Systematic review of the clinical and experimental use of pregabalin and its effects on the male reproductive system and the endocrine system




Pregabalin; Rat; Endocrine System; Testicle.


Pregabalin is a drug commonly used in psychiatry, neurology, and primary health care. It is an anticonvulsant widely used in the treatment of epilepsy, anxiety, fibromyalgia and neuropathic pain. It works by binding to voltage-gated calcium channels, exerting analgesic and anxiolytic activity. It has GABA-like properties and is involved in the dopaminergic reward system. The objective of this systematic review was to describe the status of current knowledge in relation to the topic, highlighting possible paths for future research, guiding other researchers and directing new publications with objectives correlated to the current diagnosis. In the present systematic review, we used original and comprehensive, open access scientific research, carried out between 2016 and 2021, related to the drug Pregabalin, highlighting its relationship with the testes and the Endocrine System in male rats. In order to map the scientific production, an exploratory-descriptive research was carried out, through a systematic analysis. The main collection of the Web of Science (Clarivate Analytics) was used as a search base. Studies have shown that pregabalin affects FSH, LH and testosterone levels, causing changes in spermatogenesis. Pregabalin causes significant changes in hormone levels, negatively impacting the production of healthy sperm. Psychotropic drugs, particularly pregabalin, can also reduce sperm quality, decreasing patients fertility potential.


Akamine, T., Koyanagi, S., Kusunose, N., Hashimoto, H., Taniguchi, M., Matsunaga, N., & Ohdo, S. (2015). Dosing time-dependent changes in the analgesic effect of pregabalin on diabetic neuropathy in mice. Journal of Pharmacology and Experimental Therapeutics, 354(1), 65-72.

Bender, G., Gosset, J., Florian, J., Tan, K., Field, M., Marshall, S., & Danhof, M. (2009). Population pharmacokinetic model of the pregabalin-sildenafil interaction in rats: application of simulation to preclinical PK-PD study design. Pharmaceutical research, 26(10), 2259-2269.

Benoff, S., Cooper, G. W., Hurley, I., Mandel, F. S., Rosenfeld, D. L., Scholl, G. M., ... & Hershlag, A. (1994). The effect of calcium ion channel blockers on sperm fertilization potential. Fertility and sterility, 62(3), 606-617.

Bilginer, B., Önal, B., Narin, F., Yildiz, I., Gurbuz, O., Ergün, E., & Akalan, N. (2009). The effects of long-term use of pregabalin on reproductive endocrine hormones and testicular morphology in adult male rats.

Bonnet, U., & Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. European neuropsychopharmacology, 27(12), 1185-1215.

Bostanian, S., Shariati, M., & Zamanpoor, M. (2016). Effect of pregabalin on pituitary–gonad axis and testis histological changes in adult rat. J. Appl. Environ. Biol. Sci, 6(3), 165-171.

Cao, L., Leers-Sucheta, S., & Azhar, S. (2004). Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells. The Journal of steroid biochemistry and molecular biology, 88(1), 61-67.

Chagury, A. A., Tavares, K. R. C., Camargo, R. M., Martins, D. V., Marques, L. H. D. S., & Mahmoud, A. (2020). Pregabalin treatment in a pregnant woman with glossopharyngeal neuralgia. Brazilian journal of otorhinolaryngology, 86, s17-s19.

Curvello, K. D. (2019). Uso de pregabalina para depressão comparada com outras drogas psicoativas: uma revisão sistemática. XXXI salão de iniciação científica da UFRGS.

Dimitriadis, Z., Kapreli, E., Strimpakos, N., & Oldham, J. (2015). Do psychological states associate with pain and disability in chronic neck pain patients? Journal of back and musculoskeletal rehabilitation, 28(4), 797-802.

Ding, J., Shang, X., Zhang, Z., Jing, H., Shao, J., Fei, Q., & Li, H. (2017). FDA-approved medications that impair human spermatogenesis. Oncotarget, 8(6), 10714.

Harden, C. L., & Pennell, P. B. (2013). Neuroendocrine considerations in the treatment of men and women with epilepsy. The Lancet Neurology, 12(1), 72-83.

Harden, C. L., Koppel, B. S., Herzog, A. G., Nikolov, B. G., & Hauser, W. A. (2003). Seizure frequency is associated with age at menopause in women with epilepsy. Neurology, 61(4), 451-455.

Herzog, A. G., Seibel, M. M., Schomer, D. L., Vaitukaitis, J. L., & Geschwind, N. (1986). Reproductive endocrine disorders in men with partial seizures of temporal lobe origin. Archives of neurology, 43(4), 347-350.

Hrabovszky, E., & Liposits, Z. (2013). Afferent neuronal control of type-I gonadotropin releasing hormone neurons in the human. Frontiers in endocrinology, 4, 130.

Isojärvi, J. I., Taubøll, E., & Herzog, A. G. (2005). Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy. CNS drugs, 19(3), 207-223.

Kamel, M. A., & Khalifa, H. A. (2015). Alpha 2-delta (α 2-δ) ligand pregabalin could adversely affects male fertility. Int J Pharma Sci, 5(5), 1226-1229.

Kanwar, U., Anand, R. J. K., & Sanyal, S. N. (1993). The effect of nifedipine, a calcium channel blocker, on human spermatozoal functions. Contraception, 48(5), 453-470.

Kmet, L. M., Cook, L. S., & Lee, R. C. (2004). Standard quality assessment criteria for evaluating primary research papers from a variety of fields.

Lasoń, W., Dudra-Jastrzębska, M., Rejdak, K., & Czuczwar, S. J. (2011). Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update. Pharmacological Reports, 63(2), 271-292.

Lee, J. H., Ahn, H. J., Lee, S. J., Gye, M. C., & Min, C. K. (2011). Effects of L-and T-type Ca 2+ channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis. Journal of assisted reproduction and genetics, 28(1), 23-30.

Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P., & Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of clinical epidemiology, 62(10), e1-e34.

Loureiro, S. A., Noletto, A. P. R., da Silva Santos, L., Júnior, J. B. S. S., & Júnior, O. F. L. (2016). O uso do método de revisão sistemática da literatura na pesquisa em logística, transportes e cadeia de suprimentos. Transportes, 24(1), 95-106.

Mansouri, M., & Khazali, H. (2008). Determination of the effect of the interaction between Ghrelin and serotonin agonist (R)-8-OH-DPAT on the mean plasma concentrations of T3 & T4 in rat. Physiology and Pharmacology, 12(2), 142-148.

Marieb, E. N., & Hoehn, K. (2013). The reproductive system. Human Anatomy & Physiology Nine Edition; Beauparlant, S., Ed.; Pearson, London, 1018-1063.

Martinotti, G., Lupi, M., Sarchione, F., Santacroce, R., Salone, A., De Berardis, D., & Di Giannantonio, M. (2013). The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview. Current pharmaceutical design, 19(35), 6367-6374.

Nawar, M. H., Salih, L. A., & Muhsen, S. M. (2019). The physiological and histological effect of royal jelly on some testicular function in male albino rats treated with pregabalin. Asian Jr. of Microbiol. Biotech. Env. Sc, 276-283.

Pegg, D., Bleavins, M., Herman, J., Wojcinski, Z., Graziano, M., Henck, J., ... & Duddy, S. (2012). Hemangiosarcoma in mice administered pregabalin: analysis of genotoxicity, tumor incidence, and tumor genetics. Toxicological Sciences, 128(1), 9-21.

Hareedy, M. S., Tawfik, K. M., Badary, D. M., Mahmoud, W. A., & Mohamed, E. M. (2020). Pregabalin administration and withdrawal affect testicular structure and functions in rats. Andrologia, 52(11), e13808.

Shokry, D. A., El Nabrawy, N., Yassa, H. D., Gaber, S. S., Batiha, G. E. S., & Welson, N. N. (2020). Pregabalin induced reproductive toxicity and body weight changes by affecting caspase3 and leptin expression: Protective role of wheat germ oil. Life Sciences, 260, 118344.

Taha, S. H. N., Zaghloul, H. S., Ali, A. A. E. R., Rashed, L. A., Sabry, R. M., & Gaballah, I. F. (2020). Molecular and hormonal changes caused by long-term use of high dose pregabalin on testicular tissue: the role of p38 MAPK, oxidative stress and apoptosis. Molecular Biology Reports, 47(11), 8523-8533.

Linschoten, R., Middelkoop, M., Heintjes, E. M., Bierma-Zeinstra, S. M., Verhaar, J. A., & Koes, B. W. (2011). Exercise Therapy For Patellofemoral Pain Syndrome, A Systematic Review: 1448: Board# 184 June 1 9: 30 AM-11: 00 AM. Medicine & Science in Sports & Exercise, 43(5), 308.

Zhao, F., & Wang, Q. (2012). The protective effect of peroxiredoxin II on oxidative stress induced apoptosis in pancreatic β-cells. Cell & bioscience, 2(1), 1-9.



How to Cite

SALES, J. E. de S.; VELOSO, E. V. L.; SILVA, R. C. M. da .; ARAÚJO, P. P. B. .; MACHADO, J. L. dos S.; SOUZA, J. G. de .; CALDEIRA, M. E. C.; MACHADO, R. A. de S. .; MENEZES, D. J. A. de .; SOUSA, O. B. de . Systematic review of the clinical and experimental use of pregabalin and its effects on the male reproductive system and the endocrine system . Research, Society and Development, [S. l.], v. 11, n. 3, p. e28611326407, 2022. DOI: 10.33448/rsd-v11i3.26407. Disponível em: Acesso em: 20 jun. 2024.



Review Article