Pharmacokinetic analysis of 25 mg estradiol subcutaneous bioabsorbable implant in postmenopausal women (CLARA STUDY)

绝经后妇女皮下植入25毫克雌二醇生物可吸收植入剂的药代动力学分析(CLARA研究)

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Abstract

OBJECTIVE: To investigate the pharmacokinetic profile of estradiol delivery after the subcutaneous insertion of a 25 mg estradiol bioabsorbable implant in hysterectomized women presenting with menopause-associated symptoms. METHODS: This was a prospective, open-label, single-arm study conducted at a single center between December 2023 and October 2024. Twenty hysterectomized participants received a 25 mg subcutaneous estradiol implant and were followed at weeks 4, 12, and 24 for clinical assessments, symptom evaluation, and safety monitoring. Hormone levels were measured using liquid chromatography-tandem mass spectrometry and electrochemiluminescence immunoassay. Adverse events were recorded, and menopause symptoms were assessed using the Menopause Rating Scale (MRS). RESULTS: Serum estradiol levels increased after treatment, rising from 31.6±7.0 pg/mL preinsertion to 105.2±10.7 pg/mL (mean±SD) at week 1, remaining stable (~80 pg/mL) through Week 20 and above pre-insertion levels until week 24. Estrone had a similar profile. Follicle-stimulating hormone and luteinizing hormone levels decreased throughout the treatment. Sex hormone-binding globulin, total and free testosterone, and prolactin showed minimal variation throughout the study. Subcutaneous estradiol delivery resulted in a sustained pharmacokinetic profile characterized by a Tmax of 75.6 hours and a 6439 hours notably extended half-life (T1/2). Vasomotor and psychological symptoms decreased significantly after 4 weeks of treatment, and the reduction in Menopause Rating Scale score was observed until Week 24. No serious adverse event was reported. CONCLUSION: The 25 mg estradiol implant provided sustained serum concentration of estradiol over a 24-week period of treatment, effective symptom relief, and an acceptable safety profile in hysterectomized women, thereby offering a novel therapeutic option for hormone therapy.

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