Effects of valproate on reproductive endocrine function in male patients with epilepsy: A systematic review and meta-analysis
Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfu...
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| Published in | Epilepsy & behavior Vol. 85; pp. 120 - 128 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.08.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1525-5050 1525-5069 1525-5069 |
| DOI | 10.1016/j.yebeh.2018.04.029 |
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| Abstract | Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy.
A literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs).
Six publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD = −1.33, 95% CI: −2.60 to −0.07, P = 0.039) and testosterone (SMD = −0.45, 95% CI: −0.87 to −0.03, P = 0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD = 0.41, 95% CI: −0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20, 95% CI: −0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: −0.10 to 1.57, P = 0.086), and a decrease in that of LH(SMD = −0.71, 95% CI: -1.49 to 0.07, P = 0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P > 0.05).
This meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy.
•VPA decreases the levels of FSH and testosterone in male patients with epilepsy.•VPA might disturb male reproductive function by altering some reproductive factors.•Neurologists should be cautious when prescribing VPA for male patients with epilepsy. |
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| AbstractList | Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy.
A literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs).
Six publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD = −1.33, 95% CI: −2.60 to −0.07, P = 0.039) and testosterone (SMD = −0.45, 95% CI: −0.87 to −0.03, P = 0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD = 0.41, 95% CI: −0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20, 95% CI: −0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: −0.10 to 1.57, P = 0.086), and a decrease in that of LH(SMD = −0.71, 95% CI: -1.49 to 0.07, P = 0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P > 0.05).
This meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy.
•VPA decreases the levels of FSH and testosterone in male patients with epilepsy.•VPA might disturb male reproductive function by altering some reproductive factors.•Neurologists should be cautious when prescribing VPA for male patients with epilepsy. Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy. A literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs). Six publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD = -1.33, 95% CI: -2.60 to -0.07, P = 0.039) and testosterone (SMD = -0.45, 95% CI: -0.87 to -0.03, P = 0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD = 0.41, 95% CI: -0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20, 95% CI: -0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: -0.10 to 1.57, P = 0.086), and a decrease in that of LH(SMD = -0.71, 95% CI: -1.49 to 0.07, P = 0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P > 0.05). This meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy. Valproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy.BACKGROUNDValproate (VPA) is a broad spectrum antiepileptic drug (AED) that is generally used as a first line agent for most idiopathic and symptomatic generalized epilepsies. Many studies have indicated that AEDs cause reproductive endocrine disorders in males, but the exact etiology underpinning these dysfunctions is not clear. This meta-analysis and systematic review was intended to evaluate the effect of VPA on reproductive endocrine function in male patients with epilepsy.A literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs).METHODSA literature search was performed using electronic databases up to December 2017 for eligible studies. The differences in the levels of the reproductive factors, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione (ADION) in the male patients with epilepsy treated with VPA (treatment group) were compared with the those of the healthy controls (control group) by the use of the Standardized mean difference (SMD) with 95% confidence intervals (CIs).Six publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD = -1.33, 95% CI: -2.60 to -0.07, P = 0.039) and testosterone (SMD = -0.45, 95% CI: -0.87 to -0.03, P = 0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD = 0.41, 95% CI: -0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20, 95% CI: -0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: -0.10 to 1.57, P = 0.086), and a decrease in that of LH(SMD = -0.71, 95% CI: -1.49 to 0.07, P = 0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P > 0.05).RESULTSSix publications with a total of 316 subjects were identified. The result revealed that the levels of FSH (SMD = -1.33, 95% CI: -2.60 to -0.07, P = 0.039) and testosterone (SMD = -0.45, 95% CI: -0.87 to -0.03, P = 0.038) of the treatment group were decreased significantly compared with the healthy controls. There was an increase in the levels of SHBG (SMD = 0.41, 95% CI: -0.21 to 1.03, P = 0.197), DHEAS (SMD = 0.20, 95% CI: -0.06 to 0.45, P = 0.126) and ADION (SMD = 0.73, 95% CI: -0.10 to 1.57, P = 0.086), and a decrease in that of LH(SMD = -0.71, 95% CI: -1.49 to 0.07, P = 0.075) in the male patients with epilepsy treated with VPA, but the differences did not reach statistical significance (P > 0.05).This meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy.CONCLUSIONSThis meta-analysis indicates that VPA may lead to a significant decrease in the levels of FSH and testosterone and alter the concentrations of LH, DHEAS, SHBG, and ADION to some extent, which might contribute to the reproductive endocrine dysfunction in male patients with epilepsy. It is important for clinical neurologists to be cautious when prescribing VPA to reproductive-aged male patients with epilepsy. |
| Author | Zhu, Gang Teng, Weiyu Wang, Yu Wang, Xiaoyin Zhao, Chuansheng Zhao, Shanshan Xu, Junjie |
| Author_xml | – sequence: 1 givenname: Shanshan surname: Zhao fullname: Zhao, Shanshan organization: Department of Neurology, The First Hospital of China Medical University, Shenyang, China – sequence: 2 givenname: Xiaoyin surname: Wang fullname: Wang, Xiaoyin organization: Department of Neurology, The First Hospital of China Medical University, Shenyang, China – sequence: 3 givenname: Yu surname: Wang fullname: Wang, Yu organization: Department of Neurology, The First Hospital of China Medical University, Shenyang, China – sequence: 4 givenname: Junjie surname: Xu fullname: Xu, Junjie organization: Laboratory of AIDS Immunology of Health Ministry, The First Hospital of China Medical University, Shenyang, China – sequence: 5 givenname: Gang surname: Zhu fullname: Zhu, Gang organization: Department of Psychiatry, The First Hospital of China Medical University, Shenyang, China – sequence: 6 givenname: Chuansheng surname: Zhao fullname: Zhao, Chuansheng organization: Department of Neurology, The First Hospital of China Medical University, Shenyang, China – sequence: 7 givenname: Weiyu surname: Teng fullname: Teng, Weiyu email: tengweiyucmu@126.com organization: Department of Neurology, The First Hospital of China Medical University, Shenyang, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29940375$$D View this record in MEDLINE/PubMed |
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