Petersen P M, Skakkebaek N E, Vistisen K, Rørth M, Giwercman A
Department of Growth and Reproduction, Finsencenter, Copenhagen University Hospital, Rigshospitalet, Denmark.
J Clin Oncol. 1999 Mar;17(3):941-7. doi: 10.1200/JCO.1999.17.3.941.
To obtain information about preorchiectomy gonadal function in patients with testicular germ cell cancer to improve the clinical management of fertility and other andrologic aspects in these men.
In group 1, a group of 83 consecutive patients with testicular germ cell cancer (TGCC) investigated before orchiectomy, semen analysis was carried out in 63 patients and hormonal investigations, including measurement of follicle-stimulating hormone, luteinizing hormone (LH), testosterone, estradiol, sex hormone-binding globulin (SHBG), inhibin B, and human chorionic gonadotropin (hCG), in 71 patients. Hormone levels in patients with elevated hCG (n = 41) were analyzed separately. To discriminate between general cancer effects and specific effects associated with TGCC, the same analyses were carried out in a group of 45 consecutive male patients with malignant lymphoma (group 2). Group 3 comprised 141 men employed in a Danish company who served as controls in the comparison of semen parameters. As a control group in hormone investigations, 193 men were selected randomly from the Danish National Personal Register to make up group 4.
We found significantly lower sperm concentration (median, 15 x 10(6)/mL; range, 0 to 128 x 10(6)/mL) and total sperm count (median, 29 x 10(6)/mL; range, 0 to 589 x 10(6)) in patients with testicular cancer than in patients with malignant lymphomas (sperm concentration: median, 48 x 10(6)/mL; range, 0.04 to 250 x 10(6)/mL; sperm count: median, 146 x 10(6); range, 0.05 to 418 x 10(6)) (P < .001 and P < .001) and healthy men (sperm concentration: median, 48 x 10(6)/mL; range, 0 to 402 x 10(6)/mL; sperm count: median, 162 x 10(6); range, 0 to 1253 x 10(6)) (P < .001 and P < .001). FSH levels were increased in men with testicular cancer (median, 5.7 IU/L; range, 2.0 to 27 IU/L) compared with both men with malignant lymphomas (median, 3.3 IU/L; range, 1.01 to 12.0 IU/L) and healthy controls (median, 4.1 IU/L; range, 1.04 to 21 IU/L)(P = .001 and P = .007, respectively). Surprisingly, we found significantly lower LH in the group of men with TGCC (median, 3.6 IU/L; range, 1.12 to 11.9 IU/L) than in healthy men (median, 4.7 IU/L; range, 1.3 to 11.9 IU/L) (P = .01). We could not detect any differences between men with testicular cancer and men with malignant lymphomas and healthy men with regard to serum levels of testosterone, SHBG, and estradiol. Men with testicular cancer who had increased hCG levels had significantly lower LH and significantly higher testosterone and estradiol than those without detectable hCG levels.
Spermatogenesis is already impaired in men with testicular cancer before orchiectomy. Neither local suppression of spermatogenesis by tumor pressure nor a general cancer effect seems to fully explain this impairment. The most likely explanation is preexisting impairment of spermatogenesis in the contralateral testis in men with testicular cancer. The question of whether also a pre-existing Leydig cell dysfunction is present in men with testicular cancer could not be answered in this study because the tumor seems to have a direct effect on the Leydig cells. Men with testicular cancer had low LH values as compared with controls. We speculate that increased intratesticular level of hCG also in men without measurable serum hCG may play a role by exerting LH-like effects on the Leydig cells, causing increased testosterone and estrogen levels and low LH values in the blood.
获取睾丸生殖细胞癌患者睾丸切除术前性腺功能的信息,以改善这些男性生育能力及其他男科方面的临床管理。
在第1组中,对83例连续的睾丸生殖细胞癌(TGCC)患者在睾丸切除术前进行研究,63例患者进行了精液分析,71例患者进行了激素检查,包括测量促卵泡激素、黄体生成素(LH)、睾酮、雌二醇、性激素结合球蛋白(SHBG)、抑制素B和人绒毛膜促性腺激素(hCG)。对hCG升高的患者(n = 41)的激素水平进行了单独分析。为区分一般癌症效应和与TGCC相关的特定效应,在一组45例连续的男性恶性淋巴瘤患者(第2组)中进行了相同的分析。第3组由丹麦一家公司的141名男性组成,他们作为精液参数比较的对照组。作为激素检查的对照组,从丹麦国家个人登记册中随机选择193名男性组成第4组。
我们发现,睾丸癌患者的精子浓度(中位数为15×10⁶/mL;范围为0至128×10⁶/mL)和总精子数(中位数为29×10⁶/mL;范围为0至589×10⁶)显著低于恶性淋巴瘤患者(精子浓度:中位数为48×10⁶/mL;范围为0.04至250×10⁶/mL;精子数:中位数为146×10⁶;范围为0.05至418×10⁶)(P <.001和P <.001)以及健康男性(精子浓度:中位数为48×10⁶/mL;范围为0至402×10⁶/mL;精子数:中位数为162×10⁶;范围为0至1253×10⁶)(P <.001和P <.001)。与恶性淋巴瘤患者(中位数为3.3 IU/L;范围为1.01至12.0 IU/L)和健康对照组(中位数为4.1 IU/L;范围为1.04至21 IU/L)相比,睾丸癌男性的FSH水平升高(中位数为5.7 IU/L;范围为2.0至27 IU/L)(分别为P =.001和P =.007)。令人惊讶的是,我们发现TGCC组男性的LH显著低于健康男性(中位数为3.6 IU/L;范围为1.12至11.9 IU/L)(中位数为4.7 IU/L;范围为1.3至11.9 IU/L)(P =.01)。在睾酮、SHBG和雌二醇的血清水平方面,我们未发现睾丸癌男性与恶性淋巴瘤男性及健康男性之间存在任何差异。hCG水平升高的睾丸癌男性的LH显著低于未检测到hCG水平的男性,而睾酮和雌二醇显著更高。
睾丸癌男性在睾丸切除术前精子发生就已受损。肿瘤压迫对精子发生的局部抑制或一般癌症效应似乎都不能完全解释这种损害。最可能的解释是睾丸癌男性对侧睾丸中预先存在的精子发生损害。本研究无法回答睾丸癌男性是否也存在预先存在的睾丸间质细胞功能障碍这一问题,因为肿瘤似乎对睾丸间质细胞有直接影响。与对照组相比,睾丸癌男性的LH值较低。我们推测,即使在血清hCG不可测的男性中,睾丸内hCG水平升高也可能通过对睾丸间质细胞发挥类似LH的作用,导致血液中睾酮和雌激素水平升高以及LH值降低。