Pituitary‐Testicular Function of Prostatic Cancer Patients During Treatment with a Gonadotropin‐Releasing Hormone Agonist Analog II. Endocrinology and Histology of the Testis

Abstract

Endogenous testosterone (T), LH and FSH receptors, and in vitro production of cyclic adenosine-3':5'-monophosphate (cAMP), T and some of its steroid precursors were measured in testicular tissue obtained at orchiectomy from seven prostatic cancer patients treated for 6 months with a potent gonadotropin-releasing hormone (GnRH) agonist analog (buserelin, Hoechst, 600 micrograms 3 times a day intranasally). In addition, histologic and morphometric studies were carried out on the testicular tissue. Testicular tissue from age-matched prostatic cancer patients (n = 14), whose first therapy was orchiectomy, served as controls. The peptide treatment decreased intratesticular T by 95% (P less than 0.01) and FSH receptors by 57% (P less than 0.01), but had no effect on LH receptors. The in vitro production of T decreased by 94% (P less than 0.01), but that of cAMP was unaffected. Besides T, the in vitro production of testicular 17-hydroxyprogesterone (17-OHP-4), androstenedione and 5 alpha-dihydrotestosterone (5 alpha-DHT) dropped by 71 to 90% (P less than 0.01 to 0.05) during buserelin treatment, but those of pregnenolone, progesterone and dehydroepiandrosterone (DHEA) were not affected. Histologic studies revealed considerable variation in the seminiferous epithelium of the control group, but spermatogenesis was highly suppressed in nearly all of the buserelin-treated group. The number of Sertoli cells was unaffected, but tubular diameters were reduced (P less than 0.05) by buserelin treatment. Leydig cells appeared dedifferentiated in this group, although their number per testis was not altered. These data indicate that gonadotropin suppression by GnRH agonist most likely affects testicular steroidogenesis by inhibiting 3 beta-hydroxysteroid dehydrogenase and a step(s) prior to pregnenolone formation. The treatment does not impair testicular LH binding or cAMP production, but clearly suppresses FSH receptors. Spermatogenesis in general is suppressed but with considerable variation.

Scrotal Ultrasound in Male Infertility

“…Since epididymo-orchitis is an ascending inflammation, one would expect to see epididymal involvement before testicular involvement on ultrasound. In our study, infection of epididymis and or testis showed infiltrative margins, heterogenous pa renchyma with or without mild to moderate hydrocele consistent with a previous study [6].…”

“…The changes observed in the interstitial and tubular compartments in treated patients might, there fore, result from the withdrawal of hormone stimulation due to a combination of reduced LH synthesis (GnRH-A), reduced delivery of hormones to testicular paren chyma from blood vessels (age), and block of nuclear receptors for testosterone (Cy-A). Changes in Leydig cells, already reported after GnRH-A treatment [4][5][6][7][8][9][10], were more severe in treated versus control men. It is worth mentioning that, in treated patients, the disapSpermatogenesis was arrested at spermatogonial (5 cases) or primary spermatocyte levels (6 cases, fig.…”

“…In elderly men, chronic treatment with GnRH-A seems to be responsible for a disruption in spermatogen esis, although of a variable degree [4][5][6]. Our investiga tion demonstrates that the combination of GnRH-A and Cy-A, a competitive antagonist of testosterone nuclear receptors [11,12], is also not associated with a more pearance of the characteristic tubular cristae of Leydig cell mitochondria, a key feature of an active steroido genic cell [18], was observed.…”

“…By lowering the serum levels of gonadotropins through a desensitization of gonadotroph cells to physio logic GnRH stimulation [1][2][3], chronic treatment with GnRH analogs (GnRH-A) seems responsible for a dis ruption in spermatogenesis in elderly men [4][5][6][7][8][9][10]. Cy proterone acetate (Cy-A) has a powerful antiandrogen effect antagonizing the nuclear testosterone receptor [11,12].…”

The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis

“…The outcome of the hormonal contraceptive trials usually leaves 30-40% of the men oligozoospermic and potentially fertile, for an as yet unknown reason. The normal intra- testicular T level decreases in men during antigonadotropic treatments (GnRH agonist or T) by Ϸ98%, but it still remains at about 50 nmol͞liter (26,27). This level is higher than the normal peripheral concentration and well within the range of stimulating the androgen receptor and possibly spermatogenesis.…”