By Rebecca H. Allen, MD, MPH, Editor
In this systematic literature review of 54 studies, the median typical use Pearl Index failure rate was 1.63 (range 0.00 to 14.20) and the median perfect use Pearl Index failure rate was 0.97 (range 0.40 to 6.50).
Zuniga C, Blanchard K, Harper CC, et al. Effectiveness and efficacy rates of progestin-only pills: A comprehensive literature review. Contraception 2023;119:109925.
Many providers believe that progestin-only pills (POPs) are less effective than combined oral contraceptives that contain an estrogen and a progestin. Therefore, the authors of this study sought to review the literature to estimate the typical and perfect use Pearl Index failure rates for POPs in anticipation of the approval of an over-the-counter POP in the United States.
This was a systematic literature review that searched PubMed Central, PubMed, and the Cochrane Library for articles on the effectiveness of POPs from inception through March 7, 2022. Studies, both randomized controlled trials and non-randomized trials that included any POP formulation currently or previously sold in any country, were included. Data were included on study design, POP formulation and dosage, loss to follow-up, number of total pregnancies, number of pregnancies attributed to user error and method failure, Pearl Index rates and life table data. Studies were assessed for risk of bias using the Cochrane risk of bias tools. The main outcome was median effectiveness and efficacy rates from studies that had a low or only moderate risk of bias.
The authors identified 54 studies that met eligibility criteria. Almost half of the studies were published in the 1970s. Seven were randomized controlled trials, 15 were non-randomized comparative studies, and 32 were non-comparative studies. Among 13 studies considered at low to moderate risk of bias, the median Pearl Index failure rate for typical use was 1.63 (range 0 to 14.12). Excluding studies of desogestrel and drospirenone, two POPs with longer half-lives that reliably inhibit ovulation, the median Pearl Index rate increased slightly to 2.0 (range 0.00 to 14.12). Among three studies considered at low to moderate risk of bias, the median perfect use Pearl Index failure rate was 0.97 (range 0.40 to 6.50).
COMMENTARY
Despite provider beliefs that POPs are less effective than combined oral contraceptives with both estrogen and progestin, clinical guidance reports their perfect use and typical use failure rates to be equivalent at 0.3% and 7%, respectively.1 However, the two types of pills are grouped together and failure rates for POPs are not separated out. The idea that POPs are less effective mainly relates to the older norethindrone 0.35-mg pill currently on the United States market. Patients are instructed that being as little as three hours late taking this pill requires 48 hours of back-up contraception.2 Although this is related to the half-life of norethindrone and its effect on cervical mucus, there is some debate as to whether this guideline is evidence-based and whether it should apply to other types of POPs, including the prescription-only drospirenone POP and the recently approved norgestrel over-the-counter POP, which is not yet commercially available.3 For example, the drospirenone-only pill has been shown to inhibit ovulation even with a 24-hour delay in pill-taking.4 Additionally, a pilot study showed that the norgestrel pill was more forgiving of missed and delayed doses.5 Studies have shown that the mechanism of action of POPs relates to their effect on cervical mucus but also on the prevention of ovulation in some subjects, depending on the pill type.3 Therefore, these two effects work synergistically to prevent pregnancy.
The authors of this study showed that the medial Pearl Index rate was 1.63 for typical use of POPs of all kinds. This is interpreted as approximately two pregnancies would occur if 100 people took the pill for one year, whether or not it was used perfectly. This is not much different than the rates reported for combined oral contraceptives. However, there are some limitations to this study in terms of what data were reported in the original studies. In addition, many of the studies included were published many years ago. Nevertheless, the authors wanted to demonstrate the failure rates of POPs were acceptable, which they did.
This review is especially meaningful, since the U.S. Food and Drug Administration recently approved over-the-counter status for the norgestrel 0.075-mg POP.6 This pill will be marketed as Opill and is the first over-the-counter oral contraceptive to be available to American consumers of any age. The Pearl Index for this pill was estimated to be 4.4 (95% confidence interval, 1.9 to 8.8) in the study for approval. It is monumental that people now have access to highly effective over-the-counter contraception in our country, since they previously had been limited to purchasing condoms, spermicides, and barrier methods given the many obstacles that people face in obtaining prescription contraception.
REFERENCES
- Trussell J, Aiken ARA, Micks E, Guthrie KA. Efficacy, safety, and personal considerations. In: Hatcher RA, Nelson AL, Trussell J, et al, eds. Contraceptive Technology. 21st ed. Ayer Company; 2018.
- Centers for Disease Control and Prevention. US Selected Practice Recommendations for Contraceptive Use, 2016 (US SPR). Last reviewed March 27, 2023. https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/summary.html
- Wollum A, Zuniga C, Blanchard K, Teal S. A commentary on progestin-only pills and the “three-hour window” guidelines: Timing of ingestion and mechanisms of action. Contraception 2023;122:109978.
- Duijkers IJM, Heger-Mahn D, Drouin D, et al. Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake. Contraception 2016;93:303-309.
- Glasier A, Edelman A, Creinin MD, et al. The effect of deliberate non-adherence to a norgestrel progestin-only pill: A randomized, crossover study. Contraception 2023;117:1-6.
- U.S. Food and Drug Administration. FDA approves first nonprescription daily oral contraceptive. Published July 13, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nonprescription-daily-oral-contraceptive
