Can Wyeth win back the 40 million Premarin and Prempro users it's lost since 2002 -- along with $1 billion a year in profits -- with a new menopause drug?

Or will the once-bitten women who have filed more than 5,000 lawsuits claiming the hormones gave them cancer feel fooled twice?

Pristiq, a serotonin/norepinephrine reuptake inhibitor (SNRI), is a metabolite of Wyeth's antidepressant Effexor XR -- which netted $3.7 billion in 2006 -- and an unabashed patent extender since Effexor XR goes off patent in 2010.

In February, Pristiq was approved by the FDA for the treatment of adults with major depressive disorder but its launch as the first nonhormonal treatment for menopausal symptoms is what Wyeth hopes will fill the Premarin/Prempro/Effexor black hole to the tune of $2 billion a year.

Unfortunately, instead of a green light to market Pristiq for menopause last July, the FDA -- also once bitten after Vioxx, Avandia and Vytroin -- said to Wyeth not so fast.

Why did two women in the study group taking Pristiq have heart attacks and three need procedures to repair clogged arteries compared with none taking a placebo it wanted to know? How can Wyeth assure long term safety when 604 of the 2,158 test subjects took Pristiq for only six months and 318 for a year or more? And what about serious liver complications seen in the studies?

Nor do drug industry insiders in the chatroom cafepharma sound like they're scooping up Wyeth stock.

"Pristiq is not a good drug by any standard," wrote one anonymous poster. "We tried to get 100 mg approved as the standard dose. But our patients got so sick that they could care less about the efficacy. They just couldn't tolerate the drug long enough to see any improvement."

Like longer than six months?

"No study exists showing any anti-depressant including Pristiq works any better than a placebo for reducing hot flashes, which are subjective anyway and only last a few minutes long at worst," wrote another anonymous poster. "That is a heavy price to pay to take a heavy duty drug 24/7 for a few minutes of daily relief that a sugar pill also provides. FDA is crazy (or bought) if they allow this unproven drug travesty on the market."

A third poster predicted women wouldn't trade, "hot flashes for decreased libido, nausea, increased blood pressure and incredible withdrawal issues," found with Pristiq. "Women and their physicians are not as gullible as they were back in the Premarin days."

Even psychiatrist Daniel Carlat, who wrote an expose for the New York Times magazine, called Dr. Drug Rep, last year about his experiences as a Wyeth paid spokesman, is dissing Pristiq.

"Every patient who takes Effexor produces Pristiq in their own body, at no additional charge," he writes in a blog article, called Top 5 Reasons to Forget About Pristiq.

Moreover Wyeth's own investigator on the major Pristiq trials, Dr. Michael Liebowitz, admits it is "not a revolutionary drug" writes Carlat.

Of course you can't blame a one trick company, which cut its teeth on the Feminine Forever idea that age in women is a disease that needs treating, for churning the demographics. Especially as it lays off 1,200 US workers, closes manufacturing plants and fights for its life -- lobbying the Hill for patent and tax relief and to keep drug company gifts to physicians hidden.

Was it Wyeth's fault that the hormone "therapy" it pushed for decades actually increases breast cancer by 26 percent, heart attacks by 29 percent, stroke by 41 percent and doubles the risk of blood clots and dementia?

But if US women embrace a major psychiatric drug with possible liver and heart complication side effects after the hormone hoax -- manufactured by the same company and at four times the cost of Prempro/Premarin, $4 per day . . .

Fool me twice . . . ?