Big pharma wants to take you for a ride

Susan and Brendan had been dating for a month when they decided to spend a weekend together in the city. They had met in a small town, and while Susan was not completely sold on Brendan, sneaking around the office and having a quickie in the copy room kept her interested. As they unpacked their bags and settled into a dingy hotel, the tension that had mounted during their three-hour drive snapped.

The couple dove into bed with the eagerness that accompanies a new relationship. But the much-anticipated session petered out in two minutes, before Susan could even warm up. “What the fuck is wrong with you?” she asked as Brendan rolled off her. This marked at least the fifth time in their relationship that Brendan had ejaculated too quickly for Susan’s liking, and despite the fact that he always countered “with a good munch,” her patience had peaked. Brendan retreated downstairs for a cigarette, wishing to avoid further interrogation.

Is there something wrong with Brendan? It depends on whom you ask. The prospect of a sex-filled vacation may have put him in a state of anxiety that was manifested in this sexual shortcoming. Or Brendan may be genetically predisposed to have a low ejaculatory threshold, possessing a hypersensitive penis that lets him last only a few minutes. It may be that the cascade of dopamine, serotonin, oxytocin and other neurochemicals is at fault. Some would suggest Brendan’s early ejaculation could be linked to how he masturbates or is embedded in his pubescent sexual encounters. Or, of course, there is always the possibility that nothing is wrong with Brendan, that Susan’s expectations just don’t align with his capabilities for impromptu intercourse.

Susan’s postcopulatory inquiry into what the fuck was wrong took Brendan down a notch, and their tryst fizzled out soon after. Men with rapid ejaculation worry their partners will leave them, and the added anxiety just makes the condition worse.

Sex is highly variable. A 2005 study published in The Journal of Sexual Medicine used stopwatches to measure intravaginal ejaculation latency, or how long a man lasts from the start of intercourse until ejaculation. The study looked at 500 couples and revealed a median time of 5.4 minutes. The duration of the men – who were recruited from the US, the UK, Turkey, Spain and the Netherlands – ranged from under a minute to about 45 minutes.

The average time varied for each country, with the Turks coming first at 3.7 minutes. Condoms had no impact on the average time, and being circumcised yielded an insignificant benefit. Another study, also published in 2005 in The Journal of Sexual Medicine, revealed a median time of 7.3 minutes among 1,380 US men not considered to have ejaculation difficulties (ED). The study also included 207 men considered to be premature ejaculators, who clocked an average time of 1.8 minutes.

Premature ejaculation is a term everyone has heard but few can define beyond the obvious “when a guy comes too early.” A taboo looms over the issue, with most conversations relegated to punch lines or dense medical literature. To be fair, before there was ED there was impotence, and that wasn’t a choice talking point either.

Determining what constitutes the condition has recently been open to increasing debate. Is it the inability to last more than a predetermined time? Is it not being able to recognise when ejaculation will occur?

The focus on creating a universal definition of primary premature ejaculation is driven in part by the pharmaceutical industry’s interest in selling drugs that make a man last longer. Johnson & Johnson’s drug for early ejaculation, dapoxetine, is approved in a handful of overseas markets under the brand name Priligy. The drug, rejected by the US Food And Drug Administration. (FDA) in 2005, has been shown to lead to a threefold increase in duration when taken in a 60-milligram dose about an hour before sex. Dapoxetine is a selective serotonin reuptake inhibitor (SSRI), as are the antidepressants Prozac and Paxil. A well-known side effect of most SSRIs is delayed ejaculation, leading many doctors to prescribe them to men in need of a few extra thrusts. Using a side effect of a drug to treat a condition for which the drug is not approved is hardly ideal, but no FDA-approved treatment exists.

Shionogi is a Japanese pharmaceutical company based in Osaka. It recently wrapped up Phase III studies – the last and largest stage of testing, when a drug is compared with other treatments – on an experimental compound dubbed PSD502. The drug is a combination of the topical anesthetics lidocaine and prilocaine and is sprayed on the head of the penis a few minutes before sex. In studies of about 1,000 men and their female partners, PSD502 prolonged the point of no return from an average of 0.6 minutes to 3.3 minutes. There is nothing novel about using drugs to desensitise the nether regions, but most such drugs are creams, and rubbing cream on the penis of a man who is trying to last longer seems ill-advised. Dr Donald Manning, Shionogi’s chief medical officer, says the spray appears to reduce sensation without numbing the penis – always a good thing if you actually want to enjoy sex – pointing out that fewer than two percent of men who used it reported numbness.

The pharmaceutical industry’s interest in serving a vast market of premature ejaculators isn’t the only factor behind arguments about how the condition should be defined. The Diagnostic and Statistical Manual of Mental Disorders, the American Psychiatric Association’s reference text, is being revised for its fifth edition. Some people have criticised the DSM’s current definition of premature ejaculation as being too subjective. The symptoms of PE, according to the fourth edition of the DSM, include “ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it.”

Dr Robert Taylor Segraves, Professor of Psychiatry at Case Western Reserve University and a member of the DSM revision panel, says this definition is so vague any number of people can be diagnosed with a problem. Some studies even classify men who last well beyond five minutes as premature ejaculators. “It sounds kind of meaningless at that point,” Segraves says. “We need greater precision.”

The draft proposal of the new edition of the DSM recommends dropping premature and renaming the condition “early ejaculation.” Segraves and Michael Perelman, a Manhattan-based psychologist who is President of the Society for Sex Therapy and Research, agree that premature has a pejorative connotation. However, Perelman – who also serves as a consultant for pharmaceutical companies – predicts that in the future it will likely be known as PE, just as erectile dysfunction is now called ED.

A few years back, Plethora Solutions, a UK-based drug firm, awarded an unrestricted grant to the International Society for Sexual Medicine (ISSM) to explore the evidence. A crew of 21 leaders ranging in specialties from psychiatry to neurology met in Amsterdam in 2007 to prepare a diagnostic blueprint for men who ejaculate too quickly. After wading through the data, the leaders emerged with what is now considered to be the gold-standard definition. The ISSM’s definition regards the dysfunction as “ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration,” rather than simply before a person wishes it to occur.

The ISSM, like the DSM, takes into account the strain that PE can place on a man, his partner and their relationship. But it is the one-minute benchmark – the quantitative end point – that may prove vital in bringing PE drugs to a prescription-hungry nation. Plethora Solutions’ decision to give the ISSM a grant for a definition was not just a gesture of goodwill. Plethora developed the above-mentioned ejaculation-delaying spray, PSD502, and licensed it to Sciele Pharma, which was later acquired by Shionogi. Should Shionogi succeed in becoming the first company to have an FDA-approved drug for premature ejaculation, Plethora could see a windfall in royalties. Manning, Shionogi’s head medical officer, says the company used the one-minute benchmark in the data it collected, as well as aspects of control and distress. In fact, data from the study show that men who were given the drug ranked significantly higher on a scale of ejaculatory control than men given a placebo.

Shionogi and J&J – which is analysing its own dapoxetine data for a potential FDA resubmission – aren’t the only drug-makers who hope to crack this market. Sarah Terry, President of biomedical data provider Life Science Analytics, says about 20 players are looking to get in. GlaxoSmithKline is among them, with two drugs in development: one designed to inhibit oxytocin and the other an SSRI. Both are in Phase II testing, when scientists determine if a proposed medication is actually associated with a therapeutic benefit. Premature ejaculation is attractive to drug companies because it represents an entirely new market at a time when they need to replenish their pipelines with new compounds. Big Pharma is hurtling toward a patent cliff, and generic companies are ready to pounce on the opportunity to churn out cheaper versions of Lipitor and Viagra, which come off patent in 2011 and 2012. Terry says that between 2008 and 2014, $113 billion worth of drugs will have their patents expire.

The potential of a drug for premature ejaculation dwarfs that of an erectile dysfunction drug. Estimates vary – mainly because of the definition issue and trouble in designing studies – but between 20 and 30 percent of the American population could be considered premature ejaculators. One market study, from Datamonitor, estimates that in 2010 the US population of early ejaculators between the ages of 20 and 59 was 25.8 million, compared with 9.5 million men in need of boner drugs. And that doesn’t include overseas markets. “I think the FDA is ultimately willing to approve a drug for premature ejaculation,” Terry says. “The challenge at this stage is just defining what that actually means.”

In the days of King Charles II, the last Spanish Habsburg ruler and one of the most regal premature ejaculators on record, sexual dysfunctions were the product of witchcraft. Innovative treatments included exorcisms and urinating through your wedding ring or the keyhole of the church where you were married. Fast forward to the early 20th Century and you’ll come across a sea of erotic snake oil, including an arsenic-containing elixir in Dr Frank Miller’s 1913 tome, Domestic Medical Practice. In the late 1950s, in the wake of Kinsey came the work of William Masters and Virginia Johnson, better known as Masters and Johnson. The duo developed the still popular squeeze technique to prolong sex, which, as its name implies, involves putting a stranglehold on the head of the penis before ejaculation. Studies have demonstrated its efficacy, but evidence suggests that without regular upkeep the positive effects wear off. Also, it can be awkward to ask someone you’re sleeping with for the first time to put your dick in a death grip.

“Masters couldn’t do any analysis – he didn’t have any funding – so what he did was hire prostitutes to observe them, interview them, identify how they had sex and what the sexual issues of their lives were,” says Dr Irwin Goldstein, Director of sexual medicine at Alvarado Hospital in San Diego. Goldstein, who was an acquaintance of Masters’, notes that the atmosphere surrounding sexual research was so restrictive in the early days of his work that Masters struggled to get medical texts about female reproductive anatomy. “The thing is, prostitutes saw a lot of men who were anxious and stressed, so his formulations were made on bad observations because of biased population. It was their theory, which is perpetuated even in 2010, that 90-plus percent of all sexual problems are due to psychological issues: anxiety, humiliation, fear, depression.”

Goldstein is Editor-in-Chief of The Journal of Sexual Medicine (and also a drug company consultant). For more than 20 years he was funded by the National Institutes of Health to study sexual function and dysfunction. He is highly critical of those who believe such disorders are rooted solely in psychology. When he tells you about a man who can’t watch his wife strip down without ejaculating all over himself or about a 28-year-old guy who hasn’t had an erection for more than a decade because of a damaged artery, you learn how debilitating sexual dysfunction can be.

For Goldstein, the work of a Baylor University urologist, F Brantley Scott, was the catalyst that took the treatment of sexual dysfunction from the head doctors and brought it into the medical field. “It had to end up in a physician’s hands to progress along medical thinking and diagnostics,” he explains. Scott, who died in a plane crash in 1991, played an instrumental role in developing the inflatable penile prosthesis, which has been used to treat tens of thousands of patients. The development of this surgically implanted device transformed the landscape of research and opened the field of sexual medicine. “Premature ejaculation, Viagra, orgasm dysfunction, all this stuff ended up in the field of urology,” says Goldstein.

By now pharmaceutical engineers have studied the effects on ejaculation of an array of drugs – including neuroleptics, tricyclic antidepressants, opioid agonists, phosphodiestrase inhibitors, sympatholytics and SSRIs. Beyond drugs, modern researchers have tested rings that wrap around the penis, behavioral techniques such as the stop-start approach and even virtual-reality programs intended to help men explore their sexual development for events that might have influenced their ejaculatory reflex. Much remains to be learned about the mechanisms of ejaculation, but research bolsters the notion that it is rooted in neurochemical interactions.

Numerous challenges loom over the success of any drug, and for one that extends intercourse the most significant factors will be pricing and perception. “Because premature ejaculation is in such a broad range of patients and doesn’t have a correlation with age, it is actually much more in line with a lifestyle drug,” says Terry of Life Science Analytics. “Because it will be a lifestyle drug, it won’t be reimbursed by health insurance. People will have to pay out of pocket for it.”

Getting men to schedule an appointment to talk about an ostensibly embarrassing disorder and then persuading them to cough up money for treatment will require a costly display of advertising acumen. The battle over direct-to-consumer advertising is nothing new, with one side considering it patient education and the other considering it a tool of deception. Such drug ads are almost exclusive to the US, coming to the airwaves only in the 1990s. The stakes are now huge: Pfizer recruited the likes of US presidential candidate Bob Dole, baseball superstar Rafael Palmeiro and NASCAR driver Mark Martin to pitch Viagra. Eli Lilly’s ad for Cialis that features a couple in separate bathtubs gazing toward the horizon has been cited by Nielsen as one of the most remembered commercials. As the erection market grew and competition increased, the ads became more risqué, sparking complaints and FDA warnings that the drugs were being hawked as party pills. It is unclear how American households will respond when copywriters start churning out euphemisms for ejaculate, but chances are there will be some uproar. Any opposition to such ads will give pause to drug companies and research institutes contemplating new ventures in sexual health.

But advertising is essential for any premature ejaculation drug. “We looked at the examples of Viagra, Levitra and Cialis as a benchmark for the impact of direct-to-consumer advertising,” says Terry. “What we found qualitatively is that, after the launch of Viagra, the marketing of each subsequent product expanded the opportunity of those drugs by nearly 15 to 20 percent each. The amount of marketing out there continued to push the population base that much each time.” A similar pattern will presumably emerge with premature ejaculation drugs. The market will swell by millions with each additional approval letter the FDA mails.

Some experts see the real problem as the imposition of normative structures on what is a variable phenomenon. Dr Leonore Tiefer, Associate Professor of Psychiatry at New York University, is in the vanguard of this movement. Tiefer doesn’t conceal her intention to undermine the quantification of sexual function. She admits that a drug to delay ejaculation can be useful to some but says there is no such thing as premature ejaculation, and efforts to create drugs to treat it are disingenuous. Sex, Tiefer says, is more like dancing than digestion.

“Fundamentally, being fat or thin is a matter of live variation throughout history and culture,” she says. “The same thing is true of coming quickly or not, having a hard erection when you’re 60 or not, wanting to have intercourse when you’re 60 or not. There’s a great deal of variability. To try to stuff it into some simpleminded bottom line is to deny the reality of sex.”

Michael Perelman, the New York psychologist, says ejaculatory latency is just another human characteristic, similar to blue eyes, best plotted along a skewed distribution curve. He would like to see the definition of premature ejaculation divided into four categories of severity: when a man can’t enter the vagina, when sex lasts less than a minute, when sex lasts one to two minutes and when it lasts two to four minutes. Perelman reasons that the average physician will see people who consider themselves to be suffering from premature ejaculation who last more than one minute but not as long as they would like to.

Remember that Brendan was nearing two minutes that night in the city. We don’t know if he ever felt in control, but distress certainly reared its head. No doctor can fully answer Susan’s question as to what the fuck was wrong with Brendan, and no drug can address the underlying factors that determine how long he lasts on any given occasion.
If Brendan had popped a pill that night, would he have been treating a disease or just enhancing an aspect of everyday life? Our regulatory system is designed to weigh the risks and benefits of drugs used to treat defined diseases, not to improve our lifestyles. But the line between treatment and enhancement is now more blurred than ever.
“Such uses of pharmaceuticals pose challenges for us as a country,” says Perelman. “The challenge is always greater when we talk about sex.”

Big Pharma isn’t going to shy away from this conversation. It’s adept at dictating what’s good and what’s bad and what is normal and what isn’t. Ejaculation won’t be an exception.

by Chris Sweeney
Published by Playboy South Africa June 2012