Missed Pills: The Problem That Hasn’t Gone Away

 

With all the technology available to assist patients in remembering to take their pills, wouldn’t it make sense to think that missed pills are a thing of the past? That, apparently, is not the case, though. According to the National Survey of Family Growth, in 1 month’s time, 15% of oral contraceptive users reported missing 1 pill and another 16% reported missing 2 or more pills.[1] And that is in only one month. Just what do we know about the risk for an unintended pregnancy after pills are missed? According to The Guttmacher Institute, 13% of women receiving abortions had relied on oral contraceptives in the month of becoming pregnancy.[2] But as yet, there’s no direct evidence about the risk of pregnancy following missed pills. Therefore, we look at surrogate measures—such as ovulation, follicular development, and hormone levels—extrapolating from there on what to advise patients.[3] Recent studies have looked at the effectiveness of counseling and reminders in helping users remember to take their pills daily. What practical tips might we learn from those studies? And, as ever, what are the current best missed-pill recommendations to share with your patients?

To estimate the frequency that oral contraceptive users missed their pills, the National Survey of Family Growth surveyed a nationally representative sample of women aged 15 to 49 years through in-person interviews (more sensitive questions are self-administered). Thirty-one percent had missed 1 or more pills in the 4 weeks leading up to the survey. While younger women were about as likely than older women to miss only 1 pill, they were substantially more likely to miss 2 or more pills (21% vs 13%).

Table 1.  Percentage of women who missed taking oral contraceptive pills among women aged 14-44 years who used oral contraceptive pills and had sexual intercourse—National Survey of Family Growth 2013-2015¹

While there appear to be no studies showing direct evidence on the degree of risk that these missed pills may lead to pregnancy, a 2013 review of multiple studies explored indirect evidence in looking such asthat would indicate the level of ovarian function after missed pills or extended pill-free intervals.[4] The analysis offered some reassurance:

• Extending the pill-free interval (8-14 days). Few women ovulated and those who did ovulate experienced abnormal cycles
• Missing 1-4 pills not adjacent to the pill-free interval. Women appeared to have little follicular activity and low risk of ovulation. Those who ovulated had poor cervical mucus quality
• Missing very low-dose pills. Compared to missing 30 mcg EE pills, missing 20 mcg EE pills resulted in greater follicular activity

These are, of course, surrogate measures, and it is difficult to determine how the risk of pregnancy corresponds to follicular development or ovulation with abnormal hormone levels or cervical mucus. It may be, according to the researchers, that the risk of pregnancy may not actually increase.

Nonetheless, there is that pesky difference in failure rates following perfect use vs. typical use. Perfect use is defined as correct and consistent use. Typical use includes missed pills and extended pill-free intervals, in addition to discontinuation or other imperfect use patterns.

Part of a provider’s responsibility is to help improve adherence and continuation of patients’ chosen contraceptive methods. But how is that working for you? Last year, a Cochrane Systematic Review of 10 randomized controlled trials involving 6,242 women examined the evidence on counseling and reminder systems.³ First the caveat: much of the certainty of the evidence was low due to risks of bias, imprecision, poor reporting, and such. Moreover, intensive counseling practices differ from provider to provider outside of the research setting. But we have what we have. Bottom line?

• Counseling may improve continuation and reduce discontinuation due to menstrual problems or adverse effects.
• Reminders may improve continuation but appears to make little or no difference in adherence.

What do we actually know for sure? That COC users will miss pills. So it’s helpful to know the current best recommendations are for managing missed pills.

• First, know that after patients have taken at least 7 COCs at the correct time, they are at little risk for ovulation until they subsequently miss 7 consecutive pills.[5]
• Breakthrough ovulation and unintended pregnancy are more likely to occur if the patient missing pills is using a 21/7 formulation.[6]
• COCs containing 20 mcg or less of EE are associated with more breakthrough ovulation with missed pills.[7]

Because missed pills during the first week of a pill pack pose the greatest risk of pregnancy, having the patient use the LNG emergency contraceptive pills may be appropriate if she had been sexually active around that time. Emergency contraception may also be appropriate when a patient misses too many pills (e.g., 3+ consecutive pills containing 0.03 to 0.035 mg EE or 2+ consecutive ills containing 0.02 mg or less EE.).[8]

When initiating COCs, proactively instruct your patient in what to do after missing 1 or more of her pills. Patients who have vomiting or severe diarrhea within 24 hours of taking their COC should be treated as if they had missed pills.

Managing Missed Pills—Patient Instructions

For 1 late or missed active (hormonal) pill:  

• Take 1 active pill as soon as possible.
• Continue taking your pills daily on time, which may mean taking 2 pills in one day.
• No back-up contraception is needed.
• Emergency contraception is not typically needed unless pills were also missed earlier in the packet or at the end of the previous packet.

For 2 or more late or missed active (hormonal) pills:   

• Take 1 active pill as soon as possible.
• Continue taking your pills daily on time, which may mean taking 2 pills in one day.
• Use condoms or abstain from vaginal sex until you have taken active pills for 7 days in a row.
• If pills were missed during the last week of active pills (days 15 through 21 of a packet), finish the active pills in the current packet and start a new packet the next day without using any placebo pills, OR use condoms or abstain from vaginal sex until you have taken active pills in the new packet for 7 days in a row.
• Use emergency contraceptive pills if you missed COCs during the first week of a packet and you had any unprotected intercourse. You may also need to use emergency contraception if you missed too many pills.

[1] Daniels K. Percentage of Women Who Missed Taking Oral Contraceptive Pills* Among Women Aged 15–44 Years Who Used Oral Contraceptive Pills and Had Sexual Intercourse, Overall and by Age and Number of Pills Missed — National Survey Of Family Growth, United States, 2013–2015. MMWR Morb Mortal Wkly Rep Sep 15;66:965. Published online 2017 Sep 15. doi: 10.15585/mmwr.mm6636a10

[2] Jones R. Reported contraceptive use in the month of becoming pregnant among U.S. abortion patients in 2000 and 2014. Contraception, Volume 97, Issue 4, 309-12.

[3] Mack N, Crawford TJ, Guise J-M, Chen M, Grey TW, Feldblum PJ, Stockton LL, Gallo MF. Strategies to improve adherence and continuation of shorter-term hormonal methods of contraception. Cochrane Systematic Review. Published online 23 April 2019  https://doi.org/10.1002/14651858.CD004317.pub5

[4]Zapata LB, Steenland MW, Briahna D, et al. Effect of missed combined hormonal contraceptives on contraceptive effectiveness: a systematic review. Contraception 2013;87:685-700.

[5]Cwiak C, Edelman AB. Oral contraceptives. In: Hatcher RA, Nelson AL, Trussell J, Cwiak C, Cason P, Policar MS, Edelman A, Aiken ARA, Marrazzo J, Kowal D, eds. Contraceptive technology. 21st ed. New York, NY: Ayer Company Publishers, Inc., 2018.

[6] Dinger J, Minh TD, Buttmann N, Bardenheuer K. Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen. Obstet Gynecol 2011;117:33–40.

[7] Gallo MF, Nanda K, Grimes DA, Lopez LM, Schulz KF. 20 μg versus >20 μg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev 2013:Cd003989

[8] Trussell J, Cleland K. Emergency contraception. In: Hatcher RA, Nelson AL, Trussell J, Cwiak C, Cason P, Policar MS, Edelman A, Aiken ARA, Marrazzo J, Kowal D, eds. Contraceptive technology. 21st ed. New York, NY: Ayer Company Publishers, Inc., 2018.