Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA)

Abstract

Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

Chinese abstract

功能性下丘脑性闭经（FHA）是由代谢、生理或心理因素等多因素作用造成的一种较常见疾病。该病的特征为内源性GnRH刺激产生的促性腺激素分泌减少, 导致卵巢功能抑制和低雌激素状态。目前已有包括使用激素和神经活性药物治疗在内的多种治疗方案。现已证实左-乙酰肉碱（LAC）可有效调节下丘脑激素GnRN的分泌, 而本研究的目的就在于评估12周LAC（250mg/日）和左旋肉碱

（500mg/日）联合治疗方案是否能有效改善所纳入的27名FHA患者的内分泌和代谢状态。用药后患者血浆LH水平升高而皮质醇和淀粉酶水平明显降低。根据患者LH基础值将患者分为低LH组和LH正常组后发现, 仅低LH组的LH水平明显升高且皮质醇和淀粉酶水平明显降低。 17-羟孕酮/皮质醇比值作为反映肾上腺素活动的指标表明因压力导致的肾上腺素活动有所减少。综上, 本研究结果支持LAC和左旋肉碱联合用药可减轻FHA患者代谢异常和神经内分泌损伤的假说。

Keywords:

• Amylase
• carnitine; cortisol
• functional hypothalamic amenorrhea
• stress

Disclosure statement

The authors have nothing to declare.