Therapeutic Effect of Aromatase Inhibitor in Two Azoospermic Dogs with High Plasma Estradiol-17β Levels

Abstract

ABSTRACT. Two azoospermic dogs with high plasma estradiol-17β (E 2 ) levels were subcutaneously injected with an aromatase inhibitor (AI), 4-androstene-4-ol-3,17-dione, 2 mg every other day for 4 weeks. Before the AI treatment the plasma E 2 levels of the two dogs (21 and 22 pg/ml, respectively) were higher than those of 2 normal dogs (8.1 and 12.3 pg/ml), and they fell to 11-17 pg/ml between 1 and 4 weeks after the start of AI treatment. The plasma testosterone levels after the start of AI treatment had increased to 2.1-3.1 ng/ ml. A small number of sperm were detected in the semen of the two dogs between 3 and 6 weeks after the start of AI treatment. Th ese results indicate that the testicular function of infertile dogs with high plasma E 2 levels can be temporarily improved by AI therapy. KEY WORDS: aromatase inhibitor, azoospermia, canine.J. Vet. Med. Sci. 65(12): 1343-1345, 2003 A portion of the testosterone (T) produced by the testis is converted to estradiol-17β (E 2 ) by aromatase enzyme activity [11]. In the testes of many species [2,17], including dogs [3], the E 2 -secreting cells are the Sertoli cells and/or the Leydig cells [13,20]. In men [6,19] abnormally increased testicular E 2 production causes spermatogenic dysfunction, and long-term E 2 administration has been shown to inhibit spermatogenesis in dogs [8,15]. Aromatase inhibitor (AI) blocks the aromatization of androgen to E 2 by inhibiting aromatase enzyme activity [1,18], and AI has been reported to be effective in treating spermatogenic dysfunction in men with high plasma E 2 levels [4]. In the present study, two azoospermic dogs with abnormally increased plasma E 2 levels were treated with AI to improve poor semen quality. Plasma E 2 levels after administration of follicle stimulating hormone extracted from porcine pituitary gland (FSH-P) were measured to investigate the main E 2 -secretory cells in canine testes.The two azoospermic dogs used to assess the effects of AI treatment were a Miniature Poodle (Dog 1) and a Beagle (Dog 2), aged 5 and 2 years, respectively. Dog 1 was owned by a breeder, and Dog 2 was cared for in our university. None of a few bitches mated with either of the two male dogs had conceived. Four semen specimens were collected by digital manipulation with a teaser bitch at one-week intervals. Each specimen was examine for total semen volume, total number of sperm, and morphologically abnormal sperm by the methods described previously [9]. As no sperm had been found in the semen of either Dog 1 or Dog 2 (Table 1), both of them were diagnosed as having azoospermia. Although the two azoospermic dogs were treated with 3 intramuscular injections of 1000 IU hCG per head at one-week intervals, their semen quality had failed to improve. Peripheral blood samples were collected from the two azoospermic dogs at the same time as the semen collections. Plasma E 2 and T levels were measured by the radioimmunoassay described previously [8]. The plasma E 2 levels of the two dogs (21 and 22 pg/ml, respectively) were higher than those o...

Chronic Immune-Mediated Orchitis Is the Major Cause of Acquired Non-obstructive Azoospermia in Dogs

“…Nevertheless, back in 1983, Winter et al (90) demonstrated the significance of physiological estradiol concentrations through aromatization of testosterone for the control of gonadotropin secretion in the male dog. Although increased estradiol-17 ß concentrations had been described in two canine azoospermia patients (77 and 81 pmol/l) compared with two normospermic controls (29 and 45 pmol/l) (91), based on the laboratory specific references, we conclude that NOA was not associated with "hyperestrogenism" in our patients.…”

Comparison of the Effect of the Aromatase Inhibitor, Anastrazole, to the Antioestrogen, Tamoxifen Citrate, on Canine Prostate and Semen

“…In rats, anastrazole had no histological effect on spermatogenesis (Turner et al 2000). Moreover, aromatase inhibitors improved spermatogenic function and semen parameters in oligo and azoospermic men (Pavlovich et al 2001) and dogs with high plasma oestradiol concentrations (Kawakami et al 2003(Kawakami et al , 2004.…”

“…Moreover, aromatase inhibitors improved spermatogenic function and semen parameters in oligo and azoospermic men (Pavlovich et al. 2001) and dogs with high plasma oestradiol concentrations (Kawakami et al. 2003, 2004).…”

“…Aromatase is the enzyme that catalyzes the conversion of androgens to oestrogens in the peripheral tissue (Santen 2003). Blocking this conversion may be useful for the treatment of oestrogendependent diseases while having the benefit of no effect, or possibly a positive effect upon spermatogenesis Oesterling et al 1988;Turner et al 2000;Pavlovich et al 2001;Kawakami et al 2003Kawakami et al , 2004.…”

Aromatase inhibitors in the treatment of male infertility

“…The first report on aromatase inhibitors in the management of azoospermia came from an experimental animal study performed by Kawakami et al [31], who subcutaneously injected two azoospermic dogs with high plasma estradiol-17 b [E(2)] levels with an aromatase inhibitor for 4 weeks. The plasma testosterone levels after the start of aromatase inhibitors treatment had increased and small numbers of sperm were detected in the semen of the two dogs between 3 and 6 weeks from the start of treatment.…”