Mechanism of action of levonorgestrel emergency contraception

Abstract

There has been much debate regarding levonorgestrel emergency contraception's (LNG-EC's) method of action since 1999 when the Food and Drug Administration first approved its use. Proponents of LNG-EC have argued that they have moral certitude that LNG-EC works via a non-abortifacient mechanism of action, and claim that all the major scientific and medical data consistently support this hypothesis. However, newer medical data serve to undermine the consistency of the non-abortifacient hypothesis and instead support the hypothesis that preovulatory administration of LNG-EC has significant potential to work via abortion. The implications of the newer data have important ramifications for medical personnel, patients, and both Catholic and non-Catholic emergency room protocols. In the future, technology such as the use of early pregnancy factor may have the potential to quantify how frequently preovulatory LNG-EC works via abortion.

Lay Summary: How Plan B (levonorgestrel emergency contraception) works has been vigorously debated ever since the Food and Drug Administration approved it in 1999. Many doctors and researchers claim that it has either no—or at most—an extremely small chance of working via abortion. However, the latest scientific and medical evidence now demonstrates that levonorgestrel emergency contraception theoretically works via abortion quite often. The implications of the newer data have important ramifications for medical personnel, patients, and both Catholic and non-Catholic emergency room rape protocols.

Keywords:

• Levonorgestrel emergency contraception
• Abortion
• Moral certitude
• Early pregnancy factor

Notes

1 Tirelli, Cagnacci, and Volpe (2008) did use ultrasound and hormonal evaluation in a small subset analysis in eight women.

2 ACOG was formerly the American College of Obstetricians and Gynecologists. This is still their official position today. http://www.acog.org/About_ACOG/News_Room/News_Releases/2012/April_20_Letter_to_the_Editor.

3 http://www.acog.org/About_ACOG/ACOG_Departments/Health_Care_for_Underserved_Women/Frequently_Asked_Questions_about_Hormonal_Approaches_to_Emergency_Contraception.

4 The most common protocol, called the ovulation approach, based on the Peoria Protocol is described in detail by Hamel and Panicola (2012). This protocol allows dispensing emergency contraception if a woman's progesterone level is under 1.5 ng/ml and her urine LH (Luteinizing Hormone) test is negative, that is, if she is determined to be in the preovulatory period. This method is based upon the assumption that emergency contraception efficiently inhibits ovulation when given in the preovulatory phase and therefore theoretically should not work via abortion.

5 Follicular rupture is the abrupt disappearance or a reduction in size of at least 50 percent of the echo-image of a leading follicle that had at least attained 15 mm in diameter (Massai et al. 2007).

6 Email correspondence with Dr. Gabriela Noé, January 19, 2013.

7 To the best of this author's knowledge, no one has adequately studied the effect of LNG-EC when given 0–12 hours after sexual relations. Kesserü et al. used older technology and employed a dose of LNG that was 27 percent of today's LNG-EC dose. Extrapolating retrospectively via do Nascimento et al.'s study might lead one to hypothesize that LNG-EC would have little effect upon sperm migration if given within 12 hours of sexual relations.

8 The following contraceptives contain a total of 1.925 mg of levonorgestrel in each month's supply: Tri-levlen 21, Tri-levlen 28 and Trivora.

9 Email correspondence with Dr. Espinós: January 18, 2013.

10 Email correspondence with Dr. Gabriele Noé: April 25, 2013.

11 One could argue that LNG-EC has an independent direct effect upon sperm or ova which might be expected to be present in both the pre- and postovulatory phases and would theoretically inhibit fertilization in both phases. Since this clearly does not occur, this hypothesis does not appear to be valid.

12 EPF might also be used to test whether oral contraceptives work at times by causing the destruction of the embryo, as is implied by several papers (Larimore and Stanford 2000; Pierson et al. 2003).

13 The rate of pregnancy loss in women who have newly conceived has been debated at length with markedly different estimates. In their overview, Mesrogli, Maas, and Schneider (1988) quoted four studies. One of them (Hertig, Rock, and Adams 1956) simply measured congenital abnormalities in fertilized ovum taken from women's uteri during hysterectomy; the second study (Roberts and Lowe 1975), based the estimate on multiple assumptions and admitted that this amounted to “speculative arithmetic.” The only two studies that had concrete ways of measuring early pregnancy loss were those of Miller et al. (1980) and Rolfe (1982). If we sum their findings, we note that from 170 conceptions they found 81 losses, for a total pregnancy loss rate of 48 percent.

14 Note: Men were used as controls because they cannot become pregnant.

Additional information

Notes on contributors

Chris Kahlenborn

Chris Kahlenborn, M.D. Dr. Kahlenborn is president of The Polycarp Research Institute and a board certified internist. His email address is [email protected].

Rebecca Peck

Rebecca Peck, M.D., C.C.D., Clinical Assistant Professor, Florida State University College of Medicine. Her email address is [email protected].

Walter B. Severs

Walter B. Severs, Ph.D., F.C.P. Professor Emeritus of Pharmacology & Neuroscience; College of Medicine Penn State University, Hershey, PA. His email address is [email protected].