It may seem like a strange time for the Food and Drug Administration (FDA) to approve a new hormone replacement therapy product. But the agency did so earlier this month, approving a lower-dose version of Wyeth's Prempro, the product at the center of a nearly yearlong anxiety fit over whether menopausal women who take hormone supplements do themselves more harm than good.
The new formulation will contain 28 percent less estrogen and 40 percent less progestin than its controversial forebear. The product, not yet named but likely to be referred to by doctors as Prempro .45 (as opposed to today's Prempro .625), is expected on pharmacy shelves this summer.
According to Wyeth medical director Victoria Kusiak, the company applied for approval of the product in June 2000, after the company-sponsored Women's Health, Osteoporosis, Progestin and Estrogen (HOPE) study found the lower dose to be just as effective as the regular dose at relieving the symptoms of menopause, including hot flashes, night sweats and vaginal dryness.
This was more than two years before a portion of the large, government-run Women's Health Initiative (WHI) study was halted because of findings that women taking Prempro for five years or more faced a slightly increased risk of heart attack, stroke and breast cancer, while receiving only modest protection against osteoporosis and colon cancer. The report generated enormous confusion among women who had taken or were taking the pills.
In January, the FDA required drug makers to place on all HRT products a boxed warning -- its highest level of consumer alert on packaging -- detailing the findings of the WHI study and advising women to take a low dose and stay on it for as short a time as possible.
Last week, the government reported more negative findings about HRT, citing additional data from WHI that the therapy doesn't improve quality of life for women who were not having symptoms of menopause. In other words, contrary to many doctors' and patients' beliefs, HRT had no demonstrable effect on women's vitality, sexuality, memory or mental health. However, these findings did show that HRT can help with hot flashes and vaginal dryness, which are experienced by only about one-third of menopausal women.
Kusiak says low-dose Prempro is designed to treat those symptoms, and in a way that's consistent with the FDA's lowest-dose-for-shortest-time advice. The new product, she says, is an option for women who want to take HRT despite the risks.
But is the new version of the drug any safer? Neither Wyeth nor anyone else has conducted long-term trials to determine whether low-dose forms of HRT circumvent the additional risk of breast cancer, heart attack and stroke that was found with regular doses.
The arm of the HOPE study that compared the efficacy of various dosages of Prempro lasted two years and showed no added risks. But the FDA's new labeling for HRT products states that since there are no data from the WHI on other versions of HRT, women should consider the risks of those drugs to be similar to those found in the formulation of original-dosage Prempro. It was the lack of long-term risk and benefit data on the current dose of Prempro that led to the HRT mess in the first place.
All of which has some doctors wondering if taking any HRT, even a lower dose for shorter period, is a good idea.
"It's biologically plausible that I'd have less risk if I took this [low-dose Prempro] -- but we shouldn't just assume there won't be a similar increase in heart disease, stroke and breast cancer with this drug," said JoAnn Manson, director of preventive medicine at Harvard's Brigham and Women's Hospital and one of the principal investigators in the WHI study.
But practitioners who have watched women with debilitating hot flashes cut their Prempro pills in half to get a lower dose are just happy to see the new drug on the horizon.
"For the small minority of women who really have their lives disrupted by menopausal symptoms but who want to try to avoid risk, it's great to see a low-dose HRT product come out," said Cynthia Pearson of the National Women's Health Network.
"The evidence has been there for some time -- for women who have disabling symptoms of menopause, lower doses work just as well as higher doses," said Wulf Utian, executive director of the North American Menopause Society and head of the HOPE study.
Wyeth's group of HRT drugs -- which includes Prempro and Premarin, an estrogen-only form of HRT -- have been hit hard by the results of the WHI study, with sales dropping about 30 percent last year. About 7 million women were on either Prempro or Premarin at the beginning of 2003, down from about 10 million a year prior. Sales of Prempro alone dropped by half last year, said Wyeth spokesperson Natalie de Vane.
Utian adds that he expects combination HRT to follow the path of birth control pills, which entered the market at a high dose in the 1960s, eventually coming out in smaller and smaller doses after studies showed the pills were increasing risk of heart attacks in young women.
Suz Redfearn is a frequent contributor to the Health section.