Long-term treatment of dienogest with symptomatic adenomyosis: retrospective analysis of efficacy and safety in clinical practice.

Objective: To evaluate the efficacy and safety of dienogest (DNG) in women with symptomatic adenomyosis.Methods: Women with symptomatic adenomyosis were included in this retrospective observation study. Group 1 (maximum uterine dimension ≥ 100.0 mm) began DNG after 4 months of GnRH-a administration, Group 2 (maximum uterine dimension < 100.0 mm) received DNG with no prior GnRH-a treatment. All women were assessed for their pain symptoms, uterine size, adverse effects and laboratory hematology at baseline and every 6 months during the treatment.Results: 123 women were enrolled in this study, in Group 1 (71 women) with severe uterine enlargement, the median VAS score was 80 mm prior to GnRH-a administration and 10, 10, 10, 20, and 20 mm, respectively, after 0, 6,12,18, and 24 months of DNG treatment. The mean uterine volume decreased from 262.9 ml to 104.7 ml after GnRH-a therapy, and slowly increased from 104.7 ml to 139.5 ml after 24 month-treatment of DNG. Another 52 women with mild uterine enlargement received DNG without prior GnRH-a administration, median VAS score was 70 mm at baseline and decreased to 20, 20, 10, and 10 mm at 6,12,18, and 24 months. The mean uterine volume slightly decreased from 157.9 ml to 153.3 ml after 24 months of DNG treatment (p > 0.05). All laboratory parameters were in the normal range.Conclusions: DNG is effective and well tolerated as a long-term treatment for symptomatic adenomyosis, and it can be used as maintenance therapy after discontinuation of GnRH-a administration.

Activin A Stimulates Aromatase via the ALK4-Smad Pathway in Endometriosis.

Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was regulated by the Activin-Smad pathway in endometrial lesions. The data showed that the effect of Activin A on ESCs was partially abrogated by pretreatment with an inhibitor of ALK4 (the type I receptor, ActRIB) and Smad4-siRNA. Cumulatively, these data suggest that Activin A promotes the secretion of estradiol from ESCs by increasing the expression of P450arom via the ALK4-Smad pathway. These findings indicate the ALK4-Smad pathway may promote ectopic lesion survival and development.