On July 13, 2023, a full year after the the French pharmaceutical company HRA submitted an application to the U.S. Food and Drug Administration (FDA) for its hormonal birth control pill to be approved for over-the-counter sale, the FDA announced that Opill will now be available OTC for all women of reproductive age in the United States. The Opill, which has since been acquired by Dublin-based pharmaceutical company Perrigo, is a progestin-only hormonal contraceptive. As with any other drug seeking OTC approval, the FDA was tasked with determining that Opill is “safe and effective for use by a consumer without supervision by a licensed healthcare professional.” Notably, the American College of Obstetricians and Gynecologists (ACOG) has been openly pushing for over-the-counter birth control since 2019, and therefore praised the FDA’s recent decision on Opill.
While the recent Supreme Court decision overturning Roe v. Wade has intensified public scrutiny on the availability of contraceptives and abortion pills to prevent or end unwanted pregnancies, efforts to make these drugs more easily accessible have been ongoing for years. HRA conducted studies for seven years prior to its application to the FDA to make Opill available without a prescription (though it bears mentioning that the company’s largest study followed users for just six months, and the research was partly funded by an advocacy group who pushes for over-the-counter birth control). The chief strategist for the company argued, “For a product that has been available for the last 50 years, that has been used safely by millions of women, we thought it was time to make it more available.”
Unfortunately, the reality is that birth control comes with a myriad of side effects ranging from uncomfortable to life-threatening, and Opill is no exception. Here I’ll outline how the drug works, what the dangers are, and why making it available over-the-counter poses a threat to women’s health.
Progesterone vs progestin
Progesterone is a natural hormone produced by the corpus luteum (the temporary endocrine gland that forms from the empty ovarian follicle after it releases an egg during ovulation) [1]. Progesterone levels rise after ovulation during the luteal phase of the menstrual cycle, because progesterone promotes the growth of the uterine wall lining (endometrium), and a thickened endometrium is essential for supporting a pregnancy. If an egg is not fertilized, then progesterone levels begin to fall and the endometrium breaks down and is shed during menstruation.
If an egg is fertilized and implants within the endometrium, then progesterone continues to be produced to maintain the endometrium. High progesterone levels prevent other eggs from maturing, support fetal development, and prepare the body for labor and breastfeeding.
In contrast, progestin is a synthetically-produced steroid that mimics natural progesterone. There are many forms of synthetic progestins (collectively referred to as progestogens) available, and they are often grouped by “generation” (time since being introduced to the market) and by whether they are a derivative of testosterone or progesterone.
So, what is Opill?
Opill’s active ingredient is the synthetic progestin norgestrel. Notably, norgestrel is nearly identical to the chemical makeup of levonorgestrel, the synthetic active ingredient in “Plan B” emergency contraception. But levonorgestrel is far more potent.
Oral hormonal contraceptives like Opill, with progestin as the only active ingredient, are often referred to as “the mini-pill.” This distinguishes it from “the Pill,” the most common form of hormonal birth control, which is a combination of progestin and synthetic estrogen.
Opill, aka, “the mini-pill,” works somewhat differently than the Pill
The primary mechanism of action for combined estrogen-progestin contraceptive pills (“the Pill”) is suppression of ovulation by preventing the cyclical luteinizing hormone (LH) surge that normally triggers the release of an egg during ovulation. No egg means no possibility of conception from sex [2]
The mini-pill’s primary mechanism of action is “thickening the cervical mucus to inhibit sperm penetration, lowering the midcycle LH and FSH peaks, slowing the movement of the ovum through the fallopian tubes, and altering the endometrium,” according to the product label. If an egg is fertilized, either type of pill will act to prevent the newly conceived life from implanting within the endometrium, because each type of pill also functions to thin the lining of the uterus—a mechanism of action that some consider to be abortifacient.
Due to the mini-pill’s lower doses of progestin, one would expect breakthrough ovulation to occur more often with the mini-pill (vs. the Pill), increasing the possibility that it will function to prevent pregnancy through the endometrial thinning mechanism. The American College of Obstetricians and Gynecologists reports, “Progestin stops ovulation, but it does not do so consistently. About 4 in 10 women who use progestin-only pills will continue to ovulate.”
Is progestin-only contraception safer than the Pill?
Opill likely received a somewhat speedier FDA approval because progestin-only pills are commonly viewed as a safer alternative to the Pill (which, after all, is a known carcinogen). This is because the synthetic estrogen in the Pill is the main culprit for its most serious and potentially deadly adverse effects, like blood clots, heart attacks, and stroke.
What many people don’t know, however, is that the mini-pill still comes with a host of ugly side effects, including increased risk of breast cancer, cervical cancer, and brain cancer—with one study showing that the risk of glioma nearly triples for women taking progestin-only birth control [3][4][5]. And while the Pill is associated with a decreased risk of ovarian cancer, progestin-only contraception does not protect against ovarian cancer. [6]
Progestin is also known to decrease bone density, putting women at a higher risk for osteoporosis and bone fractures. Along with all forms of hormonal birth control, progestin increases the risk of depression [7]. The FDA additionally lists high blood pressure as a side effect. This 2022 study found an increased risk of ulcerative colitis in current users of progestin-only pills [8]. As discussed above, the mini-pill also alters the endometrium and may lead, over time, to uterine lining atrophy, which can make it harder to conceive in the future [9].
A laundry list of less severe side effects also accompanies use of the mini-pill. More than 5% of women in the clinical trials for Opill reported the following adverse reactions: headache, dizziness, nausea, increased appetite, abdominal pain, cramps and bloating, fatigue, vaginal discharge, dysmenorrhea (painful menstruation), nervousness, backache, breast discomfort, and acne.
Many women on the mini-pill may also experience irregular bleeding. Because the mini-pill does not consistently suppress ovulation, this is not necessarily a surprising effect. Nevertheless, one can easily imagine a scenario where a woman or girl with an irregular period is told that birth control can make her cycles more predictable and “regular.” If this prompts her to buy and take an over-the-counter contraceptive, she may unknowingly cause even worse bleeding patterns.
Opill: Concerns about over-the-counter availability
Several of Opill’s side effects, as found on the label, raise serious concerns about its over-the-counter availability. The label lists warnings about increased risk of ectopic pregnancies for women who do become pregnant while using it, abnormal follicular growth causing ovarian cysts potentially requiring surgery, and acute disturbances of liver function.
Tellingly, page 10 of the label reads, “These are not all the possible side effects of Opill. Call your doctor for medical advice about side effects.” Making a medication available over-the-counter when the label currently recommends conversations with a medical provider before beginning use is counterintuitive.
The negative effects of deregulating access to birth control
At present, more than a dozen states already allow birth control prescriptions sans a patient-doctor relationship or prescription, requiring only approval from a pharmacist after a woman fills out a questionnaire. Undoubtedly, now that access to Opill is deregulated, many women will not hesitate to take it, believing that it must be safer because it’s over-the-counter. But the widely-held illusion that there are no serious risks or side effects involved is just that—an illusion. This false understanding can only be exacerbated by women being able to acquire hormonal contraceptives without even the most cursory of conversations with a healthcare provider.
Women deserve more education about hormonal contraception than they’re currently receiving from their healthcare providers, not less, as may now occur since Opill is easily accessible over-the-counter. Currently, doctors are not only eager to prescribe hormonal birth control, but many also downplay the risks and dismiss hesitations around the pill. (I experienced this myself when I went to an OB/GYN for the first time as a teenager due to several missed periods. The doctor’s only recommendation was hormonal birth control, which she told me had some risk of side effects “like blood clots, but it’s a very, very low risk, so it’s nothing you need to worry about.”) Deregulating birth control means women will be even less informed than they already are about the possible side effects, even the serious or fatal ones, like mental health issues and breast cancer.
In addition to the risks and side effects women will experience from OTC birth control use, there are a few indirect, negative implications of making birth control accessible without a physician encounter. In a round table discussion about the adverse outcomes of contraception use, OB/GYN Dr. Kathleen Raviele remarked, “It takes the woman away from an encounter with a physician, a nurse practitioner or a PA, and she’s going to be at high risk for having other problems that won’t be picked up.” As one example, office visits for contraceptives are often when women are diagnosed with sexually transmitted infections (STI)s.
While advocates may praise the FDA for approving an over-the-counter birth control pill in the name of women’s reproductive freedom, setting up women to suffer in silence because they’re taking a risky drug without medical guidance is certainly no way to help them.
This article was originally published on September 9, 2022. It was updated on April 4th, 2023 to include rates of breakthrough ovulation in women taking progestin-only contraception. On June 28th, 2023, it was updated to reflect progestin-only contraception’s lack of protection against ovarian cancer. On July 14th, 2023, it was updated to reflect the FDA’s official approval of Opill’s over-the-counter availability. On October 4th, 2023, it was updated to reflect research on the connection between ulcerative colitis and progestin-only pills.
References:
[1] Devoto, Luigi et al. “Human corpus luteum physiology and the luteal-phase dysfunction associated with ovarian stimulation.” Reproductive biomedicine online vol. 18 Suppl 2 (2009): 19-24. doi:10.1016/s1472-6483(10)60444-0 [2] “Mode of action of oral contraceptives.” Family planning information service vol. 1,1 (1978): 11. [3] Mørch, Lina S et al. “Contemporary Hormonal Contraception and the Risk of Breast Cancer.” The New England journal of medicine vol. 377,23 (2017): 2228-2239. doi:10.1056/NEJMoa1700732 [4] Roura, Esther et al. “The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.” PloS one vol. 11,1 e0147029. 25 Jan. 2016, doi:10.1371/journal.pone.0147029 [5] Andersen L, Friis S, Hallas J, Ravn P, Kristensen BW, Gaist D. Hormonal contraceptive use and risk of glioma among younger women: a nationwide case-control study. Br J Clin Pharmacol. 2015 Apr;79(4):677-84. doi: 10.1111/bcp.12535. PMID: 25345919; PMCID: PMC4386952. [6] Iversen, Lisa et al. “Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study.” BMJ (Clinical research ed.) vol. 362 k3609. 26 Sep. 2018, doi:10.1136/bmj.k3609 [7] Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154–1162. doi:10.1001/jamapsychiatry.2016.2387 [8] Pasvol TJ, Bloom S, Segal AW, Rait G, Horsfall L. Use of contraceptives and risk of inflammatory bowel disease: a nested case-control study. Aliment Pharmacol Ther. 2022 Feb;55(3):318-326. doi: 10.1111/apt.16647. Epub 2021 Oct 18. PMID: 34662440; PMCID: PMC7612921. [9] The ESHRE Capri Workshop Group, Ovarian and endometrial function during hormonal contraception, Human Reproduction, Volume 16, Issue 7, July 2001, Pages 1527–1535, https://doi.org/10.1093/humrep/16.7.1527Additional Reading:
Yes, birth control affects mental health. Here’s why it isn’t addressed
‘She’s not herself.’ when someone you love is struggling with birth control side effects
How my problems with irregular periods were solved by FAMs (not birth control)
It is likely more women especially younger ones are going to miss regular well women screenings if they choose OTC hormonal birth contral.