Role of Testosterone/Estradiol Ratio in Predicting the Efficacy of Tamoxifen Citrate Treatment in Idiopathic Oligoasthenoteratozoospermic Men

Abstract

Aim: It was the aim of this study to investigatethe effect ofalow testosterone/estradiol (T/E2) ratio and the normalization of this ratio by an aromatase inhibitor, anastrozole, on the treatment results of tamoxifen citrate (TAM) in idiopathic oligoasthenoteratozoospermic patients with a normal T/E2 ratio. Patients and Methods: 127 normogonadotropic men were included in this study. TAM (10 mg twice daily) was applied to 103 of the patients (group 1). The control group consisted of 25 patients who did not receive any treatment (group 2). After 3 months, TAM therapy was continued in 42 of the patients with a normal T/E2 ratio (group 1A). Of the remaining 61 patients with low ratios, 30 continued with TAM (group 1BTAM), while the remaining 31 patients underwent additional anastrozole therapy (1 mg/day) to TAM (group 1BANA). Results: In the 3rd month of the study, while the sperm concentration and motility were found significantly improved in group 1 (p < 0.05), they were significantly lower in groups 1BTAM and 1BANA than in group 1A (p < 0.01). In the 6th month of the study, the mean T/E2 ratio was normal in group 1A and group 1BANA, but was lower than normal ranges in group 1BTAM. The sperm concentration and motility significantly increased in groups 1A and 1BANA (p < 0.05). Conclusions: A significant decrease in the T/E2 ratio was seen in the majority of the patients during TAM treatment. Normalization of this ratio by addition of anastrozole to the treatment regimen improved the treatment outcomes. However, a placebo-controlled study is needed to confirm our results.

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

“…The age of the participants ranged from 20 to 49 years. All eligible male partners from the included trials had a deficient level of spermatozoa concentrate or a low motility of spermatozoa in the seminal fluid (as defined by local laboratory criteria described by each trial) and five trials further assessed men with low normal sperm morphology (R€ onnberg, 1980;Mi ci c & Dotli c, 1985;AinMelk et al, 1987;Krause et al, 1992;Cakan et al, 2009). Most trials were able to report and consider fertility status of the female partners as not a contributing factor to the couples' infertility, and excluded men with any identifiable male factor infertility such as hypogonadism, inflammatory disease, testicular trauma, varicocoele, epididymal factor, antibody problems or chromosomal problems.…”

“…The studied oestrogen antagonists were Tamoxifen citrate in 20-30 mg or Clomiphene citrate in 25 and 50 mg daily dosage. Placebo was given to the control group in nine trials, while the control group by Mi ci c & Dotli c (1985) and Cakan et al (2009) received no treatment. The duration of treatment period ranged from 3 to 12 months with average 3 months post-treatment follow-up.…”

“…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;…”

“…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.…”

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia

“…Furthermore, treatment with tamoxifen showed improved sperm variables and higher pregnancy rates in men with idiopathic oligozoospermia in a prior placebo-controlled trial [10]. Despite this controversy, tamoxifen was proposed as the first line of treatment for iOAT by the World Health Organization (WHO) [8,11].…”