Testicular position in the androgen insensitivity syndrome: implications for the role of androgens in testicular descent

PURPOSE: We compared testicular position with genital phenotype in a clinical series and a literature review of androgen receptor mutations to assess the role of androgens in testicular descent. MATERIALS AND METHODS: Our clinical reports, the androgen receptor mutations database and selected literature were reviewed. Subjects with a proved androgen receptor mutation were included in our study when a female or ambiguous phenotype was present (Quigley grade 3 to 7) and testicular position was documented. Comparison among groups was done by Fisher's exact or chi-square test. RESULTS: Of the 7 patients with detailed clinical records 5 had abdominal (bilateral in 4) and 2 had bilateral inguinal testes. Four patients with abdominal testes also had aberrant pelvic ligaments extending medially from the gonads. Including an additional 102 cases identified in the literature, abdominal testes were present in 52% and 3% of those with complete and partial androgen insensitivity, respectively. The incidence of abdominal testes was highest (86%) in patients with a complete female phenotype and no pubic hair (grade 7). It decreased significantly with increasing masculinization and was higher in phenotypic females diagnosed at or after (67%) than in those identified before (22%) puberty. Hernia was associated with inguinal and abdominal testes. CONCLUSIONS: Testicular position correlates with genital phenotype in patients with androgen receptor mutations, supporting a major role for androgens in testicular descent. Inguinal hernia and abnormal pelvic ligaments in these individuals may partially determine testicular position but to our knowledge the role of androgen receptors, if any, in their development is unknown.     

睾丸女性化综合征6例报告

目的 总结6例睾丸女性化综合征的诊断及治疗体会。方法 回顾性分析6例睾丸女性化综合征的诊断方法、治疗措施及结果。6例均行睾丸切除术，5例行阴蒂矫形术。术后均长期服用雌激素治疗。结果 6例术后均恢复顺利。1例失访。余5例术后外生殖器外观满意，感觉良好。其中1例已婚，性生活满意。结论 本病一般作女性处理，双侧睾丸应切除，术后长期服用雌激素。     

Testicular implants and patient satisfaction: a questionnaire-based study of men after orchidectomy for testicular cancer.

OBJECTIVES: To assess the satisfaction of men with their testicular implants after undergoing orchidectomy for testicular cancer, and to determine their reasons for accepting or declining a prosthesis. PATIENTS AND METHODS: In all, 424 men who had undergone radical orchidectomy and were part of the testicular cancer follow-up programme were sent an anonymous questionnaire comprising 10 questions covering two main areas. First, the reasons for accepting or declining an implant and second (if they received an implant) their satisfaction with the size, position, feel, shape and overall comfort; 234 men (55%) responded. RESULTS: About a third (71 men) accepted an implant, a third declined and a third were not offered the choice. Of the men who replied 91% felt that it was extremely important to be offered an implant at the time of surgery. Of the 71 who received an implant, 19 (27%) were dissatisfied and felt that they had an average or poor cosmetic result. The reasons for this dissatisfaction are presented and discussed. CONCLUSIONS: All men undergoing orchidectomy should be offered a testicular implant, irrespective of age. Sample implants in all sizes should be available in the outpatient department. This will give men realistic expectations and allow them to choose a suitable size of implant. The dimensions of the available implants should be improved to create a more elliptical prosthesis, to avoid dissatisfaction with the shape. Adequate fixation to the base of the scrotum is important to avoid the 'high riding' implant.     

Testicular feminization: the androgen insensitivity syndrome.

Testicular feminization (TF) is a syndrome due to androgen insensitivity. It occurs in a complete (CTF) and an incomplete (ITF) form. We have treated 21 patients with TF over the last 24 years. Eight patients presented because of ambiguous genitalia, seven presented as "females" with inguinal hernia and testes were found at surgery, five were diagnosed by karyotyping performed for a family history of TF, and one presented with an incarcerated hernia and primary amenorrhea. Two patients had prior surgery for inguinal hernia but the diagnosis was not recognized. All patients had a 46,XY karyotype. Patients with CTF were phenotypically female while those with ITF had a variable appearance of the external genitalia depending on the degree of androgen insensitivity. Seventeen patients underwent gonadectomy and one patient planned for delayed gonadectomy was lost to follow-up. Seventeen patients had been raised as females since birth. One patient with ambiguous genitalia, who was initially raised as a male, was reassigned female gender at 1 year of age when the diagnosis of ITF was made. Three patients were raised as males even after the diagnosis of ITF was made. Patients raised as males underwent multiple genital reconstructive procedures with poor results. In view of the poor anatomic and functional results of genital reconstructive surgery and the consequent psychological problems, patients with TF should be raised as female. Careful evaluation of infants with ambiguous genitalia and documentation of absent fallopian tubes in "females" presenting with inguinal hernia will lead to early diagnosis of TF, correct sex assignment, and early gonadectomy.     

睾丸女性化综合症4例

目的：探讨睾丸女性化综合症的诊断和治疗。方法：回顾性分析1985-09/2001-10收治的4例睾丸女性化综合症患者的临床特征、影像学检查、治疗方法及随访资料。结果：术后随访0.5-1.5a，患者女性第二性征显著，有2例患者服用小剂量雌激素。结论：对睾丸女性化综合征患者应以预防未成熟睾丸发生恶变及维持女性特征为治疗原则。     

Intrascrotal CGRP 8-37 causes a delay in testicular descent in mice.

The genitofemoral nerve is a key factor in the inguinoscrotal descent of the testis. The effect of androgens may be mediated via the central nervous system, which in turn secretes the neurotransmitter calcitonin gene-related peptide (CGRP) at the genitofemoral nerve endings, to cause testicular descent. The effect of endogenous CGRP was examined by weekly injections of a vehicle with or without synthetic antagonist (CGRP 8-37) into the developing scrotum of neonatal mice. The descent of the testis was delayed in the experimental group compared with the control group. At 2 weeks of age 43% of controls had descended testes compared with 0% of experimental animals. At 3 weeks of age 17% of experimentals still had undescended testes, whereas all testes were descended in controls. At 4 weeks 3 testes remained undescended in the experimental group. It is concluded that the CGRP antagonist can retard testicular descent. This result is consistent with the hypothesis that CGRP is an important intermediary in testicular descent.     

Laparoscopic bilateral orchiectomy for testicular feminization syndrome.

A 13-year-old female patient with complete androgen insensitivity (testicular feminization syndrome) had an excision of bilateral intra-abdominal testicles via the laparoscopic approach. The patient had a very smooth, fast recovery from her surgery. The laparoscopic approach should be considered for most patients in need of surgical removal of undescended or intra-abdominal testes.     

Testicular toxoplasmosis: a rare case of a testicular mass

Toxoplasma gondii is an intracellular protozoan infecting birds and mammals. Acute infection is asymptomatic in immune competent people. For immune deficient patients (acquired immune deficiency syndrome, lymphoma patients or those under steroids to prevent organ transplantation rejection) infection may be lethal. We describe an uncommon case of testicular toxoplasmosis in patient under steroids after organ transplantation with no positive serum test for HIV and/or systemic toxoplasmosis.     

Testicular descent. Normal and abnormal.

The subject of testicular descent has been reviewed. An attempt has been made to present a basic understanding of the embryology and mechanisms of this event. The abnormalities of testicular descent have also been discussed, including the pathogenesis and complications of this disorder, which is the most common developmental abnormality in childhood. The aims and results of both the hormonal and surgical treatments of cryptorchidism have been summarized. From data gleaned from the literature, a plea is made for the earlier treatment of the undescended testis in patients under five years of age.     

Gonadotrophic hormones and testicular descent.

The effect of fetal decapitation on gubernacular development and testicular descent was studied in the pig. Gubernacular development was unaffected and testicular descent occurred normally in decapitated fetuses. Neither testicular descent nor gubernacular development could be induced by HCG or LH-RH, administered to naturally unilateral cryptorchid prepuberal pigs in doses comparable to those used in human therapy. Gubernacular development and, subsequently, testicular descent seem to be independent of gonadotrophic stimulation.     

Insulin-like 3 signalling in testicular descent

Undescended testis is one of the most common congenital defects in the newborn boys and the common cause of cryptorchidism. If left untreated, this condition is strongly associated with infertility and drastically increased risk of testicular cancer in adulthood. Testis position in developing males is defined by sexual dimorphic differentiation of two gonadal ligaments, gubernaculum and cranial suspensory ligament. Recent transgenic mouse studies identified testicular hormone insulin-like 3 (INSL3), and its receptor, GREAT/LGR8, as the critical regulators of the gubernacular differentiation. Mutation analysis of the two genes in patients with undescended testis revealed functionally deleterious mutations, which may be responsible for the abnormal phenotype in some of the patients.