Irritable bowel syndrome and drospirenone-containing oral contraceptives; a comparative-safety study.
BACKGROUND
Mineralocorticoids are thought to play a role in tissue repair, including fibrous tissue formation. The antimineralocorticoid activity of spironolactone has been linked to an increased risk of gastrointestinal bleeding. Drospirenone is a synthetic progestin approved in combination with ethinyl-estradiol as an oral contraceptive (OC). It is a spironolactone-derivative, and its antimineralocorticoid effects could irritate the gastrointestinal tract leading to symptoms of irritable bowel syndrome (IBS).


METHODS
A retrospective cohort study was conducted evaluating women 18-46 years of age in the IMS claims-database. New-users of progestin-based OCs were identified between 1997-2009. Ninety days of OC therapy and one year of prior enrollment with no prior diagnosis of IBS were required for inclusion. Cases were identified using a previously validated method for the diagnosis of IBS. Cox proportional hazards models were used to estimate the hazard ratio (HR) for developing IBS with the different OC formulations using levonorgestrel as a reference.


RESULTS
The cohort included 939,281 women, averaging 29.1 years of age and 247 days of OC therapy. 3,050 incident cases of IBS were detected. The annualized incidence for IBS with drospirenone was 0.77% (1083 cases) while that for levonorgestrel was 0.46% (483 cases). The crude HR for development of IBS with drospirenone compared to levonorgestrel was 1.70 (95%CI 1.53-1.90), while the adjusted HR was 1.63 (95%CI 1.46-1.82). Multiple sensitivity analyses confirmed this association. Other OCs were unassociated with IBS.


CONCLUSIONS
Our study found a positive association between drospirenone and a diagnosis of IBS that was not observed with other OCs.
LT United States Public Health Service, DHHS/FDA/CDER/OM/CACP, BLDG 22 Rm 3425, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Steven T
ST
Bird
Wei
W
Liu
James M
JM
Brophy
Brian
B
Bressler
Joseph A C
JA
Delaney
Mahyar
M
Etminan
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D006801:Humans; D015994:Incidence; D043183:Irritable Bowel Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D016912:Levonorgestrel / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055815:Young Adult
D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D000451:Mineralocorticoid Receptor Antagonists; D016912:Levonorgestrel; C035144:drospirenone