Doctors take another look at safety of hormone therapy

Physicians increasingly are talking about prescribing hormone therapy for recently menopausal women. Meanwhile, regulators are cracking down on claims about compounded formulations, according to statements issued in January.

With regard to traditional hormone therapy, the American Assn. of Clinical Endocrinologists published on its Web site last month a position statement saying this strategy is safe for women who are younger than 60 or who are less than a decade past menopause and is a viable option for those experiencing symptoms related to this life change.

"We looked at the data carefully, and the data show that a woman who is a long time past menopause has a very different clinical course than a woman who is younger," said Richard Hellman, MD, AACE president.

This step is the latest by physicians trying to refine the use of postmenopausal hormone therapy, which was encouraged for nearly all women until July 2002, when results from the Women's Health Initiative were published in the Journal of the American Medical Association. That study found the approach increased the risk of coronary heart disease, stroke, pulmonary embolism and breast cancer. Sales plummeted as women looked for other options, and most clinical guidelines were changed to recommend that the therapy be used at the lowest dose for the shortest time possible.

"The pendulum has been swinging back to at least looking at the option," said LeRoy Sprang, MD, clinical professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine in Chicago. "It's very reasonable to offer women low-dose hormone replacement." Dr. Sprang is also a member of the AMA's House of Delegates, although he was speaking personally.

Many physicians cautioned that hormone therapy should still only be prescribed for symptom relief but said the prevention of age-related diseases was still a possibility for the future. Observational studies and subsequent analysis of WHI data suggest that not only does hormone therapy not cause harm in women closer to menopause, but that a long-term benefit may also exist.

Several projects are in the works to investigate this question. Notably, the Kronos Longevity Research Institute in Phoenix launched the Kronos Early Estrogen Prevention Study or KEEPS, a multicenter randomized double-blinded trial, in October 2003.

"The panic that ensued after the WHI was unjustified," said S. Mitchell Harman, MD, PhD, the institute's director and president. "KEEPS was conceived by a consortium of scientists and physicians who were interested in women's health. We thought that perhaps the problem was that women who were in WHI were much older than women who started on hormones in the big observational studies. Perhaps hormones would be beneficial if started early?"

FDA issues bioidenticals warning

The Food and Drug Administration took action last month on hormone replacement therapy labeled as "bioidentical," one of the options that some women turned to in the WHI's wake. These products are compounded by pharmacists out of hormones manufactured with the intent of matching those made by the human body and marketed as potentially safer alternatives to mass-manufactured prescription formulations.

The agency issued warning letters to seven pharmacies involved in the manufacture of these products, calling for them to no longer be identified as "bioidentical." Claims that they are better than traditional prescription hormones and treat or prevent Alzheimer's disease, stroke and cancer can no longer be made. In addition, compounding pharmacists have been told to stop using estriol, a form of estrogen, because it does not have regulatory approval.

"[This] action demonstrates FDA's commitment to ensuring that consumers are well informed about the risks and benefits of the drugs that they take and that pharmacy operations do not hide inappropriate and sometimes unsafe practices behind the veil of traditional compounding," said Deborah Autor, director of the Research Office of Compliance in the agency's Center for Drug Evaluation.

Several medical societies supported this action, including the AMA. Many physicians are concerned about the use of these products because of lack of evidence for many of the claims about their safety and efficacy.

"I'm very pleased [about the FDA action]," said JoAnn E. Manson, MD, DrPh, chief of the division of preventive medicine at Brigham and Women's Hospital in Boston and a KEEPS investigator. "I have a lot of concerns about the claims that custom compounded hormones are safer and more effective than traditional hormones. I don't think they have substantiated these claims. Women are being mislead."

But while much of organized medicine and many physicians backed the FDA, doctors who work with these formulations expressed alarm.

"I think that the FDA action about bioidentical hormone replacement is pretty egregious," said C. W. Randolph Jr., MD, medical director of the Natural Hormone Institute of America and a registered pharmacist. He uses compounded hormone formulations as part of his gynecology practice in Jacksonville Beach, Fla. "These hormones are the same hormones made in the human body."

Pharmacists also expressed concerns that this move was a sign of greater restrictions on compounding. Estriol is not included in any currently available FDA-approved medication, but it does have a U.S. Pharmacopeia monograph, which some say should allow for its use.

The American Pharmacists Assn. "believes that limiting compounded medications to those that include bulk ingredients of FDA-approved drug products greatly limits patient access to medications that address their unique needs," said John A. Gans, PharmD, executive vice president and CEO of the organization.