How does Plan B really work? Don’t ask the Supreme Court, ask an OB/GYN

Never has a medication been more misunderstood than poor Plan B (levonorgestrel or LNG), a post coital contraceptive (a.k.a. morning-after pill).

It’s not just Justices Alito, Thomas, Roberts, Scalia, Kennedy and Dr. Hobby Lobby who fail to grasp the mechanism of action, but many other people are confused including journalists (the NY Times has an error in the mechanisms of action in a recent article) and even some doctors. The misinformation about LNG post coital contraception has essentially become urban medical myth, sometimes perpetuated with good intentions (reporters trying to strive for due diligence or health care professionals trying to teach students or explain to patients) and sometimes with bad intentions (Justice Alito et al and the American Association of Pro-Life OB/GYNs I’m looking at you).

Fortunately there are excellent studies that tell us exactly how Plan B works so let’s get to it:

Plan B is levonorgestrel, a progestin (a synthetic version of the hormone progesterone). The hormone progesterone is released by the sac that stays behind after ovulation (called the corpus luteum). The job of progesterone is to get the uterus primed to accept a fertilized egg and if implantation happens it maintains the pregnancy until the placenta can produce its own progesterone. This hormone is pro-gestational, hence the choice of the name pro-gesterone. This is a bit of a spoiler alert because a synthetic version of a pro-gestational hormone is unlikely to do the exact opposite.

How does plan B work? It has one and only one mechanism of action, it inhibits ovulation.

A variety of hormonal changes happen as the ovary readies an egg (a.k.a follicle) for ovulation. Ovulation, the actual release of the egg, is triggered by a massive surge of a hormone called luteinizing hormone (LH). After ovulation the egg has a 24 hour window to be fertilized (it has a pretty short shelf life). Plan B when given 2 to 3 days BEFORE the LH surge can inhibit,delay, or blunt the LH surge and prevent ovulation. Outside of that 48 hours window Plan B is very ineffective.

The dose of levonorgestrel in Plan B is not enough to affect cervical mucous and since it is given AFTER sex that’s a moot point. By the time you have taken Plan B the sperm has already passed the cervix and within minutes it’s in the fallopian tube. Waiting.

The single dose of levonorgestrel in Plan B is not enough to damage sperm. this has also been well-studied.  (FYI sperm can live for 5-6 days in the upper reproductive tract), so we can cross damaging sperm off the how-does-Plan-B-work list.

The single dose of levonorgestrel in Plan B is also not enough to do  anything to uterine lining and animal studies tell us that embryos exposed to the Plan B dose of LNG develop just fine and there is no impact on implantation. So even if you use the Justice Alito/Dr. Hobby Lobby version of abortion (i.e. affecting a fertilized egg) there is no possible impact. At all. This is what we call scientific fact, it is not open to interpretation. 

Hold on you say. It only works before ovulation? Why would I take it then if I weren’t about to ovulate? Well…

• Ovulation can be unpredictable. many women have irregular cycles and even those with cycles like clock work can pop an egg out early every now and then
• Sperm lives for 5-6 days, so even of you have sex on day 7 or 8 of your cycle (i.e. days when you are not normally fertile) the sperm might actually be there when you are fertile 4-6 days later.
• Plan B has no contraindications and very few, if any, side effects

Basically the permutations and combinations of when you are actually fertile are almost impossible to work out (especially at 2 a.m. when the condom broke), so it is really just better to use it if you have unprotected intercourse regardless of the day of the month. That is how it was studied. However, ella (ulipristal) is more effective as a post coital contraceptive and a Copper IUD is the most effective, although both require a prescription and are significantly more expensive than generic Plan B. If you absolutely do not want to get pregnant ella or a post-coital copper IUD are better choices, but just less practical.

Just as we know that condoms work by mechanically preventing sperm from getting into the uterus, we know that Plan B works by inhibiting ovulation. To say otherwise isn’t a belief, it’s a lie.

Note: someone asked why does Plan B labeling indicate that it might affect implantation when I say that it does not? I felt my reply important enough to add that to the body of the post in case someone else has the same question.

Package inserts are notorious for being a “cover you legal ass and assets” rather than a reflection of state of the art science. This is because they are legal documents not medical ones, the FDA has very specific requirements as to what can and can not be put into a package insert based in the studies presented to the FDA at the time of application, and they are often outdated due to the science that has been produced since the original application.

The Plan B package insert was approved in 2006 and since that time there have been at least three studies evaluating endometrial receptivity that disprove an implantation disruption hypothesis (Palomino in 2010 Fertility Sterility, Meng 2010 Human Reproduction and Vargas 2012 Journal of Molecular Endocrinology). There was a 2001 study that indicated no impact on endometrial receptivity (Durand Contraception), however whether that one study was considered sufficient at the time of FDA submission or was even submitted I don’t know.

Our understanding of how mechanisms of action of medications evolves as new technology develops. in addition, once products become available many researchers become interested in further study. The company who makes the product is typically not invested in this specific kind of post market research as it brings them nothing financially. To get a package insert changed on new data requires a significant amount of paper work with the FDA and is very expensive. Once a product is generic (such as Plan B) there is zero motivation to make the correction.

Relying on a package insert which contains by nature a myriad of biases from 2006 and thus based on data from pre-2005 to be scientifically accurate in 2014 (especially given the robust studies published in peer reviewed journals since) is ludicrous.

In addition, the 2008 FIGO statement on LNG post coital contraception says a “review of the evidence suggests that LNG ECPs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling.”