{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:12:04Z","timestamp":1790223124983,"version":"4.1.0"},"reference-count":28,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Fam Plann Reprod Health Care"],"accepted":{"date-parts":[[2012,2,10]]},"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 \u03bcg\/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. <\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study design<\/jats:title>\n                  <jats:p>In this Phase III, multicentre, open-label study, women (aged 18\u201335 years) were randomised to EE\/DRSP in the following regimens: flexible<jats:sub>MIB<\/jats:sub> (24\u2013120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible<jats:sub>MIB<\/jats:sub> regimen. Safety\/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced \u22651 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible<jats:sub>MIB<\/jats:sub>, conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>EE\/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen\/progestogen oral contraceptives.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jfprhc-2011-100214","type":"journal-article","created":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T11:35:47Z","timestamp":1332848147000},"page":"84-93","source":"Crossref","is-referenced-by-count":24,"title":["Long-term tolerability of ethinylestradiol 20 \u00b5g\/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre 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