What are the adverse effects of the progestin-only pill (POP)?

Adverse Effects of Progestin-Only Pills

The most common adverse effect of progestin-only pills is irregular menstrual bleeding, including breakthrough bleeding, spotting, prolonged bleeding, and amenorrhea, which is the primary reason for discontinuation in up to 25% of users. 1, 2

Primary Adverse Effects

Menstrual Irregularities

• Irregular bleeding patterns are the most frequently reported side effect, occurring because POPs work primarily by thickening cervical mucus rather than consistently inhibiting ovulation 1, 3
• Specific bleeding disturbances include:
  • Increased frequency of bleeding 2
  • Breakthrough bleeding and spotting 2
  • Prolonged bleeding episodes 2
  • Lengthened menstrual cycles 2
  • Amenorrhea (absence of periods) 1
• Menstrual irregularity accounts for 47.5% of discontinuations among POP users 4
• However, approximately 40% of long-term users maintain a mostly regular menstrual pattern 4

Management of Bleeding Irregularities

• NSAIDs can be used for 5-7 days to manage bleeding irregularities 3
• Enhanced counseling about expected bleeding patterns and reassurance that these irregularities are generally not harmful can reduce method discontinuation 5
• If unscheduled spotting or bleeding persists and is unacceptable to the patient, consider alternative contraceptive methods 5

Other Reported Adverse Effects

Non-Menstrual Side Effects

• Non-menstrual side effects are generally minor and were reported by only 77 out of 358 women in one clinical study 4
• Inconsistent evidence exists for mood or libido changes associated with POP use 6
• Natural progesterone formulations have fewer reported side effects compared with synthetic progestins 7

Weight and Body Composition

• Limited evidence suggests POPs are not significantly associated with weight gain, unlike depot medroxyprogesterone acetate (DMPA) 8
• Studies comparing POPs to non-hormonal methods showed no significant differences in weight change or body composition measures 8

Efficacy Considerations (Related to Adverse Outcomes)

Contraceptive Failure Risk

• With typical use, approximately 9 out of 100 women become pregnant in the first year of POP use 5, 3
• POPs are markedly less effective than other progestin-only methods including progestin IUDs, implants, and injectable progestin 1
• The reduced effectiveness is due to:
  • Continued potential for ovulation 1
  • Strict timing requirements (must be taken within 3 hours of the same time daily for traditional POPs) 3
  • Dependence on cervical mucus thickening rather than ovulation suppression 1, 3

Special Safety Considerations

Thrombosis Risk

• POPs do not increase venous thromboembolism (VTE) risk in healthy women (RR 0.90,95% CI 0.57-1.45) 1
• This makes POPs appropriate for women with contraindications to estrogen, including those with positive antiphospholipid antibodies or history of thrombosis 1

Clinical Recommendations for Use

• POPs are not typically recommended as first-choice contraceptives in healthy adolescents due to lower effectiveness and strict timing requirements 1
• POPs are appropriate for selected patients with demonstrated excellent medication adherence 1
• Ideal candidates include:
  • Breastfeeding women (no effect on milk production) 3
  • Women with contraindications to estrogen (history of VTE, hypertension) 3
  • Women unable or unwilling to use IUDs 1

Important Clinical Pitfalls

• POPs do not protect against sexually transmitted diseases; consistent condom use is recommended for STD protection 5
• If a dose is missed, users should take one pill as soon as possible, continue daily pills at the same time, use backup contraception for 2 consecutive days, and consider emergency contraception if unprotected intercourse occurred 3
• No routine follow-up visit is required after initiating POPs, but women should be advised to return if they experience unacceptable side effects or want to change methods 3