Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.
BACKGROUND
This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol.


METHODS
This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years.


RESULTS
Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG.


CONCLUSIONS
A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.
Ahrendt
Hans-Joachim
HJ
Gynekologická a Porodnická Ambulance, Prague, Czech Republic.
Makalová
Dagmar
D
Parke
Susanne
S
Mellinger
Uwe
U
Mansour
Diana
D
D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004338:Drug Combinations; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects / Q000494:pharmacology*; D008597:Menstrual Cycle / Q000187:drug effects*; D008599:Menstruation Disturbances / Q000139:chemically induced; D008796:Metrorrhagia / Q000139:chemically induced; D008875:Middle Aged; D009277:Nandrolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D017060:Patient Satisfaction / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult
D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C454300:estradiol valerate-dienogest; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone