An interview with Rowan Chlebowski, MD, a lead investigator of the Women�s Health Initiative.

Rosenberg: The Women�s Health Initiative findings about hormone therapy (HT) were definitive enough that both the estrogen and estrogen plus progestin arms of the study were terminated. Yet claims of heart and memory benefits for women, if HT is started early enough, continue in the media. Is there new information that has changed the risk/benefit ratio?

Chlebowski: The new information was a secondary analysis of WHI data which ran in JAMA in 2007 and found HT may not be as detrimental for coronary heart disease as previously thought, if started in early menopause. Risk for stroke did not change, however, and there are indications that breast cancers appeared earlier, when hormones were started earlier.

Rosenberg: Why are some doctors and continuing medical education courses presenting HT as cardioprotective?

Chlebowski: That claim is heard more from the gynecological community which had been the biggest HT prescribers rather than from the general medicine or the oncology community. The FDA has not changed the prescribing label on the basis of the WHI secondary analysis. HT is still not a desirable chronic disease risk reduction agent though for short term relief of vasomotor systems like hot flashes no other therapy comes close.

Rosenberg: Do you believe the �timing theory� -- that HT has greater benefits than WHI revealed because women began therapy too late -- will be found to have merit?

Chlebowski: Of course, the timing theory is just a theory. It would require a very expensive study to investigate. So far, on the basis of secondary analysis from WHI at seven years, the National Institutes of Health has not indicated an interest in a new study about timing.

Rosenberg: What about memory and cognition benefits and the claim that HT could prevent dementia?

Chlebowski: The Women�s Health Initiative Memory Study which was a sub-study of women 65 or older found, after four years of HT, all types of dementia doubled in women. Some of these findings could be related to the increase in stroke that was seen in this group.

Rosenberg: Why do doctors still promote HT despite its cancer, heart disease, stroke and blood clot risks? Are they influenced by drug companies?

Chlebowski: Certainly the estrogen drug used in the trials, Premarin, and the estrogen plus progestin drug Prempro are best selling products of Pfizer, previously Wyeth. These companies are also big supporters of the gynecology community. It is reasonable for companies to support groups who use their products so it becomes a chicken and the egg question. The gynecology community tends to focus more on heart problems than the data about breast or lung cancer that is increasingly emerging from WHI.

Rosenberg: Why is WHI billed as a landmark study? Haven�t a lot of studies looked at these issues like the PEPI, HERS, the Million Women Study and the Nurses� Health studies?

Chlebowski: The PEPI study[Postmenopausal Estrogen/Progestin Interventions Trial] largely investigated estrogen�s effect on the uterus and led to WHI�s addition of a progestin to estrogen to prevent endometrial cancers. The HERS study[Hormone Therapy Estrogen Cardiovascular Protection Clinical Trials] looked at women with established coronary heat disease and found no beneficial effect of HT looking at cardiovascular end-points. The Million Women Study in the UK is an observational study and the Nurses� Health Study also is an observational study at Harvard of younger women. The WHI trial is the only fully powered randomized, placebo controlled trial able to address the most frequent causes of death and disability in postmenopausal women -- cardiovascular disease, cancer, and osteoporosis.

Rosenberg: Critics of WHI say the large numbers of women who stopped taking estrogen and progestin or who took them when assigned placebo invalidate its status as a random controlled trial.

Chlebowski: The adherence rates were similar to those seen in other prevention large trials. When the intervention ended, after five and a half years, about 60 percent of women were still adhering to their study medication.

Rosenberg: You delivered an abstract at the annual San Antonio Breast Cancer Symposium in December about the bisphosphonate bone drugs some women now take in lieu of long-term HT to prevent osteoporosis. What about HT�s other clear benefit -- reduction of the risk of colon cancer?

Chlebowski: WHI data do demonstrate that HT lowers the risk of colon cancer. However those colon cancers that do develop tend to be more advanced and we are exploring why. This is why you haven�t heard the colon cancer figures emphasized much.

Rosenberg: The New York Times reporter Tara Parker-Pope reported that there was internal discord at WHI over stopping the trials. Is that true?

Chlebowski: There was no disagreement with the estrogen plus progestin discontinuation but there was a difference of opinion about the decision to stop the estrogen alone trial because the risks appeared less. Of course these decisions are not made by the investigators but by data safety panels and external advisory committees.

Rosenberg: WHI has 40 centers and hundreds of researchers. How did you become first author on so many articles?

Chlebowski: I used to think you had to be the meanest of the bunch to be first author, but evidently not. (laughs) First authorship decisions are made from recommendations by a WHI Publication and Presentation Committee of those able -- and willing -- to do it. I believe the reason I have been asked to lead several cancer papers is that I am a medical oncologist and have published quite extensively about breast cancer and hormones. I�m grateful to the entire WHI team of investigators for their support.

Rosenberg: So as an oncologist and the �face� of WHI for several years, do you tell women to not take HT -- except for very short-term use?

Chlebowski: Unless you have limiting climacteric symptoms (hot flashes, sexual difficulty), when you look at the emerging cancer data, is this really something you want to take?