BACKGROUND Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits. OBJECTIVE AND RATIONALE The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences. SEARCH METHODS Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound. OUTCOMES The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients. WIDER IMPLICATIONS Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis. REGISTRATION NUMBER Not applicable.

中文翻译：

---

功能性下丘脑闭经和多囊卵巢形态学：关于有趣关联的叙述性回顾。


背景 功能性下丘脑闭经 （FHA） 占所有继发性闭经病例的 20-35%，因此是继多囊卵巢综合征 （PCOS） 之后继发性闭经的第二大最常见原因。大量 FHA 患者在超声上显示多囊卵巢形态 （PCOM）。闭经和 PCOM 的组合会导致混淆。首先，患有 PCOM 的闭经女性符合修订后的 Rotterdam 标准，因此很容易被误诊为 PCOS。此外，据称，一些患有 FHA 和伴随 PCOM 的女性在内分泌调节和代谢特征方面与没有 PCOM 的女性不同。客观和基本原理 本文的主要重点是关于 FHA 的研究，FHA 区分了有或没有 PCOM 的患者。目的是估计 PCOM 的患病率，并查看它是否对病理生理学、诊断和治疗问题以及长期后果有影响。检索方法 同行评议、原始文章和综述文章是从 PubMed 检索中选出的。使用检索词“多囊和功能性下丘脑闭经”进行检索。检索找到的出版物的参考文献列表以查找相关的其他研究。出版物的纳入标准是：英语、患者年龄≥ 18 岁、出版年份 >1980、原始研究、经阴道超声验证的 FHA 诊断和 PCOM 的验证诊断。结果 FHA 女性 PCOM 的患病率从 41.9% 到 46.7% 不等，高于健康的非 PCOS 对照。假设，高患病率可能是由于一般人群中无症状 PCOM 和预先存在的 PCOS 的混合。 在 FHA-PCOM 和 FHA-non-PCOM 患者之间发现代谢和激素参数的几个差异。虽然雌激素缺乏在两组患者中都很常见，但 FHA-PCOM 患者的 BMI 较高，抗苗勒管激素 （AMH） 和睾酮水平较高，GnRH 测试过程中 LH 增加较高，性激素结合球蛋白 （SHBG） 水平低于 FHA 非 PCOM 患者。FHA-PCOM 和 PCOS 之间的鉴别诊断，尤其是 PCOS 表型 D （PCOM 和无雄激素过多症的少排卵/无排卵），可能具有挑战性。已经提出了几个参数，这些参数虽然不是绝对可靠的，但很有帮助。它们包括 FHA 的典型原因（过度运动、能量不足和/或心理压力）、血清 LH、睾酮和 SHBG 水平，以及孕激素激发试验。FHA-PCOM 是否对患者的代谢和心血管状况以及他们的骨量的长期后果具有不同的风险状况，目前尚不清楚。在治疗方面，与 FHA-non-PCOM 相比，关于 FHA-PCOM 的数据很少。为了治疗无排卵，使用搏动性 GnRH 治疗似乎在两组中同样有效。与 FHA 非 PCOM 患者类似，在 FHA-PCOM 患者中，搏动性 GnRH 治疗比外源性促性腺激素更有效。更广泛的影响 患有 FHA-PCOM 的女性代表了 FHA 患者的一个特殊亚群。FHA-PCOM 的诊断陷阱应在有关 FHA 和 PCOS 的临床指南中强调。几乎一半的 FHA 女性卵巢卵泡过多（即 PCOM） 面对低促性腺激素血清水平表明卵泡发生的卵巢内调节受个体差异的影响，原因未知，无论是遗传的还是表观遗传的。需要进一步的研究来调查这一假设。注册号 不适用。