Background: In our systematic review and meta-analysis we aim to summarize and evaluate user
satisfaction, body weight control and general well-being of estetrol (E4) in combination with
drospirenone (DRSP).
Methods: We followed the standard methods of Cochrane Handbook of Systematic Reviews for
interventions and the PRISMA statement guidelines 2020 when conducting and reporting this study.
A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of
Controlled Trials was conducted from inception until January 31, 2022. We selected randomized
controlled trials (RCTs) assessing the efficacy of Estetrol (E4) when combined with drospirenone
(DRSP) on women Safety and menopausal bleeding as well as general well-being, and all relevant
outcomes were pooled in the meta-analysis using Review Manager Software
Results: We included ten RCTs in our study with only five RCTs included in the meta-analysis. In
the fixed-model effect and the random-effect model there was significant difference with the use of
E4 in combination with DRSP regarding all our outcomes as following: abdominal pain [2.2%, CI
95% (1.7,2.7), P< 0.001], acne [3.7%, CI 95% (3.1,4.3), P< 0.001], metrorrhagia [5%, CI 95%
(4.2,5.7), P< 0.001], nausea [3.8%, CI 95% (2.9,4.7), P< 0.001], weight increase [2.4%, CI 95%
(1.9,2.9), P< 0.001], treatment related adverse events [34.9%, CI 95% (27.2,42.6), P< 0.001], any
adverse event lead to discontinuation [6.9%, CI 95% (2.6,11.2), P= 0.002], breast pain [3.6%, CI
95% (1.5,5.4), P< 0.001], dysmenorrhea [3.6%, CI 95% (1.9,5.3), P< 0.001], headache [6.8%, CI
95% (4.3,9.4), P< 0.001], and anxiety [2%, CI 95% (1.4,2.6), P< 0.001]. For absence of scheduled
bleeding after second, third and sixth menopausal cycles there was no significant difference as
following: [6.3%, CI 95% (-4.3,17), P= 0.243], [7.5%, CI 95% (-4.5%,17%), P=0.243], and [8.3%,
CI 95% (-2.1,18.7), P=0.117]. While there was no significant difference in the percentage of
occurrence of unscheduled bleeding after first: [1.3%, CI 95% (0,2.7), P=0.05], second [4.4%, CI
95% (1.7,7), P= 0.001], third [3.1%, CI 95% (0.8,5.3), P=0.007], sixth [2.6%, CI 95% (0.6,4.6),
P=0.012], and twelfth [1.1%, CI 95% (0.7,1.5), P< 0.001].
Conclusion: In conclusion, our meta-analysis showed that use of E4 in combination with DRSP was
associated with decrease abdominal pain, acne, metrorrhagia, nausea, and weight increase treatment
related adverse events, any adverse event led to discontinuation, breast pain, dysmenorrhea,
headache, and anxiety. On the other hand, it’s not associated with decrease unscheduled bleeding
after first, second, third, sixth, and twelfth month of menstrual cycle |
