Studies Raise Questions About Safety Of Personal Lubricants

Although most people will list only K-Y Jelly when asked to recall the names of personal lubricants, hundreds of the products are being used for sex across the globe. These sex aids are designed to make things easier. So it’s a little unsettling that experiments carried out in recent years have indicated that some of the products might be smoothing the way for disease transmission.

Used to reduce friction and increase pleasure during intercourse, lubricants are about a $219 million market in the U.S. alone, according to the Chicago-based market research firm SymphonyIRI Group.

But a handful of studies have called into question the safety of these sex aids, although none have shown cut-and-dried proof of risk. Some of the experiments have shown that personal lubricants can damage cells lining both the vagina and rectum, potentially making the body more vulnerable to sexually transmitted infections (STIs). And one epidemiological investigation, published early this year, reported that participants who consistently used personal lubricants for rectal intercourse had a higher prevalence of STIs, such as chlamydia, than inconsistent users (Sex. Transm. Dis., DOI: 10.1097/olq.0b013e318235502b).

Complicating matters is that these same lubricants are being eyed as components of low-cost microbicide gels that could protect people from HIV. The thinking is that because so many people already use the sex aids, they will go right on using them for pleasure as well as protection once a virus-killing drug is added. But the new safety concerns about lubricants have made researchers consider reformulating the gels.

Still, most of the recent lab-based safety studies conducted on personal lubricants fall short of indicting the products. “We have signals that are concerning,” says Jim Pickett, chair of the International Rectal Microbicide Advocates (IRMA) group, a global network pushing for safe and effective STI-preventing products. “But we don’t know what they mean yet. Just because a lubricant causes cell damage in the lab, we don’t know whether that has anything to do with disease transmission in humans in the real world.”

In response, Johnson & Johnson, which dominates the personal lubricant market with its K-Y brand products, says, “We continually review new research as it evolves. K-Y brand products have provided effective lubrication and moisturization for millions of couples and are safe when used as directed.”

Right now, the Food & Drug Administration doesn’t typically require testing of personal lubricants in humans. The agency classifies them as medical devices, so the sex aids have to be tested on animals such as rabbits and guinea pigs. Rectal use of lubricants is viewed by the agency as an “off-label” application—use at your own risk.

According to a spokeswoman, the agency is staying abreast of the ongoing discussion about personal lubricants in the research community. Future decisions, actions, or changes regarding oversight of the sex aids, FDA says, “will be based on a review of the scientific evidence.”

Questions about lubricant safety arose nearly a decade ago when micro­bicide developers were testing whether the detergent nonoxynol-9 could block HIV transmission. Manufacturers had been incorporating the compound into spermicidal lubricants for years because of its ability to punch holes in the cell membranes of sperm.

In 2002, however, a Phase II/III clinical trial of a nonoxynol-9 vaginal gel failed to protect women from HIV infection. Not only that, but the detergent actually increased the risk of HIV infection in the sex workers tested—women living in countries such as South Africa and Thailand who used the product three or four times per day (Lancet, DOI: 10.1016/s0140-6736(02)11079-8).

Lab work eventually revealed the reason for the paradoxical increase: Nonoxynol-9 is so good at punching holes in cell membranes that it not only bores into sperm but also into the cells lining the vagina and rectum. The mucosal lining of the vagina is a good barrier to infection all by itself, says Richard A. Cone, a biophysicist at Johns Hopkins University. But if that barrier gets compromised, all bets are off, he explains.

After nonoxynol-9—still used on some condoms today—went from promising microbicide candidate to malevolent cell killer, scientists like Cone began to question the safety of other supposedly innocuous spermicide and personal lubricant ingredients.

Two years ago, Cone and his group at Johns Hopkins published work showing that damaging effects of over-the-counter lubricants seem to depend on a factor called osmolality. Measured in moles (osmoles) of solute per kilogram of solvent, osmolality is a parameter describing the overall concentration of molecular ingredients in a product. After examining mouse vaginal cells, the researchers discovered that, when mice were exposed to high-osmolality lubricants followed by herpes simplex virus, the rodents were more susceptible to infection.

For instance, K-Y Warming Jelly, which has an osmolality more than 30 times the body’s own fluid, increased herpes transmission more than ninefold compared with rodents not administered lubricant (BMC Infect. Dis., DOI: 10.1186/1471-2334-10-331).

Researchers say that the high osmolality of some lubricants likely causes epithelial cell damage because of simple physics. “We’re full of sugar, salts, and proteins that make up the constituents in our cells,” explains Charlene S. Dezzutti, a professor in the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh. And there is a certain concentration of those components in the human body.

“So if you eat a big candy bar, there’s a gradient in concentration between your cell insides and cell outsides,” Dezzutti says. To maintain equilibrium, the body reacts by releasing water from its cells to dilute the sugar outside. “When that happens in gut epithelial tissue,” Dezzutti adds, “the cells shrivel up to the point that they look like little raisins under a microscope.”

Similarly, adding hyperosmolar lubricants—those products containing concentrations of components higher than the body’s cells—to the vagina or rectum causes the cells there to shrivel up and come off, Dezzutti says. This may weaken the body’s defenses in these areas, she adds.

The reason many personal lubricants are hyperosmolar, Cone contends, is that they contain large amounts of ingredients such as glycerin and propylene glycol. Without these “humectants,” he says, a water-based lubricant would evaporate more rapidly when spread onto skin, causing an unpleasant cold sensation. Manufacturers have been formulating skin care products with these ingredients for many moons, Cone adds, so the firms assumed they’d work just as well in personal lubricants.

But skin cells on a person’s arm are a far cry from cells in a woman’s vagina—or in the rectum, for that matter.

In 2007, a research team led by Craig W. Hendrix, a clinical pharmacologist at Johns Hopkins, demonstrated that ID Glide, a hyper­osmolar lubricant similar to Astro­glide and K-Y Jelly, caused significant damage to the rectal tissue of human study participants. The scientists observed major shedding of cells from tissue samples biopsied 60 to 90 minutes after lubricant application (J. Infect. Dis., DOI: 10.1086/511279).

Because human studies of this sort can’t ethically test the effect of lubricant on the acquisition of STIs, Hendrix and others in the research community must try to find answers to safety questions in other ways. Specifically, they are exposing animals such as monkeys and cultured human tissue to lubricants and pathogens.

Dezzutti and coworkers conducted a test of this sort on cultured human rectal and cervical tissue, publishing their results in PLoS One last month (DOI: 10.1371/journal.pone.0048328). Although the researchers observed some killing of cells in both types of tissue by hyperosmolar lubricants, they did not observe an increase in HIV infection when the same samples were challenged with virus. Lubricants with osmolalities closer to that of the body, such as agar-based Good Clean Love, didn’t damage the tissue samples or boost HIV infection rates.

In separate tests, Dezzutti’s team also found that hyperosmolar lubricants and spermicidal gels killed microbes commonly found in the vagina. For example, K-Y Jelly killed all three species of Lactobacillus it was applied to. Dezzutti says the bacterial kill off is likely caused by the ingredient chlorhexidine, an antibacterial agent. Unbalancing the natural flora in the vagina is another possible strike against personal lubricants, she adds, because it might lead to infections such as bacterial vaginosis.

Using these cell culture studies to draw conclusions and make recommendations about personal lubricants, though, is dicey at best, Dezzutti says. “This is just a model in a test tube, and it’s hard to equate that with real-life activity,” she says.

Some studies have even reported no signs of cell toxicity from hyperosmolar lubricants. When testing a new microbicide on the vaginas of rhesus monkeys, Ashley T. Haase, a microbiologist at the University of Minnesota Medical School, and coworkers didn’t see any irritation of the vaginal lining over six months of application (Antimicrob. Agents Chemother., DOI: 10.1128/aac.00989-08). The active ingredient in the microbicide, glycerol monolaurate, was delivered in K-Y Warming Jelly.

Johns Hopkins’ Cone, on the other hand, did observe cell toxicity in his mouse model with the same glycerol monolaurate/K-Y formulation. His team also saw a 10-fold increase in susceptibility to herpes with the gel.

On the basis of his own research, Cone believes that “virtually all sex lubricants need to be reformulated.” In the face of all the gaps in available data, other sources interviewed by C&EN are more conservative, not willing to recommend against certain personal lubricants just yet.

“The message about lube safety at this stage has to be in the context of overall risk for STIs,” Hendrix says. “If you use lubricant infrequently and have one partner, you don’t have the same risk” as someone using it four times per day. For people who don’t use condoms and have more than one sex partner, though, “you could hedge your bets thoughtfully and choose a product that has not been shown to cause epithelial cell changes.”

IRMA’s Pickett has a similar view. “We know that the use of lube with condoms ensures that the condoms are used correctly—that they don’t break or slip off during sex,” he says. Although these new results are troubling, “we don’t want to scare people away from using lube” while researchers try to figure out what the data mean.

Meanwhile, more epidemiological tests are on the horizon, and the Centers for Disease Control & Prevention is currently conducting its own studies in monkeys, Pickett tells C&EN. “I’m hopeful and optimistic that in 2013, we’ll be able to fill in the gaps and answer the questions that need answering.”