Harlow B L, Cramer D W, Baron J A, Titus-Ernstoff L, Greenberg E R
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Epidemiol Biomarkers Prev. 1998 Aug;7(8):697-702.
Long-term use of psychotropic medication may increase the risk for epithelial ovarian cancer through increased gonadotropin secretion or direct ovarian stimulation of adrenergic receptors, effects which may affect ovarian cancer pathogenesis. An earlier case-control study found that prior use of antidepressants or benzodiazepine tranquilizers was associated with a 2-fold increase in risk of epithelial ovarian cancer. However, that study lacked details on all types of psychotropic medications, length of use, and the categorization of the specific action of these medications on the hypothalamic-pituitary-ovarian axis. In a new case-control study conducted in eastern Massachusetts (MA) and all of New Hampshire (NH), we identified all women with newly diagnosed ovarian cancer between May 1992 and March 1997. We interviewed 563 women diagnosed with malignant or borderline epithelial ovarian tumors and 523 controls identified through random digit dialing and the use of Town Books (residential listings by name, age, and precinct). Participants were asked to provide the name of medications used for 6 months or longer, the age at first use, and total months or years of use. Psychotropic medications included amphetamines, sedatives, barbiturates/anticonvulsants, antidepressants, and antipsychotics. Self-reported use of psychotropic medication for 6 months or longer was associated with a statistically significant increase in risk of invasive ovarian cancer [odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.3]. Relative to nonusers, risk was greatest in those whose first use occurred premenopausally for more than 2 years (OR, 2.9; CI, 1.3-6.6). The association was largely confined to use of medications that operate through dopaminergic mechanisms (OR, 2.9; CI, 1.3-6.4) or gabaergic pathways (OR, 1.5; CI, 0.9-2.5) as opposed to serotoninergic pathways (OR, 1.0; CI, 0.4-2.1). These results are consistent with the hypothesis that psychotropic medications induce gonadotropin secretion, which in turn may increase ovarian cancer risk. However, until other studies confirm our findings and determine whether they apply to medications with specific neuroendocrine actions, it is premature to advise a change in clinical practice and conclude that these medications indeed play a role in the etiology of ovarian cancer.
长期使用精神药物可能通过增加促性腺激素分泌或直接刺激卵巢肾上腺素能受体而增加上皮性卵巢癌的风险，这些作用可能会影响卵巢癌的发病机制。一项较早的病例对照研究发现，既往使用抗抑郁药或苯二氮䓬类镇静剂会使上皮性卵巢癌风险增加两倍。然而，该研究缺乏关于所有类型精神药物、使用时长以及这些药物对下丘脑 - 垂体 - 卵巢轴具体作用分类的详细信息。在一项在马萨诸塞州东部（MA）和新罕布什尔州全境（NH）进行的新病例对照研究中，我们确定了1992年5月至1997年3月期间所有新诊断为卵巢癌的女性。我们采访了563名被诊断患有恶性或交界性上皮性卵巢肿瘤的女性以及523名通过随机数字拨号和使用城镇名录（按姓名、年龄和选区列出的居民名单）确定的对照者。参与者被要求提供使用6个月或更长时间的药物名称、首次使用年龄以及使用的总月数或年数。精神药物包括苯丙胺、镇静剂、巴比妥类/抗惊厥药、抗抑郁药和抗精神病药。自我报告使用精神药物6个月或更长时间与侵袭性卵巢癌风险在统计学上显著增加相关[比值比（OR），1.6；95%置信区间（CI），1.1 - 2.3]。相对于未使用者，首次使用发生在绝经前超过2年的人群风险最高（OR，2.9；CI，1.3 - 6.6）。这种关联主要局限于通过多巴胺能机制起作用的药物（OR，2.9；CI，1.3 - 6.4）或γ - 氨基丁酸能途径（OR，1.5；CI，0.9 - 2.5），而非5 - 羟色胺能途径（OR，1.0；CI，0.4 - 2.1）。这些结果与精神药物诱导促性腺激素分泌进而可能增加卵巢癌风险的假设一致。然而，在其他研究证实我们的发现并确定它们是否适用于具有特定神经内分泌作用的药物之前，建议改变临床实践并得出这些药物确实在卵巢癌病因中起作用的结论还为时过早。
