June 18, 2001 -- In 1875, Mrs. Lydia E. Pinkham of Lynn, Mass., began selling her famous Vegetable Compound, which she advertised as "a positive cure for all these Painful Complaints and Weaknesses so common to our best female population. It will cure entirely all Ovarian troubles, Inflammation and Ulceration, Falling and Displacements, and any consequent Spinal Weakness, and is particularly adapted to the Change of Life."
In 2001, drugmaker Eli Lilly and Co. began selling a product called Sarafem, also intended to treat a condition specific to women. According to the manufacturer's package insert, Sarafem is indicated for the treatment of premenstrual dysphoric disorder (PMDD), a newly proposed mental disorder not yet officially accepted by the American Psychiatric Association but listed in the appendix of that group's diagnostic manual.
No doubt part of what made Lydia Pinkham's miracle cure so successful was that it consisted of a blend of herbs in a 20% mixture of alcohol, a common 19th-century approach to taking care of a variety of ills. Lilly's Sarafem, on the other hand, is completely new millennium in approach. For women struggling with PMDD, this repackaged, relabeled version of the antidepressant fluoxetine hydrochloride -- better known to millions by the brand name Prozac -- "helps you be more like the woman you are, every day of the month, even during your most difficult days," according to the company's web site.
Although separated by more than a century, the tonics promoted by both Mrs. Pinkham and by Eli Lilly are emblematic of what is to many people an ancient but troubling tradition in medicine: The tendency to categorize the normal bodily functions of women as "diseases" or "disorders" that need to be treated.
"From the time you're a preteen, from your very first inklings of hormonal rhythms all the way to the end of life, you're given the message that your body doesn't work or that it's not OK," says Madeline Behrendt, DC, in an interview with WebMD.
Behrendt, a chiropractor in private practice in Boise, Idaho, is also vice chairwoman of the Council on Women's Health of the World Chiropractic Alliance. In that capacity, she recently spoke on the issue at the United Nations Women's Conference, where, she says, she found that people all over the world appear to share her concerns.
"Over the past year there have been so many shifts: Now girls are being given hormonal drugs because so many of them are starting puberty early. Another big topic is menstrual suppression, where they're saying that menstruation is not normal -- it's a nuisance, it's unnatural, it's unhealthy. When I was growing up, if you didn't have your cycle that was called amenorrhea and that was a problem. Then it goes into the reproductive years where there are birth control pills, or PMDD, or a new specialty created last year called female sexual dysfunction," she says.
A Disorder Is Born
Behrendt and others point to the marketing of PMDD as being just the latest example of this trend. The package insert for Sarafem cites a definition of PMDD from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the psychiatrist's bible. According to the manual, the essential features of PMDD are "symptoms such as markedly depressed mood, marked anxiety, marked affective lability [mood swings], and decreased interest in activities."
What the prescription information fails to mention, however, is that PMDD is mentioned briefly in the main body of the manual as a "depressive disorder." But the full entry on PMDD is included in an appendix that lists conditions for which "there was insufficient information to warrant inclusion of these proposals as official categories ... in DSM-IV."
In other words, some critics charge, Sarafem is indicated for a disorder that may or may not exist.
"I have concerns about [formalizing] a social tradition of blaming women's behavior and bad moods on women's reproductive function," says Nada Stotland, MD, MPH, professor of psychiatry and obstetrics and gynecology at Rush Medical College in Chicago, and a member of a task force that determined DMS-IV diagnostic criteria.
Stotland, who acknowledges that she has given talks in venues supported by Lilly, tells WebMD that she argued against including PMDD in the main text of the manual.
"I would prefer to see us approach this interesting and worthwhile issue from the point of view, for example, of the effect of male and female hormones on behavior and mood, rather than picking out one sort of traditional condition," she says.
But Robert L. Spitzer, MD, professor of psychiatry at Columbia University in New York City and chairman of the work group to revise DSM-III criteria, has a different point of view.
"Many women's groups objected to the inclusion of the disorder, fearing it would stigmatize normal women, a view that I don't share," Spitzer says in an interview with WebMD. "My own view -- and the view of the people who originally proposed the category -- is that there is a small subset of women who suffer from this disorder, and the best thing you can do for these women is to recognize and develop effective treatments for it."
Behrendt, Stotland, and other critics acknowledge that some women have distinct physical changes related to their menstrual cycles, and that some women have debilitating problems that could be alleviated significantly by medication.
Where they draw the line, however, is in the classification of menstruation-related phenomena as disorders.
Cash or Compassion?
In medicine, some old habits are hard to break: The very word "hysteria" comes from the Greek for uterus (hystera). And if you think we've come a long way since then, baby, consider the following excerpt from an article titled "Eleven Tips on Getting More Efficiency Out of Women Employees," published in the July 1943 issue of the trade journal Transportation:
"4. Retain a physician to give each woman you hire a special physical examination -- one covering female conditions. This step not only protects the property against the possibilities of lawsuit, but also reveals whether the employee-to-be has any female weaknesses, which would make her mentally or physically unfit for the job."
Allyne Rosenthal, DC, a Chicago-based chiropractor and practitioner of functional medicine, has studied and written about the creation of PMDD as a distinct medical entity. She tells WebMD that new attention being paid by the medical and pharmaceutical industries to PMDD, female sexual dysfunction, and menopause may be motivated as much by cash as by compassion.
"The hallmark of adolescence is hormonal imbalance. Therefore, the numbers of young girls who will deemed to be candidates for this medication are astronomical if they go ahead with this, and that is one of the major problems," she says.
Rosenthal also expresses concern that fluoxetine was not tested for long-term use prior to FDA approval, yet giving it to combat the hormonal effects of menstruation is, in effect, writing a reproductive-length prescription.
"The tests on it were 6-8 weeks, but PMS is not a short-term syndrome," she says. She points to evidence suggesting that long-term use of Prozac and similar drugs could cause serious side effects, such as those seen with the older generation of powerful antidepressants that were prescribed in the 1950s, '60s, and '70s.
Asked by WebMD to comment on the concerns of critics, Lilly spokeswoman Laura Miller drew attention to an FDA "talk paper" issued in July 2000 to coincide with the agency's approval of Sarafem for PMDD. The document states that "on November 3, 1999, FDA's Psychopharmacologic Advisory Committee unanimously recommended approval for fluoxetine to treat women with PMDD. The committee concluded that fluoxetine was effective for the condition and that PMDD has well defined, accepted diagnostic criteria."
The very next sentence, however, offers this caveat: "The committee also advised that the drug should be used only to treat women whose symptoms are severe enough to interfere with functioning at work or school, or with social activities and relationships."
Miller also forwarded a "roundtable discussion" published in the Journal of Women's Health and Gender-Based Medicine, in which panelists from highly respected research centers in the U.S. and Canada conclude that "PMDD is a distinct entity with clinical biologic profiles dissimilar to those seen in other disorders. Thus, the relative safety and efficacy of potential treatments for PMDD can be evaluated, and, indeed many of those present thought that sufficient evidence is now available to support the use of [Prozac and similar antidepressants] in this disorder."
Natural Alternatives Also Work
"The vision of millions of women being put on this drug for a condition that can be so effectively treated in other ways is just stunning," Rosenthal says. "PMS is something that bothers a lot of women. There's no question about that, but it responds incredibly well -- and quickly -- to a combination of things, like vitamin B-6, magnesium, zinc, and the correct balance of proteins and carbohydrates in the diet."
In its marketing materials, Lilly draws a sharp distinction between PMS and PMDD, but others say the line is blurry, and that PMDD -- if it exists at all -- is really at the extreme end of a continuum representing the normal range of women's physiologic responses to hormonal variations.
"We need to give more credit to women for knowing what's going on in their own mind and bodies, and here we have a situation in which we have data quite conclusively showing that in this case women often do not know -- because it's OK for women to be crabby and because women don't allow themselves room to be sad, even if there are sad circumstances," Stotland says.
"And because psychiatric disorders are stigmatized, people who have just plain depression may not want to deal with that, and they have a tremendous tendency to blame it on PMS," she tells WebMD. "The dangers are that because women's hormonal changes happen to be in cycles, we forget that hormones have impact on men, and one might even say that we're neglecting men in that sense."
She notes that teenage boys tend to be at highest risk for driving accidents -- a fact reflected in their high insurance rates -- and that the adolescent surge of testosterone is probably to blame. No one, yet, however, is suggesting that teenage boys take hormone-adjusting drugs to keep them -- and other drivers -- safe.
"So which is worse: being crabby or being run over?" she asks.
Nevertheless, Stotland agrees that for a small subset of women who meet the very strict and serious symptom criteria for having PMDD, Sarafem probably helps. She also acknowledges that drugmakers have a right to make a buck.
"I have nothing against that. We live in a capitalist society in which we leave it to the pharmaceutical companies to develop nearly all the drugs, and any time they have a drug that's good for something, especially if it is for something especially widespread like the flu, they're going to try and get people to use that medication," she says.
But in this case, Behrendt worries, the desire to wring the maximum profit out of a product may have led the pharmaceutical company to put the cart before the horse.
"In terms of PMDD, I think the evidence speaks for itself," she tells WebMD. "Prozac's patent was running out, and suddenly a new disorder appeared -- PMDD -- that changed the classification to mental disorders. So with that a new class was formed, a new market was formed, and a new patent was formed."