癫痫所致生殖内分泌功能障碍的研究进展_Journal of Epilepsy

Authors：

包婉莹 ¹ , 方壮霖 ¹ , 朱慧莉 ² , 段亦霏 ³ ,  陈蕾 ³

1. ;
2. ;
3. ;

Corresponding author：

陈蕾, Email: leilei_25@126.com

Keywords：

癫痫; 内分泌系统; 生殖; 性功能障碍

DOI：

10.7507/2096-0247.202112001

Video：

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Abstract Full text Figures/Tables Video References Cited by

癫痫是脑部神经元过度异常放电导致的临床综合征，生殖内分泌功能紊乱是癫痫患者的常见疾病，对患者婚姻生育造成不良影响，目前尚未见到癫痫诱发患者生殖内分泌功能紊乱病因的总结报道。癫痫导致的神经内分泌功能障碍、抗癫痫药物引起的不良反应以及癫痫共患病的不良影响皆可导致患者生殖内分泌功能紊乱。本综述对目前已有的关于上述影响因素的研究结论进行总结，并提出了对预防癫痫所致的生殖内分泌功能紊乱的见解。

Citation： 包婉莹, 方壮霖, 朱慧莉, 段亦霏, 陈蕾. 癫痫所致生殖内分泌功能障碍的研究进展. Journal of Epilepsy, 2022, 8(3): 236-250. doi: 10.7507/2096-0247.202112001 Copy

1.	Editorial. A voice for people with epilepsy. Lancet, 2015, 385(9967): 482.
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4.	Quinta Gomes AL, Nobre PJ. Prevalence of sexual problems in portugal: results of a population-based study using a stratified sample of men aged 18 to 70 years. J Sex Res, 2014, 51(1): 13-21.
5.	Herzog AG, Seibel MM, Schomer DL, et al. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol, 1986, 43(4): 341.
6.	何晓彤, 孟祥雯, 张雪娇, 等. 多囊卵巢综合征病因与发病机制的研究进展. 中国妇幼保健, 2017, 32(7): 1588-1591.
7.	陈蕾. 女性癫痫(第二版). 北京:人民卫生出版社, 2017: 123-124.
8.	Edwards HE, Burnham WM, MacLusky NJ. Partial and generalized seizures affect reproductive physiology differentially in the male rat. Epilepsia (Copenhagen), 1999, 40(11): 1490-1498.
9.	Ranjbar M, Mehvari HJ, Poorazarian F, et al. Frequency of menstrual abnormalities and their associated neuroimaging findings in women with focal refractory epilepsy. Acta Neurol Belg, 2020, 121(5): 1247-1250.
10.	Harden CL, Koppel BS, Herzog AG, et al. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology, 2003, 61(4): 451-455.
11.	Bauer J, Stoffel-wagner B, Flügel D, et al. Serum androgens return to normal after temporal lobe epilepsy surgery in men. Neurology, 2000, 55(6): 820-824.
12.	Hamed S, Mohamed K, Eltaher A, et al. The sexual and reproductive health in men with generalized epilepsy: a multidisciplinary evaluation. Int J Impot Res, 2006, 18(3): 287-295.
13.	Hamed SA, Moussa EMM, Tohamy AM, et al. Seminal fluid analysis and testicular volume in adults with epilepsy receiving valproate. J Clin Neurosci, 2015, 22(3): 508-512.
14.	Hamed SA, Hermann BP, Moussa EMM, et al. Evaluation of penile vascular status in men with epilepsy with erectile dysfunction. Seizure, 2015, 25: 40-48.
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16.	Kuba R, Pohanka M, Zákopčan J, et al. Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia, 2006, 47(12): 2135-2140.
17.	Mahesh V, Brann D. Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids, 1998, 63(12): 616-629.
18.	罗蔚锋. 癫痫发作与雌孕激素的相互影响. 国外医学神经病学神经外科学分册, 1996, 23(1): 9-12.
19.	Xu XT, Zhang HZ, Xu Y, et al. Effects of antiepileptic drugs on reproductive endocrine function, sexual function and sperm parameters in Chinese Han men with epilepsy. J Clin Neurosci, 2013, 20(11): 1492-1497.
20.	Chang C, Liao C, Lin C, et al. Patients with epilepsy are at an increased risk of subsequent stroke: a population-based cohort study. Seizure, 2014, 23(5): 377-381.
21.	Hamed SA. The effect of antiepileptic drugs on thyroid hormonal function: causes and implications. Expert Rev Clin Pharmacol, 2015, 8(6): 741-750.
22.	Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol, 2004, 58(7): S854-S863.
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24.	Morrell MJ, Flynn KL, Doñe S, et al. Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy & Behavior, 2005, 6(3): 360-365.
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28.	Walker RM, Smith GS, Barsoum NJ, et al. Preclinical toxicology of the anticonvulsant calcium valproate. Toxicology (Amsterdam), 1990, 63(2): 137.
29.	Kose-Ozlece H, Ilık F, Cecen K, et al. Alterations in semen parameters in men wıth epilepsy treated with valproate. Iran J Neurol, 2015, 14(3): 164-167.
30.	Isojärvi Jit, Pakarinen Aj, Rautio A, et al. Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Eur J Clin Pharmacol, 1995, 47(5): 461-464.
31.	Post RM, Chuang SRBW. Mechanisms of action of anticonvulsants in affective disorders: comparisons with lithium. J Clin Psychopharmacol, 1992.
32.	张冬梅, 孙凤英. 抗癫痫药丙戊酸镁缓释片对女性癫痫患者生殖内分泌的影响. 中国全科医学, 2015, 18(14): 1727-1728.
33.	Andretta RR, Okada FK, Paccola CC, et al. Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring. Reprod Toxicol, 2014, 44: 52-62.
34.	Oliva SU, Engelbrecht RDM, Miraglia SM. Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty. Andrologia, 2020, 52(9).
35.	Shamaila Fraz AHLJ. Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes. Aquat Toxicol, 2018.
36.	Aaron Lazorwitz ADMS. The effect of carbamazepine on etonogestrel concentrations in contraceptive implant users. Contraception, 2017, 95(6): 571-577.
37.	Livanainen M, Savolainen H. Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Acta Neurol Scand Suppl, 1983, 97(68): 49-67.
38.	Waddell WJ, Mirkin BL. Distribution and metabolism of diphenyl-hydantoin-¹⁴C in fetal and maternal tissues of the pregnant mouse. Biochem Pharmacol, 1972, 21(4): 547-552.
39.	Makatsori A, Michal D, Eduard U, et al. Neuroendocrine changes in adult female rats prenatally exposed to phenytoin. Neurotoxicol Teratol, 2005, 27(3): 509-514.
40.	QUINN DL. Influence of Diphenylhydantoin on spontaneous release of ovulating hormone in the adult rat. Proc Soc Exp Biol Med, 1965, 119(4): 982-985.
41.	Tamura K, Abe Y, Kogo H. Phenytoin inhibits both the first ovulation and uterine development in gonadotropin-primed immature rats. Eur J Pharmacol, 2000, 398(2): 317-322.
42.	Kwan P, Yip FP, Hui ACF, et al. Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: A prospective randomized study. Epilepsy Behav, 2009, 14(4): 610-616.
43.	Morrell MJ, Isojärvi J, Taylor AE, et al. Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy. Epilepsy Res, 2003, 54(2-3): 189-199.
44.	Sahota P, Prabhakar S, Kharbanda PS, et al. Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study. Epilepsia, 2008, 49(12): 2069-2077.
45.	Sidhu HS, Srinivasa R, Sadhotra A. Evaluate the effects of antiepileptic drugs on reproductive endocrine system in newly diagnosed female epileptic patients receiving either Valproate or Lamotrigine monotherapy: A prospective study. Epilepsy Res, 2018, 139: 20-27.
46.	Duncan S, Blacklaw J, Beastall GH, et al. Antiepileptic Drug Therapy and Sexual Function in Men with Epilepsy. Epilepsia (Copenhagen), 1999, 40(2): 197-204.
47.	Morrell MJ, Flynn KL, Doñe S, et al. Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy Behav, 2005, 6(3): 360-365.
48.	Reis RM, de Angelo AG, Sakamoto AC, et al. Altered sexual and reproductive functions in epileptic men taking carbamazepine. J Sex Med, 2013, 10(2): 493-499.
49.	Svalheim S, Taubøll E, Luef G, et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav, 2009, 16(2): 281-287.
50.	Herzog AG, MSc, Drislane FW, et al. Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy. Neurology, 2005, 65(7): 1016-1020.
51.	Wilner AN, Sharma BK, Soucy A, et al. Common comorbidities in women and men with epilepsy and the relationship between number of comorbidities and health plan paid costs in 2010. Epilepsy & Behavior, 2014, 32: 15-20.
52.	杨雪, 迟兆富. 癫痫共患病研究进展. 中国现代神经疾病杂志, 2012, 12(5): 507-515.
53.	游小林, 谢聪, 干晓琴. 抗精神病药与高催乳素血症及月经紊乱. 中华妇幼临床医学杂志(电子版), 2019, 15(4): 472-475.
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55.	Tellez-Zenteno JF, Matijevic S, Wiebe S. Somatic comorbidity of epilepsy in the general population in Canada. Epilepsia, 2005, 46(12): 1955-1962.
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1. Editorial. A voice for people with epilepsy. Lancet, 2015, 385(9967): 482.
2. Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy. Neurology, 2017, 88(3): 296-303.
3. Khani A. Female sexual dysfunction: prevalence and risk factors. JCDR, 2013, 7(12): 2877-2880.
4. Quinta Gomes AL, Nobre PJ. Prevalence of sexual problems in portugal: results of a population-based study using a stratified sample of men aged 18 to 70 years. J Sex Res, 2014, 51(1): 13-21.
5. Herzog AG, Seibel MM, Schomer DL, et al. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol, 1986, 43(4): 341.
6. 何晓彤, 孟祥雯, 张雪娇, 等. 多囊卵巢综合征病因与发病机制的研究进展. 中国妇幼保健, 2017, 32(7): 1588-1591.
7. 陈蕾. 女性癫痫(第二版). 北京:人民卫生出版社, 2017: 123-124.
8. Edwards HE, Burnham WM, MacLusky NJ. Partial and generalized seizures affect reproductive physiology differentially in the male rat. Epilepsia (Copenhagen), 1999, 40(11): 1490-1498.
9. Ranjbar M, Mehvari HJ, Poorazarian F, et al. Frequency of menstrual abnormalities and their associated neuroimaging findings in women with focal refractory epilepsy. Acta Neurol Belg, 2020, 121(5): 1247-1250.
10. Harden CL, Koppel BS, Herzog AG, et al. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology, 2003, 61(4): 451-455.
11. Bauer J, Stoffel-wagner B, Flügel D, et al. Serum androgens return to normal after temporal lobe epilepsy surgery in men. Neurology, 2000, 55(6): 820-824.
12. Hamed S, Mohamed K, Eltaher A, et al. The sexual and reproductive health in men with generalized epilepsy: a multidisciplinary evaluation. Int J Impot Res, 2006, 18(3): 287-295.
13. Hamed SA, Moussa EMM, Tohamy AM, et al. Seminal fluid analysis and testicular volume in adults with epilepsy receiving valproate. J Clin Neurosci, 2015, 22(3): 508-512.
14. Hamed SA, Hermann BP, Moussa EMM, et al. Evaluation of penile vascular status in men with epilepsy with erectile dysfunction. Seizure, 2015, 25: 40-48.
15. Morrell MJ, Guldner GT. Self-reported sexual function and sexual arousability in women with epilepsy. Epilepsy Behav, 1996, 37(12): 1204-1210.
16. Kuba R, Pohanka M, Zákopčan J, et al. Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia, 2006, 47(12): 2135-2140.
17. Mahesh V, Brann D. Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids, 1998, 63(12): 616-629.
18. 罗蔚锋. 癫痫发作与雌孕激素的相互影响. 国外医学神经病学神经外科学分册, 1996, 23(1): 9-12.
19. Xu XT, Zhang HZ, Xu Y, et al. Effects of antiepileptic drugs on reproductive endocrine function, sexual function and sperm parameters in Chinese Han men with epilepsy. J Clin Neurosci, 2013, 20(11): 1492-1497.
20. Chang C, Liao C, Lin C, et al. Patients with epilepsy are at an increased risk of subsequent stroke: a population-based cohort study. Seizure, 2014, 23(5): 377-381.
21. Hamed SA. The effect of antiepileptic drugs on thyroid hormonal function: causes and implications. Expert Rev Clin Pharmacol, 2015, 8(6): 741-750.
22. Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol, 2004, 58(7): S854-S863.
23. Isojarvi JIT, Repo M, Pakarinen AJ, et al. Carbamazepine, phenytoin, sex hormones, and sexual function in men with epilepsy. Epilepsia (Copenhagen), 1995, 36(4): 366-370.
24. Morrell MJ, Flynn KL, Doñe S, et al. Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy & Behavior, 2005, 6(3): 360-365.
25. Luine VN, Wu V, Hoffman CS, et al. GABAergic regulation of lordosis: influence of gonadal hormones on turnover of GABA and interaction of GABA with 5-HT. Neuroendocrinology, 1999, 69(6): 438-445.
26. McCarthy MM, Malik KF, Feder HH. Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area. Brain Res, 1990, 507(1): 40.
27. Verrotti A, Mencaroni E, Cofini M, et al. Valproic acid metabolism and its consequences on sexual functions. Curr Drug Metab, 2016, 17(6): 573-581.
28. Walker RM, Smith GS, Barsoum NJ, et al. Preclinical toxicology of the anticonvulsant calcium valproate. Toxicology (Amsterdam), 1990, 63(2): 137.
29. Kose-Ozlece H, Ilık F, Cecen K, et al. Alterations in semen parameters in men wıth epilepsy treated with valproate. Iran J Neurol, 2015, 14(3): 164-167.
30. Isojärvi Jit, Pakarinen Aj, Rautio A, et al. Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Eur J Clin Pharmacol, 1995, 47(5): 461-464.
31. Post RM, Chuang SRBW. Mechanisms of action of anticonvulsants in affective disorders: comparisons with lithium. J Clin Psychopharmacol, 1992.
32. 张冬梅, 孙凤英. 抗癫痫药丙戊酸镁缓释片对女性癫痫患者生殖内分泌的影响. 中国全科医学, 2015, 18(14): 1727-1728.
33. Andretta RR, Okada FK, Paccola CC, et al. Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring. Reprod Toxicol, 2014, 44: 52-62.
34. Oliva SU, Engelbrecht RDM, Miraglia SM. Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty. Andrologia, 2020, 52(9).
35. Shamaila Fraz AHLJ. Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes. Aquat Toxicol, 2018.
36. Aaron Lazorwitz ADMS. The effect of carbamazepine on etonogestrel concentrations in contraceptive implant users. Contraception, 2017, 95(6): 571-577.
37. Livanainen M, Savolainen H. Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Acta Neurol Scand Suppl, 1983, 97(68): 49-67.
38. Waddell WJ, Mirkin BL. Distribution and metabolism of diphenyl-hydantoin-¹⁴C in fetal and maternal tissues of the pregnant mouse. Biochem Pharmacol, 1972, 21(4): 547-552.
39. Makatsori A, Michal D, Eduard U, et al. Neuroendocrine changes in adult female rats prenatally exposed to phenytoin. Neurotoxicol Teratol, 2005, 27(3): 509-514.
40. QUINN DL. Influence of Diphenylhydantoin on spontaneous release of ovulating hormone in the adult rat. Proc Soc Exp Biol Med, 1965, 119(4): 982-985.
41. Tamura K, Abe Y, Kogo H. Phenytoin inhibits both the first ovulation and uterine development in gonadotropin-primed immature rats. Eur J Pharmacol, 2000, 398(2): 317-322.
42. Kwan P, Yip FP, Hui ACF, et al. Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: A prospective randomized study. Epilepsy Behav, 2009, 14(4): 610-616.
43. Morrell MJ, Isojärvi J, Taylor AE, et al. Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy. Epilepsy Res, 2003, 54(2-3): 189-199.
44. Sahota P, Prabhakar S, Kharbanda PS, et al. Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study. Epilepsia, 2008, 49(12): 2069-2077.
45. Sidhu HS, Srinivasa R, Sadhotra A. Evaluate the effects of antiepileptic drugs on reproductive endocrine system in newly diagnosed female epileptic patients receiving either Valproate or Lamotrigine monotherapy: A prospective study. Epilepsy Res, 2018, 139: 20-27.
46. Duncan S, Blacklaw J, Beastall GH, et al. Antiepileptic Drug Therapy and Sexual Function in Men with Epilepsy. Epilepsia (Copenhagen), 1999, 40(2): 197-204.
47. Morrell MJ, Flynn KL, Doñe S, et al. Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy Behav, 2005, 6(3): 360-365.
48. Reis RM, de Angelo AG, Sakamoto AC, et al. Altered sexual and reproductive functions in epileptic men taking carbamazepine. J Sex Med, 2013, 10(2): 493-499.
49. Svalheim S, Taubøll E, Luef G, et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav, 2009, 16(2): 281-287.
50. Herzog AG, MSc, Drislane FW, et al. Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy. Neurology, 2005, 65(7): 1016-1020.
51. Wilner AN, Sharma BK, Soucy A, et al. Common comorbidities in women and men with epilepsy and the relationship between number of comorbidities and health plan paid costs in 2010. Epilepsy & Behavior, 2014, 32: 15-20.
52. 杨雪, 迟兆富. 癫痫共患病研究进展. 中国现代神经疾病杂志, 2012, 12(5): 507-515.
53. 游小林, 谢聪, 干晓琴. 抗精神病药与高催乳素血症及月经紊乱. 中华妇幼临床医学杂志(电子版), 2019, 15(4): 472-475.
54. Kinon BJ, Gilmore JA, Liu H, et al. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone11This work was sponsored by Eli Lilly and Company. Psychoneuroendocrinology, 2003, 28: 55-68.
55. Tellez-Zenteno JF, Matijevic S, Wiebe S. Somatic comorbidity of epilepsy in the general population in Canada. Epilepsia, 2005, 46(12): 1955-1962.
56. Bauer PR, Carpay JA, Terwindt GM, et al. Headache and epilepsy. Curr Pain Headache Rep, 2013, 17(8).
57. 雷荣. 抑郁障碍患者雌激素水平的临床意义探讨. 华北理工大学, 硕士学位论文, 2020.
58. 荣晗, 刘铁榜, 杨海晨, 等. 研究双相抑郁患者性激素水平治疗前后的变化. 中国实用医药, 2017, 12(20): 43-45.
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