David Portman

Adding low-dose estrogen to the hormone-free interval: impact on bleeding patterns in users of a 91-day extended regimen oral contraceptive.

BACKGROUNDnA cross-study analysis of contraceptive clinical trials for two different 91-day oral contraceptive (OC) regimens was performed to examine the impact on bleeding patterns when supplementing the 7-day hormone-free interval with 10 mcg ethinyl estradiol (EE) daily.nnnSTUDY DESIGNnTwo separate 1-year Phase 3 clinical programs were conducted using similar study designs. The percentages of subjects reporting bleeding and spotting using electronic diaries for each 91-day cycle were compared.nnnRESULTSnScheduled bleeding with the EE regimen was less than that reported with the regimen utilizing placebo during Days 85-91, with significant differences noted for all four 91-day cycles. Unscheduled bleeding decreased more quickly with the 91-day regimen containing low-dose EE in place of placebo, with significant differences noted during the third cycle.nnnCONCLUSIONSnThis cross-study comparison suggests that the administration of low-dose estrogen in place of placebo in a 91-day extended regimen OC improves the bleeding profile.

The creeping pearl: why has the rate of contraceptive failure increased in clinical trials of combined hormonal contraceptive pills?

BACKGROUNDnDespite several drawbacks, the Pearl Index continues to be the most widely used statistical measure of contraceptive failure. However, Pearl indices reported in studies of newer hormonal contraceptives appear to be increasing.nnnSTUDY DESIGNnWe searched PubMed and Medical Intelligence Solutions databases for prospective trials evaluating oral contraceptive (OC) efficacy to examine potential factors that could contribute to increasing Pearl indices.nnnRESULTSnNumerous potential factors were identified, including an increased rate of failures of newer OCs, deficiencies in methods of calculating contraceptive failure rates, differences in study design and changes in patient populations resulting in increased rates of contraceptive failures due to the inappropriate or inconsistent use of the method.nnnCONCLUSIONSnThe two most likely important contributors to the increase in Pearl indices are more frequent pregnancy testing with more sensitive tests and less adherent study populations. Because study populations appear to be increasingly representative of the likely actual users once the product is marketed, we can expect to see even higher failure rates in ongoing and future studies. This result poses challenges for companies and regulatory agencies.