Should you double dose Plan B if you weigh more than 70 kg?

New study shines some, but not enough, light

There has been concern that Plan B (one type of morning after pill) is less effective for those with an increased weight/body mass index (BMI). When I last wrote about Plan B and weight/BMI (read that post here), a study was underway looking at the effect of a double dose of Plan B on ovulation for women with a higher weight/BMI. Meaning might a higher dose be more effective? That study is now published, so let’s take a look. 

To catch you up…

Plan B is a single 1.5 mg dose of the hormone levonorgestrel. When taken within five days of a single act of unprotected intercourse it reduces the risk of pregnancy by 61-95%. Most studies suggest it is most effective within 72 hours, and the sooner it is taken the better (which accounts for the range in effectiveness). 

Some studies have shown a reduced effectiveness with Plan B based on weight/BMI, but these studies either had small numbers of people, or weren’t designed to specifically address the impact of weight/BMI. Meaning, drawing firm conclusions wasn’t possible. The consensus was Plan B was likely less effective, but by how much was uncertain. This is obviously unacceptable.

Some research shows the blood levels of the hormone levonorgestrel are about 50% lower for those with an elevated BMI, yet other data suggests that while they are lower, they are still high enough to prevent ovulation. Because levonorgestrel is very safe, many experts recommended a double dose (3 mg) for people with a higher weight/BMI, but this was with no real data showing whether this approach impacted ovulation or pregnancy rates.

The New Study

Researchers didn’t test Plan B in the field, meaning they didn’t give it to people and then follow them to see who got pregnant. What this study did was looking at the impact of Plan B on ovulation for people with an elevated BMI. Plan B works by stopping the surge of a hormone called luteinizing hormone (LH), which triggers ovulation. This makes ovulation a good proxy, because no ovulation, no risk of pregnancy. 

This new study is a randomized controlled trial of people aged 18–35 years with BMIs greater than 30, and who weighed 176 lbs or more (average BMI in the study 38). The participants had regular cycles every 21-35 days and were evaluated to ensure they were ovulating before entry into the study. This is key, because cycles without ovulation are more common with a BMI over 30. To be of value, this study has to evaluate people who are known to ovulate so they can assess the impact of Plan B on ovulation. If you enroll a significant percentage of people who aren’t ovulating, then the medication may look like it is more effective than it truly is.

On days 6-8 of the menstrual cycle, researchers started monitoring the study participants to see how their follicles (the structures in the ovaries that contain the eggs) were developing. They did this using blood work for hormones and transvaginal ultrasound, which monitors the size of the follicles. When blood work and the ultrasound indicated ovulation was getting close (for ultrasound this meant the dominant follicle was 15 mm), participants received either a standard dose of Plan B, 1.5 mg of levonorgestrel, or a double dose, 3 mg of levonorgestrel. Participants were then followed for 5 days to see if ovulation occurred. 

A total of 70 women were enrolled, 35 in each arm. Among those who received the standard dose, 51% failed to ovulate within 5 days and with the double dose the result was 68%. This difference isn’t statistically significant, meaning 3 mg of levonorgestrel was not more effective at suppressing ovulation than 1.5 mg. Basically, about 50% of people ovulated in each group. 

This study didn’t include patients with a lower BMI. As we don’t have a comparison group with a lower BMI, we can’t say that Plan B is less effective based on BMI. Interestingly, ovulation rates in this study are not out of line with ovulation rates overall for Plan B with a BMI between 19 and 24. This is something the authors mention, but don’t expand upon. This is all they say about it:

However, a prior study has shown ovulation rates similar to those seen in our study with standard emergency contraception dosing in individuals with normal BMIs.

If the ovulation rates are the same in this study with participants with an average BMI of 38 versus those with a BMI of 19-24, then how is Plan B less effective with a higher BMI? I admit I was frustrated that no hypothesis was offered. 

Other researchers have included dysfunctional ovulation in their evaluation of the effectiveness of Plan B, based on the theory that if ovulation happens with Plan B, but it is abnormal, then conception is less likely. But that wasn’t evaluated here as it’s controversial whether ovulatory dysfunction contributes to the contraception effect or not.

It is possible that there is less of an impact on ovulatory function based on weight/BMI, meaning when ovulation occurs with Plan B with a higher weight/BMI it is more likely to be normal, and hence pregnancy is possible, and for those with a lower weight/BMI more likely to be abnormal. However, this is purely a hypothesis on my part and I could be way off base. 

What Does This Mean?

A higher dose of levonorgestrel doesn’t reduce the likelihood of ovulation, so that definitely questions the value of a double dose, but it doesn’t tell us if Plan B is less effective for those with a higher weight or BMI and if so, by how much.  

To answer that question, what we really need is a study comparing the two doses of levonorgestrel and the subsequent risk of pregnancy, and fortunately that is happening. There is a phase 2b single-blind, randomized study to compare the effectiveness of Ella (ulipristal 30 mg) vs. levonorgestrel 1.5 mg vs. levonorgestrel 3.0 mg as postcoital contraception for women with a weight ≥ 80 kg. This is the data we need. The study is listed here and appears to have completed enrollment, so hopefully we will actually have the information that we need very soon. 

In many ways we are still in limbo, meaning studies suggest that Plan B is less effective for people with a higher weight/BMI, but by how much isn't known? What we do know right now is that Ella and a post-coital IUD are the preferred methods of choice for people who weigh more than 70 kg and that a higher dose of levonorgestrel doesn’t decrease ovulation further.

And hopefully we’ll have more data soon.

References

1. Edelman AB, Hennebold JD, Bond K, et. al. Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity. A Randomized Controlled Trial. Obstet Gynecol Obstet Gynecol 2022;00:1–7.

1. Croxatto HB, Brache V, Pavez M., et al. Pituitary ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation. Contraception 2004;70: 442-450.

1. Natavio M, Nelson A, Segall-gutierrez et al. Ovulation rates after oral administration of the 1.5-mg levonorgestrel emergency contraception regimen among normal-weight and obese women. Contraception 2018;98:359-360. Abstract only.

1. WHO Fact Sheet, Emergency Contraception https://www.who.int/news-room/fact-sheets/detail/emergency-contraception

1. Glasier A, Cameron ST, Blithe D, Scherrer B, Mathe H, Levy D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011 Oct;84(4):363-7.

1. Festin MP, Peregoudov A, Seuc A, Kiarie J, Temmerman M. Effect of BMI and body weight on pregnancy rates with LNG as emergency contraception: analysis of four WHO HRP studies.Contraception. 2017 Jan;95(1):50-54.

1. FSRH Clinical Guideline: Overweight, Obesity and Contraception (April 2019)

1. Emergency contraception, UpToDate. Author: David Turok, MD

1. International Consortium for Emergency Contraception. Clinical Summary: Emergency Contraceptive Pills. December 2018.