Fact Sheet: Opill, the First Over-the-Counter Hormonal Contraception

Opill, the first nonprescription oral contraceptive pill (OCP) to be granted FDA approval,[1] is a synthetic progesterone (norgestrel) 0.075 mg tablet taken daily (with no placebo week). The following are important facts for women and physicians to know as Opill hits the market for the first time in 2024.

GENERAL CONSIDERATIONS

• Opill, which is a progesterone-only pill (POP), was approved for nonprescription use, rather than the more common combination estrogen/progesterone pills, because it is generally safer to use POPs than combination pills.[2] There are some women who should not take estrogen due to medical concerns, such as clotting disorders, hypertension, diabetes, or obesity.

• Many gynecologists believe POPs are less effective than combination pills based on anecdotal experience and due to the need to take POPs with strict adherence to dosing intervals (taking the pill at the same time each day).^[3] However, it has been difficult to prove lower effectiveness because most studies combine the two formulations without differentiation. The FDA’s approval document is a case in point, referencing a 7% failure rate with real-world use but failing to cite any study performed only on Opill to justify this number.^[4] The research they did cite also contained combination pills.^[5] Thus, it is likely the failure rate of Opill is even higher than 7%, though this may be obscured by data that lump POPs and combination pills together.

• There are many medications that will either reduce the effectiveness of, or generate adverse effects if used in combination with, Opill.[6] Medscape, a medical information website geared towards physicians and medical scientists, lists 10 medications that are of definite concern for Opill’s effectiveness and 98 that merit close observation regarding effectiveness and potential adverse effects.^[7] These include several medications commonly used by women, such as the antibiotics doxycycline, erythromycin, metronidazole, and tetracycline; the yeast infection treatment fluconazole; the anti-depressant sertraline; and the blood pressure treatment verapamil. St. John’s Wort, an herbal supplement and grapefruit, may also diminish efficacy.

• Opill itself may cause adverse effects, including irregular bleeding, headaches, dizziness, nausea, increased appetite, abdominal pain, and cramps or bloating that may lead a woman to discontinue the medication.[8] Unwanted bleeding and weight gain are particularly likely to cause a woman to stop taking these pills, increasing the risk of unintended pregnancy.

• Opill does not inhibit ovulation (release of an egg) as well as the other hormonal contraceptive methods (about four in ten progesterone only pill users will continue to ovulate).[9] It also thickens cervical mucous, which prevents fertilization, but if these primary mechanisms fail and an embryo is created, it may also cause an abortion-inducing effect due to failure of implantation into the progesterone-thinned uterine lining.[10]

• Progesterone-only methods of oral contraception are also documented to slow transit of an embryo through the fallopian tubes, potentially increasing the risk of an ectopic pregnancy, which can result in tubal rupture, catastrophic bleeding, and even maternal death.

RISKS OF DISTRIBUTING OPILL WITHOUT A PHYSICIAN’S VISIT

• Risk avoidance, i.e. abstinence, is the only 100% effective method of preventing pregnancy. Risk reduction occurs when contraception is used, reducing but not entirely avoiding the risk of pregnancy, because every contraceptive method has been associated with some failures. Risk compensation, on the other hand, occurs when a person engages in more risky behavior when they feel more secure or protected. In the present context, risk compensation may occur if a woman has a false sense of security when using a poorly effective contraceptive method. In other words, some women may pursue riskier sexual activity because of the false security, and easy obtainability, of Opill.

• Opill will likely disincentivize some women from obtaining more effective contraception. Long-Acting Reversible Contraceptive methods (LARCs), such as copper or levonorgestrel intrauterine devices, or Nexplanon inserts, have very low failure rates: 0.5-3 per 1000 women.[11] They require, however, insertion by a health care provider. Similarly, Depo-Provera injections, combination estrogen/progesterone oral contraceptive pills, patches, and vaginal rings may have lower failure rates and higher compliance than Opill but require a prescription from a healthcare provider.[12]

• Opill removes an opportunity for preventative healthcare because an office visit is not required. Preventative assessments that might be relevant to a woman’s oral contraceptive use, as well as her overall health, such as blood pressure measurement, healthy weight counseling, cancer screenings, depression screening, and domestic abuse screening and referral, may either be missed or become less frequent due to Opill’s over-the-counter availability.

• Opill also removes the opportunity for counseling on healthy sexual behavior and relationships, as well as screening for sexually transmitted infections, which may lead to emotional trauma, chronic pain, serious infections, or infertility, if undiagnosed and untreated. It also may remove the opportunity for identification and intervention of women who are the victims of sex-trafficking.[13]

[1] “FDA Approves First Nonprescription Daily Oral Contraceptive,” U.S. Food and Drug Administration, July 13, 2023, www.fda.gov/news-events/press-announcements/fda-approves-first-nonprescription-daily-oral-contraceptive.

[2] “Progestin-Only Contraceptives,” American Academy of Family Physicians, October 15, 2000, https://www.aafp.org/pubs/afp/issues/2000/1015/p1849.html;  Danielle B. Cooper, Preeti Patel, and Heba Mahdy, “Oral Contraceptive Pills,” StatPearls, (November 24, 2022), https://www.ncbi.nlm.nih.gov/books/NBK430882/.

[3] James Trussell, “Understanding Contraceptive Failure,” Best Pract Res Clin Obstet Gynaecol 23, no. 2 (April 29, 2013): 199-209, https://doi.org/10.1016%2Fj.bpobgyn.2008.11.008.

[4] “Opill (NORGESTREL 0.075 MG tablets) For Rx-To-Otc Switch Sponsor Briefing Document,” U.S. Food and Drug Administration, May 9-10 2023, https://www.fda.gov/media/167893/download.

[5] James Trussell, “Contraceptive Failure in the United States,” Contraception 83, no. 5 (May 1, 2011): 397–404, https://doi.org/10.1016/j.contraception.2011.01.021.

[6] Paul D. Blumenthal and Alison Edelman, “Hormonal Contraception,” Obstet Gynecol 112, no. 3 (September 2008): 681, doi: 10.1097/AOG.0b013e31818425b7.

[7] “Opill (Norgestrel) Dosing, Indications, Interactions, Adverse Effects, and More,” accessed September 21, 2023, https://reference.medscape.com/drug/opill-norgestrel-342790?ecd=ppc_google_rlsa-traf_mscp_ref_md_us&gclid=Cj0KCQjwwvilBhCFARIsADvYi7Lq6hZsUibsbqF5aBpd_9XyDlLMWCuv4blFoLioZyIFX__E5sVpxVQaAhXMEALw_wcB.

[8] Ibid.

[9] “Progestin-Only Hormonal Birth Control: Pill and Injection,” Frequently Asked Questions, ACOG, last updated January 2023, https://www.acog.org/womens-health/faqs/progestin-only-hormonal-birth-control-pill-and-injection.

[10] W.L. Larimore and J.B. Stanford, “Postfertilization effects of oral contraceptives and their relationship to informed consent,” Arch Fam Med. 9, no. 2 (February 2000): 126-33, https://pubmed.ncbi.nlm.nih.gov/10693729/.

[11] Brooke Winner et al., “Effectiveness of Long-Acting Reversible Contraception,” N Engl J Med 366 (May 24, 2012): 1998-2007, DOI: 10.1056/NEJMoa1110855;  “Long-Acting Reversible Contraception: Implants and Intrauterine Devices,” Practice Bulletin Number 186, ACOG, accessed October 11, 2023, https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2017/11/long-acting-reversible-contraception-implants-and-intrauterine-devices.

[12] Ibid.

[13] Tiffany Dovydaitis, “Human Trafficking: The Role of the Health Care Provider,” J Midwifery Womens Health 55, no. 5 (Sept-Oct 2010): 462-67, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125713/.