Vitale Salvatore Giovanni, Di Michele Stefano, Tassi Alice, Succu Claudia, Angioni Stefano, Fulghesu Anna Maria
Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Via Università 40, 09124, Cagliari, Italy.
Obstetrics and Gynecology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.
Adv Ther. 2025 Jun 6. doi: 10.1007/s12325-025-03251-2.
This study aimed to evaluate metformin treatment's immediate and long-term efficacy in adolescent patients with polycystic ovary syndrome (PCOS) and hyperinsulinemia and the subsequent metabolic evolution post-treatment discontinuation.
This single-center, retrospective cohort study included 168 adolescent girls (12-17 years) diagnosed with PCOS between December 2018 and August 2024. All participants underwent an oral glucose tolerance test to evaluate insulin sensitivity and were stratified into two groups: patients with normal insulinemia (n = 21) and patients with hyperinsulinemia (n = 147). Patients with hyperinsulinemia were offered low-dose metformin (500 mg twice daily); 80 accepted and formed the treatment arm, while 53 declined and served as controls. Simultaneously, every subject received a continuous regimen of combined oral contraceptives (COCs) (30 µg ethinyl estradiol/3 mg drospirenone). Clinical, biochemical, and ultrasound assessments were conducted at baseline, at regular intervals during therapy, at the end of treatment, and at least 24 months after metformin discontinuation to evaluate immediate and long-term outcomes.
Metformin therapy yielded favorable body mass index, insulin sensitivity, and androgenic profile outcomes. Remarkably, these benefits persisted beyond the cessation of treatment. Metformin responders showed a ≥ 20% decrease in the insulin area under the curve values post-treatment. Our investigation revealed a substantial reduction in insulin resistance indices, evident both after therapy (p < 0.001) and during post-therapy follow-up (p = 0.001) compared to baseline values. Furthermore, patients showed improvements in clinical hyperandrogenism and reductions in ovarian volume.
Our study highlights the effectiveness of low-dose metformin therapy in improving insulin resistance and metabolic parameters among adolescent patients with PCOS. Sustained benefits were observed even after treatment cessation. These findings underscore the potential for early intervention with metformin during adolescence to confer long-lasting advantages in managing metabolic abnormalities associated with PCOS.
本研究旨在评估二甲双胍治疗对患有多囊卵巢综合征（PCOS）和高胰岛素血症的青少年患者的近期和长期疗效，以及治疗停药后的代谢演变情况。
这项单中心回顾性队列研究纳入了2018年12月至2024年8月期间诊断为PCOS的168名青春期女孩（12 - 17岁）。所有参与者均接受口服葡萄糖耐量试验以评估胰岛素敏感性，并分为两组：胰岛素血症正常的患者（n = 21）和高胰岛素血症患者（n = 147）。为高胰岛素血症患者提供低剂量二甲双胍（每日两次，每次500毫克）；80人接受并形成治疗组，而53人拒绝并作为对照组。同时，每个受试者接受连续的复方口服避孕药（COC）方案（30微克炔雌醇/3毫克屈螺酮）。在基线、治疗期间定期、治疗结束时以及二甲双胍停药后至少24个月进行临床、生化和超声评估，以评估近期和长期结果。
二甲双胍治疗产生了有利的体重指数、胰岛素敏感性和雄激素谱结果。值得注意的是，这些益处持续到治疗停止之后。二甲双胍治疗有反应者治疗后曲线下胰岛素面积值下降≥20%。我们的研究表明，与基线值相比，胰岛素抵抗指数在治疗后（p < 0.001）和治疗后随访期间（p = 0.001）均显著降低。此外，患者的临床高雄激素血症有所改善，卵巢体积减小。
我们的研究强调了低剂量二甲双胍治疗在改善PCOS青少年患者胰岛素抵抗和代谢参数方面的有效性。即使在治疗停止后仍观察到持续的益处。这些发现强调了青春期早期使用二甲双胍进行干预在管理与PCOS相关的代谢异常方面具有持久优势的潜力。
