Progestin-only pills for contraception.
BACKGROUND
The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined oral contraceptives containing an estrogen plus progestin, these pills contain only a progestin (progestogen) and are taken without interruption. How these pills compare to others in their class or to combined oral contraceptives is not clear.


OBJECTIVE
This review examined randomized controlled trials of progestin-only pills for differences in efficacy, acceptability, and continuation rates.


METHODS
Through October 2013, we searched the computerized databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), POPLINE, and LILACS for studies of progestin-only pills. We also searched for current trials via ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE.


METHODS
We included all randomized controlled trials in any language that included progestin-only pills for contraception.  We incorporated any comparison with a progestin-only pill; this could include different doses, other progestin-only pills, combined oral contraceptives, or other contraceptives.


METHODS
The first author abstracted the data and entered the information into RevMan 5. Another author performed a second, independent data abstraction to verify the initial data entry.We attempted to extract life-table rates (actuarial or continuous) and used the rate difference as the effect measure. Where life-table rates were not published, we used the incidence rate ratio (ratio of Pearl rates). Where only the crude number of events was published, we calculated the Peto odds ratio with 95% confidence interval (CI) using a fixed-effect model. For continuous variables, the mean difference (MD) was computed with 95% CI. Because of disparate exposures, we were not able to combine studies in meta-analysis.


RESULTS
Six trials met the inclusion criteria. We have not found any new studies since the initial review. In the trial comparing the desogestrel versus levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin-only pill containing levonorgestrel 30 μg had higher efficacy than did the pill containing norethisterone 350 μg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial.


CONCLUSIONS
Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives.
Obstetrics and Gynecology, University of North Carolina, School of Medicine, CB#7570, Chapel Hill, North Carolina, USA, 27599-7570.
David A
DA
Grimes
Laureen M
LM
Lopez
Paul A
PA
O'Brien
Elizabeth G
EG
Raymond
D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D017135:Desogestrel / Q000008:administration & dosage / Q000009:adverse effects; D005040:Ethynodiol Diacetate / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage; D011372:Progestins / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D014592:Uterine Hemorrhage / Q000139:chemically induced
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D011372:Progestins; D016912:Levonorgestrel; D005040:Ethynodiol Diacetate; D017135:Desogestrel