The aim of the study is to evaluate the efficacy of combined therapy, including the preparation of pineamine and low-dose menopausal hormone therapy, in patients with severe menopausal syndrome, as well as the dynamics of menopausal symptoms and levels of kisspeptin and neurokinin B neuropeptides in the blood against the background of treatment. Results. The results of menopausal syndrome severity assessment showed that all patients had severe menopausal disorders before treatment. At the 3rd visit a statistically significant decrease in the degree of menopausal syndrome severity was found in both groups. However, at all stages of the study a more pronounced effect was found in patients of the 1st group who received combined therapy with MHT and pinepamine, which was achieved faster both for vasomotor and other menopausal syndromes (sleep disturbance). It is important that a more significant clinical effect was obtained without increasing the dose of menopausal hormone therapy. Against the background of the performed therapy there was established a decrease in neuropeptide levels (kisspeptin and neurokinin B), which is more pronounced in the use of combined therapy, which clearly demonstrates the main mechanism of antagonistic action of menopausal hormonal therapy and pineamine on activated vasomotor triggers of hypothalamic neurons. Conclusion. Pineamine may be recommended to be used in combination with MHT as an effective and safe medicine with an alternative mechanism of action for the treatment of menopausal symptoms not require MHT dose increase.