Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program.
BACKGROUND
In four randomized, controlled, European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis.


METHODS
All 332 women treated with dienogest 2 mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics.


RESULTS
Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in <10% of women. All these adverse events were generally of mild-to-moderate intensity and associated with low discontinuation rates. The bleeding pattern associated with dienogest 2 mg was well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation. Laboratory and vital sign assessments indicated no safety concerns for dienogest. Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency.


CONCLUSIONS
In this pooled analysis of 332 women with endometriosis, dienogest was well tolerated with a favorable safety profile extending over a period of up to 65 weeks. There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis. These pooled analyses from four clinical trials of dienogest 2 mg represent a contribution to evidence-based medicine in endometriosis, providing outcomes of potential relevance to daily practice.
Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Heidelberg, Germany.
Thomas
T
Strowitzki
Bayer Pharma AG, Global Medical Affairs Women's Healthcare, Berlin, Germany.
Thomas
T
Faustmann
Bayer Pharma AG, Global Research and Development Statistics, Berlin, Germany ; Department of Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg/Saar, Germany.
Christoph
C
Gerlinger
Jenapharm GmbH & Co KG, Medical Affairs Support, Jena, Germany ; Center for Clinical Studies, Universitätsklinikum Jena, Jena, Germany.
Ulrike
U
Schumacher
Bayer Pharma AG, Global Integrated Analysis and Lifecycle Management Statistics, Wuppertal, Germany.
Christiane
C
Ahlers
Bayer Pharma AG, Global Clinical Development Therapeutic Area Primary Care and Women's Healthcare, Berlin, Germany.
Christian
C
Seitz
clinical trials; endometriotic lesions; progestins; side effects; women