Abstract
(1) Background: The aim of the present pilot study was to study the effect of a new oral gonadotropin-releasing hormone antagonist on adenomyosis. (2) Methods: Eight premenopausal women, aged between 37 and 45 years, presenting with heavy menstrual bleeding, pelvic pain, and dysmenorrhea due to diffuse and disseminated uterine adenomyosis, confirmed by magnetic resonance imaging (MRI), received 200 mg linzagolix once daily for a period of 12 weeks, after which they were switched to 100 mg linzagolix once daily for another 12 weeks. The primary efficacy endpoint was the change in volume of the adenomyotic uterus from baseline to 24 weeks, evaluated by MRI. Secondary efficacy endpoints included the change in uterine volume from baseline to 12 and 36 weeks by MRI, and also weeks 12, 24, and 36 assessed by transvaginal ultrasound (TVUS). Other endpoints were overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, amenorrhea, quality of life measures, bone mineral density (BMD), junctional zone thickness, and serum estradiol values. (3) Results: Median serum estradiol was suppressed below 20 pg/mL during the 12 weeks on linzagolix 200 mg, and maintained below 60 pg/mL during the second 12 weeks on linzagolix 100 mg. At baseline, the mean ± SD uterine volume was 333 ± 250 cm3. After 24 weeks of treatment, it was 204 ± 126 cm3, a reduction of 32% (p = 0.0057). After 12 weeks, the mean uterine volume was 159 ± 95 cm3, a reduction of 55% from baseline (p = 0.0001). A similar pattern was observed when uterine volume was assessed by TVUS. Improvements in overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, and dyschezia, as well as quality of life measured using the EHP-30 were also observed. Mean percentage BMD loss at 24 weeks was, respectively, −2.4%, −1.3%, and −4.1% for the spine, femoral neck, and total hip. The most common adverse events were hot flushes, which occurred in 6/8 women during the first 12 weeks, and 1/8 women between 12 and 24 weeks. (4) Conclusions: Linzagolix at a dose of 200 mg/day reduced uterine volume, and improved clinically relevant symptoms. Treatment with 100 mg thereafter retains the therapeutic benefits of the starting dose while minimizing side effects. This ‘hit hard first and then maintain’ approach may be the optimal way to treat women with symptomatic adenomyosis.
Highlights
The current definition of adenomyosis is largely based on a publication by Bird et al [1], who defined it as benign invasion of the endometrium into the myometrium, producing a diffusely enlarged uterus which microscopically exhibits ectopic, non-neoplastic, endometrial glands, and stroma surrounded by hypertrophic-hyperplastic musculature [1]
We investigated changes from baseline to weeks 12, 24, and 36 in dysmenorrhea, non-menstrual pelvic pain, and dyspareunia according to the modified Biberoglu and Behrman scale, global pelvic pain over the preceding 4-week period using the numerical rating scale (NRS), the average monthly dyspareunia score defined as the mean of available daily dyspareunia scores over the preceding 4-week period evaluated by the verbal rating scale (VRS) and the NRS, the average monthly dyschezia score defined as the mean of weekly dyschezia scores over the preceding 4-week period using the NRS, and the comprehensive Endometriosis Health Profile (EHP-30) questionnaire
According to two further alternative theories, adenomyotic lesions may originate from metaplasia of displaced embryonic pluripotent Müllerian remnants, or differentiation of adult stem cells that are present in the myometrium [2]
Summary
Jacques Donnez 1,2, *,†,‡ , Olivier Donnez 3,† , Jean Tourniaire 4 , Michel Brethous 5 , Elke Bestel 5 , Elizabeth Garner 6 , Sébastien Charpentier 5 , Andrew Humberstone 5 and Ernest Loumaye 5. Secondary efficacy endpoints included the change in uterine volume from baseline to 12 and 36 weeks by MRI, and weeks 12, 24, and 36 assessed by transvaginal ultrasound (TVUS). Other endpoints were overall pelvic pain, dysmenorrhea, non-menstrual pelvic pain, dyspareunia, amenorrhea, quality of life measures, bone mineral density (BMD), junctional zone thickness, and serum estradiol values. After 12 weeks, the mean uterine volume was 159 ± 95 cm , a reduction of 55% from baseline (p = 0.0001). Treatment with 100 mg thereafter retains the therapeutic benefits of the starting dose while minimizing side effects. This ‘hit hard first and maintain’ approach may be the optimal way to treat women with symptomatic adenomyosis
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