Hormonal Treatment

Human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) are being used in patients with cryptorchidism for both diagnostic and therapeutic purposes. No uniform regimen for hCG is superior for either purpose, and it is likely that most regimens provide maximal stimulation. Treatment for 3 to 4 d is practical and provides a reliable assessment of testicular responsiveness (119). The use of the diagnostic test is limited to the situation in which neither testis is palpated. In the boy with bilateral nonpalpable testes that may be either absent or abdominal, hCG stimulation is useful during the childhood years (120). Testes may become palpable, or testosterone levels may rise. Because testes will respond to brief stimulation by hCG during childhood with increased testosterone secretion, this test is useful in determining the presence of testicular tissue containing responsive Leydig cells. This test does not differentiate between unilateral anorchia and a unilateral undescended testis, and an increase in testosterone does not ensure a normal testis. Because of the transient physiological increase in gonadotropin secretion, an infant male with absent testes will likely have markedly elevated LH levels consistent with primary hypogonadism. However, gonadotropin levels are low beyond infancy until the peripubertal period. It has also been reported that inhibin-B levels rise in young boys in response to hCG stimulation. This may prove to be a method by which Sertoli cell integrity can be assessed (75); however, false negative results may occur (121) from a lack of differentiated Ley-dig cells. During childhood, there is dedifferentiation or apoptosis of Leydig cells that were functional during infancy, with other Leydig cells becoming functional at puberty or after gonadotropin stimulation (22).

Hormonal treatment with hCG or gonadotropin-releasing hormone (GnRH) analogs (96) or historically with FSH, human menopausal gonadotropin (hMG), and testosterone has been used for undescended testes. There are no data to indicate that the success rate in inducing permanent testicular descent differs between hCG and GnRH (123,124). Overall, a meta-analysis showed that both treatments are more effective than placebo, but each was only approx 20% successful (125). Earlier reports of 50-70% success rates likely resulted from the inadvertent inclusion of many patients with retractile testes.

Hormonal therapy with either hCG or GnRHa has become a secondary treatment modality, because only a small portion of patients respond with full descent (126). An immediate response rate as high as 40% has been reported, although some studies found a higher response in the unilateral group (126), and others find no difference between those with unilateral or bilateral cryptorchidism (124). A significant percentage of medically treated patients have subsequent re-ascent of the testis. The portion of boys with descent after hormonal stimulation is inversely related to age, with such a poor response in the first 2 yr of life that some authors recommend that medical therapy should not be used (124).

The results of testicular biopsies at orchiopexy in boys treated unsuccessfully with GnRH showed a negative correlation between germ cell count and age at surgery (127). This was interpreted as evidence to favor early surgery. Moreover, prolonged GnRH therapy has been reported to increase numbers of germ cells (96). More recent data suggest, however, that hCG or GnRHa treatment may have a detrimental effect on germ cell numbers when given to boys younger than 4 yr of age (128).

Successful hormonal treatment is precluded when an anatomic problem prevents descent (e.g., ectopic testes). In one series, 40% of patients with unsuccessful hormonal therapy subsequently had successful surgical treatment (110). Hormonal therapy is generally reserved for special circumstances: (1) patients with nonpalpable testes, (2) patients in whom the testis is in the upper scrotum, (3) patients with a high likelihood of retractile testes that cannot be confirmed by routine physical examination, and (4) patients with a high anesthesia risk. It has been suggested that with hormonal therapy,

Cryptorchidism Testosterone
Fig. 3. Testosterone levels (ng/dL) in men who formerly had unilateral or bilateral cryptorchidism and control men. Solid line depicts the median, the shaded area the interquartile range, and the cross-lines the minimum and maximum values.

the abdominal testis, its vascular supply, and its supporting structures may enlarge and descend partially, making the testis palpable and enhancing subsequent surgery. However, there are no data to support this contention. For the low-lying, but not fully descended, testis, the goal is to achieve full descent with hormone stimulation. It is noteworthy that boys with cryptorchidism with Klinefelter's syndrome have poorer hormonal and descent responses than other patients with cryptorchidism to hormonal therapy (29). In cases in which the history is strongly suggestive of previously descended testes but the child is difficult to examine and has highly retractile testes, successful hormonal therapy might well be reassuring and obviate unnecessary orchiopexy.

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