Chelsea Polis and Kathryn Curtis wrote a paper that asked whether hormonal contraceptives affected your likelihood of being infected with HIV, Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Here’s the abstract:
Whether or not the use of hormonal contraception affects risk of HIV acquisition is an important question for public health. We did a systematic review, searching PubMed and Embase, aiming to explore the possibility of an association between various forms of hormonal contraception and risk of HIV acquisition. We identified 20 relevant prospective studies, eight of which met our minimum quality criteria. Of these eight, all reported findings for progestin-only injectables, and seven also reported findings for oral contraceptive pills. Most of the studies that assessed the use of oral contraceptive pills showed no significant association with HIV acquisition. None of the three studies that assessed the use of injectable norethisterone enanthate showed a significant association with HIV acquisition. Studies that assessed the use of depot-medroxyprogesterone acetate (DMPA) or non-specified injectable contraceptives had heterogeneous methods and mixed results, with some investigators noting a 1·5—2·2 times increased risk of HIV acquisition, and others reporting no association. Thus, some, but not all, observational data raise concern about a potential association between use of DMPA and risk of HIV acquisition. More definitive evidence for the existence and size of any potential effect could inform appropriate counselling and policy responses in countries with varied profiles of HIV risk, maternal mortality, and access to contraceptive services.
In short, hormonal contraceptives don’t affect your chances of getting AIDS, with the possible exception of DMPA (better known as Depo-Provera), which a few studies with different methods found to elevate the risk. So, basically, it’s saying that there’s not a problem with contraception endangering women in this regard, but that inconsistent results with Depo-Provera warrant further investigation (later, they would publish an update (pdf) that suggests women ought to be warned about the uncertainty of this side effect of Depo-Provera). It seems reasonable. So they sent it off to The Lancet for review and publication, and that’s where the mess began.
There are actually two problems here: The Lancet‘s sloppy review policies and their failure to adequately respond to a screw-up, and the abuse of the data in the paper by a group of religious ideologues.
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The paper was sent out to three reviewers, only one of whom bounced it back with an unprofessional and strongly negative review. It happens. The authors responded with a thorough rewrite of the paper, which is a cautious over-reaction, but I think they were trying their best to be meticulous. Then it turns out that the negative reviewer is a peculiar kind of AIDS-denialist crank with absolutely no professional affiliation — he’s a guy with a degree crusading for his pet theory, that HIV is not sexually transmitted at all, but is spread by medical injections.
So one question is why this guy is even on The Lancet‘s list of reviewers. They’ve removed him now, which is one positive response, but it’s unfortunate that he was given the opportunity to play the poison pill on papers that didn’t share his weird hobby horse. At the very least, his bad reviews ought to have flagged him to the editors as someone who ought to be checked out.
Overall, though, I think The Lancet‘s response was muted but appropriate. It should have acknowledged the loss of time and effort by researchers that was lost because they let a wackaloon have his hand on the brake of publication.
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The second problem is one The Lancet has little control over: it’s that anti-science kooks tend to be unscrupulous and unethical. That third reviewer not only tried to squelch the paper, but then published the reviewer’s copy on an anti-contraception web site, and somehow distorted it’s message to be that Depo-Provera was inarguably deadly, and that there was a government cover-up to conceal it.
DEPO-PROVERA — DEADLY REPRODUCTIVE VIOLENCE AGAINST WOMEN,
they announced. It has been cited on LifeSite News, the mouthpiece for a conservative Christian “pro-life” group that opposes contraception and abortion.The second classified document obtained by Fosu was authored by Chelsea Polis of USAID and Kathryn Curtis with CDC. It heavily influenced the WHO review staff to determine there was “insufficient reason” to withdraw Depo Provera and enforce mandatory warnings. Fosu claims the Polis and Curtis analysis “water[ed] down available evidence” by ignoring key research.
Oh, really? It was published in The Lancet. That doesn’t sound very “classified” to me. It was stolen in violation of copyright and reviewer ethics before publication — I don’t quite see how they can claim an unpublished paper that was just working its way through the review process could have “heavily influenced” the World Health Organization, and further, its conclusion is a moderate call for caution and further research.
Polis is rightly annoyed at all this. The Lancet is not responsible for the theft and ignorant misuse of a scientific paper by a gang of fanatics, but they do have a responsibility to do a better job screening out said fanatics, and they ought to do a better job of recognizing the concerns of their contributors.
In sum, Lancet Infectious Diseases failed to perform due diligence in selecting an unbiased and professional peer reviewer, allowed unscientific and offensive comments to move forward in the review process, failed to protect my work from being leaked by an unethical reviewer who the journal was unable to follow up on, dragged their feet in taking my case formally to COPE, failed to fully describe the situation to COPE, and shrugged their shoulders at the violation of copyright given “reputational concerns”. They’ve never apologized for this situation, or shown any interest in implementing more meaningful solutions to prevent this from happening in the future (e.g., telling reviewers that if they breach confidentiality that their names will be publicly shared so that other scientists can avoid being reviewed by them, or putting additional measures in place when asking unaffiliated individuals to serve as peer reviewers). Why not?
I agree that naming and shaming ought to be the very least action taken, so it’s a little odd that she didn’t come right out and name David Gisselquist as the unethical reviewer (although the links in her article do make it very easy to figure out who it was).
One more annoying little twist, that I’ve heard a thousand times before…
Recently, the journal did a Tweetchat called #AskLancet – and I had some follow up questions on my situation. How this conversation unfolded is best encapsulated in a Storify; in short, my questions were not responded to, until they were retweeted by a man who shared my concern. Click here to read the Storify.
Can we go back to that first sentence of the abstract, though? What makes them think that there would be any connection between hormonal levels and the ability of a virus to infect? They seem to assume it, but is there any evidence that exists that links hormonal swings to immune system function? Or are they talking about human behavior, that if a woman is on hormonal birth control then she and her male partner won’t be as strict with the condom use? I’m lost right from the premise.
That was one of my questions, too. These hormonal contraceptives provide NO protection against STDs, so one side effect might be overconfidence in the degree of protection leading to more risky behavior. These were epidemiological studies, though, and didn’t really drill down to the biological basis of any hypothetical increase in HIV infection rates.
I wish people wouldn’t try Yiddishing, if they’re terrible at it. It’s not like I inflict my ‘singing’ on the world.
Nor does penicillin help against a cold, but that doesn’t stop people from demanding them.
The main worry I’ve heard is behaviour modification (lower risk of pregnancy => have riskier sex), which most studies I’ve seen summarized indicate is a non-problem.
Presumably there have been other worries floated, or there wouldn’t be so many studies?
I am not a doctor or a researcher but I’m pretty certain estrogen receptors (and androgen receptors etc) are a key component in immune response and so there’s at least the possibility that synthetic hormonal contraceptives could be looked at as impacting virus rates.
Hormones are very much linked to immune system responses, so it’s not out of the realm of reason for them to have looked at this. The fact that they didn’t find a link between most contraceptives and HIV infection just means they actually did the work as they should.
As if anti-choice arsehats have ever cared about reproductive violence against women – they are the one’s advocating for gendered sexual slavery and forced birth, even where it results in the entirely preventable death of the mother, afterall.
It always infuriates me when misogynistic bigots appropriate the lexicon of women’s rights language in order to attack those self same rights while hypocritically trying to insincerely wrap themselves in the flag of feminism. It is nauseating to witness.
Oh my word! Publication of a review copy is close to the worst thing you can do, up there near plagiarizing. This “reviewer” needs to be drummed out of any science circle he’s in. Lancet needs to publish some sort of editorial apologizing for their gross carelessness and naming this person and explicitly warning others about his immense ethical breach, so that no one will trust him in any sort of association.
The whole system is wide open to abuse – see http://www.nature.com/news/publishing-the-peer-review-scam-1.16400 – e.g. authors reviewing their own papers. Reviewers don’t get paid, and don’t have to sign contracts, so peer-review is totally dependent on goodwill and academics being generous with their time (not to mention getting to find out what the competition are up to).
garnetstar no. 8.
Did you read the post at all?
Numerobis wrote, “Presumably there have been other worries floated, or there wouldn’t be so many studies?”
I suspect there’s a feeling that if it lets women have more sex, there must be something wrong with it — but maybe I’m just soured by the amount of anti-woman prejudice floating around.
…Link, please?
@Markita Lynda:
You’re not wrong. There’s been a huge and sustained effort by sex-haters and women-haters (often the same haters) to portray contraception as somehow “causing” the HIV epidemic. (Not the disease itself, just the epidemic of the disease, as if HIV would never have spread if contraception hadn’t become widely available.)
The Vatican, for instance, insists that **condoms** cause HIV disease, b/c without condoms no one would have sex, for fear of god, dontchaknow, but with condoms, no one ever thinks that ze is going to be the one having sex with a condom that breaks, and then *BOOM* ze has AIDS.
Remember the brouhaha over HPV vaccine? These people are seriously nutty, but seriously influential and therefore the epidemiological community can’t simply snort and say, “Look at the basic math + the past history of other new vaccines + whatever the hell you want, there’s no actual evidence that risky behavior will increase so much as to increase health risks in toto.”
The unfortunate, money-wasting truth is that even when the answers are obvious, the research has to be done to have any hope of making policy based on something other than superstition.
All because some people really, really hate women. And especially women who have sex. Unless it’s with them. In private. Where no one will know they touched a slut.
Oy.
It seems to be common knowledge that a woman’s immune system is depressed during pregnancy. It isn’t much of a stretch to conclude that it might be hormonal and to want to test whether deliberately altered hormones do a similar thing.
llyris
Or the fact that a pregnant person’s body is using their resources to grow a whole other person? I don’t think it’s wrong to investigate hormonal effects on the immune system, but to conclude that hormones are the probable or even most significant cause when so many other things are going on in a pregnant person’s body is jumping to conclusions.
Why didn’t someone, like, say, the editor assigned to this paper, read the review, determine that it was unprofessional crap, and send the manuscript to some other reviewers rather than sending it back to the poor authors? Some editor at least rubber stamped the response. He or she should be held accountable for his/her poor reviewing.
Who concluded it? Apart from the religious douchebags? Scientists considered it as a possibility, tested it, and found little evidence for it.
toska
Infact its the old correlation and causation confusion, which leads to fun things like this: http://www.tylervigen.com/
On the review thing I seem to remember a few years ago a whole lot of talk about post publication review. I don’t know how serious that discussion was but it seems to me that that would involve putting drafts “out there” and editing them after the fact. Wouldn’t that produce the same kind of result, but more often, as this case of the missused review draft?
This is a new meaning of the phrase “peer review” with which I am up to now unfamiliar.
(to paraphrase Douglas Adams).
Toska @15.
Exactly what part of pregnancy do you think is not hormonally triggered?
Also, what is the problem with coming up with a hypothesis and then testing it? That they tested it and found it was wrong, or, more to the point, contraceptive hormones don’t have that effect, doesn’t make it wrong to think up the idea in the first place. That is why we test them.
You have taken “conclude it might and want to test” as meaning “jump to an untried assumption”.
The problem with talking hormones is confusing the types of hormones. Steroids won’t always interact strongly with protein/peptide receptors, and vice versa. For AIDS, my guess would be that the protein/peptide receptors have more to do with the immune response than the steroids, which are the birth control APIs.
For my #22, API = Active Pharmaceutical Ingredient.
Haven’t read the study, but it seems to me that if there’s a weak correlation between Depo and higher HIV infection risk, rather than any side effect of Depo itself, it’s probably that:
1) use of Depo, compared to other contraceptives would be expected to be biased in favor of people who are relatively comfortable with needles.
2) people with a history of intravenous drug use are more likely to be comfortable with needles than the rest of the population.
3) people with a history of intravenous drug use have a much higher HIV infection rate than the general population.
I wonder if this occurred to anyone else parsing it…
@carlie #1 – “What makes them think that there would be any connection between hormonal levels and the ability of a virus to infect? ”
It is not the hormones themselves so much as the effects the hormones have on the body. Depo-Provera belongs to a class of contraceptives containing only a high dose of progestogen. They work by preventing egg follicles from maturing, thus preventing ovulation. They also have a secondary action of thickening the the cervical mucus, making it more difficult for sperm to move. It appears that this secondary action decreases the mucus’ ability to protect against viruses. How, exactly, is still a matter of research.
As for why this is being looked at, a line of HIV research began some years ago in Africa using a vaginal gel containing tenofovir. (This is the same research that led to the use of tenofovir pills as a pre-exposure prophylaxis.) The results were quite promising, but compliance was an issue, so researchers looked at using vaginal rings, similar to the ones used to provide hormonal birth control, to provide the antiretroviral. Those studies have also been promising. The next step is to combine hormonal contraception and antiretroviral drugs into a single device, which would cut costs and help women from having to decide between one or the other. The first part of that research is to evaluate various combinations of anti-HIV drugs and hormonal contraception to see if there are any contraindications.
Some minor points:
1. Hormonal contraceptives do provide some small STI protection — they thicken the cervical mucus, thus making it harder for bacterial infections to ascend into the uterus; it is true, though, that condoms provide much greater protection against most STIs and users certainly shouldn’t rely on hormonal contraception for STI protection.
2. Depo-Provera is no longer a popular choice of contraceptive. It’s highly effective at preventing pregnancies but it requires an intramuscular injection every 12 weeks, it is associated with weight gain (although there’s some controversy about the effect size) and osteoporosis (although we can’t say how much). Meanwhile, Implanon offers all the advantages of Depo-Provera without needing 12-weekly injections, and with more tolerable side-effects. So essentially this reviewer is complaining about a vast government conspiracy to suppress evidence against a contraceptive choice that almost nobody uses anymore. It makes about as much sense as a huge conspiracy to hide the dangers of listening to A Flock of Seagulls.
3. We need to be careful about invoking “no known mechanism” argument in medicine as it has a long history of being used to justify inaction against major public health threats. I’m not saying we shouldn’t take note that there is no known mechanism, but that this is only a minor counter-argument, not a powerful rebuttal.
None of this, of course, goes against the essential point of the OP. The Lancet screwed up its review process; its rogue reviewer *really* screwed up…and unethically to boot.
@Azkyroth
Melinda Gates has said that via work with her foundation she’s found demand for depo is particularly high with women in at risk populations because it’s easy to conceal its use from their husbands and doesn’t require weekly or monthly trips for refills. That would be in keeping with your alternative explanations.
And anyone is surprised when The Lancet fucks up peer review? It’s a medical journal, they always have shit peer review, and, of course, it’s the journal that published Wakefield’s shit.
Wouldn’t that mean that women’s susceptibility to diseases in general goes up and down during each menstrual cycle?
Shouldn’t rather the sheer stress of pregnancy, the diversion of resources to the fetus, be expected to depress the immune system?
I’m not surprised, but I didn’t know that…
Long ago, with different editors and most likely different reviewers, right? Also, this isn’t The Lancet, it’s The Lancet Infectious Diseases, while Wakefield got his fraud into The Lancet itself.
llyris,
Even though many parts of pregnancy are triggered by hormones, it does not mean hormones are necessarily the direct cause of a depressed immune system related to pregnancy. Here are a few things I came up with as a person who is not a doctor or biologist:
1. Some of the nutrients a pregnant person consumes are going to what is essentially a parasite rather than her own well being.
2. Just the damage that pregnant bodies experience as they rapidly expand and have a foreign body that sometimes interferes with other body systems. (Ever had a third trimester fetus block your urethra for several weeks? It does happen)
3. This is the most obvious for me, but people who are pregnant usually have a higher than normal stress load. Some of that could be related to hormones, but a lot of it is just a normal response to life changing events and long term pain and/or disability. Stress is already known to depress immune systems.
There is nothing wrong with testing hypotheses, as I stated in my previous comment. I have no problem with that. I think I did react too quickly to your use of the word “conclude,” and for that I apologize. But you also should understand that in the context of women’s health, “hormones did it” is a knee jerk response to nearly everything in a way that it isn’t for men’s health issues, and this causes many other factors to be overlooked (and it turns out to be overblown or just plain wrong in many instances, such as those who thought the type of person women are attracted to changes depending on what stage of her hormonal cycle she is in). I think you are overlooking other explanations, especially when you respond by suggesting all parts of pregnancy are hormonal.
tl;dr – Women are often seen as being so completely controlled physically and mentally by hormones that it impacts the research on women’s health issues, and I think that is a serious problem.
The immune system is actively suppressed in pregnancy to stop it attacking the foetus. The suppression is thought to be triggered by HCG (human chorionic gonadotropin), but I suspect more research is needed, and obviously ‘the immune system’ is a little more complex than that. You don’t want all your pregnant people dying from minor infections.
As a person who has been through 5 years of IVF I can confirm that hormones do a lot of weird stuff. (I’ve been hospitalised twice from the ‘side effects’, because they can kill you). I did quite a lot of reading on possible causes of infertility and pregnancy loss. I asked my specialists questions about what was happening and why they thought certain things would help.
@ Toska # 30 part 2
I agree that it is a serious problem, but the problem is that people make the rather bizarre assumption that men don’t have hormones. We ARE controlled by our hormones. The problem is the assumption that this is just some weird female thing and that it doesn’t effect men.
@ Toska # 30 part 1
No. That’s just insulting. You say that dismissing women’s health as ‘hormones’ is a problem but you don’t see a problem with dismissing it as ‘stress’. You may as well say it’s all in their heads and call it hysteria. You are dismissing the action of hormones and their very important functions in favour of ‘it’s in your head’, ‘pregnancy causes terrible physical trauma’, and ‘you aren’t eating properly’.
… and yet you think there is a problem with saying ‘maybe hormones are doing something’…. when talking about either pregnancy or HIV transmission…