癫痫模型大鼠动情周期、卵巢形态学及生长卵泡超微改变
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摘要
目的研究杏仁核电刺激点燃的癫痫模型大鼠动情周期、卵巢形态学及生长卵泡的超微变化。
方法取35只8周龄SD雌性大鼠,随机分为癫痫模型组(n=15)、假手术组(n=10)和对照组(n=10)。癫痫模型组,双极电极植入大鼠左侧杏仁基底外侧核,给予连续电刺激,建立电点燃的癫痫模型;假手术组,电极植入后不给予电刺激;对照组为正常雌性大鼠。所有大鼠每天清晨行阴道细胞涂片,以监测动情周期。癫痫模型大鼠在点燃20d后于动情周期的间期取双侧卵巢组织,同期其他两组大鼠也分别于动情间期摘取双侧卵巢组织,右侧卵巢做病理切片,HE染色后镜下阅片,采用Image-Pro Plus 6.0分析软件进行形态学分析,左侧卵巢选择窦状卵泡进行透射电镜观察。
结果癫痫模型组大鼠失去正常动情周期,日均体重增加的克数及卵巢重量均较假手术组及对照组显著增高(P<0.05);病理显示,癫痫模型组大鼠卵巢切面面积增大,窦前卵泡、总生长卵泡数及闭锁卵泡显著增多(P<0.05),卵巢发生多囊性改变;电镜下显示癫痫组大鼠窦状卵泡中的颗粒细胞凋亡增多,增生的卵泡膜细胞更加富含脂滴。
结论癫痫发作可影响大鼠排卵功能,并导致大鼠发生卵巢多囊性改变,生长卵泡凋亡增多,卵泡膜细胞增生分泌增强。
To explore changes of estrous cycle and ovarian morphology and ultrastructure of growing follicles in amygdale-kindled seizures female rats.Methods Thirty five SD rats of 8-week-old were randomly divided to Kindling electrodes (n=15), sham-kindled (n=10), and controls (n=10). Kindling electrodes were implanted in the left basolateral amygdala in adult female rats. The rats were kindled by brief, daily, suprathreshold stimulations with a bipolar electrode. The sham-kindled rats only implanted bipolar electrode in the left basolateral amygdala. Controls were normal female rats. Estrous cycles were monitored with daily vaginal smears. Electrographic and behavioral seizures were monitored,.right Ovary tissues were taken after 20 days of kindled in the diestrus. At the same time, sham-kindled subjects and their yoked controls were sacrificed and their right ovaries were taken in their diestrus. Ovarian morphometric analyses were examined. Results Kindled rats lost ovarian periodicity and they displayed significantly weight gained and ovarian increasing(P<0.05). The result of HE staining showed that,compared with control group and shamed-kindled group, kindled female rats had enlarged ovaries with numerous growing follicles, espically many preantral follicles, and the total number of follicles and atretic follicles increased(P<0.05). The ovarian in study group exhibited polycystic changes. Ultrastructure of growing follicles of kindled rats exhibited increase of apoptotic granulose cells, theca cell hyperplasia, and more secretory granules can be found in theca cells, their ovarian exhibited polycystic changes. Conclusions Seizures initiated in amygdala result in polycystic ovary and loss of normal estrus cycle. Seizures initiated in amygdala result in polycystic ovary,growing follicles showed more apoptosis and increase of the secretion in the theca cell hyperplasia .
方法取35只8周龄SD雌性大鼠,随机分为癫痫模型组(n=15)、假手术组(n=10)和对照组(n=10)。癫痫模型组,双极电极植入大鼠左侧杏仁基底外侧核,给予连续电刺激,建立电点燃的癫痫模型;假手术组,电极植入后不给予电刺激;对照组为正常雌性大鼠。所有大鼠每天清晨行阴道细胞涂片,以监测动情周期。癫痫模型大鼠在点燃20d后于动情周期的间期取双侧卵巢组织,同期其他两组大鼠也分别于动情间期摘取双侧卵巢组织,右侧卵巢做病理切片,HE染色后镜下阅片,采用Image-Pro Plus 6.0分析软件进行形态学分析,左侧卵巢选择窦状卵泡进行透射电镜观察。
结果癫痫模型组大鼠失去正常动情周期,日均体重增加的克数及卵巢重量均较假手术组及对照组显著增高(P<0.05);病理显示,癫痫模型组大鼠卵巢切面面积增大,窦前卵泡、总生长卵泡数及闭锁卵泡显著增多(P<0.05),卵巢发生多囊性改变;电镜下显示癫痫组大鼠窦状卵泡中的颗粒细胞凋亡增多,增生的卵泡膜细胞更加富含脂滴。
结论癫痫发作可影响大鼠排卵功能,并导致大鼠发生卵巢多囊性改变,生长卵泡凋亡增多,卵泡膜细胞增生分泌增强。
To explore changes of estrous cycle and ovarian morphology and ultrastructure of growing follicles in amygdale-kindled seizures female rats.Methods Thirty five SD rats of 8-week-old were randomly divided to Kindling electrodes (n=15), sham-kindled (n=10), and controls (n=10). Kindling electrodes were implanted in the left basolateral amygdala in adult female rats. The rats were kindled by brief, daily, suprathreshold stimulations with a bipolar electrode. The sham-kindled rats only implanted bipolar electrode in the left basolateral amygdala. Controls were normal female rats. Estrous cycles were monitored with daily vaginal smears. Electrographic and behavioral seizures were monitored,.right Ovary tissues were taken after 20 days of kindled in the diestrus. At the same time, sham-kindled subjects and their yoked controls were sacrificed and their right ovaries were taken in their diestrus. Ovarian morphometric analyses were examined. Results Kindled rats lost ovarian periodicity and they displayed significantly weight gained and ovarian increasing(P<0.05). The result of HE staining showed that,compared with control group and shamed-kindled group, kindled female rats had enlarged ovaries with numerous growing follicles, espically many preantral follicles, and the total number of follicles and atretic follicles increased(P<0.05). The ovarian in study group exhibited polycystic changes. Ultrastructure of growing follicles of kindled rats exhibited increase of apoptotic granulose cells, theca cell hyperplasia, and more secretory granules can be found in theca cells, their ovarian exhibited polycystic changes. Conclusions Seizures initiated in amygdala result in polycystic ovary and loss of normal estrus cycle. Seizures initiated in amygdala result in polycystic ovary,growing follicles showed more apoptosis and increase of the secretion in the theca cell hyperplasia .
引文
[1] Bilo L, Meo R, Valentino R et al. Characterization of reproductive endocrine disorders in women with epilepsy [J]. Clin Endocrinol Metab, 2001, 86(7):2950-2956.
[2] R?ste LS, Taub?ll E. Women and epilepsy: review and practical recommendations [J]. Expert Rev Neurother, 2007, 7: 289-300.
[3] Herzog AG, Schachter SC. On the association between valproate and polycystic ovary syndrome. Epilepsia [J]. 2001, 42:311–315
[4] Kalinin VV, Zheleznova EV. Chronology and evolution of temporal lobe epilepsy and endocrine reproductive function in females relationships with foci laterality and catameniality [J] . Epilepsy Behav. 2007, 11:185–191. CrossRef
[5] Herzog AG. Disorder of reproduction in patients with epilepsy: Primary neurological mechanisms [J]. Seizure, 2008, 17:101-110.
[6] Herzog AG. Reproductive endocrine regulation in men with epilepsy: effects on reproductive function and neuronal excitability [J]. Ann Neurol, 2002, 51:539-542.
[7] Herzog AG, Coleman AE, Jacobs AR, et al. Interictal EEG discharges, reproductive hormones and menstrual disorders in epilepsy [J]. Ann Neurol, 2003, 54:625-637.
[8] R?ste LS, Taub?ll E. Women and epilepsy: review and practical recommendations [J]. Expert Rev Neurother, 2007, 7: 289-300.
[9] Verrotti A,Greco R.Latini G,et al.Endocrine and metabolic changes in epileptic patients receiving valproic acid [J].J Pediatr Endocrinol Metab, 2005, 18(5):423-430.
[10] Pack A. effects of treatment on endocrine function in patients with epilepsy. Curr Treat Options [J]. Neurol, 2005, 7(4):273-280.
[11] Gorkemli H, Genc BO, Dogan EA, et al. Long-Term Effects of Valproic Acid on Reproductive Endocrine Functions in Turkish Women with Epilepsy. [J] Gynecol ObstetInvest, 2009(67):223-227
[12] Lofgren E, Mikkonen K, Tolonen U, Pakarinen A, Koivunen R, Myllyla VV, et al. Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication [J]. Epilepsy Behav, 2007, 10:7-83.
[13] Isojarvi JI, Taub?ll E, Herzog AG. Effects of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy—a review [J]. CNS Drugs, 2005, 19:207-223.
[14] Mikkonen K, Vainionpaa LK, Pakarinen AJ, et al. Long-term reproductive endocrine health in young women with epilepsy during puberty[J]. Neurology, 2004, 62(3):445-450.
[15] Tauboll E, Roste LS, Svalheim S, et al Gender Issues in Epileps:.Disorders of reproduction in epilepsy—What can we learn from animal studies [J]. Seizure, 2008, 17(2): 120-126.
[16] Edwards HE, Burnham WM, Ng MM, et al. Limbic seizures alter reproductive function in the female rat [J]. Epilepsia, 1999, 40:1370-1377.
[17] Scharfman HE, Kim M, Hintz TM, et al. Seizures and reproductive function: Insights from female rats with epilepsy[J]. Ann Neurol, 2008, 64(6):687-697..
[18] Freeman ME. The neuroendocrine control of the ovarian cycle of the rat. In Knobil E, Neill JD (Eds) The physiology of reproduction. Raven Press, 1994:613–650.
[19] Racine RJ. Modification of seizure activity by electrical stimulation:ⅡMotor seizure[J]. Electroenceph clin Neurophysiol, 1972, 32(3):281-294.
[20] Liu G, Shi F, Blas-Machaodo U, et al. Ovarian effects of a high diet in the female rat [J]. Reprod Nuu Dev, 2005, 45(2):185.
[21] Nestorovic N, Lovren M, Sekulic M, et al. Chronic somatostatin treat ment affects pituitary gonadotrophs, ovaries and onset of puberty in rats[J]. L ife Sci, 2004, 74 (11): 1359- 1373.
[22] Borman SM, VanDePol BJ, Kao S, et al. A single dose of the ovotoxicant4-vinylcyclohexene diepoxide is protective in rat primary ovarian follicles.Toxicol Appl Pharmacol. 1999, 158(3):244-52.
[23] Sylaja PN, Radhakrishnan K. Problems and pitfalls in developing countries. Epilepsia 2003; 44 (11):48-50.
[24]曹泽毅主编.中华妇产科学:女性生殖生理.第二版,北京:人民卫生出版社,2007:33
[25] Bauer J, Isojarvi JI, Herzog AG, et al. Reproductive dysfunction in women with epilepsy: r ecommendations for evaluation and management [J]. Neurol Neurosurg Psychiatry. 2002, 73:121-125.
[26] The Rotterdam ESHRE/ASRM? Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long ? term health risks related to polycystic ovary syndrome (PCOS) [J]. Hum Reprod, 2004, 19(1):41-47
[27] Miller LJ, Grigis C, Grpta R. Depression and related disorders during the female reproductive cycle [J].Womens Health (Lond Engl), 2009, 5(5):577-587.
[28] Kathryn M, Hum, Sofia Megna, et al. The effects of right and left amygdale kindling on the female reproductive system in rats [J]. Epilepsia, 2009, 50(4):880-886.
[29] Cynthia L, Harden MD. Polycystic ovaries and polycystic ovary syndrome in epilepsy: evidence for neurogonadal disease [J]. Epilepsy Currents, 2005, 5(4):142-146.
[30] Polson DW, Wadsworth J, Adams J, et al. Polycystic ovaries-a common finding in normal women [J]. Lancet, 1988, 331(8590)870-872.
[31] Morrell MJ, Giudice L,Flynn KL, et al. Predictors of ovulatory failure in women with epilepsy [J]. Ann Neurol, 2002, 52(6):704-711
[32]石红.多囊卵巢综合症[M].妇产科学(第七版).北京:人民卫生出版社,2008,315-316.
[33] Otala M, Makinen S, Tuuri T, et al. Effects of testosterone, dihydrotestosterone, and17β-estradiol on human ovarian tissue survival in culture [J]. Fertil Steril, 2004, 82(Suppl 3):1077-85
[34] Perez GI, Trbovich AM, Gosden GR, et al. Reproductive biology: Mitochondria and the death of oocytes [J]. Nature, 2000, 403:500-501.
[35] Boone DL, Yan W, Tsang BK. Identification of a deoxyribonuclease I-like endonuclease in rat granulose and luteal cell nuclei [J]. Biol Reprod, 1995, 53(5):1057-65
[1] William O, Tatum IV, DO, Joyce Liporace, MD, et al. Updates on the Treatment of Epilepsy in Women [J]. Arch Intern Med, 2004, 164:137-145.
[2]陈子江,李媛,周灿权,等.多囊卵巢综合征与辅助生殖的热点问题讨论.现代妇产科进展, 2004, 13: 241～245.
[3] Herzog AG, Coleman AE, Jacobs AR, et al. Interictal EEG discharges, reproductive hormones and menstrual disorders in epilepsy [J]. Ann Neurol, 2003, 54:625-637.
[4] Hum KM, Megna S, Burnham WM. The effects of right and left amygdale a kindling on the female reproductive systemin rats [J]. Epilepsia, 2009, 50(4):880–886
[5] Meo R, Bilo L. Polycystic ovary syndrome and epilepsy: a review of the evidence [J]. Drugs, 2003, 63(12): 1185-1227
[6] Nestorovic N, Lovren M, Sekulic M, et al. Chronic somatostatin treat ment affects pituitary gonadotrophs, ovaries and onset of puberty in rats [J]. L ife Sci, 2004, 74 (11): 1359- 1373.
[7] Herzog AG. Disorder of reproduction in patients with epilepsy: Primary neurological mechanisms [J]. Seizure, 2008, 17(2):101-110.
[8] Herzog AG. Menstrual disorders in women with epilepsy [J]. Neurology 2006; 66(suppl 3):S23-S28
[9] Hamed SA, Hamed EA, Shokry M, Omar H, Abdellah MM. The reproductive conditions and lipid profile in females with epilepsy [J]. Acta Neurol Scand, 2007, 115:12-22.
[10] Lofgren E, Mikkonen K, Tolonen U, Pakarinen A, Koivunen R, Myllyla VV, et al. Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication.Epilepsy Behav 2007;10:77—83.
[11] Harden CL, Koppel BS, Herzog AG, Nikolov BG, et al. Seizure frequency is associated with age of menopause in women with epilepsy. Neurology, 2003, 61:451-5
[12] L?fgren E, Mikkonen K, Tolonen U, et al. Reproductive endocrine function in womenwith epilepsy: The role of epilepsy type and medication [J]. Epilepsy & Behavior, 2007, 10(1):77-88
[13] Mikkonen K, Vainionpaa LK, Pakarinen AJ, et al. Long-term reproductive endocrine health in young women with epilepsy during puberty. Neurology, 2004, 62(3): 445-450
[14] Betts T, YarrowH, Dutton N. A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy [J]. Seizure, 2003, 12(6): 323-329
[15] Rasgon N. The relationship between polycystic ovary syndrome and antiepileptic drugs: a review of the evidence [J]. Clin Psychopharmacology, 2004, 24(3): 322-334
[16] Kaplan PW. Reproductive health effects and teratogenicity of antiepileptic drugs[J]. Neurology, 2004, 63(10), 13-23
[17] Fawley JA, Pouliot WA, Dudek FE, et al. Epilepsy and reproductive disorders: the role of t he gonadotropin releasing hormone network [J].Epilepsy Behav. 2006; 8 (3): 477 - 82.
[18] Veliskova J. The role of estrogens in seizures and epilepsy: the bad guys or t he good guys [J]. Neuroscience, 2006; 138(3): 837 - 44.
[19] Hamed SA. Neuroendocrine Hormonal Conditions in Epilepsy: Relationship to Reproductive and Sexual Functions. The Neurologist, 2008, 14(3):157-169
[20] Roste LS, Tauboll E. Women and epilepsy: review and practical recommendations. Expert review of neurotherapeutics[J], 2007, 7(3):289-300
[2] R?ste LS, Taub?ll E. Women and epilepsy: review and practical recommendations [J]. Expert Rev Neurother, 2007, 7: 289-300.
[3] Herzog AG, Schachter SC. On the association between valproate and polycystic ovary syndrome. Epilepsia [J]. 2001, 42:311–315
[4] Kalinin VV, Zheleznova EV. Chronology and evolution of temporal lobe epilepsy and endocrine reproductive function in females relationships with foci laterality and catameniality [J] . Epilepsy Behav. 2007, 11:185–191. CrossRef
[5] Herzog AG. Disorder of reproduction in patients with epilepsy: Primary neurological mechanisms [J]. Seizure, 2008, 17:101-110.
[6] Herzog AG. Reproductive endocrine regulation in men with epilepsy: effects on reproductive function and neuronal excitability [J]. Ann Neurol, 2002, 51:539-542.
[7] Herzog AG, Coleman AE, Jacobs AR, et al. Interictal EEG discharges, reproductive hormones and menstrual disorders in epilepsy [J]. Ann Neurol, 2003, 54:625-637.
[8] R?ste LS, Taub?ll E. Women and epilepsy: review and practical recommendations [J]. Expert Rev Neurother, 2007, 7: 289-300.
[9] Verrotti A,Greco R.Latini G,et al.Endocrine and metabolic changes in epileptic patients receiving valproic acid [J].J Pediatr Endocrinol Metab, 2005, 18(5):423-430.
[10] Pack A. effects of treatment on endocrine function in patients with epilepsy. Curr Treat Options [J]. Neurol, 2005, 7(4):273-280.
[11] Gorkemli H, Genc BO, Dogan EA, et al. Long-Term Effects of Valproic Acid on Reproductive Endocrine Functions in Turkish Women with Epilepsy. [J] Gynecol ObstetInvest, 2009(67):223-227
[12] Lofgren E, Mikkonen K, Tolonen U, Pakarinen A, Koivunen R, Myllyla VV, et al. Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication [J]. Epilepsy Behav, 2007, 10:7-83.
[13] Isojarvi JI, Taub?ll E, Herzog AG. Effects of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy—a review [J]. CNS Drugs, 2005, 19:207-223.
[14] Mikkonen K, Vainionpaa LK, Pakarinen AJ, et al. Long-term reproductive endocrine health in young women with epilepsy during puberty[J]. Neurology, 2004, 62(3):445-450.
[15] Tauboll E, Roste LS, Svalheim S, et al Gender Issues in Epileps:.Disorders of reproduction in epilepsy—What can we learn from animal studies [J]. Seizure, 2008, 17(2): 120-126.
[16] Edwards HE, Burnham WM, Ng MM, et al. Limbic seizures alter reproductive function in the female rat [J]. Epilepsia, 1999, 40:1370-1377.
[17] Scharfman HE, Kim M, Hintz TM, et al. Seizures and reproductive function: Insights from female rats with epilepsy[J]. Ann Neurol, 2008, 64(6):687-697..
[18] Freeman ME. The neuroendocrine control of the ovarian cycle of the rat. In Knobil E, Neill JD (Eds) The physiology of reproduction. Raven Press, 1994:613–650.
[19] Racine RJ. Modification of seizure activity by electrical stimulation:ⅡMotor seizure[J]. Electroenceph clin Neurophysiol, 1972, 32(3):281-294.
[20] Liu G, Shi F, Blas-Machaodo U, et al. Ovarian effects of a high diet in the female rat [J]. Reprod Nuu Dev, 2005, 45(2):185.
[21] Nestorovic N, Lovren M, Sekulic M, et al. Chronic somatostatin treat ment affects pituitary gonadotrophs, ovaries and onset of puberty in rats[J]. L ife Sci, 2004, 74 (11): 1359- 1373.
[22] Borman SM, VanDePol BJ, Kao S, et al. A single dose of the ovotoxicant4-vinylcyclohexene diepoxide is protective in rat primary ovarian follicles.Toxicol Appl Pharmacol. 1999, 158(3):244-52.
[23] Sylaja PN, Radhakrishnan K. Problems and pitfalls in developing countries. Epilepsia 2003; 44 (11):48-50.
[24]曹泽毅主编.中华妇产科学:女性生殖生理.第二版,北京:人民卫生出版社,2007:33
[25] Bauer J, Isojarvi JI, Herzog AG, et al. Reproductive dysfunction in women with epilepsy: r ecommendations for evaluation and management [J]. Neurol Neurosurg Psychiatry. 2002, 73:121-125.
[26] The Rotterdam ESHRE/ASRM? Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long ? term health risks related to polycystic ovary syndrome (PCOS) [J]. Hum Reprod, 2004, 19(1):41-47
[27] Miller LJ, Grigis C, Grpta R. Depression and related disorders during the female reproductive cycle [J].Womens Health (Lond Engl), 2009, 5(5):577-587.
[28] Kathryn M, Hum, Sofia Megna, et al. The effects of right and left amygdale kindling on the female reproductive system in rats [J]. Epilepsia, 2009, 50(4):880-886.
[29] Cynthia L, Harden MD. Polycystic ovaries and polycystic ovary syndrome in epilepsy: evidence for neurogonadal disease [J]. Epilepsy Currents, 2005, 5(4):142-146.
[30] Polson DW, Wadsworth J, Adams J, et al. Polycystic ovaries-a common finding in normal women [J]. Lancet, 1988, 331(8590)870-872.
[31] Morrell MJ, Giudice L,Flynn KL, et al. Predictors of ovulatory failure in women with epilepsy [J]. Ann Neurol, 2002, 52(6):704-711
[32]石红.多囊卵巢综合症[M].妇产科学(第七版).北京:人民卫生出版社,2008,315-316.
[33] Otala M, Makinen S, Tuuri T, et al. Effects of testosterone, dihydrotestosterone, and17β-estradiol on human ovarian tissue survival in culture [J]. Fertil Steril, 2004, 82(Suppl 3):1077-85
[34] Perez GI, Trbovich AM, Gosden GR, et al. Reproductive biology: Mitochondria and the death of oocytes [J]. Nature, 2000, 403:500-501.
[35] Boone DL, Yan W, Tsang BK. Identification of a deoxyribonuclease I-like endonuclease in rat granulose and luteal cell nuclei [J]. Biol Reprod, 1995, 53(5):1057-65
[1] William O, Tatum IV, DO, Joyce Liporace, MD, et al. Updates on the Treatment of Epilepsy in Women [J]. Arch Intern Med, 2004, 164:137-145.
[2]陈子江,李媛,周灿权,等.多囊卵巢综合征与辅助生殖的热点问题讨论.现代妇产科进展, 2004, 13: 241～245.
[3] Herzog AG, Coleman AE, Jacobs AR, et al. Interictal EEG discharges, reproductive hormones and menstrual disorders in epilepsy [J]. Ann Neurol, 2003, 54:625-637.
[4] Hum KM, Megna S, Burnham WM. The effects of right and left amygdale a kindling on the female reproductive systemin rats [J]. Epilepsia, 2009, 50(4):880–886
[5] Meo R, Bilo L. Polycystic ovary syndrome and epilepsy: a review of the evidence [J]. Drugs, 2003, 63(12): 1185-1227
[6] Nestorovic N, Lovren M, Sekulic M, et al. Chronic somatostatin treat ment affects pituitary gonadotrophs, ovaries and onset of puberty in rats [J]. L ife Sci, 2004, 74 (11): 1359- 1373.
[7] Herzog AG. Disorder of reproduction in patients with epilepsy: Primary neurological mechanisms [J]. Seizure, 2008, 17(2):101-110.
[8] Herzog AG. Menstrual disorders in women with epilepsy [J]. Neurology 2006; 66(suppl 3):S23-S28
[9] Hamed SA, Hamed EA, Shokry M, Omar H, Abdellah MM. The reproductive conditions and lipid profile in females with epilepsy [J]. Acta Neurol Scand, 2007, 115:12-22.
[10] Lofgren E, Mikkonen K, Tolonen U, Pakarinen A, Koivunen R, Myllyla VV, et al. Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication.Epilepsy Behav 2007;10:77—83.
[11] Harden CL, Koppel BS, Herzog AG, Nikolov BG, et al. Seizure frequency is associated with age of menopause in women with epilepsy. Neurology, 2003, 61:451-5
[12] L?fgren E, Mikkonen K, Tolonen U, et al. Reproductive endocrine function in womenwith epilepsy: The role of epilepsy type and medication [J]. Epilepsy & Behavior, 2007, 10(1):77-88
[13] Mikkonen K, Vainionpaa LK, Pakarinen AJ, et al. Long-term reproductive endocrine health in young women with epilepsy during puberty. Neurology, 2004, 62(3): 445-450
[14] Betts T, YarrowH, Dutton N. A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy [J]. Seizure, 2003, 12(6): 323-329
[15] Rasgon N. The relationship between polycystic ovary syndrome and antiepileptic drugs: a review of the evidence [J]. Clin Psychopharmacology, 2004, 24(3): 322-334
[16] Kaplan PW. Reproductive health effects and teratogenicity of antiepileptic drugs[J]. Neurology, 2004, 63(10), 13-23
[17] Fawley JA, Pouliot WA, Dudek FE, et al. Epilepsy and reproductive disorders: the role of t he gonadotropin releasing hormone network [J].Epilepsy Behav. 2006; 8 (3): 477 - 82.
[18] Veliskova J. The role of estrogens in seizures and epilepsy: the bad guys or t he good guys [J]. Neuroscience, 2006; 138(3): 837 - 44.
[19] Hamed SA. Neuroendocrine Hormonal Conditions in Epilepsy: Relationship to Reproductive and Sexual Functions. The Neurologist, 2008, 14(3):157-169
[20] Roste LS, Tauboll E. Women and epilepsy: review and practical recommendations. Expert review of neurotherapeutics[J], 2007, 7(3):289-300