Tamoxifen treatment in male infertility. I. Effect on spermatozoa

Kotoulas, Ion-George; Cardamakis, E.; Michopoulos, John G.; Mitropoulos, Dionysis; Dounis, A.

doi:10.1016/s0015-0282(16)56705-3

Cited by 61 publications

(45 citation statements)

References 15 publications

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“…This review had elicited from its sub-group analysis that both clomiphene in 50 mg and tamoxifen 20-30 mg daily dose are the mode of treatment to institute the significant treatment effect of oestrogen antagonists. A major difference of this meta-analysis from the two prior meta-analyses is the exclusion of two previously considered RCTs (Abel et al, 1982;Hargreave et al, 1986) that used Vitamin C as placebo and included three new RCTs (Kotoulas et al, 1994;Adamopoulos et al, 1997;Cakan et al, 2009) into quantitative analysis. The basis of excluding the trials considered by the prior reviews was backed by the evidence from a recent Cochrane review of Showell et al (2011) describing that antioxidant itself can significantly improve pregnancy outcome and semen parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Pooled effect estimates from nine studies with the result from Wang et al (1983) further sub-categorized, pregnancy outcome analysis showed an overall beneficial effect favouring oestrogen antagonists (pooled OR: 2.42; 95% CI 1.48, 3.94; p = 0.0004) ( (R€ onnberg, 1980;AinMelk et al, 1987;Sokol et al, 1988;WHO, 1992) 36.4 5 (Wang et al, 1983;Mi ci c & Dotli c, 1985;Krause et al, 1992;Kotoulas et al, 1994;Adamopoulos et al, 1997) 45.5 2 (T€ or€ ok, 1985;Cakan et al, 2009) 18.1 Blinding 6 (R€ onnberg, 1980;T€ or€ ok, 1985;AinMelk et al, 1987;Sokol et al, 1988;WHO, 1992;Cakan et al, 2009) 54.5 5 (Wang et al, 1983;Mi ci c & Dotli c, 1985;Krause et al, 1992;Kotoulas et al, 1994;Adamopoulos et al, 1997) 45.5 0 -Outcome assessor blinding 5 (R€ onnberg, 1980;T€ or€ ok, 1985;AinMelk et al, 1987;Sokol et al, 1988;WHO, 1992) 45.5 6 (Wang et al, 1983;Mi ci c & Dotli c, 1985;Krause et al, 1992;Kotoulas et al, 1994;Adamopoulos et al, 1997;Cakan et al, 2009) 54.5 0 -Incomplete outcome data addressed 8 (R€ onnberg, 1980;Wang et al, 1983;Mi ci c & Dotli c, 1985;T€ or€ ok, 1985;Sokol et al, 1988;Krause et al, 1992;WHO, 1992;…”

Section: Effects Of Interventionmentioning

confidence: 99%

“…Other source of bias 3 (Sokol et al, 1988;WHO, 1992;Adamopoulos et al, 1997) 27.3 1 ( Wang et al, 1983) 7 (R€ onnberg, 1980;Mi ci c & Dotli c, 1985;T€ or€ ok, 1985;AinMelk et al, 1987;Krause et al, 1992;Kotoulas et al, 1994;Cakan et al, 2009) 754 Andrology, 2013, 1, 749-757 p = 0.13; I 2 35%). Based on raw data pooled from the included trials, the calculated NNT is equivalent to 10.…”

Section: Effects Of Interventionmentioning

confidence: 99%

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Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis

et al. 2013

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SUMMARYThe aim of this study was to synthesize and present the latest available evidence regarding the use of oestrogen antagonists as empiric medical therapy for idiopathic male infertility with oligo and/or asthenoteratozoospermia through meta-analysis of randomized controlled trials (RCTs). Systematic literature acquisition was done for English and other foreign language biomedical databases up to March, 2013. RCTs relevant to the topic were identified and critically appraised independently by two physician reviewers. Dichotomous data of pregnancy rate and adverse events were extracted for calculation of odds ratio (OR) and 95% confidence interval (CI). Effect estimates were pooled using Peto method with fixed effect model. The continuous data of semen and endocrine parameters were calculated for the mean difference between pre-and post-treatment effects, the weighted mean difference (WMD) and SD between the control and intervention group were determined and pooled using the random effects model. Inter-study heterogeneity and publication bias were assessed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for meta-analysis reporting was followed. Eleven RCTs of good methodological quality were included for meta-analysis. The pooled effect estimates showed that oestrogen antagonists use was associated with a statistically significant increased pregnancy rate compared with controls (pooled OR 2.42; 95% CI 1.47-3.94; p = 0.0004). Significant increase in sperm concentration (WMD 5.24; 95% CI 2.12, 88.37; p = 0.001) and per cent sperm motility (WMD 4.55; 95% CI 0.73, 8.37; p = 0.03) were also noted. While significant elevation of serum follicle stimulating hormone (WMD 4.19 95% CI 2.05, 6.34; p = 0.0001) and testosterone (WMD 54.59; 95% CI 15.92, 93.27; p = 0.006) was associated with its use. No significant difference in adverse event was noted between oestrogen antagonists-treated group and controls. The evidence suggests that oestrogen antagonists as empiric medical therapy for idiopathic male infertility with low non-serious adverse event associated, may increase spontaneous pregnancy rate, improve sperm concentration and per cent sperm motility.

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of Interventionmentioning

confidence: 99%

Section: Effects Of Interventionmentioning

confidence: 99%

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Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis

et al. 2013

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“…Tamoxifen citrate enhances spermatogenesis by increasing FSH, leydig cells sensibility to LH, and testosterone levels, which lacks an intrinsic oestrogenic effect, so it may be more appropriate to use in male infertility (Buvat et al, 1983;Kadioglu et al, 1999). Previous studies demonstrated that tamoxifen significantly increased sperm concentration in infertile men with oligozoospermia, but does not affect other semen values, such as volume, pH, motility, morphology, or viability, because of tamoxifen's effectiveness on the seminiferous tubules during the early stages of spermatogenesis (Vermeulen and Comhaire, 1978;Kotoulas et al, 1994). Other studies have shown that given tamoxifen citrate alone exerts a limited effect on sperm morphology and motility; it appears that the superior functional sperm fraction response was probably related to administration of testosterone undecanoate (Adamopoulos et al, 1997;.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia

Tang

Zhao

Ding

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Tamoxifen citrate, as the first line of treatment for infertile men with idiopathic oligozoospermia, was proposed by the World Health Organization (WHO), and testosterone undecanoate has shown benefits in semen values. Our objective was to assess the effectiveness of treatment with tamoxifen citrate and testosterone undecanoate in infertile men with idiopathic oligozoospermia, and whether the results would be affected by polymorphisms of CYP2D6*10. A total of 230 infertile men and 147 controls were included in the study. Patients were treated with tamoxifen citrate and testosterone undecanoate. Sex hormone, sperm parameters, and incidence of spontaneous pregnancy were detected. There were no significant differences between the control and patient groups with respect to CYP2D6*10 genotype frequencies (P>0.05). The follicle-stimulation hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were raised, and sperm concentration and motility were increased at 3 months and became significant at 6 months, and they were higher in the wild-type allele (C/C) than in the heterozygous variant allele (C/T) or homozygous variant allele (T/T) subgroups (P<0.05). In addition, the percentage of normal morphology was raised at 6 months, and represented the highest percentage in the C/C subgroup (P<0.05). The incidence of spontaneous pregnancy in the C/C subgroup was higher than that in the C/T or T/T subgroups (P<0.01). This study showed that the CYP2D6*10 variant genotype demonstrated worse clinical effects in infertile men with idiopathic oligozoospermia.

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“…TAM is also known to exert a beneficial effect on sperm density and number of live spermatozoa but it has no substantial effect on sperm motility and morphology (Kotoulas et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress in the testis induced by tamoxifen and its effects on early embryo development in isogenic mice

Lee

Lee²,

Park³

et al. 2012

J. Toxicol. Sci.

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-Oxidative stress induced by tamoxifen (TAM) in male testis and its effects on fertility and early embryo development were investigated. TAM was orally administered for 4 weeks repeatedly to two isogenic male mice strains, inbred strain of C57BL/6J (B6) mice and hybrid strain of C57BL/6J x CBA F1 (B6CBAF1) mice. Oxidative stress in mice testis was measured based on the level of lipid peroxidation (LPO). The LPO level was significantly increased in inbred strain of B6 mice (p < 0.05), but not hybrid strain of B6CBAF1 mice. Paternal exposure to TAM led to a significant decrease in the fertilization rate in B6 mice (p < 0.05), but not their B6CBAF1 counterparts. Interestingly, TAM had no impact on the cell number and apoptosis status in blastocysts. These results indicate that susceptibility to TAMinduced oxidative stress in the testis differs between isogenic mice strains, and genetic variations play an important role in promoting differential degrees of toxic response. Key words: Tamoxifen, Oxidative stress, Male fertility, Early embryonic development, IsogenicityCorrespondence: Dong Il Jin (E-mail: dijin@cnu.ac.kr) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.37, No.4, 675-679, 2012 Vol. 37 No. 4 675 MATERIALS AND METHODS AnimalsInbred C57BL/6J (B6) and hybrid C57BL/6J X CBA (B6CBAF1) mice were used. Mice were bred and maintained at a temperature of 22-23°C, relative humidity of 50-55% and a 14 hr light:10 hr dark cycle. Animals were fed sterilized mouse pellets and allowed access to water ad libitum. All animal care and use procedures were approved by the Institutional Animal Care and Use Committee of Chungnam National University. TAM treatmentMale mice aged 4 weeks (n = 6 per group) were administered 0.4 mg/kg/day tamoxifen citrate (Sigma Co., Saint Louis, MO, USA), which dose level was reported to reduce the fertility of adult male rat (Saberwal et al., 2002), orally for 4 weeks. The drug was suspended uniformly in saline via sonication. Saline was used as the vehicle control. Lipid peroxidation (LPO) assay in testisMice were sacrificed 24 hr after the final treatment in the morning between 09:00 and 11:00 am to minimize the circadian cycle effects. Testes were removed, immediately immersed in liquid nitrogen and stored at -80°C. Testes were sliced into sections and homogenized in cold 50 mM phosphate buffer (pH 7.0) containing 0.1 mM EDTA. Homogenates were centrifuged at 600 g for 10 min at 0°C, and the supernatant fractions used for LPO assay and protein determination. In the LPO assay, the malondialdehyde (MDA) level was measured as described by Ohkawa et al. (1979). A 100 μl aliquot of tissue extract was added to 50 μl of 8.1% sodium dodecyl sulfate (SDS), mixed by vortexing, and incubated for 10 min at room temperature. Next, 375 μl of 20% acetic acid (pH 3.5) and 375 μl of thiobarbituric acid (0.6%) were added and the mixture placed in a boiling water bath for 60 min. Samples were allowed to cool down to room temperature. A 250 μl aliquot of distilled water...

show abstract

Tamoxifen treatment in male infertility. I. Effect on spermatozoa

Cited by 61 publications

References 15 publications

Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis

Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis

Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia

Oxidative stress in the testis induced by tamoxifen and its effects on early embryo development in isogenic mice

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