Abstract Introduction Sotatercept, a first-in-class activin ligand trap targeting the TGF-β superfamily, modulates inflammatory and proliferative pathways implicated in pulmonary arterial hypertension (PAH), leading to significant hemodynamic and clinical improvements. Preclinical studies have demonstrated extrapulmonary effects, including dose-dependent reductions in follicle-stimulating hormone (FSH) and increases in hemoglobin concentration. However, the impact of sotatercept on the menstrual cycle has not been previously described. Methods In this retrospective, single-center study, we evaluated menstrual cycle changes in premenopausal women with PAH treated with sotatercept. Among 100 female patients with PAH, we identified 10 premenopausal patients, not on hormonal contraceptive therapy, with regular menstrual cycles who were treated with sotatercept. The Menstrual Bleeding Questionnaire (MBQ), a validated tool assessing menstrual flow, pain, and quality of life, was administered before and after therapy initiation. Laboratory data, including hemoglobin concentration and platelet count, were collected at baseline and follow-up. Results The mean age was 35.8 years, with an average BMI of 31.9 kg/m². One patient was on oral contraceptives. Two patients had a prior history of abnormal uterine bleeding (baseline MBQ 24). The median duration of sotatercept use was 11.5 months. At follow-up, the median MBQ score improved from 12.0 to 9.5 (Wilcoxon signed-rank test, r = 0.47, p = 0.16). Although not statistically significant, most patients reported reductions in menstrual flow, pain, and duration. In both patients with MBQ score 24, follow up score declined by 50%. Mean hemoglobin increased significantly from 14.7 ± 2.3 g/dL to 16.6 ± 1.3 g/dL (p = 0.007, 95% CI 0.67, 3.17). Mean platelet count was 200, without significant variation post intervention. Conclusion Sotatercept was associated with decreased menstrual flow, reduced pain, and shorter cycle duration in premenopausal women with PAH, accompanied by a significant rise in hemoglobin concentration. Although the improvement in MBQ scores did not reach statistical significance, the observed trends suggest potential clinical benefit. Changes in FSH levels related to sotatercept likely drive the observed changes, but FSH levels were not measured in this study. Larger studies are warranted to confirm these findings and further characterize the effects of sotatercept in women reproductive health. This abstract is funded by: None
Khasawneh et al. (Fri,) studied this question.