Wednesday, November 25, 2009

Women: Should We Really Put A Rumble in the Jungle With Pills?

A wonder drug hailed as a "Viagra for Women" has been discovered by accident — after it failed trials as an antidepressant.

The once-daily pill, developed by Boehringer Ingelheim GmbH, was said to increase female sex drive in late-stage trials, putting the biotechnical group in the lead to launch the first non-hormonal treatment for women with low libido.

The compound, known as flibanserin, was said to promote sexual desire and increase the number of "satisfying sexual events" in women suffering from abnormally low libido, Boehringer researchers claim. The company is hoping to market the pill in Great Britain in 18 months.

If the drug performs as advertized, it has the potential to revolutionize sexual medicine much as Pfizer Inc.’s blue pill (Viagra) did a decade ago. That would put family-owned Boehringer at the center of a debate about whether the medicine is a chemical shortcut around a complex dysfunction involving body and mind, or even if disinterest in sex is a legitimate medical condition in the first place.

Originally, flibanserin was developed as an anti-depressant, but turned out to be a poor one. Questionnaires given to patients helped discover the drug possessed libido-boosting side effects, and many of the women who participated in the trial seemed reluctant to give back the drug.

According to biotech BI researchers, one tester revealed: “It changed my life. It filled me with excitement and lust.”

One of the most interesting aspects of this announcement, is that it underscores the fundamental difference between the way sexual arousal works in men and women. The drug expected to be marketed to women works on their brains, while male impotency pills such as Viagra, Eli Lilly's Cialis and Bayer's Levitra, widen blood vessels to increase the blood flow to the penis needed for an erection. These same male impotence pills, have failed to show notable aphrodisiac effects in women.

Let’s see: Women=Brain; Men=Penis. Haven’t we always suspected that very equation, hmmmm?

Boehringer, based in the German town of Ingelheim on the Rhine’s west bank, was searching for a depression treatment in the 1990s when it stumbled on the compound. By 2002, Boehringer researchers found the drug wasn’t lifting patients’ mood, but were startled when test subjects rated one measure of well-being, sexual appetite, consistently higher than the others.

But Paula Hall, of Relate, urges caution. "Female loss of libido is a big problem and it is not going away. It can cause problems within a relationship and affect self-esteem.

"This research is really quite exciting for women with loving partners whose loss of libido is a physical thing. But it is not going to fix a broken relationship or help with looking after the kids or cleaning the house," Hall said.

For some women AND men, reduced sexual interest or response may be "normal," doctors say.

Nonetheless, the biotech company now says it is "putting the finishing touches on a pill designed to reawaken desire by blunting female inhibitions," hoping that their compound will rival the sales of Viagra, which has become the Holy Grail for drug manufacturers.

Men’s Viagra was originally meant to be a treatment for high blood pressure, and the heart condition angina. As with the women in this study, men taking part in early trials of the drug realized it had an interesting and unexpected side effect: Erections! Arriving in 1998, the drug has since been prescribed for over 25-million men.

Flibanserin is being developed as a non-hormonal treatment for low sexual desire in women, a market that's thought to be more financially lucrative than even the $2 billion dollar erectile dysfunction market.

The market to women is so potentially lucrative because research has shown that, depending on their age and whether they have undergone menopause, between 9 percent and a whopping 26 percent of adult women report experiencing low libido, or reduced sexual desire.

However, the new drug has proven controversial among sex researchers, with some arguing the pharmaceutical companies are exaggerating the number of women affected by low libidos, simply as a market expansion ploy by pushing a pill unable to deal with psychological issues responsible for putting someone off sex, e.g. poor body image, former abuse, or stress.

I find it even more interesting that the firestorm ‘erupting’ over this drug has far exceeded anything related to male impotency drugs. In fact, discussions focusing on the meaning of sexual desire were sadly, and noticeably missing when Viagra-type medications were on the horizon. It was the primarily the physical impact of those medications on patients that were discussed, not their psychological effects on users.

In comparison, little if any discussion of a woman’s safety has ‘arisen’ in discussions of this drug. Instead, the primary discussion has been whether or not the compound will, or even should, work. Apparently, women do not have the inherent intelligence to be able to choose to take a drug to increase desire, or decide they do not wish to. Sooooooo typical!

In 2003, a year after Boehringer researchers began the clinical trials, an article written by Ray Moynihan in the British Medical Journal called female sexual dysfunction, “the freshest, clearest example we have” of a disease created by pharmaceutical companies to make healthy people think they need medicine.

“This is for some an ideological battle,” said psychiatrist Michael Berner of the Freiburg University Clinic, who had patients in Boehringer’s studies. “One view is the multi-dimensional view you get from people like me. And then you have these people that say you should work only on relationship issues and that medication cannot have a place.”

Flibanserin reportedly works on the pleasure center of a woman's brain to restore flagging libido. Women who take flibanserin once a day make love more often and enjoy it more, large-scale trials have reportedly shown.

Researchers had abandoned previous efforts to develop a similar drug for women because it wasn't clear what constituted a normal sexual drive for women. A lack of sexual desire in women has often been linked to a woman's relationship with her partner. Apparently, what’s normal for men must be clear! Such stereotying is a great disservice to men.

"This drug has the potential to finally open the door to acceptance of the idea that decreased desire can be something that involves a dysfunctional way the brain works, and not only a bad partner," said Jim Pfaus, a neurologist at Concordia University in Montreal, who conducted early tests of the drug in rats. "Of course it's in your head."

“An erection is obvious, it’s easy,” Pfaus said. “But desire – how do you get at that?”

The explanation may be partly evolutionary, some scientists suggest. Male primates are driven by a need to spread their semen, while for females it’s important to be able to care for and rear the offspring.

Some researchers believe the social components of intercourse mean that sexual problems can’t be addressed in the same way as heart failure or cancer.

Sex is a “historical and cultural phenomenon,” said Leonore Tiefer, a psychiatry professor at New York University. There’s no baseline of normalcy by which to define a disorder, she contends.

It’s like dancing, or music, or piano-playing,” Tiefer said. “You do it with the body, but the part the body plays isn’t the largest part.”

Flibanserin works on the brain by putting “two feet on the brakes” to block the release of a chemical called serotonin, which regulates mood, appetite, sleep and memory, Pfaus said. In time, the process should trigger the production of dopamine, a chemical that, among other jobs, helps stimulate desire.

The drug differs from testosterone, a hormone that’s also been tested to reawaken women’s desire. Berner, interviewed at his study in Freiburg, sketched the picture of a wall to explain how flibanserin works.

“You’re standing here, sad, inhibited,” he said, drawing a stick figure next to the wall on a scrap of paper. “Testosterone would give you a little bit more excitement, so you’d climb over. Flibanserin would take away one of the stones.”

Boehringer researchers recruited women for clinical studies using print advertisements. The patients were largely professionals in their early 30’s to mid-40’s, and most chose to continue in the trial in a subsequent phase that ensured they would get the real drug instead of a placebo. Boehringer researchers have said it is recruiting older women for a follow-up study.

After what Pfaus described as an initial period of hesitation about developing a sex pill, Boehringer officials decided to move forward. The company needs new drugs because it faces the loss of 1 billion euros ($1.5 billion) in annual revenue when two older medicines, Mirapex for Parkinson’s disease and Flomax to treat enlarged prostate, lose patent protection next year.

Professor John Thorp, from the University of North Carolina in the US, led the research. He said Flibanserin was a “poor” antidepressant. “It’s essentially a Viagra-like drug for women in that diminished desire is the most common feminine sexual problem, like erectile dysfunction is in men,” he said.

The main criterion for the clinical trials, which the company named after flowers (give me a break!), was how many “satisfying sexual events” women said they had experienced after starting treatment. If the results are good, the so-called Bouquet studies, dubbed Violet, Daisy, Dahlia and Orchid, could form the basis for applications to U.S. and European regulators.

The German company is taking a page from Pfizer’s book. The U.S. drugmaker broadened the appeal of Viagra in 1998 by steering clear of the word “impotence” and saying the blue pill addressed a disease called erectile dysfunction. Boehringer is avoiding potentially offensive words such as frigidity and refers to the problem its pill cures by its clinical name, hypoactive sexual desire disorder, or HSDD.

“An increasing body of evidence shows that hypoactive sexual desire disorder causes substantial emotional distress,” said Heike Specht, a spokesman for the company. The drugmaker “has conducted late-stage clinical trials in over 5,000 women from which we hope will result the first available pharmaceutical treatment.”

In fact, the pill proved so popular in its trials that its manufacturers are poised to apply for permission to sell it across Europe, meaning it could be on UK bedside tables by 2011. A spokeswomen for Boehringer, Germany's second-largest drugmaker after Bayer, said the company was preparing regulatory filings in the U.S. and subsequently for Europe and other markets. She declined to provide a time-frame for filings and market launch and said Boehringer would not publish an assessment for the drug's annual peak sales potential.

Last week, biotech BI orchestrated several media releases, webcasts, and a presentation at a major sexual medicine conference in Europe, all to release data from its Phase III trials on the pre-menopausal women labeled with low sex drive, HSDD.

Unfortunately, all of this has everything to do with marketing and little to do with science. The data hasn't been released by the company, and no breakthroughs have been discovered. Nonetheless, it provides an opportunity to have a global conversation about female sexuality.

As any woman can attest, sexual desire is difficult to define, a fact that even the researchers involved in the flibanserin studies acknowledged. The following is the model, in three elements, presented by BI researchers that they used to measure that illusive zing that women feel:

• Drive: A finding that spontaneous sexual interest is somehow hardwired in a woman’s brain
• Belief and Values: Including social, cultural, ethnic, religious, and other factors that impact how often women might experience sexual desire, how intensely it is felt, and how comfortable women are with sexual desire
• Motivation: Considering the psychological and interpersonal factors that create a willingness for a woman to be sexual and experience sexual desire.

BI researchers claim that while effective treatments exist for women suffering from low sexual desire caused by beliefs, values, and motivation, there is nothing to treat the drive component (which they call the "biologic" component). According to the researchers, they allege that flibanserin effectively treats that “drive” component of sexual desire in women.

Here’s the BIG problem: These same researchers have no flipping clue how flibanserin actually does this! They know only that the drug reduces serotonin levels (FYI: Most antidepressants work by raising these levels.) As a result, their guess is that the drug impacts sexual desire by reducing inhibitory effects in women’s brains.

Thus, the researchers suspect that the drug works directly on the brain's pleasure zones, correcting levels of the chemicals involved in generating feelings of desire. Unlike Procter & Gamble's hormone patch Intrinsa, targeted at woman after the menopause, flibanserin apparently directly manipulates the chain of chemical reactions in the brain believed to trigger sexual desire.

"By modulating the neurotransmitter system, flibanserin may help to restore a balance between inhibitory and excitatory factors leading to a healthy sexual response," said Elaine Jolly, a Canadian gynecologist and medical researcher who helped oversee the trials.

However, unlike Viagra, it takes several weeks for the effect to build up, meaning it cannot simply be "popped" on demand, researchers said.

It also has side-effects, with up to one in eight of the women in the trials dropping out with dizziness, fatigue and sleep problems, researchers said.

In its release of partial findings, BI researchers said they conducted several studies in North America and Europe involving over 5,000 pre-menopausal women who had been diagnosed with HSDD. Researchers focused on the North American studies, which included just over 1,300 women. The average age of the women was 35, and most were married and the average length of their relationships were over 10 years.

Every day for six months, the women were asked to record their subjective evaluation of their own sexual desire, as well as their sexual activity, defined as “Satisfying Sexual Events (SSEs).” For the study, sexual events were not defined solely as intercourse or orgasm. An SSE was defined in the study as sexual intercourse, oral sex, masturbation or genital stimulation by the partner, but which was subjectively evaluated by the woman as satisfying (with prompts like gratifying, fulfilling, satisfactory and/or successful).

The company used personal “digital assistants” to check whether the pill was working. Participants were beeped once a day and asked to rate their level of desire, and say whether they had been sexually active and whether it was enjoyable.

Comparing the women in the North American study taking daily doses of flibanserin with women taking a placebo, the data revealed that women taking the drug increased their SSE’s by 1.7 per month, while women taking the placebo had one more satisfying sexual event per month.

Women taking flibanserin also allegedly reported an increase in sexual desire, and a reduction in distress about sexual desire. Women taking the placebo also reported increased desire, and decreased distress, but the difference between the two groups was statistically significant.

Thus, after taking the drug, the women in the North American study had sexual encounters 60 percent more often, and also found it more satisfying. They also felt less stressed about their sex lives, researchers alleged.

Very importantly, in the European study there was NOT significant increases in sexually satisfying events.

Researchers have offered no explanation for the geographic differences in the test results. The answer to that may be very, very problematic for the study and overall project. Researchers may not have performed the studies consistently regardless of cultural differences, or those cultural differences regarding sexual attitudes between continents may nullify the benefits of the pill. Whatever the reason, researchers will have to address this glaring problem at some point down the road to financial, if not physical, nirvana.

In addition, after the six month study had concluded, there were participants who reported that their sexual desire did not diminish after they stopped taking the drug. Whether this suggests that the drug may have a longer lasting effect on brain chemistry, or that brain chemistry is not as an important a factor in developing sexual desire as researches believe, also remains to be proven.

Even if the drug does perform as represented, women should be very cautious. Petra Boynton, a healthcare researcher at University College London warns the pill is not a 'magic bullet' and could prevent couples from thrashing out their underlying issues.

She said couples should pay attention and talk about their problems. She said: “It’s not going to make you feel better about your body and it won’t make your partner better in bed.”

Because there as so many unanswered questions regarding this drug, I believe it is premature at best to tout any potential benefits of flibanserin. The decision by the biotech company to release just enough information to make it appear that the drug will be effective to help women with sexual dysfunction may be an effective marketing strategy, but may end up hurting the very demographic they claim to care about.

Procter & Gamble's Intrinsa testosterone patches are licensed for use in Europe but not in the U.S., where regulators voted in 2004 against approving the patches that deliver the male hormone, citing lack of evidence for their long-term safety.

To date, the only female sexual dysfunction therapy approved in the U.S. is NOT a drug, it’s Eros-CTD, from NuGyn, Inc., a suction pump that fits over the clitoris much like the erection pumps that predated Viagra. The U.S. specialty drug company BioSante is developing a testosterone skin gel to treat a decline in libido in menopausal women.

It remains to be seen how much this new drug will cost if approved, but it is unlikely to be widely prescribed by Health Services in the UK already struggling to find cash to fund treatment of life-threatening illnesses.

The results from the flibanserin trials were presented last week at the congress of the European Society for Sexual Medicine in Lyon, France.

Researchers around the world will be watching Boehringer’s results carefully. “There are probably a lot of companies holding their breath,” Pfaus said.

— The Curator

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