The effect of prolactin on the course of extrasystolic arrhythmia in women during lactation

Introduction. Evaluation of the effect of dysprolactinemia during lactation in women on the course of extrasystolic arrhythmia seems important for cardiology and obstetrics. Proarrhythmic effect of prolactin was noted in studies on mice. However, the effect of prolactin on cardiac repolarization, as well as thyroid function in women during lactation, is currently insufficiently studied.

Aim. To study the effect of dysprolactinemia during lactation in women on thyroid hormones, electrocardiographic, hemodynamic parameters of the heart and the number of extrasystoles.

Materials and methods. The study included 33 lactating women with normal prolactin levels and euthyroidism, 34 with hyperprolactinemia and subclinical hypothyroidism, 28 with hyperprolactinemia and overt hypothyroidism, 32 with hypoprolactinemia and subclinical thyrotoxicosis, and 25 with hypoprolactinemia and overt thyrotoxicosis. The study methods included: electrocardiography (ECG) recording, electrophysiological study (EPS) of the heart, echocardiography (EchoCG), 24-hour Holter ECG monitoring (HM ECG), determination of prolactin, thyroid-stimulating hormone (TSH), and free thyroxine (free T4).

Results. Correlation analysis showed that during lactation, an increase and decrease in prolactin levels are accompanied by an increase in the number of extrasystoles (r = 0.975, p < 0.001; r = 0.973, p < 0.001). Regression analysis revealed that during lactation, an increase in prolactin levels over 57.19 ng/ml is accompanied by an increase in the number of extrasystoles. The sensitivity of the method was 66.7%, specificity – 92.9%, AUC = 0.837.

Conclusions. During lactation, women were found to have a relationship between prolactin, TSH and the number of extrasystoles. An increase and decrease in prolactin levels are accompanied by an increase in the number of extrasystoles. Hyperprolactinemia and hypoprolactinemia affect the clinical course of extrasystole and the rate of excitation conduction through the conduction structures of the heart.

1. Kosimova SI, Hodzhamurodova DA. Reproductive function in women with hyperprolactinemia in subclinical hypothyroidism and euthyroidism. Medicinskij Vestnik Nacional’noj Akademii Nauk Tadzhikistana. 2020;10(1):16–21. (In Russ.) Available at: https://elibrary.ru/tuydrl.

2. Nad’ YuG. Combination of hyperprolactinemia and subclinical hypothyroidism. Meditsinskiy Sovet. 2009;(2):42–44. (In Russ.) Available at: https://cyberleninka.ru/article/n/sochetanie-giperprolaktinemii-i-subklinicheskogo-gipotireoza.

3. van der Ham K, Stekelenburg KJ, Louwers YV, van Dorp W, Schreurs MWJ, van der Wal R et al. The prevalence of thyroid dysfunction and hyperprolactinemia in women with PCOS. Front Endocrinol. 2023;14:1245106. https://doi.org/10.3389/fendo.2023.1245106.

4. Rymar OD, Voevoda SM, Denisova DV, Shakhtshneider EV, Stakhnyova EM, Shcherbakova LV. Thyroid-stimulating hormone and prolactin levels in a population-based sample of women aged 25 to 45. Doctor.Ru. 2019;(10):46–51. (In Russ.) https://doi.org/10.31550/1727-2378-2019-165-10-46-51.

5. Fliers E, Boelen A, van Trotsenburg AS. Central regulation of the hypothalamopituitary-thyroid (HPT) axis: focus on clinical aspects. Handb Clin Neurol. 2014;124:127–138. https://doi.org/10.1016/B978-0-444-59602-4.00009-5.

6. Khakimov ZK. Hypothalamic-pituitary system and cardiovascular pathology. Ekonomika i Socium. 2022;(11):957–960. (In Russ.) Available at: https://www.iupr.ru/_files/ugd/b06fdc_b8a7185716104f69b28e4bb67baaf9bf.pdf.

7. Smirnov VV, Morozkina AI, Utev MD. Hyperprolactinemia syndrome in children and adolescents: reasons, diagnostics, treatment (part 1). Lechaschi Vrach. 2014;(12):58–60. (In Russ.) Available at: https://www.lvrach.ru/2014/12/15436121.

8. Kolesnikova GS, Malysheva NM, Zuraeva ZT, Nikankina LV, Melnichenko GA. Determination of prolactin reference intervals in different age groups. Problemy Endokrinologii. 2023;69(3):16–23. (In Russ.) https://doi.org/10.14341/probl13095.

9. Gorin VS, Portnova AV, Resnichenko EV, Kalugin SA. Endometrial hyperplasia in women of reproductive age at thyroid pathology. Siberian Medical Review. 2009;(1):9–17. (In Russ.) Available at: https://cyberleninka.ru/article/n/giperplasticheskie-protsessy-endometriya-u-zhenschinreproduktivnogo-vozrasta-s-patologiey-schitovidnoy-zhelezy.

10. Sirohi T, Singh H. Estimation of serum prolactin levels and determination of prevalence of hyperprolactinemia in newly diagnosed cases of subclinical hypothyroidism. J Family Med Prim Care. 2018;7(6):1279–1282. https://doi.org/10.4103/jfmpc.jfmpc_155_18.

11. Chen AX, Burt MG. Hyperprolactinaemia. Aust Prescr. 2017;40(6):220–224. https://doi.org/10.18773/austprescr.2017.060.

12. Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol. 2007;66(3):309–321. https://doi.org/10.1111/j.13652265.2007.02752.x.

13. Vilar L, Fleseriu M, Bronstein MD. Challenges and pitfalls in the diagnosis of hyperprolactinemia. Arq Bras Endocrinol Metabol. 2014;58(1):9–22. https://doi.org/10.1590/0004-2730000003002.

14. Morreale de Escobar G, Obregon MJ, Escobar del Rey F. Role of thyroid hormone during early brain development. Eur J Endocrinol. 2004;151(Suppl. 3):U25–U37. https://doi.org/10.1530/eje.0.151u025.

15. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–288. https://doi.org/10.1210/jc.2010-1692.

16. Augustine RA, Ladyman SR, Bouwer GT, Alyousif Y, Sapsford TJ, Scott V et al. Prolactin regulation of oxytocin neurone activity in pregnancy and lactation. J Physiol. 2017;595(11):3591–3605. https://doi.org/10.1113/JP273712.

17. Alex A, Bhandary E, McGuire KP. Anatomy and Physiology of the Breast during Pregnancy and Lactation. Adv Exp Med Biol. 2020;1252:3–7. https://doi.org/10.1007/978-3-030-41596-9_1.

18. Lopez-Vicchi F, De Winne C, Brie B, Sorianello E, Ladyman SR, Becu-Villalobos D. Metabolic functions of prolactin: Physiological and pathological aspects. J Neuroendocrinol. 2020;32(11):e12888. https://doi.org/10.1111/jne.12888.

19. Chen H, Fu J, Huang W. Dopamine agonists for preventing future miscarriage in women with idiopathic hyperprolactinemia and recurrent miscarriage history. Cochrane Database Syst Rev. 2016;7(7):CD008883. https://doi.org/10.1002/14651858.CD008883.pub2.

20. Dedov II, Melnichenko GA, Dzeranova LK, Andreeva EN, Grineva EN, Marova EI et al. Clinical guidelines ‘Hyperprolactinemia’ (draft). Obesity and Metabolism. 2023;20(2):170–188. (In Russ.) https://doi.org/10.14341/omet13002.

21. Nad YuG, Nad RB. Hyperprolactinemia: myth or reality? East European Scientific Journal. 2015;1(1):45–48. (In Russ.) Available at: https://cyberleninka.ru/article/n/gipoprolaktinemiya-mif-ili-realnost.

22. Nassar BA, Manku MS, Reed JD, Tynan M, Horrobin DF. Actions of prolactin and frusemide on heart rate and rhythm. Br Med J. 1974;2(5909):27–29. https://doi.org/10.1136/bmj.2.5909.27.

23. Bodi I, Sorge J, Castiglione A, Glatz SM, Wuelfers EM, Franke G et al. Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2. Europace. 2019;21(7):1126–1138. https://doi.org/10.1093/europace/euz037.

24. Tamirisa KP, Elkayam U, Briller JE, Mason PK, Pillarisetti J, Merchant FM et al. Arrhythmias in Pregnancy. JACC. 2022;8(1):120–135. https://doi.org/10.1016/j.jacep.2021.10.004

25. Bett GC. Hormones and sex differences: changes in cardiac electrophysiology with pregnancy. Clin Sci. 2016;130(10):747–759. https://doi.org/10.1042/CS20150710.

26. Compagnone M, Marinelli A, Dall’Ara G, Ziacchi M, Grotti S et al. Prolactin Inhibition to Treat Postpartum Arrhythmic Storm. JACC Case Rep. 2024;29(4):102211. https://doi.org/10.1016/j.jaccas.2023.102211.

27. Odening KE, Choi BR, Liu GX, Hartmann K, Ziv O, Chaves L et al. Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective. Heart Rhythm. 2012;9(5):823–832. https://doi.org/10.1016/j.hrthm.2012.01.009.

28. Stupak II, Lakhno IV. Regulatory mechanisms of prolactin biological effects realization (review). The Journal of V.N. Karazin Kharkiv National University, Series Medicine. 2006;(12):102–106. (In Russ.) Available at: https://cyberleninka.ru/article/n/regulyatornye-mehanizmy-realizatsii-biologicheskih-effektov-prolaktina-obzor-literatury.

29. Ghoreshi ZA, Akbari H, Sharif-Zak M, Arefinia N, Abbasi-Jorjandi M, Asadikaram G. Recent findings on hyperprolactinemia and its pathological implications: a literature review. J Investig Med. 2022;70(7):1443–1451. https://doi.org/10.1136/jim-2022-002351.

30. Sharma LK, Sharma N, Gadpayle AK, Dutta D. Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism. Eur J Intern Med. 2016;35:106–110. https://doi.org/10.1016/j.ejim.2016.07.012.