Editorial - The Avandia Saga Continues - NYTimes.com

A panel of expert advisers to the Food and Drug Administration delivered a confusing verdict on Wednesday after two days of hearings on the safety of the diabetes drug Avandia. A majority of the 33-member panel expressed concern that Avandia raises the risk of heart attacks compared with other diabetes drugs. But a majority also voted to leave the drug on the market anyway, with various degrees of restrictions or warnings. It will now be up to patients and their doctors to decide whether the risk is worth taking in particular cases.

In the crucial votes on Wednesday, the experts were asked to choose among five options for regulatory actions that the F.D.A. might take. Twelve voted to remove Avandia from the market. Ten voted to leave it on the market while further beefing up warning labels and adding restrictions on use, such as allowing only certain physicians to prescribe it or requiring special education for doctors and patients. Another 10 would settle for the current or somewhat stronger warnings. (One expert abstained.)

Some analysts see a victory for Glaxo, in that 20 of the panelists voted to retain the drug. But it is hardly reassuring that 22 of the panelists voted either for severe restrictions or complete banishment. The process doesn’t end here. The panel also voted to continue a large Glaxo-sponsored clinical trial to compare the cardiovascular risks of Avandia with those of Actos, its major rival, and with standard treatments for diabetes. Even if that trial is allowed to go forward, the results won’t be in for years. Right now, doctors and patients will have to think very hard before using a drug that a majority of these experts has deemed risky.

The clearest lesson to emerge from the hearings and other recent revelations is that GlaxoSmithKline, the maker of Avandia, can’t be trusted to report adverse clinical results fairly. The most troubling aspect of the Avandia saga is evidence — from internal company documents and investigations by a Senate committee and an F.D.A. investigator — that Glaxo sought to hide emerging indications of Avandia’s heart risks. Glaxo failed to report the results of a 1999 study that showed Avandia might be riskier for the heart than a competing drug (“these data should not see the light of day,” cautioned an internal e-mail message). And Glaxo made Avandia look good in a major clinical trial by failing to include in its tally of adverse events at least a dozen patients who suffered serious heart problems. The company found reasons to drop them from the study or misreport their ailments.

The company must be watched like a hawk as additional trials that it sponsors go forward.

New Position Statement on Menopausal Hormone Therapy

The Endocrine Society (USA) issued a scientific statement titled "Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement" that was published in the July 2010 issue of the Journal of Clinical Endocrinology & Metabolism (JCEM). This statement evaluates benefits and risks for postmenopausal hormone replacement therapy (HRT), now known as menopausal hormone therapy (MHT).

MHT was in widespread use in the 1990’s due to the belief that it prevented heart disease, fractures, memory loss and dementia in addition to its established role in relieving uncomfortable menopausal symptoms. This situation changed drastically in 2002 mainly due to the publication of the Women's Health Initiative (WHI) Study that showed that MHT was actually associated with an increased risk for heart disease, stroke, and breast cancer. It was reported then that MHT use declined as much as 80% from before.

Despite its huge impact, WHI nevertheless had its criticisms.  The average age of the study group, 63 years, was rather advanced. Women typically contemplate initiating MHT between the ages of 50 to 54 years, and this group only made up 3.5% of the total participants in that study. WHI also did not consider menopausal symptom relief amongst these patients. Data from later studies evaluating the effects of MHT in women aged 50 to 55 years have thus been taken into consideration in issuing this latest scientific statement.

Recent evidence suggests that the afore mentioned health risks may not be applicable to all women using MHT. An important factor to consider is the time after onset of menopause when MHT is started, a factor not considered in the WHI assessment of MHT safety and efficacy.

According to the findings of Santen et al in their study published in the JCEM, women who begin MHT a short time after the onset of menopause at ages 50 to 59 years actually appear to benefit from that treatment. It is further evidenced that women in the short-time group using MHT for 5 years had a 30% to 40% reduction in mortality risk and no increased cardiovascular disease risk. In addition, they had a 90% decrease in hot flashes, overactive bladder, or other menopausal symptoms.

A very large portion of the anxiety among perimenopausal women is the risk of occurrence of breast cancer. Santen et al found that some patients who utilized MHT even in its short-time form nevertheless developed this dreaded disease. However, this only applied to those who used the combination of estrogen plus a progestogen and not with estrogen alone. They postulate that this may have been due to the stimulation and uncovering of very small, undiagnosed breast cancers, rather than de novo cancers.

In summary, the Endocrine Society states urges physicians and their patients to re-think the use of MHT based on data pertinent to the 50-55 year old age group and to individualize therapy based on symptoms and underlying risks of breast cancer and heart disease.