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

Andrology. 2019 Jul;7(4):441-448. doi: 10.1111/andr.12581. Epub 2019 Jan 4.


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 β-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 β-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 β-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, β-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone.

Keywords: hypogonadism; insulin-like factor 3; luteinizing hormone; testicular cancer; testosterone; β-hCG.

MeSH terms

  • Adult
  • Antineoplastic Agents / adverse effects
  • Biomarkers / blood
  • Chorionic Gonadotropin, beta Subunit, Human / blood
  • Epidemiologic Studies
  • Humans
  • Hypogonadism / blood*
  • Hypogonadism / diagnosis
  • Hypogonadism / etiology
  • Insulin / blood*
  • Leydig Cells / metabolism*
  • Luteinizing Hormone / blood
  • Male
  • Middle Aged
  • Orchiectomy
  • Postoperative Complications / blood*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / etiology
  • Proteins
  • Testicular Neoplasms / blood*
  • Testicular Neoplasms / complications
  • Testicular Neoplasms / drug therapy
  • Testicular Neoplasms / surgery
  • Testosterone / blood


  • Antineoplastic Agents
  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • Insulin
  • Leydig insulin-like protein
  • Proteins
  • Testosterone
  • Luteinizing Hormone