What is the difference between monophasic and biphasic contraceptives?

Monophasic vs Biphasic Contraceptives

Start with monophasic oral contraceptives as the first-line choice for women beginning hormonal contraception, as there is no evidence that biphasic formulations offer any clinical advantage in efficacy, bleeding patterns, or side effects. 1

Key Definitions

• Monophasic pills: Each active tablet contains the same fixed dose of estrogen and progestin throughout the entire cycle 1
• Biphasic pills: Contain two different dose combinations of estrogen and progestin during the cycle, with varying hormone levels 1
• Triphasic pills: Contain three different dose combinations throughout the cycle 1

Clinical Evidence and Recommendations

Efficacy

• Only one limited-quality randomized trial has directly compared biphasic versus monophasic formulations, finding no significant differences in contraceptive effectiveness 2
• No accidental pregnancy data were reported in this trial, limiting conclusions about comparative efficacy 2
• Both formulations have typical-use failure rates of approximately 9% in adults 1

Bleeding Patterns and Cycle Control

• The single available trial found no significant differences between biphasic and monophasic pills for:
  • Intermenstrual bleeding (breakthrough bleeding or spotting) 2
  • Amenorrhea (absence of withdrawal bleeding) 2
  • Study discontinuation due to bleeding problems 2

Side Effects and Tolerability

• No important differences in side effect profiles have been demonstrated between biphasic and monophasic formulations 2
• Both types share similar noncontraceptive benefits including decreased menstrual cramping, reduced blood loss, and improvement in acne 1

Practical Prescribing Approach

Initial Selection

Begin adolescents and women new to oral contraceptives on a monophasic pill containing 30-35 μg ethinyl estradiol with levonorgestrel or norgestimate. 1 This recommendation is based on:

• Extensive safety and efficacy data available for monophasic formulations 1
• No clear rationale exists for biphasic pills given the lack of demonstrated advantages 2
• Monophasic pills are simpler to use with consistent daily dosing 1

When to Consider Alternatives

• If a patient experiences unacceptable side effects or poor cycle control on the initial monophasic pill, switch to a different monophasic formulation rather than automatically moving to biphasic or triphasic options 1
• Among low-dose pills, choose formulations with the lowest copay on the patient's insurance formulary when clinically appropriate 1

Extended or Continuous Regimens

• Consider monophasic pills with shortened or eliminated hormone-free intervals for patients with:
  • Severe dysmenorrhea, endometriosis, or heavy menstrual bleeding 1
  • Anemia or bleeding disorders (Von Willebrand disease) 1
  • Conditions exacerbated cyclically: migraine without aura, epilepsy, irritable bowel syndrome 1
  • Frequent missed pills (optimizes ovarian suppression) 1

Important Caveats

Limitations of Current Evidence

• Conclusions about biphasic versus monophasic pills are severely limited by only one available trial with methodological shortcomings 2
• The single trial examined specific formulations (norethindrone-based biphasic versus norethindrone acetate monophasic), so results may not generalize to other formulations 2
• Meta-analysis of triphasic versus monophasic trials was not possible due to differences in measuring and reporting bleeding patterns 3

Clinical Pitfalls to Avoid

• Do not assume that multiphasic formulations (biphasic or triphasic) provide better "physiologic" hormone delivery—this theoretical advantage has not translated into clinical benefits 2, 3
• Avoid switching to biphasic or triphasic pills solely to address bleeding irregularities without first trying a different monophasic formulation 1
• Do not prescribe biphasic pills as first-line when monophasic options with more robust evidence are available 2

Counseling Points

• Emphasize that 7 consecutive hormone pills are needed to prevent ovulation 1
• Provide clear instructions on missed pill management regardless of formulation type 1
• Discuss that extended or continuous monophasic regimens may cause unscheduled bleeding initially but optimize contraceptive effectiveness 1