POPs historically have about 25% of the amount of circulating progestin as combined oral contraceptives (COCs); hence, they are commonly referred to as the “minipill.”⁶ For POPs containing levonorgestrel, norgestrel, and norethindrone, this low dose of progestin results in predominantly cervical and endometrial effects, though the precise mechanism of action is based on very limited clinical evidence.⁹ POPs appear to cause the cervical mucus to become thick and impermeable, likely the major contraceptive effect.² These progestins have less of an effect on ovulatory function, as the gonadotropins are not consistently suppressed. Hence, approximately 40% of patients using these POPs ovulate normally.^10,11,12 Tubal physiology may also be affected, but this is speculative.

However, POPs containing desogestrel and drospirenone provide more inhibition of ovulation. The desogestrel POP suppresses ovulation comparable to that of COCs.^13,14 The drospirenone POP also suppresses ovulation; this suppression is maintained over a 4-day hormone-free interval and is comparable to desogestrel POPs dosed daily.^7,8,15

Because of the low dose, and lack of ovulation inhibition, norethindrone norgestrel, levonorgestrel, ethynodiol diacetate, and lynestrenol POPs must be taken every day at about the same time of day. Based on limited data, the changes in cervical mucus associated with the POP appear to develop quickly and diminish quickly.⁹ Thickened cervical mucus reportedly occurs within 2 to 4 hours of dosing, with impermeability to sperm declining 22 hours after administration, and by 24 hours, some sperm penetration occurs.¹⁶ While the available data support the need for consistent “on-time” dosing of POPs, and use of a backup method in the event of a late pill, the quality of this evidence is weak.⁹ The requirement for maintaining this rigorous schedule may present a barrier to some potential users. In contrast, users of desogestrel POPs can miss a pill by up to 12 hours, and drospirenone POP users can delay taking a pill for 24 hours without impacting the contraceptive efficacy.^8,17

Perfect-use failure rates have been documented to be as low as 1.1 per 100 women in the first year of use.^18,19 The actual use failure rate for all contraceptive pills (COCs and POPs) reported from the National Survey of Family Growth 2006 to 2010 is 7.2 per 100 women in the first year of use.²⁰ In this cohort, failure rates differ by age (10.4 per 100 women aged 25 to 29 vs. 4.1 per 100 women aged 30 to 44) and by race/ethnicity (13.1 per 100 black women and 6.1 per 100 white women). A systematic review of POPs for contraception did not find statistically significant differences in efficacy between POP types, though the analyses favored desogestrel over levonorgestrel and norethindrone over desogestrel.⁶ Higher rates of discontinuation were seen with desogestrel due to bleeding irregularities, which likely limited its overall efficacy. There are no published efficacy data comparing
drospirenone POPs with any other formulations. When women are able to adhere to recommended timing of POP administration, the failure rate may be comparable to the rate (<1 per 100 woman-years) with COCs.¹⁸ However, use of population data to compare effectiveness of POPs and COCs is limited by selection bias, as users of POPs may have lower fertility risk for a variety of reasons (e.g., age, breastfeeding).

POPs can be an effective, well-tolerated contraceptive method for many women. This method is frequently used by individuals who prefer an oral contraceptive and have an intolerance to, a personal preference to avoid, or a medical contraindication to estrogen-containing contraceptives. According to the U.S. Medical Eligibility Criteria (MEC) for Contraceptive Use, POPs are category 1 (no restrictions) or category 2 (advantages generally outweigh theoretical or proven risks) for women over the age of 35 who smoke or for those who have migraines with aura, history of venous or arterial thrombosis, hypertension, diabetes with vascular disease, or cardiovascular disease.²¹ In general, women with liver tumors, cirrhosis, or breast cancer should not use the POP or other methods of hormonal contraception. Individuals with certain forms of bariatric surgery (malabsorptive procedures) that impair drug absorption should not use oral contraceptives.

All potential POP users must be counseled regarding the need for consistent timing to maximize efficacy, using a patient-centered approach. Theoretically, POPs may be associated with decreased efficacy in certain populations, such as adolescents and obese women. Use of POPs in adolescent women is poorly studied and less common, so precise estimates of failure rates are not available. However, clinicians may avoid the use of POPs in adolescents due to concerns about their compliance with the dosing regimen. Studies of obese women using COCs demonstrate they may require a longer period of time to reach full contraceptive efficacy, though the data do not suggest higher doses of hormones are necessary.²² Based on very limited epidemiologic data, obese women who use POPs are not at higher risk of pregnancy than nonobese women.²³