The department of Health and Human Services (HHS) clarified the contraception coverage in the Affordable Care Act last week. Initially, HHS relied on “good faith” that insurance companies would cover contraception at no cost to the patient. This new clarification specifies that one medication from each of 18 specific categories of contraception must be covered at no cost. The 18 categories are predictable including combination hormonal contraceptives, progestin only pills, IUDs, and more. The final category, however, seems out of place and warrants a second look. This category contains only one drug — Ella.
Ella is a fairly new medication being marketed as an emergency contraceptive. They call it the “week after pill.” Why then is Ella in its own category, separated from other emergency contraceptives? And why of the 18 categories, is Ella the only one identified by the name of the medication, rather than a type?
The simple answer is that Ella’s mechanisms of action are different than other emergency contraceptives (ECs) like Plan B and One-Step. Other ECs contain synthetic progestins like levonorgestrel. Only differing with progestin only pills in dosage, these ECs behave in a similar way to regular hormonal contraception. By inundating the body with large amounts of extra hormones all at once ECs can delay ovulation, block sperm and thin the lining of the endometrium making it inhospitable to implantation. 1
Ella, on the other hand, contains 30mg of ulipristal acetate, and is categorized as an Selective Progesterone Receptor Modulator (SPRM). The FDA has only approved two SPRMs to date: Mifepristone (RU-486) and Ella 2
(although SPRMs are being investigated for other uses regarding reproductive health).
The drugs are certainly not identical, but their placement in the same category should make us curious, and spur further examination. Mifepristone is an antagonist SPRM and it is used to terminate a pregnancy before 20 weeks gestation by blocking the body’s ability to appropriate 3 the progesterone needed to continue a pregnancy. 4 Ella is said to be incapable of this, but it is classified as both an agonist and antagonist SPRM. The main mechanism of action of Ella is (due to its agonist properties) to delay ovulation, and if ovulation were to occur, it attempts to create a luteinized unruptured follicle (LUF: i.e. keep the egg in it’s casing, which makes it impossible for fertilization to take place). Ella also decreases the thickness of the endometrium making it difficult for a fertilized egg to implant. 5 These traits make Ella very similar to other ECs. But Ella, like Mifepristone, is also an antagonist SPRM and is similarly able to bind to the progestin receptors, although its effects are not as potent.
In an article published in McGraw Hill’s Access Medicine, Dr. Stephen R. Hammes writes, “As may be expected, ulipristal has also provoked an adverse reaction in the United States by opponents of the termination of pregnancy.” Hammes goes on to explain the mechanisms of action for the drug saying, “Ulipristal is known to have anti-proliferative effects in the uterus at high doses; however, its most relevant actions to date are its ability to inhibit ovulation.” (While inhibiting ovulation may be the most relevant mechanism, it does not negate the drug’s other mechanisms). He concludes his article with this warning, “The drug should not be taken by women who are breastfeeding or who are pregnant and wish to remain so” (emphasis added).6
Ella’s ability to terminate an existing pregnancy is seen in animal trials of its only ingredient, Ulipristal Acetate. The European Medical Association says, “Ulipristal, mifepristone and lilopristone were approximately equipotent at the dose levels of 10 and 30 mg/day in terminating pregnancies in guinea-pigs when the animals were treated on days 43 and 44 of gestation.” In monkey trials half of the fetuses died when given Ulipristal Acetate in the first month of pregnancy.7
Admittedly, these animals were given a higher dosage of Ulipristal Acetate than Ella gives a human in one dose, but the drugs ability to bind progesterone receptors in an antagonist way, regardless of dosage, is significant. Anyone who has suffered miscarriage can tell you the importance of progesterone in the early stages of pregnancy.8 Low progesterone is cited as a major influence in the continuation of a pregnancy. 9 While progesterone is not completely blocked by Ella, it certainly is inhibited. Any inhibition of progesterone is likely to affect an “established pregnancy” and at higher doses, Ella is just as effective as Mifepristone.
Ella creates its own category in the HHS contraception coverage because its action as an “emergency contraceptive” is significantly different than other ECs. And now, it is available at no cost to the American public. Moreover, being the only drug in the category ensures government enforced subsidization of Ella’s manufacturer Afaxys.
This information should be no more infuriating than the fact that all 18 categories of pharmaceutical contraceptives act in a way that can cause a fertilized egg to be expelled from the body. More on this topic here and here.
- “Emergency Contraception (Morning After Pill).” Emergency Contraception (Morning After Pill). Accessed May 21, 2015. https://web.archive.org/web/20100809110008/http://www.plannedparenthood.org/health-topics/emergency-contraception-morning-after-pill-4363.htm#. ↩
- Bastianelli, Carlo, and Manuela Ferris. “Emergency Contraception.” Expert Rev of Obstet Gynecol 6, no. 5 (2011): 569-76. ↩
- Olive, DL. “Role of Progesterone Antagonists and New Selective Progesterone Receptor Modulators in Reproductive Health.” Obstet Gynecol Surv. 57, no. 11 (2002): S55-63. ↩
- “Prescribing Information.” : Mifeprex (mifepristone) Medical Abortion Pill (ru486). Accessed May 21, 2015. ↩
- “Ella Full Prescribing Information.” Accessed May 21, 2015. http://www.ellanow.com/pdf/ella-full-prescribing-information.pdf. ↩
- Hammas, Stephen R., and Laurence L. Brunton. “Ella: A Newly-Approved Selective Progesterone Receptor Modulator.” Access Medicine from McGraw Hill. Accessed May 21, 2015. http://www.medscape.com/viewarticle/735277. ↩
- “CHMP Assessment Report for Ellaone.” European Medicines Agency Evaluation of Medicines for Human Use, 2009. Accessed May 20, 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001027/WC500023673.pdf ↩
- DAYA, S. (1989), Efficacy of progesterone support for pregnancy in women with recurrent miscarriage. A meta-analysis of controlled trials. BJOG: An International Journal of Obstetrics & Gynaecology, 96: 275–280. doi: 10.1111/j.1471-0528.1989.tb02386.x ↩
- “Causes.” Pregnancy Loss. Accessed May 21, 2015. http://www.pregnancyloss.info/causes.htm. ↩