Efficacy, Adverse Events, and Challenges of Dienogest in the Management of Symptomatic Adenomyosis: A Comparison with Different Hormonal Treatments

BACKGROUND: Adenomyosis is an estrogen-dependent gynecologic condition that can cause pain symptoms, heavy menstrual bleeding, and infertility. Several treatments, including hormonal therapy, can improve patients' quality of life through alleviating symptoms. Dienogest (DNG), a 19-norsteroid derivative oral progestin, is a promising treatment option for adenomyosis. OBJECTIVES: This review aims to summarize the clinical outcomes (efficacy and adverse events) of DNG treatment for symptomatic adenomyosis compared with other hormonal treatments, discuss the mechanism underlying adverse events, and identify future challenges. METHODS: A literature search was performed across the PubMed and Google Scholar databases up to March 2022 to identify relevant literature. OUTCOME: Out of 449 identified records, 37 articles met the inclusion and exclusion criteria. Five prospective and three retrospective studies showed that DNG and other hormonal agents had similar efficacy for pain relief; however, the most common adverse event of DNG was abnormal uterine bleeding. Specific demographic and clinicopathologic characteristics have been identified as associated with an increased risk of bleeding. Several factors, such as diffuse or type 1 adenomyosis, advanced reproductive age, severe dysmenorrhea, elevated serum CA125 levels, or low hemoglobin levels, may be implicated in bleeding risk; however, there is no accurate and reliable parameter. Future challenges with the widespread use of DNG include validation of candidate risk indicators and approaches to treat diffuse or type 1 adenomyosis. CONCLUSIONS AND OUTLOOK: DNG represents an important therapeutic option to be included in the treatment algorithm for adenomyosis owing to sufficient pain relief, despite high rates of bleeding-related adverse events. Clinicians should consider an individual's potential risk factors for bleeding until high-quality evidence is available.