Treatment of symptomatic uterine adenomyosis with linzagolix, an oral gonadotrophin-releasing hormone antagonist: a pilot study.

Research Question: Does a once-daily regimen of linzagolix, a new oral gonadotrophin-releasing hormone (GnRH) antagonist, given at a fully suppressive dose (200 mg) for 12 weeks, followed by a partially suppressive dose (100 mg) for a further 12 weeks, reduce adenomyotic uterine size and associated symptoms?

Design: Eight women (aged 37-45 years) with adenomyosis confirmed by magnetic resonance imaging (MRI) were enrolled in a single-centre, open-label pilot study. The primary efficacy end-point was the change in uterine volume on MRI at 24 weeks. Secondary efficacy end-points included serum oestradiol, overall pelvic pain, dysmenorrhoea, non-menstrual pelvic pain, dyspareunia, dyschezia and quality of life (QoL). Bone mineral density (BMD) was assessed at baseline and 24 weeks.

Results: At baseline, uterine volume (mean ± SD) was 333 ± 250 cm. After 24 weeks, it was 204 ± 126 cm, a reduction of 32% from baseline (P = 0.0057). After 12 weeks, it was 159 ± 95 cm, a reduction of 55% (P < 0.0001). Median serum oestradiol was suppressed below 20 pg/ml during the 12 weeks on 200 mg linzagolix, and maintained below 60 pg/ml on 100 mg linzagolix. Improvements in overall pelvic pain, dysmenorrhoea, non-menstrual pelvic pain, dyspareunia, dyschezia and QoL were observed. Mean percentage change in BMD loss at 24 weeks was -2.4%, -1.3% and -4.1% for the spine, femoral neck and total hip, respectively. The most common adverse events were hot flushes.

Conclusions: A once-daily regimen of 200 mg linzagolix for 12 weeks and then 100 mg for another 12 weeks decreased adenomyotic uterine volume and improved associated symptoms.