Ovarian failure caused by Gardasil? Not so fast…

Well, I’m home.

AFter spending a fun-filled three days in Nashville at CSICon communing with fellow skeptics and trying to awaken them to the problem of quackademic medicine, I made it back home. There were plenty of attendees who didn’t make it back on time because flights to the East Coast were being cancelled left and right, courtesy of Hurricane Sandy. For example, Steve Novella and the entire SGU crew were forced to rent a van and drive 950 miles to Boston after their flight was cancelled sometime Saturday night. Difficulties aside, if there’s one thing that almost always happens whenever I go out of town, regardless of whether it’s for my real job, my blogging avocation, or an actual vacation, it’s that something pops up right before I’m scheduled to leave that I want to blog about but don’t get to. Rarely do I make it back to such topics, but this time around I felt as though I wanted to get back to this one. The reason is that I noticed something going on that rose above the usual chatter coming from antivaccine cranks.

Antivaccinationists, of course, fear and loathe vaccines. However, they fear and loathe certain vaccines more than others, and the level of fear and loathing depends somewhat upon location. Here in the U.S., if there’s one vaccine that’s feared and loathed perhaps more than any other, it’s the vaccine against the human papilloma virus (HPV). That usually means Gardasil. I’ve speculated before why certain antivaccinationists seem to hate Gardasil more than any other vaccine, and I think I’ve come up with a plausible explanation. Basically, the hatred of Gardasil is the result of an unholy fusion of antivaccine beliefs with the fundamentalist religion so prevalent in the U.S. that makes the brain dead argument that protecting young women against infection by sexually transmitted organisms that can lead to cervical cancer will somehow inevitably lead to promiscuity, godlessness, and the Downfall Of The American Way of Life, because, you know, if women didn’t have sex before marriage and only had sex with one man for the sole purpose of reproduction they wouldn’t need Gardasil. I exaggerate, but only a little. No, wait. Actually, I don’t exaggerate. This is the basic belief behind the fundamentalists’ fear of Gardasil. Sometimes this belief leads to some of the absolute dumbest canards ever. (Just use the search box to search this blog for “Gardasil” if you don’t believe me.)

What I had noticed is that the arguments coming from the antivaccine fringe had been flying fast and furious right before CSICon, and I was curious why. For instance, the antivaccine crank blog Age of Autism ran a series of posts with titles like Spotlight on Gardasil, complete with three chapter excerpts from Mark Blaxill and Dan Olmsted’s epic paean to pseudoscience, Age of Autism, and Age of Autism Science Summary: Death after Quadrivalent Human Papillomavirus (HPV) Vaccination. Meanwhile, over at Gaia Health, The Refusers’ blog, and something called the Population Research Institute, antivaccinationists were going wild over a case report published in, appropriately enough, BMJ Case Reports that suggests (to antivaccinationists at least) that Gardasil caused premature ovarian failure leading to menopause a 16 year old girl.

I am not impressed.

Let’s start with the last one first, because it’s hard to believe that gruel this thin was published in the peer-reviewed literature. The case report is, beginning to end, the speculative chasing of the specter of Gardasil, trying desperately to blame it for this unfortunate girl’s ovarian failure leading to premature menopause at the extremely young age of 16. And the antivaccine movement is eating it up, too. For instance, the PRI states:

It is very rare for a healthy 16-year-old girl to go through menopause. It is also a personal tragedy of the first order, one that will only grow in magnitude as she marries and yearns to start a family.

While Dr. Little could not confirm that Gardasil caused the destruction of the girl’s reproductive system, she was able to rule out all other possible causes. The circumstantial evidence implicating Gardasil is strong.

And Gaia Health opines:

The girl has been thoroughly examined and tested. There is no known explanation other than the series of three Gardasil vaccinations she had.

That is the basic argument at the heart of this case report: Because investigations didn’t turn up any obvious cause for this unfortunate girl’s premature ovarian failure, it must have been the Gardasil that done it. Yes, the argument is just that vacuous and weak. Let’s go back to the report itself, and then let’s go to how antivaccinationists are spinning it. This case report was published by Deirdre Therese Little and Harvey Rodrick Grenville Ward from Australia. The case is basically described thusly:

A 16-year-old girl presented with a history of 5 months amenorrhoea, preceded by approximately 12 months oligomenorrhoea. Menarche had occurred at the age of 13 in 2007 with initially light periods which became heavier and developed a regular monthly pattern over the following 12 months.

Early in 2009 menses became irregular. In early 2010 they became scant and occurred infrequently, two or more months apart. Menstrual periods ceased in January 2011. Following the development of amenorrhoea, the patient experienced hot flushes. She identified that an alteration in the menstrual pattern had started following HPV vaccination.

On first presentation to her local doctor she was prescribed the OC for amenorrhoea after exclusion of pregnancy. She elected not to take the contraceptive pill at that time and sought further opinion regarding her continuing amenorrhoea.

Investigations were quite thorough, including a complete battery of tests related to reproductive function, including prolactin levels, androgen profile, FSH and LH levels, and many others. They even did a karyotype to check and make sure that the girl had two X chromosomes. Well, I shouldn’t say “even.” It’s part of the routine investigation. Now here’s where the authors reveal their bias. They point out in the introduction that premature ovarian failure has an estimated incidence of 10/100,000 person-years between the ages of 15 and 29. Other sources suggest that the incidence of such ovarian dysfunction might be as high as 1 in 1,000 before the age of 40. The authors also cite sources that find that the cause of ovarian failure before the age of 40 “remains unknown in up to 90% of cases.” In other words, in the vast majority of cases premature ovarian failure is idiopathic. We don’t know what caused it. In the cases where a cause can be identified, potential causes are several and include autoimmune disorders (I bet you know where this is going), genetics, chemotherapy, hysterectomy (a rather obvious cause), thyroid dysfunction (no word in the case report whether thyroid studies were done; I’ll assume that they were), Turner syndrome, inadequate gonadotropin secretion or action, and viral infections.

Because Little and Ward can’t find any evidence that any of these causes were the root cause of this girl’s premature menopause, they gleefully leap to the conclusion that—you guessed it!—it must have been the Gardasil! I kid you not. And when did this girl receive her anti-HPV vaccine? According to the case report, she received doses in May and August of 2008. Now let’s go back to the case report. this girl started to have irregular menses in early 2009, more than five months after her last dose of Gardasil, and then she didn’t stop menstruating until a year later, in early 2010.

Yes, obviously, it must have been the Gardasil. (That’s sarcasm, in case you didn’t notice it.) In fact, the authors think it’s the Gardasil so much that not only did they report this girl’s premature ovarian failure as a possible adverse event to the Therapeutic Goods Administration of Australia, but they undertook a search for reports examining whether the HPV vaccine had any effects on rat ovaries, after having found a report that showed no effect due to Gardasil on rat testes. They even went so far as to submit a Freedom of Information request for such data, which, they darkly point out, hasn’t panned out yet.

Obviously, it must have been the Gardasil, and obviously the pharmaceutical companies are hiding something. (That’s more sarcasm, in case you didn’t realize it.) The authors even go so far as to write:

Had this young woman taken the OC as prescribed for correction of her oligomenorrhoea/amenorrhoea, her diagnosis of premature ovarian insufficiency may not have been determined for perhaps some years. The possibility of its link to an adverse pharmaceutical event might also have been lost.

Anecdotal evidence from an informal discussion with high-school students suggests that one in three girls of this age is taking an OC for reasons of cycle control, acne management or for contraception. Given the prevalence of OC usage in this age group, combined with the possibility of initial OC prescription for the management of oligomenorrhoea (presumably to reduce associated anxiety, re-establish a ‘normal’ cycle and to protect bone mass, etc), conditions affecting menstrual function in this age group will be undetected and undiagnosed. Menstrual abnormalities and particularly ovarian insufficiency at this time may therefore be under-reported as possible adverse events following vaccination or other medication.

You read it right. The authors are saying that, because the first symptom of premature ovarian failure is irregular menstrual cycles and because the treatment for irregular menstrual cycles is often oral contraceptives, menstrual abnormalities up to and including premature ovarian failure might actually be underreported, leading to the underreporting of ovarian insufficiency due to Gardasil. Yes, according to Little and Ward’s insinuation, we’d see this horrific epidemic of young girls robbed of their womanhood before they even had the chance to experience it and bring new life into the world if it weren’t for those darned birth control pills! Now, I realize that journals tend to have a laxer standard for the sorts of speculation allowed in case reports (their being case reports and all and hypothesis-generating rather than hypothesis testing), but this is ridiculous. It goes far beyond the pale. Even though the authors say multiple times that their observations do not prove that the quadrivalent HPV vaccine is toxic to ovaries, based on the way they wrote this case report it is breathtakingly obvious that this is exactly what they think and that the reviewers probably made them put those caveats into their case report.

Little and Ward even suggest an epidemiological study of young women vaccinated with quadrivalent HPV vaccine versus those not vaccinated against HPV with long term followup of ovarian function. This is a ridiculous suggestion. Unless Gardasil is pure poison to the ovaries, it would take thousands of women to detect differences between vaccinated and unvaccinated women even if the incidence of premature ovarian failure were as high as 1 in 1,000, and it would take many years of followup. That doesn’t even take into account how hard it would be to control for confounding variables. It would be one thing if Little and Ward had actually observed correlation between Gardasil vaccination and premature ovarian failure, but in reality they confused correlation with causation without even having the correlation. It is a common failing of antivaccinationists.

Meanwhile, over in the antivaccine underground, this report is being used to resurrect even wilder speculation about L-histidine somehow invoking autoimmune disease (which, by the way, this girl appears not to have had), all because girls not infrequently complain of joint pain and because weight gain has been reported in girls who have received Gardasil. The L-histidine gambit is one of the dumbest of many dumb antivaccine gambits, but, like the formaldehyde gambit, it keeps rearing its ugly head, just not as frequently. Then, of course, there’s the polysorbate 80, which has become another vaccine additive that antivaccinationists love to hate, so much so that they take reports that polysorbate 80 can cause infertility in rats and extrapolate them to humans, even huge doses were required to cause the effect in rats. In Gaia Health, polysorbate 80 allegedly combines with aluminum in a horrific fashion:

The most frightening trait of polysorbate 80 may be that it crosses the blood-brain barrier and can take other substances with it. It is used for that purpose. The drugs loperamide4 and doxorubicin5 are coated with polysorbate for just this purpose—to drag them into the brain.

So what else can polysorbate 80 drag into the brain? Gardasil utilizes aluminum as an adjuvant, even though it’s a dangerous neurotoxin. Injection of aluminum is associated with several neurological disorders, as is reported in Gaia Health and Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations6, rheumatoid arthritis, autoimmune thyroid disease, inflammatory bowel disease, multiple sclerosis, diabetes, and autism may all be associated with aluminum adjuvants in vaccines.

Can polysorbate open the blood-brain barrier to let aluminum in? No one really knows because no one has looked. There is, though, no legitimate reason to assume that it cannot.

No evidence whatsoever is presented to support this speculation. These guys are starting to sound like Mark and David Geier and their “theory” about how testosterone somehow binds mercury and keeps it from being chelated. Gaia Health’s speculation is what we in the biz like to call pulling it out of one’s nether regions. The result is just as stinky.

There’s almost no limit to the ridiculousness to which antivaccinationists will descend to attack Gardasil, and, unfortunately (or, depending on your point of view, fortunately) I just realized that I’ve gone on longer than I had planned (big surprise!) on the first article, leaving myself no room for a discussion of the claim of death by Gardasil publicized by AoA, the subject of which is the latest spew by Lucija Tomljenovic and Christopher A Shaw, whose previous spew you might remember.

Maybe tomorrow. It would allow me to follow up a case I discussed about three months ago, and—who knows?—maybe Christopher Shaw would notice and deign to comment again. On the other hand, his latest paper is pretty bad; I don’t know if I can deal with two papers this bad two days in a row.

Either way, the attack on Gardasil continues apace.

ADDENDUM: I intentionally concentrated on the biased and utterly speculative nature of this particular case report, which was so speculative and biased that the editors of BMJ Case Reports should hang their heads in shame for having published such twaddle. What I didn’t mention (although I thought about mentioning it) is that whenever you see a publication as bad as Little and Ward’s case report, it’s at least 95% likely that the authors have a serious axe to grind and that they are publishing because of ideology leading them to twist the case report or data to fit rather than having their conclusions flow naturally from the data. In this case, some of my commenters have pointed out that Dr. Little is on the board of advisors for an Australian Catholic anti-abortion group called Family Life International, whose official patron laments the growth of promiscuity and the “redefining” of marriage (big surprise, the group is against gay marriage as well). On the website is a diatribe against Gardasil, which, FLI gravely notes, is “often associated with promiscuity,” along with a link to a YouTube video of the antivaccine propaganda film The Greater Good. It also turns out that Ward is, as one of my commenters put it, cut from the same cloth, described as a “pro-life obstetrician/gynecologist.” He also apparently helps an antiabortion activist named Stephanie Gray give talks at local churches in Canada in which she shows graphic abortion videos to convince the audience that abortion is “wrong 100% of the time.”