Diabetes, Obesity, and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
University of Alcalá, Alcalá de Henares, Madrid, Spain.
Sci Rep. 2021 Nov 11;11(1):22097. doi: 10.1038/s41598-021-01606-7.
Normoferritinemic women with functional hyperandrogenism show a mild iron overload. Iron excess, hyperandrogenism, and cardioautonomic dysfunction contribute to blood pressure (BP) abnormalities in these patients. Furthermore, combined oral contraceptives (COC) prescribed for hyperandrogenic symptoms may worse BP recordings. Iron depletion by phlebotomy appears to lower BP in other acquired iron overload conditions. We aimed to determine the effect of iron depletion on the office BP, ambulatory BP monitoring, and frequency of hypertension in patients with functional hyperandrogenism submitted to standard therapy with COC. We conducted a phase 2 randomized, controlled, parallel, open-label clinical trial (NCT02460445) in adult women with functional hyperandrogenism including hyperandrogenic polycystic ovary syndrome and idiopathic hyperandrogenism. After a 3-month run-in period of treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate, participants were randomized (1:1) to three scheduled bloodlettings or observation for another 9 months. Main outcome measures were the changes in office BP, 24-h-ambulatory BP, and frequency of hypertension in both study arms. From June 2015 to June 2019, 33 women were included in the intention-to-treat analyses. We observed an increase in mean office systolic BP [mean of the differences (MD): 2.5 (0.3-4.8) mmHg] and night-time ambulatory systolic BP [MD 4.1 (1.4-6.8) mmHg] after 3 months on COC. The percentage of nocturnal BP non-dippers also increased, from 28.1 to 92.3% (P < 0.001). Office and ambulatory BP did not change throughout the experimental period of the trial, both when considering all women as a whole or as a function of the study arm. The frequency of the non-dipping pattern in BP decreased during the experimental period [OR 0.694 (0.577-0.835), P < 0.001], regardless of the study arm. Decreasing iron stores by scheduled bloodletting does not override the BP abnormalities caused by COC in women with functional hyperandrogenism.
铁蛋白正常的功能性高雄激素血症妇女表现出轻度铁过载。铁过载、高雄激素血症和心脏自主神经功能障碍导致这些患者的血压（BP）异常。此外，为治疗高雄激素血症而开具的复方口服避孕药（COC）可能会使 BP 记录恶化。放血去铁似乎可以降低其他获得性铁过载情况下的 BP。我们旨在确定铁耗竭对接受 COC 标准治疗的功能性高雄激素血症患者的诊室 BP、动态血压监测和高血压频率的影响。我们进行了一项 2 期随机、对照、平行、开放标签临床试验（NCT02460445），纳入了包括高雄激素多囊卵巢综合征和特发性高雄激素血症在内的功能性高雄激素血症的成年女性。在接受 35μg炔雌醇加 2mg环丙孕酮醋酸酯治疗 3 个月的导入期后，参与者按 1:1 随机分为 3 次定期放血或再观察 9 个月。主要结局指标是两个研究组诊室 BP、24 小时动态血压和高血压频率的变化。2015 年 6 月至 2019 年 6 月，共有 33 名女性纳入意向治疗分析。我们观察到 COC 治疗 3 个月后，诊室收缩压[差异的平均值（MD）：2.5（0.3-4.8）mmHg]和夜间动态收缩压[MD 4.1（1.4-6.8）mmHg]升高。夜间血压非杓型的比例也从 28.1%增加到 92.3%（P<0.001）。整个试验的实验期间，诊室和动态 BP 均未发生变化，无论是考虑所有女性整体还是作为研究臂的函数。BP 非杓型的频率在实验期间下降[比值比 0.694（0.577-0.835），P<0.001]，与研究臂无关。定期放血降低铁储存并不能消除 COC 引起的功能性高雄激素血症妇女的 BP 异常。
