Insulin‐like factor 3, luteinizing hormone and testosterone in testicular cancer patients: effects of β‐hCG and cancer treatment

Abstract

Background: Primary hypogonadism (low testosterone and high luteinizing hormone, LH) is present in approximately 20% of testicular cancer (TC) survivors after orchidectomy with or without chemotherapy. Objectives: We investigated insulin-like factor 3 (INSL3), a novel marker of Leydig cell function, in TC patients. Materials and Methods: We analyzed: (I) a cross-sectional cohort of TC patients after orchidectomy with or without chemotherapy (1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999) at long-term follow-up (median 36 and 35 years of age at follow-up, respectively) and healthy men of similar age; (II) a longitudinal cohort of chemotherapy-treated TC patients (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008), analyzed before and 1 year after chemotherapy (median 29 years of age at chemotherapy). INSL3, testosterone, and LH were compared between groups and over time and related to pre-chemotherapy b-hCG levels. Results: In the cross-sectional cohort, TC patients at median 7 years after orchidectomy and chemotherapy (n = 79) had higher LH (p < 0.001), lower testosterone (p = 0.001), but similar INSL3 as controls (n = 40). After orchidectomy only (n = 25), higher LH (p = 0.02), but no differences in testosterone or INSL3 were observed compared to controls. In the longitudinal cohort, patients with normal pre-chemotherapy b-hCG (≤5 mU/L, n = 35) had increased LH 1 year after chemotherapy compared to pre-chemotherapy (p = 0.001), and no change in testosterone or INSL3. In contrast, patients with high b-hCG pre-chemotherapy (n = 42) had suppressed LH, markedly elevated testosterone, and low INSL3 at start of chemotherapy, with increased LH, decreased testosterone, and increased INSL3 1 year later (all p < 0.001). Discussion: Changes in LH show that gonadal endocrine function is disturbed before chemotherapy, 1 year later, and at long-term follow-up in chemotherapy-treated TC patients. Conclusion: Pre-chemotherapy, b-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone.

Testicular cancer: low testosterone and the metabolic syndrome

“…These results showed that in chemotherapy‐treated TC patients, gonadal endocrine function was disturbed pre‐chemotherapy, one year after, and at long‐term follow up …”

“…In the longitudinal cohort, TC survivors with normal β‐hCG levels (≤5mU/L, n=35) pre‐chemotherapy had increased LH levels one year after chemotherapy versus their pre‐chemotherapy levels ( p =0.001) but no change in testosterone or INSL3. In contrast, TC survivors with high β‐hCG levels pre‐chemotherapy (n=35) had decreased LH, markedly raised testosterone, and low ISNL3 levels pre‐chemotherapy, but increased LH, decreased testosterone and increased INSL3 levels one year later ( p <0.001 for all) …”

“…Primary TD, characterised by low testosterone and high luteinising hormone (LH) levels, has been reported to affect around 20% of TC survivors after orchidectomy, with or without chemotherapy …”

“…Steggink et al , investigated insulin‐like factor 3 (INSL3; a novel marker of Leydig cell function), testosterone and LH levels in TC survivors in cross‐sectional and longitudinal cohorts. At a median of seven years after orchidectomy and chemotherapy, TC patients in the cross‐sectional cohort (n=79) had higher LH levels, ( p <0.001) and lower testosterone levels ( p =0.001) versus controls (n=40), but similar INSL3 levels.…”

“…In Steggink's study, β‐hCG‐producing tumours were found to affect the gonadal endocrine axis, resulting in increased testosterone and decreased LH levels pre‐chemotherapy. The changes in testosterone and LH one year post‐chemotherapy were considered largely attributable to successful treatment of the cancer and elimination of the β‐hCG stimulus …”