madman
Super Moderator
SUMMARY
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 (1988–1999) 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 (2000–2008), 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
In conclusion, 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. Pre-chemotherapy, b-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. Remarkably, INSL3 as a marker of Leydig cell activity and differentiation is simultaneously suppressed. INSL3 does not seem to be a suitable marker to predict hypogonadism as a late effect of chemotherapy in TC patients. After longer follow-up, INSL3 levels are comparable to levels in healthy men, implicating potentially ongoing Leydig cell recovery more than 2 years after treatment.
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 (1988–1999) 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 (2000–2008), 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
In conclusion, 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. Pre-chemotherapy, b-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. Remarkably, INSL3 as a marker of Leydig cell activity and differentiation is simultaneously suppressed. INSL3 does not seem to be a suitable marker to predict hypogonadism as a late effect of chemotherapy in TC patients. After longer follow-up, INSL3 levels are comparable to levels in healthy men, implicating potentially ongoing Leydig cell recovery more than 2 years after treatment.
