Hormonal Treatment May Harm the Germ Cells in 1 to 3-Year-Old Boys With Cryptorchidism

Cortes, Dina; Thorup, Jørgen; Visfeldt, Jakob

doi:10.1016/s0022-5347(05)67763-4

Cited by 95 publications

(44 citation statements)

References 18 publications

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“…In the first week hCG stimulation principally increases the mean weight of testes probably mediated by testosterone increase. In this period gonadotropin and testosterone are physiologically suppressed, thereby the impact of early hCG treatment is important [9]. In our study, in the hCG treated rats it has been observed a poor differentiation of the seminiferous epithelium, with high Leydig cell evidence and increased intertubular eosinophilic material.…”

Section: Discussionsupporting

confidence: 44%

“…Nevertheless its use in the management of cryptorchidism has been debated and potential harmful effects of hormonal therapy on the testis including apoptosis, inflammation and reduced number of germ cells continue to be explored [21]. Cortes and Thorup demonstrated that in one to three year boys with cryptorchidism HCG treatment may be hazardous to germ cells, therefore, they cannot be recommended [9]. Therefore considering the efficacy and the possible side effects of the hormonal treatment, the general use of hCG and GnRH in the treatment of cryptorchidism cannot be further recommended [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

“…In adult rats a single dose of hCG can acutely induce disruption and spermatogenesis disorder, seminiferous tubule damage and inflammation-like changes in testicular microcirculation [8]. Furthermore cryptorchids patients who underwent surgery had an increased volume and number of spermatogonia per tubule respect to the patient who underwent unsuccessful hormonal treatment, suggesting that it may harm germ cells [9].…”

Section: Open Accessmentioning

confidence: 99%

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Morphologic changes due to human chorionic gonadotropin in the rat testis: Role of vascular endothelial growth factor

Papparella¹,

Nino²,

Noviello³

et al. 2013

OJPed

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Introduction: Human chorionic gonadotropin (hCG) has an important role in the regulation of reproductive system and a high capacity to stimulate angiogenesis by secretion of vascular endothelial growth factor (VEGF). It could be also used for medical treatment of cryptorchidism, as it stimulates Leydig cells to produce testosterone, but its use has been discussed. Aim of the study was to evaluate the testicular morphological changes due to cyclic administration of hCG possibly related to VEGF effect. Methods: 80 pre-puberal male Sprague-Dawley rats were randomly divided in two groups hCG (50 U/I/ Kg) (n = 55/S) and placebo (n = 25/C) treated. The animals were sacrificed respectively after one (S1 n = 10; C1 n = 5), two (S2 n = 10; C2 n = 5) and three weeks of hCG or placebo treatment (S3 n = 35; C3 n = 15); a blood serum was obtained for evaluation of plasmatic testosterone. The testis, prostates, epididymides and seminal vesicles were drawn and weighted. Specimens were fixed in formalin and coloured by hematoxylin-eosin. Morphometric analysis of Leydig cell number, nuclear area and perimeter was carried out. Immunoistochemistry for VEGF has been performed with the avidin-biotin peroxidase technique. Statistical differences between groups, each of different age, were calculating using Student's T-test. Results: After the first week of hCG treatment it has been observed an increased testicular weight and volume (+/−6%) in experimental respect to control group. This result was not observed after the second and third week of treatment. Significant variations were also observed in the mean prostate weight, whereas mean seminal vesicles weight was significant in the S2 and S3 groups respect to control. In the hCG treated rats it has been observed a poor differentiation of the seminiferous epithelium, with high Leydig cell evidence and increased intertubular eosinophilic material. An interstitial edema was demonstrated without inflammatory cell changes. Morphometric analysis confirmed an increased number of Leydig cells that were always strongly immunostained for VEGF. Low-medium reactivity was present in spermatogonial, peritubular, endothelial and Sertoli cells. Testosterone plasmatic values showed a statistically significant and progressive increase. Conclusions: hCG treatment clutters the germinative line and modifies VEGF testicular expression, suggesting its role in male reproductive system. The increased number of Leydig cells and the immunostaining for VEGF suggests an intense interstitial and metabolic arrangement. The morphologic modifications induced by hCG treatment and its influence on testis function raise the question about its use in the medical treatment of cryptorchidism.

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Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Section: Open Accessmentioning

confidence: 99%

See 1 more Smart Citation

Morphologic changes due to human chorionic gonadotropin in the rat testis: Role of vascular endothelial growth factor

Papparella¹,

Nino²,

Noviello³

et al. 2013

OJPed

View full text Add to dashboard Cite

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“…In a study by Hadziselimovic et al, in which the effect of LHRH nasal spray on testicular descent was analysed, neither a stimulatory effect nor an inhibitory effect on the number of germ cells was seen (Hadziselimovic, 1980). This in contrast to Cortes et al, who found a negative effect on germ cells in 1-3-year-old boys with cryptorchidism after gonadotropin releasing hormone (GnRH) (Cortes, 2000). They hypothesized that these young boys may be sensitive for exogenous GnRH stimulation resulting in increased FSH, LH, and testosterone, which may have a negative impact on germ cells.…”

Section: Discussionmentioning

confidence: 93%

Fertility potential in men with a history of congenital undescended testes: a long‐term follow‐up study

et al. 2012

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Men with a history of congenital undescended testes (UDT) have an increased risk of fertility problems. Despite no definitive proof, current guidelines recommend early surgical intervention because this may have a positive effect on future fertility potential by preventing degenerative changes of the testes in early life. Also surgical intervention facilitates observability of the testes in view of possible malignancy. We evaluated testicular function in adult men with previous UDT treated at different ages before puberty. A longterm follow-up study of men with previous UDT was performed. Andrological evaluation included medical history taking, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Findings were compared with those of a control group of men with normal testicular descent. The influence of age at orchiopexy on future fertility parameters was evaluated in a multivariate regression analysis. 62 men were included of whom seven had had bilateral UDT. Twenty-four patients had had their orchiopexy before the age of 24 months of whom eight men had it before 12 months of age. Forty-eight men had had unsuccessful luteinizing-hormone-releasing-hormone (LHRH) nasal spray treatment during childhood, whereas 14 of 24 men operated before 24 months of age had not received LHRH treatment before orchiopexy. Fertility potential in men with a history of UDT is compromised in comparison with controls. We could not detect any influence of age at orchiopexy on fertility parameters. However, the number of patients operated before the age of 12 months is limited. This study does not support the assumption that early orchiopexy results in better fertility potential.

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“…However, adverse effects of the hCG on testicular histology have been studied and demonstrated in many other clinical and experimental studies, some evidencing little benefit in the hormonal treatment of cryptorchidism and even deleterious effects 3,[11][12][13]17,18,25,26 .…”

Section: Discussionmentioning

confidence: 99%

Effects of human chorionic gonadotropin on the normal testicular tissue of rats

et al. 2014

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PURPOSE:To investigate the effects of human chorionic gonadotropin (hCG) on the testicular tissue of young male rats. METHODS:Male Wistar rats were assigned to groups (10 rats/group).Control Group received subcutaneous saline solution; Group 1 received hCG 50UI/Kg/dose; and Group 2 received hCG 100UI/Kg/dose, daily for 15 days. Half was submitted to bilateral orchiectomy on the 16 th day and the other half 45 days after the beginning of the hormone application. Testicles were weighed, measured and has their volumes determined. The diameter of the tubules and the thickness of the seminiferous epithelium were measured. RESULTS:Control Group presented the highest values of testicles volume and weight. Rats in the Control presented normal histology.In G1 and G2 atrophy of the seminiferous tubules, apoptosis of germ cells and multinucleated giant cells were observed. Comparing groups, in the first operation Control rats had higher diameter values. In the second operation, the Control was only different from G1.As for thickness, Control had higher values in both operations. Comparing the time of operation, the diameter values were higher in G1and G2 in the second operation. For all groups, the thickness of the epithelium was higher in the second operation. CONCLUSIONS:Human chorionic gonadotropin is gonadotoxic in rats. This effect was temporary and can affect reproductive potential. The total recovery of testicular damage in the studied range could not be proved, and the effects were not dose-dependent.

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Hormonal Treatment May Harm the Germ Cells in 1 to 3-Year-Old Boys With Cryptorchidism

Abstract: In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells.

Cited by 95 publications

References 18 publications

Morphologic changes due to human chorionic gonadotropin in the rat testis: Role of vascular endothelial growth factor

Morphologic changes due to human chorionic gonadotropin in the rat testis: Role of vascular endothelial growth factor

Fertility potential in men with a history of congenital undescended testes: a long‐term follow‐up study

Effects of human chorionic gonadotropin on the normal testicular tissue of rats

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