,000 women not receiving the hormone combination, there would be six fewer woman with colorectal cancers and five fewer women with hip fractures; but, eight more women receiving combination hormone therapy would develop invasive breast cancer, seven more would have a heart attack or other coronary event, eight more would have a stroke, and eight more would suffer a pulmonary embolism. In light of these findings, and considering that there are already existing alternatives (such as bisphosphonates and selective estrogen receptor modulators) that effectively prevent and treat osteoporotic fractures, it is difficult to justify definitive recommendations on the use of combination hormone therapy for the primary prevention of chronic disease.
The authors of our article3 recognize that the WHI trial1 has not sufficiently assessed the effects of combination therapy on other important outcomes, such as ovarian cancer, dementia and cognitive function, and the benefits of hormones given for the treatment of menopausal symptoms.4,5 We also recognize that the WHI trial1 has been criticized for certain weaknesses in its study design.6 It has been suggested that the women selected for the WHI trial (mean age: 63 years, with two thirds of the participants older than 60 years) may be too old to be included in a primary prevention trial examining cardiovascular outcomes.6 Nonetheless, based on the WHI findings1 and existing evidence in the literature, the most prudent conclusion is that “the estrogen-progestin combination is not a viable intervention for primary prevention of chronic diseases.”3 The U.S. Preventive Services Task Force made a similar conclusion5 in 2002, shortly after the release of the WHI findings.1
Dr. Brzezny correctly suggested that select patient groups may benefit from combination hormone therapy. However, which of these subgroups will benefit requires further scientific characterization. Continued counseling on an individual basis about the risks, benefits, and uncertainties of combination hormone therapy before deciding to start or stop treatment remains an essential, but difficult part of managing women with risk factors for hip fracture and other chronic conditions.4