Vascular Anomalies Unit, Department of Pediatric Surgery, Children's Hospital La Paz, Madrid, Spain.
Pediatr Blood Cancer. 2021 Mar;68(3):e28867. doi: 10.1002/pbc.28867. Epub 2020 Dec 27.
Sirolimus has become a pillar in the treatment of vascular anomalies due to its inhibition of the mammalian target of rapamycin (mTOR). Adverse effects include metabolic and hematologic disorders among others, although menstrual disorders have not been well described.
Retrospective review of patients with vascular anomalies on sirolimus treatment was performed. Patients presenting menstrual alterations were included.
One hundred and thirty-six patients with vascular anomalies on treatment with sirolimus were reviewed, finding seven women out of 74 (9.4%) who presented menstrual alterations attributable to the treatment. These seven patients presented with different vascular malformations and three showed pathogenic variants in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in affected tissue. Partial response in six and stability in one patient was obtained after treatment, administered for an average of 27.5 months (6-48). Five patients have completed treatment and two patients continue on after 12 and 15 months, respectively. All patients reported regular menstrual cycles prior to sirolimus treatment. One patient presented with amenorrhea for 4 months after treatment initiation that later spontaneously resolved. The other six patients presented with hypermenorrhea, four of them associating metrorrhagia. Most patients presented with mild menstrual alterations, without needing dose reduction or withdrawal, although one discontinued sirolimus due to hypermenorrhea, metrorrhagia, and hematuria. After sirolimus withdrawal, regular menstrual cycles were restored in five patients.
Sirolimus treatment can produce menstrual disorders as adverse effects. Although mild and reversible upon dose reduction or cessation of treatment, patients and physicians should be aware on this potential side effect.
由于雷帕霉素（Sirolimus）能够抑制哺乳动物雷帕霉素靶蛋白（mTOR），因此它已成为血管异常治疗的主要药物之一。其不良反应包括代谢和血液系统紊乱等，但月经紊乱尚未得到很好的描述。
对接受雷帕霉素治疗的血管异常患者进行回顾性研究。纳入出现月经改变的患者。
共对 136 例接受雷帕霉素治疗的血管异常患者进行了回顾，发现 74 例女性患者中有 7 例（9.4%）出现与治疗相关的月经改变。这 7 名患者患有不同的血管畸形，其中 3 名患者在受影响的组织中发现磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位α（PIK3CA）的致病性变异。经过平均 27.5 个月（6-48 个月）的治疗，6 名患者获得部分缓解，1 名患者病情稳定。5 名患者已完成治疗，2 名患者分别在治疗后 12 个月和 15 个月继续治疗。所有患者在接受雷帕霉素治疗前均有规律的月经周期。1 名患者在治疗开始后出现闭经 4 个月，后来自行缓解。其余 6 名患者出现月经过多，其中 4 名患者伴有经间期出血。大多数患者的月经改变轻微，无需减少剂量或停药，但有 1 名患者因月经过多、经间期出血和血尿而停用雷帕霉素。停用雷帕霉素后，5 名患者的月经周期恢复正常。
雷帕霉素治疗可引起月经紊乱等不良反应。虽然这种不良反应在减少剂量或停药后是轻度和可逆的，但患者和医生都应该意识到这种潜在的副作用。
