Risk factors for medication-induced amenorrhea in first-episode female Chinese patients with schizophrenia treated with risperidone Translated title: 汉族女性精神分裂症首发患者利培酮治疗所致闭经的危险因素

Abstract

Background

Amenorrhea is a common adverse effect of treatment with antipsychotic medications that influences both fertility and adherence to medication regimens. Most research suggests that medication-induced prolactinemia is the main cause of amenorrhea but few prospective studies have assessed this hypothesis.

Aim

Identify risk factors for amenorrhea following treatment with antipsychotic medication.

Methods

The study used a prospective, nested case-control design. First-episode, drug naïve female patients with schizophrenia who were in the middle of their menstrual cycle at the time of admission were enrolled. Serum levels of six reproductive hormones were assessed before and after a 12-week course of treatment with risperidone: progesterone, estradiol, prolactin, follicular stimulating hormone, luteinizing hormone, and testosterone. The hormone levels of 31 patients who had no menstruation during the entire 12 weeks of treatment (the amenorrhea group) were compared to those of 31 age-matched subjects who had normal menstrual periods over the 12 weeks of treatment (the control group).

Results

We found a dramatic 4-fold increase in prolactin levels in women of childbearing age treated with risperidone, but the pretreatment and posttreatment levels of prolactin were not different between patients who did and did not develop amenorrhea with treatment. However, there were significantly lower pretreatment levels of estradiol and progesterone in patients who subsequently developed amenorrhea with risperidone treatment than in patients who did not develop amenorrhea. A conditional logistic regression analysis found that pretreatment levels of estradiol remained significantly associated with the development of amenorrhea during treatment even when adjusting for the pretreatment levels of the other five reproductive hormones assessed.

Conclusion

These findings do not support the suggestion that amenorrhea associated with the use of antipsychotic medication is the result of hyperprolactinemia. If our finding of the predictive power of pretreatment levels of estradiol is confirmed in larger studies, this information would be of use to clinicians in selecting antipsychotic medications for female patients with schizophrenia; patients at highest risk of developing amenorrhea could be preferentially treated with the medications that are at lowest risk of inducing amenorrhea.

Translated abstract

背景

闭经是抗精神病药治疗时常见的不良反应。这一不良反应不仅会影响生育，还会影响患者对药物治疗方案的依从性。多数研究提示药物所致高泌乳素血症是闭经的主要原因，但是极少有前瞻性研究评估这一假设。

目的

找出抗精神病药治疗后出现闭经的危险因素。

方法

研究采用前瞻性巢式病例－对照设计。将入院时处于月经周期的中间时段、未接受抗精神病药治疗的首发精神分裂症患者纳入研究。分别在利培酮治疗前和治疗 12 周后测定血清中 6 种生殖激素的水平，即孕酮、雌二醇、泌乳素、促卵泡激素、促黄体生成素以及睾酮水平。将利培酮治疗 12 周内未来月经的 31 例患者（闭经组）与年龄匹配、月经仍然规律的 31 例患者（对照组）对照，比较上述激素水平。

结果

我们发现育龄妇女利培酮治疗后泌乳素水平升高 4 倍，但无论治疗前还是治疗后闭经组和对照组之间的泌乳素水平差异不明显。然而，治疗前闭经组的雌二醇及孕酮水平均显著低于对照组。条件Logistic回归分析发现，在校正了治疗前其他 5 种生殖激素水平后，治疗前雌二醇水平仍然与治疗期间出现闭经显著相关。

结论

本研究结果不支持高泌乳素血症导致抗精神病药物治疗相关的闭经这一观点。如果本研究结果中雌二醇水平的预测作用能够得到大样本研究的证实，那么临床医师可以利用这一信息为女性精神分裂症患者选择合适的抗精神病药物，对易发生闭经的高风险患者而言可以优先选用导致闭经风险低的药物治疗。