The role of heat shock proteins in predicting the course of the climacteric syndrome




perimenopause, climacteric syndrome, menopausal hormone therapy, HSP60, GroEl


The problem of menopause has been relevant for many decades. A pathogenetically justified method of treatment, taking into account the change in the hormonal background of a woman, is hormone replacement therapy. Determination of immune markers of cellular homeostasis is one of the promising directions, therefore, the study of changes in the levels of antibodies to HSP60 can become a reliable marker of both the course and compensation of disorders of the neurovegetative state in perimenopause.

Purpose - to study the role of anti-Müllerian, follicle-stimulating, luteinizing, thyroid-stimulating hormones, antibodies (IgG) to human heat shock protein 60 (HSP60) and its bacterial homologue (GroEl), and obstetric history on the diagnosis and treatment of vasomotor symptoms in perimenopausal women.

Materials and methods. 158 patients with climacteric syndrome in perimenopause were examined in the period October 2019 - March 2022. The Group 1 (main) included 80 patients who agreed to treatment and received it according to the standard scheme: combined treatment in a cyclical regimen - estrogens (17β-estradiol) + progestogens (dydrogesterone); the Group 2 (comparison) included 78 women who refused treatment due to estrogen deficiency.

Results. Revealed a decrease (p<0.01) in the risk of not achieving a high treatment effect with vasomotor symptoms for treated patients, OR=0.04 (95% CI: 0.01-0.18) compared to the group of untreated patients. With the number of deliveries, the risk of not achieving a high treatment effect in women with vasomotor symptoms increases (p=0.01), OR=2.27 (95% CI: 1.2-4.27) for each delivery. A lower (p=0.039) risk of not achieving a high treatment effect was found in women with vasomotor symptoms at a higher GroEl level, ОR=0.994 (95% CI: 0.987-1.000) for each ng. When standardizing by the thyrotropin hormone and the manifestation of vasomotor symptoms before or without treatment, a decrease (p<0.001) in the risk of not achieving a high effect of treatment in women with vasomotor symptoms for treated patients was found, OR=0.04 (95% CI: 0.01-0.20).

Conclusions. This study found that there is no informative indicator for predicting the effectiveness of treatment in women with vasomotor symptoms. It was established that the HSP60 indicator does not affect, and the GroEl indicator affects the effectiveness of the treatment of vasomotor clinical manifestations.

The research was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of the institutions. The informed consent of the women was obtained for conducting the studies.

No conflict of interest was declared by the authors.


Bauer M, Heinz A, Whybrow PC. (2002). Thyroid hormones, serotonin, and mood: synergy and significance in the adult brain. Mol Psychiatry. 7 (2): 140-156.; PMid:11840307

Benhalima K, Van Crombrugge P, Moyson C et al. (2018). A modified twostep screening strategy for gestational diabetes mellitus based on the 2013 WHO criteria by combining the glucose challenge test and clinical risk factors. J Clin Med. 7 (10). pii:E351.; PMid:30322138 PMCid:PMC6210855

Berestoviy V, Mahmood A, Venckivska I, Ginzburg V, Sokol I, Berestoviy O, Govsieiev D. (2021). The overview and role of heat shock proteins (HSP) especially HSP 60 and 70 in reproduction and other pathologies (a literature review). Medicni perspektivi. 26 (1): 54-62.

De Villiers T, Tatarchuk T, Avramenko N, Bulavenko O, Gabal V et al. (2016). National consensus on management of female patients in menopause. Reproductive endocrinology. 27: 8-25.

Del Ghianda S, Tonacchera M, Vitti P. (2014). Thyroid gland and menopause. Menopause. 17 (3): 225-234.; PMid:23998691

Dillon KE, Gracia CR. (2013). What is normal ovarian reserve? Seminars in reproductive medicine. 31 (6): 427-436.; PMid:24101223

Fait T. (2019). Menopause hormone therapy: latest developments and clinical practice. Drugs in context: 8.; PMid:30636965 PMCid:PMC6317580

Ferrell RJ, Simon JA, Pincus SM et al. (2006). The length of perimenopausal menstrual cycles increases later and to a greater degree than previously reported. Fertil Steril. 86: 619-624.; PMid:16889776

Hall JE. (2015). Endocrinology of the Menopause. Endocrinol Metab Clin North Am. 44 (3): 485-496.; PMid:26316238 PMCid:PMC6983294

Kase NG. (2009). Impact of hormone therapy for women aged 35-65 years, from contraception to hormone replacement. Gend Med. 6 (1): 37-59.; PMid:19318218

Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WHB. (2011). A validated model of serum anti-müllerian hormone from conception to menopause. PloS one. 6 (7): e22024.; PMid:21789206 PMCid:PMC3137624

Makarenko M, Govsieiev D, Vorona R, Tsisarenko A, Vasil'tchuk O et al. (2016). Identification and characterization of antibodies against human HSP60 at pregnancy. Health of woman. 8 (114): 75-75.

Oi N, Ohi K. (2013). Comparison of menopausal symptoms and thyroid disease symptoms in Japanese women aged 35-59 years. Climacteric. 16 (5): 555-560.; PMid:23025806

Partyka Ł, Hartwich J, Kieć-Wilk B, Polus A, Wybrańska I, Dembińska-Kieć A. (2001). Is atherosclerosis an autoimmunological process? Przeglad Lekarski. 58 (12): 1067-1070.

Pinkerton J. (2017). The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The North American Menopause Society, New York. 24 (7): 728-753.; PMid:28650869

Rajtar-Ciosek A, Kacalska-Janssen O, Zmaczyński A, Wyroba J et al. (2015). Reduction in the level of antibodies against heat shock proteins 60 during different hormonal protocols in postmenopausal women. Menopause Review/Przegląd Menopauzalny. 14 (4): 218-222.; PMid:26848292 PMCid:PMC4733899

Razvi S, Shakoor A, Vanderpump MPJ et al. (2008). Effect of age on the association between subclinical hypothyroidism and coronary heart disease: a meta-analysis. J Clin Endocrinol Metab. 93: 2998-3007.; PMid:18505765

Santoro N. (2017). Using Antimüllerian hormone to predict fertility. Jama. 318 (14): 1333-1334.; PMid:29049571

Surks MI, Hollowell JG. (2007). Age distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism J Clin Endocrinol Metab. 92: 4575-4582.; PMid:17911171

Troìa L, Martone S, Morgante G, Luisi S. (2020). Management of perimenopause disorders: hormonal treatment. Gynecological Endocrinology. 37: 3.; PMid:33263443