Assessment of Testicular Function

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The male reproductive tract is very susceptible to the toxic effects of chemotherapy and radiation, which may disrupt the endocrine axis or damage the testes directly. Assessment of testicular maturation and function involves pubertal staging, plasma hormone analysis and semen analysis. Pubertal staging provides clinical information about both of these testic-ular functions (i.e. the production of hormones and the production of semen). The development of normal secondary sexual characteristics suggests intact Leydig cell function, with normal steroidogenesis, and testicular volumes are an important indicator of spermatogenesis. Testicular volume of <12 ml, determined using the Prader orchidometer, is strongly suggestive of impaired spermatogenesis.

Hormone analysis involves measurement of plasma FSH, LH and sex steroids (Table 14.5). In prepubertal children, however, this is an unreliable predictor of gonadal damage, since the prepubertal hypothalamic pituitary-testicular axis is quiescent. In post-pubertal boys, elevated LH and diminished testosterone levels are indicative of Leydig cell dysfunction, while elevated FSH and diminished inhibin B suggest germ cell failure. HCG may be given to confirm the diagnosis of end organ failure as a cause of hypogonadism. An abnormal response to HCG is suggestive of disturbed Leydig cell function. Patients with hypogonadotrophic hypogonadism should have a brisk response, while those with decreased Leydig cell function will have little or no response. GnRH may be administered to determine whether the primary defect is in the hypothalamus or in the pituitary. If it's in the hypothalamus, the pituitary and testicles themselves should respond normally to exogenous GnRH. Alternatively, if the primary defect is in the pituitary, there will be an inadequate response. An exaggerated response of FSH and LH to GnRH suggests a "failing" testis; hence, this test may be useful in detecting early testicular failure. Depressed gonadotropins may also be found in patients after the administration of exogenous androgen. The determination of elevated FSH, along with small testicular size, may offer the most practical approach for predicting subsequent testicular damage in boys with malignancies.

Recently, there has been an interest in estimating the gonadal function of male cancer survivors directly by measuring the serum levels of the bioactive gonadal peptide hormone, inhibin B, using a newly devel oped enzyme-linked immunosorbent assay [3]. It has been postulated that inhibin B is produced by the Sertoli cells and germ cells of the testes and reflects the degree of seminiferous tubular damage [37, 60, 71]. Furthermore, inhibin B exerts negative feedback regulation on the pituitary production and release of FSH [22]. In a study examining the gonadal status of childhood brain tumor survivors, researchers found a significant inverse correlation between basal FSH and inhibin B, as well as a significant correlation between inhibin B and total testicular volume [71].

Following pubertal staging and hormone analysis, semen analysis is necessary to confirm spermatogen-esis. The sample should be fresh and properly collected. This usually involves abstaining from sexual intercourse for 3-5 days and collecting the specimen by masturbation. Sperm count and quality can provide useful information about the likelihood of natural fertilization and, hence, whether assisted reproduction may be required. The sperm count should be at least 20 x 106 per ml. Since recovery from damage to germinal epithelium may occur 5-10 years (or even later) after therapy, these counts should be repeated from time to time, as such evaluation is indicated.

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