Dysmenorrhea: Pathogenesis, Therapy Resistance, and New Clinical Evidence

Dysmenorrhea is one of the most prevalent gynecological conditions, significantly affecting the quality of life of women of reproductive age, leading to work productivity loss and reduced social activity. Its pathogenesis is multifactorial, involving prostaglandin-mediated mechanisms, local inflammation, and hormonal regulation. Resistance, particularly to progestins, is a common challenge during long-term treatment, limiting the efficacy of standard hormonal approaches. A recently conducted randomized, double-blind, placebo-controlled trial in Japan has, for the first time, provided high-quality evidence supporting the efficacy of the cyclic regimen combining estetrol (15 mg) and drospirenone (3 mg) (Drovelis^®) for both primary and secondary dysmenorrhea. After 16 weeks, therapy achieved a statistically significant reduction in pain intensity measured by the Harada score, improvements in quality-of-life indicators, and minimal impact on hemostatic parameters. Estetrol demonstrates more stable interaction with estrogen receptors and a lower tendency to induce desensitization, which supports the potential for long-term use without loss of efficacy. These findings expand therapeutic options for chronic forms of dysmenorrhea and provide a basis for further research in individualized hormonal therapy.