CHU Lille, Unité Fonctionnelle de Gynécologie Endocrinienne, Service de Gynécologie Médicale, Orthogénie et Sexologie, Hôpital Jeanne de Flandre, Lille, France.
Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean- Pierre Aubert Research Centre, Lille 59945, France.
Hum Reprod. 2021 Mar 18;36(4):1043-1051. doi: 10.1093/humrep/deab024.
Are serum levels of anti-Müllerian hormone (AMH) normal in patients with functional hypothalamic anovulation (FHA)?
Our study confirms that in the general FHA population, serum AMH levels are not decreased, but if patients with polycystic ovarian morphology (PCOM) are excluded, levels become significantly lower, as in other situations of gonadotropic insufficiency.
In most situations of low LH (physiological, pharmacological or pathological), serum AMH levels are low. However, paradoxically, many publications have reported normal or even increased serum AMH levels in FHA patients.
STUDY DESIGN, SIZE, DURATION: Retrospective observational study conducted in an academic centre. The data concerning the study population was collected between 2006 and 2015 from a database including clinical, biological and ultrasound information.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 45 FHA patients were compared to 37 controls matched based on age and body mass index (BMI). Serum LH, FSH, androstenedione, total testosterone, prolactin and AMH levels were measured by immunoassay. We defined PCOM with strict criteria: a follicle number per ovary (FNPO) ≥ 12 or ≥ 19 per ovary, depending on the date on which the assessment was carried out and the ultrasound device. An AMH level ≥ 35 pmol/l could be a substitute for an excess FNPO. Controls meeting these criteria were not included in this study.
There was no significant difference in the ranges of AMH levels between FHA and controls. Using strict criteria to define PCOM status, 46.7% of FHA patients had PCOM. After excluding these patients, the levels of AMH were significantly lower (P < 0.002) in FHA patients compared to controls. Within the FHA group, patients with PCOM had significantly higher ranks of AMH levels and BMI than those without PCOM. However, within the PCOM+ subgroup, the ranks of LH, FSH and A levels were still lower than in controls (P < 0.0001, <0.002 and <0.05, respectively). The positive correlation between AMH and LH was significant in the controls but not in the FHA group. However, in the FHA PCOM+, there was a strong positive correlation between BMI and LH.
LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study; our controls did not represent the general population as they were recruited in an ART centre; we used a modified classification for PCOM using follicle count and/or AMH level with in-house thresholds to define the follicle excess; the AMH assay used is no longer commercially available.
Besides biasing the results of AMH assay in FHA patients, the presence of PCOM in FHA patients despite low gonadotropin and androgen levels raises the issue of epigenetically acquired amplification of androgen and/or FSH sensitivity within granulosa cells from polycystic ovaries. In terms of clinical practice, it seems important not to diagnose a low ovarian reserve in FHA patients too quickly on the basis of a decreased AMH level alone. On the contrary, a high AMH level in the context of a menstrual disorder and PCOM should not lead to a misdiagnosis of polycystic ovary syndrome (PCOS) if the basal LH is low.
STUDY FUNDING/COMPETING INTEREST(S): None.
N/A.
功能性下丘脑性无排卵（FHA）患者的血清抗苗勒管激素（AMH）水平是否正常？
我们的研究证实，在一般 FHA 人群中，血清 AMH 水平没有降低，但如果排除多囊卵巢形态（PCOM）患者，则水平显著降低，与其他促性腺激素不足情况相同。
在大多数 LH 水平较低的情况下（生理性、药理学或病理性），血清 AMH 水平较低。然而，矛盾的是，许多出版物报告 FHA 患者的血清 AMH 水平正常甚至升高。
研究设计、大小和持续时间：在一个学术中心进行的回顾性观察性研究。2006 年至 2015 年期间，从包括临床、生物学和超声信息的数据库中收集了有关研究人群的数据。
参与者/材料、设置、方法：将 45 例 FHA 患者与 37 例基于年龄和体重指数（BMI）匹配的对照进行比较。通过免疫测定法测量血清 LH、FSH、雄烯二酮、总睾酮、催乳素和 AMH 水平。我们使用严格的标准定义 PCOM：每个卵巢的卵泡数（FNPO）≥12 或≥19，具体取决于评估日期和使用的超声设备。AMH 水平≥35pmol/L 可以替代 FNPO 过多。符合这些标准的对照不包括在本研究中。
FHA 和对照组之间的 AMH 水平范围没有显著差异。使用严格的标准定义 PCOM 状态，46.7%的 FHA 患者存在 PCOM。排除这些患者后，FHA 患者的 AMH 水平明显低于对照组（P<0.002）。在 FHA 组中，患有 PCOM 的患者的 AMH 水平和 BMI 等级明显高于没有 PCOM 的患者。然而，在 PCOM+亚组中，LH、FSH 和 A 水平的等级仍然低于对照组（P<0.0001、<0.002 和<0.05）。在对照组中，AMH 与 LH 之间存在显著的正相关，但在 FHA 组中则不存在。然而，在 FHA PCOM+中，BMI 和 LH 之间存在很强的正相关。
局限性、谨慎的原因：这是一项回顾性研究；我们的对照组不能代表一般人群，因为他们是在 ART 中心招募的；我们使用改良的分类方法，使用卵泡计数和/或 AMH 水平以及内部阈值来定义卵泡过多；使用的 AMH 检测方法不再商业化。
除了偏倚 FHA 患者 AMH 检测结果外，尽管 FHA 患者的促性腺激素和雄激素水平较低，但仍存在 PCOM，这引发了关于多囊卵巢内颗粒细胞中雄激素和/或 FSH 敏感性的表观遗传获得性扩增的问题。在临床实践中，似乎很重要的是，不要仅仅基于降低的 AMH 水平，在 FHA 患者中过快地诊断卵巢储备功能低下。相反，如果基础 LH 较低，在月经失调和 PCOM 的情况下，高 AMH 水平不应导致多囊卵巢综合征（PCOS）的误诊。
研究资金/利益冲突：无。
无。
