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Malatkova et al 13 reported that sex hormone disorders in 12 patients returned to normal after CBZ was replaced by OXC. Verrotti et al 14 showed that OXC can have a dose?dependent effect on reproductive endocrine function, and serum testosterone, sex hormone–binding protein, and gonadotropin levels all increased when OXC doses were >900 mg/d.

Harden et al 15 reported that a marked increase in testosterone levels was observed after 1 month of LEV treatment in 8 male adult patients with epilepsy. However, Spencer showed that in 26 adult male patients with epilepsy, no statistically significant changes were found in sex hormone levels measured before taking LEV and after taking it for 13.7 weeks.

16 Herzog et al 17, 18 and Gil?Nagel et al 18 observed no

change

We speculated that conventional doses of OXC, LEV, or LTG alone or their metabolites do not mainly affect the cytochrome P450 enzyme system. Semen quality decline is also one of the important factors that causes impaired fertility disorders of male patients with epilepsy. In the maturation of sperm, sex hormone regulation plays a very important role; LH stimulates testicular stromal cells to synthesize testosterone, and FSH acts on supporting cells in the seminiferous tubules, leading to synthesis of androgen?binding globulin (ABP).

Then, ABP and testosterone are combined and carried in spermatogonia and spermatocytes, so that germ cells obtain stable, high concentrations of androgen, and effectively differentiate into mature sperm.

Many studies have shown that epilepsy and a variety of AEDs can cipla viagra tablets adversely affect the quality of semen, particularly older AEDs, most of which can affect the sex hormones and in turn have an impact on the occurrence and maturation of sperm.

19, 20 The epileptic abnormal discharge of brain neurons can cipla viagra tablets also affect the function of the hypothalamic?pituitary?gonadal axis, indirectly affecting the quality of sperm. The effect of the AEDs on semen quality has only been reported by a few authors. Calabro et al 21 reported the case of a male patient with epilepsy who was diagnosed as infertile and had a marked reduction in semen quality.

After 3 months of LTG treatment, the sperm count increased 2.7?fold and sperm motility increased 68%, and a pregnancy resulted after 5 months. Cansu et al 22 found in an animal study that OXC can reduce the number of spermatocytes at all developmental stages, although the difference was not statistically significant.

Kose?Ozlece et al 23 observed a significant decrease in sperm count and viability as the dose of VPA was increased, but the semen quality was restored after the VPA dose was tempered by combination with LTG. Baysal et al 24 found that when male rats received oral LEV for 70 days, histological examination of the rat's genital histopathology and semen analysis showed that at 300 mg/kg/d LEV, the male rats had obvious testicular damage, and the effect of LEV on rat semen quality was shown to be dose?dependent. In our study, the semen quality of the patients with epilepsy was significantly decreased compared with the healthy control group, suggesting that the reduction of semen quality may be mainly because of the seizures themselves. There was a trend toward improvement in all sperm parameters before and after treatment with the 3 different novel AEDs compared with those before treatment, but there was only a statistically significant difference in the OXC treatment group.

In the LEV and LTG treatment groups, although comparison between before and after treatment showed a substantial improvement, no significant difference was observed.

We believe that these 3 AEDs have no significant negative effects on male semen quality at therapeutic doses and may improve the semen quality to some extent; treatment with OXC can improve the survival rate and FFMR of the sperm. It has been reported that men with epilepsy experience sexual dysfunction, including loss of libido, erectile dysfunction, and orgasm disorders. 25 In addition, some studies have reported that in male patients with epilepsy, the degree of sexual dysfunction is negatively correlated with anxiety and depression, not correlated with the frequency of seizures, but closely correlated with the location of epileptic seizures.

This includes temporal lobe epilepsy, in which sexual dysfunction occurs more often than in other types of epilepsy. 26 The possible mechanism is the temporal lobe area,

especially

27 Newer AEDs (OXC, LEV, or LTG) might affect sexual function less than older AEDs.

4, 5, 28 They can cause sexual dysfunction by affecting the secretion of sex hormones 11 or by increasing the inhibition of GABA, inhibiting nerve conduction and reducing the transmission of sexual stimuli.

29 The effect of these AEDs on sexual function has been less reported, with contrasting results.

Different studies have pointed out that OXC can both improve sexual function in patients with epilepsy and can also cause sexual dysfunction.

Luef et al 6 reported that among 228 adult male epilepsy patients with partial seizures and sexual dysfunction, 181 (79.4%) of them improved their sexual function after being treated with OXC monotherapy or by replacing other AEDs with OXC monotherapy for 12 weeks of treatment; moreover, 23 (10.1%) patients did not get worse, and the improvement in sexual function was more obvious in patients who had previously used enzyme?inducing AEDs. Calabro et al 7 reported that treatment with OXC at 1800 mg/d caused retrograde ejaculation in a 35?year?old man with traumatic epilepsy, and the retrograde ejaculation disappeared after switching to other AEDs.

However, Calabro et al 30 also reported that 2 young men with epilepsy had loss of libido and a lack of sex appeal after taking LEV, and recovered sexual function after switching to other AEDs.

In case studies or sample studies, LTG has not been found to have any adverse effects on sexual function, and it has been shown to have a positive effect on sexual function. 18, 31 A clinical study by Gil?Nagel et al 18 followed 141 patients with epilepsy treated with LTG as initial or replacement therapy for 4?8 months; male patients with epilepsy showed significant improvement in their sexual function compared with function before treatment.

The authors thought that this was probably a multivariate result of an improvement in seizures, the elimination of adverse effects of other AEDs, and the stabilizing effect of LTG. In this study, the patients with epilepsy had a lower erectile function score than the healthy control group.

In patients with epilepsy, premature ejaculation levels have a lower trend, but it was not statistically significant.

These results, to some extent, suggest that epilepsy itself can adversely affect the erectile function score.

The scores of erectile function and premature ejaculation were increased in the OXC, LEV, and LTG groups when compared between before and after treatment, but no statistical significance was found.

This may be related to the small case number in this study. We also presume that these 3 AEDs may have effects on improvement of erectile function.

In conclusion, this study suggests that seizures may lead to a decrease in semen quality and lower marriage and fertility rates in male adult patients with epilepsy compared to healthy controls, but have no significant effect on erectile function, premature ejaculation, or sex hormones. Treatment with OXC improved the FFMR and survival rate of sperm; treatment with LEV and LTG showed a notable improvement on semen quality, but this did not reach statistical significance. Therefore, using these AEDs to treat adult male patients with epilepsy may be a more appropriate choice.

None of the authors has any conflict of interest to disclose.

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Stember is an Assistant Professor of Urology at Icahn School of Medicine at Mount Sinai in New York City.

As a board certified urologist and fellowship trained surgeon, he has a special interest and training in minimally invasive and microsurgical techniques

for

Stember is a leading authority in the research and treatment of erectile dysfunction. He is one of a handful of surgeons in the United States who is fellowship trained in both sexual medicine and penile prosthetic surgery (at Memorial Sloan-Kettering Cancer Center) and male infertility and microsurgery (at Weill-Cornell Medical College).

Stember has developed several novel medical products and holds a patent for the design of a device to assist with improved outcomes for penile prosthesis surgery. He is Chair of the Membership Committee of the Sexual Medicine Society of North America. Stember reviews and selects articles for publication in medical journals including the Journal of Sexual Medicine, European Urology, The Journal of Urology, Andrology, Sexual Medicine, and the Asian Journal of Andrology. He is a member of multiple organizations including the Sexual Medicine Society of North America (SMSNA), the International Society for Sexual Medicine (ISSM), the American Urological Association (AUA), and the New York Section of the American Urological Association (NYAUA).

Stember is the recipient of the prestigious Scholars in Sexuality Research Grant Award from the Society for Sexual Medicine in 2010. He has authored more than 100 articles, book chapters, and abstracts in the field of reproductive and sexual medicine. His research and discoveries have been presented at national and international conferences and published in leading journals including The Journal of Urology, Annual Review in Medicine, and the Journal of Sexual Medicine . Stember frequently lectures and presents his clinical

research

He has given clinical talks throughout the United States, as well as Canada and South Korea. He teaches and mentors medical students, residents, and fellows, and received the Beth Israel Urology Faculty Teaching Award in 2013.

He has also been a faculty member for surgical skills workshops where he has taught other practicing urologists his technique of penile prosthesis surgery.

Bladder Cancer Congenital Kidney Disease Cystoscopy Frequent Urination Hypogonadism Impotence Infertility Neurogenic Bladder Penile Prosthesis Insertion Peyronie's Disease Prostate Cancer Prostate Cancer Screening Vasectomy.

Internship, General Surgery Mount Sinai School of Medicine. Fellowship, Microsurgery and Male Fertility Weill Cornell Medical College. Fellowship, Sexual Medicine Memorial Sloan-Kettering Cancer Center. 2014 Super Doctors - NY Rising Star Urology New York Times. 2014 Center of Excellence - Penile Prosthesis Surgery Coloplast.

2010 Scholars in Sexuality Research Grant Award Sexual Medicine Society of North America.

Pseudo-malfunction of the Coloplast Titan Inflatable Penile Prosthesis One-Touch Release Pump.

Is there a rationale for penile rehabilitation following radical prostatectomy?. Katz BF, Gaunay GS, Barazani Y, Nelson CJ, Moreira DM, Dinlenc CZ, Nagler HM, Stember DS. Use of a preoperative checklist reduces risk of penile prosthesis infection.

Reproductive sequelae of diabetes in male patients.

Endocrinology and metabolism clinics of North America 2013 Dec; 42(4). Lifestyle, environment, and male reproductive health.

The Urologic clinics of North America 2014 Feb; 41(1).

Outcomes of abdominal wall reservoir placement in inflatable penile prosthesis implantation: a safe and efficacious alternative to the space of Retzius.

Concordance between patient and physician assessment of the magnitude of Peyronie's disease curvature. Tal cipla viagra tablets R, Stember DS, Logmanieh N, Narus J, Mulhall JP. Erectile dysfunction in men treated for testicular cancer. Preoperative erectile function is an independent predictor for decision to spare cavernous nerves during radical prostatectomy.

Sullivan JF, Stember DS, Deveci S, Akin-Olugbade Y, Mulhall JP.

Ejaculation profiles of men following radiation therapy for prostate cancer. Defining the aetiology of erectile dysfunction in cipla viagra tablets men with chronic pelvic pain syndrome.

Microsurgical epididymal sperm aspiration: indications, techniques and outcomes. Management of ejaculatory disorders in infertile men.