Modes of application of gonadotropin-releasing hormone agonists for endometriosis treatment

Abstract

Gonadotropin-releasing hormone (GnRH) agonists have gained extensive clinical use, ranging from reproduction to oncology. There are many clinically available GnRH agonists and these can be used via various methods of delivery, ranging from nasal application to daily subcutaneous injection and various forms of depot preparations. The depot preparations are available as once-monthly intramuscular or subcutaneous injections or 3-month depot moieties. In addition, there is also a 1-month subcutaneous implant available. However, the mode of action of all preparations is identical. The question arises of whether or not the mode of application is important for the treatment effects of endometriosis. Indeed, the course and extent of circulating serum estradiol level are different when comparing nasal with depot preparations. The serum estradiol concentration decreases more rapidly and distinctly with depot than with nasal preparations. Over a period of 24 weeks, the levels of serum estradiol remain higher under nasal GnRH agonist treatment, compared with the depot preparations. Histomorphological changes, such as gland diameter, gland area, cytoplasm and nuclear area, and stromal extension, change less with nasal GnRH agonist therapy than under depot GnRH-agonist treatment. This is also reflected in the spectrum and severity of side effects of nasal and depot preparations. Side effects were more prominent with depot preparations. In addition, bleeding/spotting control was better with the depot preparations. Furthermore, depot preparations had a lower recurrence rate and the time till recurrence was longer. In addition, subsequent surgical and/or medical treatments were significantly less often required with depot preparations (p < 0.05).