多囊卵巢综合征女性脑脊液中 GABA、睾酮和雌二醇水平升高。
Increased cerebrospinal fluid levels of GABA, testosterone and estradiol in women with polycystic ovary syndrome.
机构信息
Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA.
Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
出版信息
Hum Reprod. 2017 Jul 1;32(7):1450-1456. doi: 10.1093/humrep/dex086.
STUDY QUESTION
Do cerebrospinal fluid (CSF) concentrations of gamma-aminobutyric acid (GABA), testosterone (T) and estradiol (E2) differ in women with polycystic ovary syndrome (PCOS) as compared to eumenorrheic, ovulatory women (EW)?
SUMMARY ANSWER
Women with PCOS displayed higher CSF levels of GABA and E2, and possibly T, than EW.
WHAT IS KNOWN ALREADY
The chronic anovulation characteristic of PCOS has been attributed to increased central GnRH drive and resulting gonadotropin aberrations. Androgens are thought to regulate GABA, which in turn regulates the neural cascade that modulates GnRH drive.
STUDY DESIGN, SIZE, DURATION: This cross-sectional observational study included 15 EW and 12 non-obese women with PCOS who consented to a lumbar puncture in addition to 24 h of serum blood collection at 15-min intervals.
PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 27 women were studied at a the General Clinical Research Center (GCRC) at the University of Pittsburgh. Serum analytes included T, E2 and androstenedione. CSF analytes included GABA, glutamate, glucose, T and E2.
MAIN RESULTS AND THE ROLE OF CHANCE
Women with PCOS had higher CSF GABA as compared to EW (9.04 versus 7.04 μmol/L, P < 0.05). CSF glucose and glutamate concentrations were similar between the two groups. CSF T was 52% higher (P = 0.1) and CSF E2 was 30% higher (P < 0.01) in women with PCOS compared to EW. Circulating T was 122% higher (P < 0.01) and circulating E2 was 75% higher (P < 0.01) in women with PCOS than in EW.
LIMITATIONS REASONS FOR CAUTION
The study is limited by its small sample size and the technical limitations of measuring CSF analytes that are pulsatile and have short half-lives.
WIDER IMPLICATIONS OF THE FINDINGS
Women with PCOS displayed significantly higher circulating levels of T and E2, significantly higher CSF levels of E2, and higher levels of CSF testosterone, although the latter was not statistically significant. A better understanding of the central milieu informs our understanding of the mechanisms mediating increased the GnRH drive in PCOS and lends a new perspective for understanding the presentation, pathogenesis and potential health consequences of PCOS, including gender identity issues.
STUDY FUNDING/COMPETING INTEREST(S): No conflicts of interest. The study was funded by NIH grants to SLB (RO1-MH50748, U54-HD08610) and NIH RR-00056 to the General Clinical Research Center of the University of Pittsburgh.
TRIAL REGISTRATION NUMBER
NCT01674426.
研究问题
多囊卵巢综合征（PCOS）患者与月经正常排卵的女性（EW）相比，其脑脊液（CSF）中γ-氨基丁酸（GABA）、睾丸酮（T）和雌二醇（E2）的浓度是否存在差异？
总结答案
与 EW 相比，PCOS 患者的 CSF 中 GABA 和 E2 水平升高，而 T 水平可能也升高。
已知情况
PCOS 的慢性无排卵特征归因于 GnRH 驱动的中枢增加和随之而来的促性腺激素异常。雄激素被认为可以调节 GABA，而 GABA 又可以调节调节 GnRH 驱动的神经级联反应。
研究设计、规模、持续时间：这项横断面观察性研究纳入了 15 名 EW 和 12 名非肥胖的 PCOS 女性，她们除了在匹兹堡大学的综合临床研究中心（GCRC）接受 15 分钟间隔的 24 小时血清血液采集外，还同意进行腰椎穿刺。
参与者/材料、地点、方法：共有 27 名女性在 GCRC 接受了研究。血清分析物包括 T、E2 和雄烯二酮。CSF 分析物包括 GABA、谷氨酸、葡萄糖、T 和 E2。
主要结果和机遇的作用
与 EW 相比，PCOS 患者的 CSF GABA 水平更高（9.04 对 7.04 μmol/L，P<0.05）。两组 CSF 葡萄糖和谷氨酸浓度相似。与 EW 相比，PCOS 患者的 CSF T 水平高 52%（P=0.1），CSF E2 水平高 30%（P<0.01）。与 EW 相比，PCOS 患者的循环 T 水平高 122%（P<0.01），循环 E2 水平高 75%（P<0.01）。
局限性和谨慎的原因
该研究受到样本量小以及测量具有脉冲性和半衰期短的 CSF 分析物的技术限制的限制。
研究结果的广泛意义
与 EW 相比，PCOS 患者的 T 和 E2 循环水平显著升高，E2 的 CSF 水平显著升高，T 的 CSF 水平升高，但后者无统计学意义。对中枢环境的更好理解有助于我们理解 PCOS 中 GnRH 驱动增加的中介机制，并为理解 PCOS 的表现、发病机制和潜在健康后果（包括性别认同问题）提供了新的视角。
研究资金/利益冲突：无利益冲突。该研究由 NIH 授予 SLB 的 RO1-MH50748 和 NIH RR-00056 资助，用于匹兹堡大学综合临床研究中心的 U54-HD08610。
临床试验注册号
NCT01674426。
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