Individualizing Hormone Therapy to Minimize Risk

Accurate Assessment of Risks and Benefits

Donna Shoupe


Women's Health. 2011;7(4):475-485. 

In This Article

Accurate Evaluation of the WHI: Risks & Benefits

Clinical practice was abruptly changed after data from the WHI were released to the media in June 2002. Rather than a first presentation to the medical profession to allow wide peer review, the results were first presented to a media conference in a manner that allowed a media-driven frenzy and an exaggerated public view of the risks associated with hormone therapy.

The WHI results were published in July 2002 showing small increases (often borderline or not statistically significant) in the risk of cardiovascular disease, breast cancer and stroke in postmenopausal women taking combination estrogen and progestin therapy compared with untreated controls.[3] These results were in stark contrast to the vast majority of earlier studies that reported large decreases in overall death rate, cardiovascular disease, osteoporosis, bone fractures, dementia, colon cancer and a host of other diseases in postmenopausal women taking hormone therapy compared with nontreated age-matched women.[4–14] The public has yet to understand the limitations of the study or to appreciate the study reported benefits associated with hormone therapy including a decreased hip fracture rate, decreased overall fracture rate and decreased colorectal cancer risk associated with combination estrogen plus progestin therapy (Table 1).

Despite the wealth of evidence contrary to this single study and the fact that the paper was criticized heavily for a number of important reasons as shown in Box 1, the report quickly became the defining evidence against using hormone therapy. In August 2002, the US FDA released a statement acknowledging the WHI findings and a new consensus opinion emerged. In direct contrast to earlier guidelines, the new consensus opinion was that the risks associated with hormone therapy were unacceptably high and women were discouraged from using anything but short-term estrogen therapy for symptomatic relief.

The dismissal of estrogen as a long-term beneficial treatment for postmenopausal women was not universally accepted. The beneficial effects of estrogen on bone and urogenital health remained important reasons to continue estrogen therapy beyond the early years of menopause. And even more importantly, it was not easy to dismiss the numerous studies demonstrating significant protection from cardiovascular disease and dementia and lowered risks of mortality associated with long-term estrogen therapy in women. Detailed analysis of older studies and the WHI data revealed important findings that helped to explain why the studies had such disparate results.[15–17] A major factor affecting the risk–benefit profile, that was appreciated before is the age of initiation of estrogen therapy. Estrogen therapy if started within 10 years of the menopause or generally between 50 and 60 years minimizes the risk of therapy (Table 1). The risk–benefit profile of estrogen therapy is also strongly affected by the dose of estrogen and route of administration. Initiation of high-dose hormone therapy in elderly women as was done in the WHI would be expected to result in a high complication route.


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