Acetyl-l-carnitine as possible drug in the treatment of hypothalamic amenorrhea

Several neuroendocrine disregulations have been demonstrated in patients with hypothalamic amenorrhea, but a definite therapeutic strategy has not yet been found. Since acetyl-l-carnitine (ALC) has been reported to have a specific effect on central cholinergic, serotoninergic, dopaminergic and opioidergic systems, 20 patients with hypothalamic amenorrhea were treated with ALC (2 g/day, per os). Both the clinical efficacy and the endocrine parameters were evaluated after 6 months. The patients were subdivided in two groups according to their LH plasma levels: A) hypogonadotropic: 10 subjects with plasma LH < 3 mIU/ml, and B) normogonadotropic: 10 subjects with plasma LH > 3 mIU/ml. All subjects underwent: 1) a pulsatility study (4 h sampling every 10 min), 2) GnRH test (two bolus injections of 10 mu g at time 0 and +120), 3) TRH test (200 mu g). These parameters were evaluated before and after 6 months of ALC administration. The occurrence of a spontaneous menstruation was observed in 6 out of 10 hypogonadotropinemic and in 4 out of 10 normogonadotropinemic patients. Menstrual bleeding occurred between the 3rd and the 6th month of therapy. Major hormonal changes after ALC administration were observed in the hypogonadotropic subjects. They showed a significant increase in baseline plasma LH levels (from 0.9 +/- 0.1 to 3.5 +/- 0.7 mIU/ml, p < 0.05) (mean +/- SEM), a significant increase in LH pulse amplitude 0, < 0.01) with no changes in LH pulse frequency, and a significantly increased response of LH to the latter GnRH bolus during the GnRH test. Hypogonadotropic patients also showed a significant increase in both estradiol (from 18.8 +/- 2.5 to 48 +/- 3.3 pg/ml, p < 0.05) and PRL (from 6 +/- 1 to 11.4 +/- 1.7 ng/ml, p < 0.05). No significant differences were observed in the hormonal parameters of normogonadotropic patients after 6 months of ALC therapy. Thus, ALC treatment was effective in some patients with hypothalamic amenorrhea, inducing a menstrual bleeding and a normal menstrual cycle. Moreover, in patients with hypogonadotropic amenorrhea, ALC treatment raised the LH plasma levels and LH response to exogenous GnRH. These data support the possible use of acetyl-l-carnitine as drug for the treatment of some forms of hypothalamic amenorrhea.