More than eight years＇ hands-on experience with the novel long-acting parenteral testosterone undecanoate

Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.

Testosterone deficiency：a historical perspective

The biological effects of the testes and testosterone are known since antiquity. Aristotle knew the effects of castration and his hypothesis on fertilization is one of the first scientific encounters in reproductive biology. Over centuries, castration has been performed as punishment and to produce obedient slaves, but also to preserve the soprano voices of prepubertal boys. The Chinese imperial （and other oriental） courts employed castrates as overseers in harems who often obtained high-ranking political positions. The era of testis transplantation and organotherapy was initiated by John Hunter in London who transplanted testes into capons in 1786. The intention of his experiments was to prove the ＇vital principle＇ as the basis for modern transplantation medicine, but Hunter did not consider endocrine aspects. Arnold Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849 in Gottingen and is thus considered the father of endocrinology. Following his observations, testicular preparations were used for therapy, popularized by self-experiments by Charles-Edouard Brown-Sequard in Paris （1889）, which can at best have placebo effects. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproved. Today testicular transplantation is being refined by stem cell research and germ cell transplantation. Modern androgen therapy started in 1935 when Enrest Lacquer isolated testosterone from bull testes in Amsterdam. In the same year testosterone was chemically synthesized independently by Adolf Butenandt in G6ttingen and Leopold Ruzicka in Basel. Since testosterone was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl testosterone, now obsolete because of liver toxicity. The early phases of testosterone treatment coincide with the first description of the most prominent syndromes of hypogonadism by Klinefelter, by Kallmann, DelCastillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy.

Targeted expression of human FSH receptor Asp567Gly mutant mRNA in testis of transgenic mice: role of humanFSH receptor promoter

Aim: To specifically express the Asp567Gly human follicle-stimulating hormone receptor (FSHR) under the control of its promoter to evaluate the phenotypic consequences in the presence of normal pituitary function. Methods: We produced transgenic mice overexpressing the Asp567Gly human FSHR under the control of a 1.5kb 5' flanking region fragment of its promoter. Results: Mice were phenotypically normal and fertile. In males, mRNA could be detected in the testis and the brain, indicating that the 1.5kb promoter fragment drives expression not only in the gonads. The testis weight/body weight ratio and the testosterone levels in transgenic and non-transgenic litter mates were similar. By in situ hybridisation we found that the transgenic FSHR was highly expressed in Sertoli cells, spermatocytes and round spermatids. However, a radioligand receptor assay failed to show a significant difference in total FSHR binding sites in testis homogenates of transgenic and wild type animals, suggesting that the transgenic FSHR is probably not translated into functional receptor protein. Conclusion: A 1.5kb 5 '-region of the human FSHR drives mRNA expression of the transgene in the testis but leads to ectopic expression in germ cells and in the brain. No phenotypic consequences could be documented due to the lack of protein expression.

Optimising workflow in andrology: a new electronic patient record and database

Aim： To improve workflow and usability by introduction of a new electronic patient record （EPR） and database. Methods： Establishment of an EPR based on open source technology （MySQL database and PI-IP scripting language） in a tertiary care andrology center at a university clinic. Workflow analysis, a benchmark comparing the two systems and a survey for usability and ergonomics were carried out. Results： Workflow optimizations （electronic ordering of laboratory analysis, elimination of transcription steps and automated referral letters） and the decrease in time required for data entry per patient to 71% ± 27%, P 〈 0.05, lead to a workload reduction. The benchmark showed a significant performance increase （highest with starting the respective system： 1.3 ± 0.2 s vs. 11.1 ± 0.2 s, mean ± SD）. In the survey, users rated the new system at least two ranks higher over its predecessor （P 〈 0.01） in all sub-areas. Conclusion： With further improvements, today＇s EPR can evolve to substitute paper records, saving time （and possibly costs）, supporting user satisfaction and expanding the basis for scientific evaluation when more data is electronically available. Newly introduced systems should be versatile, adaptable for users, and workflow-oriented to yield the highest benefit. If ready-made software is purchased, customization should be implemented during rollout. （Asian J Andro12006 Mar; 8： 235-241）

Epidermal growth factor receptor pathway substrate 8 (Eps8) expression in maturing testis

Aim: Although epidermal growth factor receptors are expressed in the testes, whether they signal through epidermal growth factor receptor pathway substrate 8 (Eps8) is unknown. Here we evaluated the expression pattern of Eps8 in the maturing testis. Methods: The expression of Eps8 was analysed by Northern blotting, immunocy-tochemistry and Western blotting in primary Sertoli cell cultures and in testicular tissue of rodents. Results: Eps8 is specifically expressed in gonocytes, Leydig and Sertoli cells of the neonatal rats and in Leydig and Sertoli cells of the adult rats and mice. Although gonocytes express Eps8, no signal was found in prepubertal or mature spermatogonia and the expression level of Eps8 in Sertoli cells increases with age. No regulation of Eps8 expression in primary immature rat Sertoli cells by Follicle stimulating hormone (FSH) was detected by Western blotting. Conclusion: Eps8 seems to be involved in the growth factor-controlled regulation of cell proliferation and differentiation in the seminiferous epithelium. Eps8 is a possible marker for gonocytes and in Sertoli cells it could be involved in crosstalk with other growth factor pathways.

Sperm crisis： what crisis？

For 20 years the so-called ＂sperm crisis＂ caused unrest among the public as well as the scientific community. Studies precipitated by this virtual crisis have refuted its existence, but have also illuminated hitherto neglected aspects of male reproductive function and indicated a need for prospective, long-term monitoring systems.