Effects of an extended flexible regimen of an oral contraceptive pill containing 20 μg ethinylestradiol and 3 mg drospirenone on menstrual-related symptoms: a randomised controlled trial.
OBJECTIVE
The aim of the study was to assess the efficacy for menstrual-related symptoms of an extended flexible regimen of an oral contraceptive pill containing 20 μg ethinylestradiol and 3 mg drospirenone in comparison with a 24/4 d cyclical regimen of the same formulation.


METHODS
This randomised, non-inferiority, open-label, multicentre study was conducted in women aged 18-39 years. Their menstrual-related symptoms were assessed using the Penn Daily Symptom Rating (DSR17). Participants were randomised to use an extended flexible regimen of 20 μg ethinylestradiol and 3 mg drospirenone (EE/DRSPe.flex), comprising 168 consecutive days with a 4-d hormone-free interval (HFI, allowing for management of unexpected bleeding) or a conventional 24/4 cyclical regimen of the same pill (EE/DRSP24/4). The primary measure of efficacy was the percentage change in DSR17 total score from baseline to cycle 6. The secondary measures of efficacy were the percentage changes in DSR17 total score from baseline after each 28-d interval throughout the entire study and in the scores for individual DSR17 symptoms.


RESULTS
The primary analysis demonstrated that EE/DRSPe.flexwas not inferior to EE/DRSP24/4(Mean DSR17 score 9.1; 95% confidence interval (CI) - 2.5, 20.6; p = 0.123). Analysis at intervals throughout the entire evaluation period showed greater reduction in DSR17 total score for EE/DRSPe.flexthan for the 24/4 regimen (p < 0.001). The decreases in individual scores for the symptoms 'poor coordination' and 'depression/feeling sad/down or blue' were greater for the extended flexible regimen than for the cyclical regimen (p < 0.05).


CONCLUSIONS
The extended flexible regimen was not inferior to the 24/4 cyclical regimen in terms of the primary endpoint. It significantly improved symptoms in the interval analysis, and the effects on specific DSR17 symptoms, compared with the cyclical regimen.
a Department of Gynaecology and Obstetrics , Jundiaí School of Medicine , Jundiaí , Brazil.
Rogério Bonassi
RB
Machado
b Department of Gynaecology and Obstetrics , ABC School of Medicine , Santo André , Brazil.
Luciano Melo
LM
Pompei
c Department of Gynaecology and Obstetrics , PUC-RS, Porto Alegre , Brazil.
Mariangela
M
Badalotti
d Department of Gynaecology and Obstetrics , University of São Paulo (FMRP-USP) , Ribeirão Preto , Brazil.
Rui
R
Ferriani
e Department of Clinical Research , Libbs Farmacêutica Ltda , São Paulo , Brazil.
Achilles M
AM
Cruz
f Department of Gynaecology and Obstetrics , Botucatu School of Medicine (FMB-UNESP), UNESP - Sao Paulo State University , Botucatu , Brazil.
Eliana
E
Nahas
g Centre for Research and Assistance in Human Reproduction , Federal University of Bahia , Salvador , Brazil.
Hugo
H
Maia
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000008:administration & dosage*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage*; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects*; D008599:Menstruation Disturbances / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D055815:Young Adult
D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D004967:Estrogens; D000451:Mineralocorticoid Receptor Antagonists; D004997:Ethinyl Estradiol; C035144:drospirenone
Combined oral contraceptives; drospirenone; extended regimen; low-dose oral contraceptive; premenstrual symptoms