Effect of tamoxifen citrate on reproductive parameters of male dogs

Abstract

Tamoxifen is a synthetic, nonsteroidal Type I antiestrogenic compound that competitively blocks estrogen receptors with a mixed antagonist-agonist effect. The manifestation of these different actions depends on each species, organ, tissue and cell type considered. Very little is known about the effect of antiestrogens in dogs. The objectives of this study were to determine the effects of tamoxifen citrate on some testis, prostate, hormone, and semen parameters in seven Beagle dogs with uncomplicated spontaneous benign prostatic hyperplasia. Two dogs were normospermic, four were oligozoospermic, and one was azoospermic. The dogs were allocated to a control pre-treatment period, followed by a treatment period, and five post-treatment periods (the duration of each period was 4 weeks). During the treatment period, 2.5mg tamoxifen citrate was given p.o. daily for 28 days to all the dogs. Maximum scrotal width, testicular consistency, libido semen parameters, prostatic volume, serum testosterone concentrations, and side effects were assessed. Tamoxifen negatively affected testis size and libido (P<0.01), and decreased prostatic volume (P<0.01) and testosterone concentrations during treatment. Semen quality deteriorated to nadir values (P<0.01) approximately one spermatic cycle after treatment and returned to pre-treatment values on the second cycle after treatment in all the dogs, except one young oligoazoospermic dog, in which the sperm count was higher ( P<0.01 ) at that time. No side effects were observed and fertility was conserved at the end of the study. Tamoxifen acted more like an agonist than antagonist on the gonadal axis and, therefore, upon both the prostate and testis. Therefore, tamoxifen may have therapeutic applications in dogs.

Effect of tamoxifen treatment on the semen quality and fertility of the male rat

“…Moreover, Rolf et al reviewed the treatment of male infertility in 29 clinical trials with a total of 1,586 patients and concluded that the benefits may not justify the risks (thrombocytopenia, carcinogenicity) of using tamoxifen in otherwise healthy males (44). In addition, tamoxifen has been reported to have detrimental effects in the fertility status of males from different strains, such as rats, monkeys, and dogs (45)(46)(47), decreasing the ability of males to sire normal pups. Most of the studies were conducted evaluating the consequences of tamoxifen treatment in the capacity of the males to sire viable litters, but little has been done regarding the semen quality in males that were subjected to tamoxifen treatment.…”

“…Seminal plasma normally constitutes an enriched medium for sperm survival, and it was reported previously that tamoxifen induced alterations in the prostate and seminal vesicles (45,46). Taking these into account, it could be speculated that the sperm alterations originating in the testis possibly could have worsened after ejaculation because of an altered composition of the seminal plasma, resulting from an impaired function of the male accessory glands.…”

Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

“…Furthermore, steroid hormones have important roles in prostate growth and maturation and prostate development is mediated by androgen-regulated stromal factors [21, 165]. The role of estrogens and stromal-epithelial interactions in the prostate is less clear.…”

“…In another study, Raloxifene and Tamoxifen did not affect proliferation induced by E 2 of a stromal cell line (WPMY-1) or BPH epithelial cell line (BPH-1), but both SERMs inhibited proliferation of prostate stromal cells in a rat model of prostatic hyperplasia induced by estrogen and androgen treatment [197]. In a study of seven beagles with spontaneous BPH, treatment with the SERM Tamoxifen resulted in decreased prostate volume [165]. A randomized trial of Tamoxifen in dogs with BPH showed an average 28.5% decrease in prostate volume compared to placebo [198].…”

Chemical Control of Fertility in Male Dogs: A Review

“…Tamoxifen citrate @ 2.5 mg. was given orally for 28 days to male dogs which led to deterioration of semen quality to nadir values approximately one spermatic cycle after treatment and returned to pre-treatment values on the second cycle after treatment in all the dogs, except one young oligoazoospermic dog (Corrada et al, 2004).…”