Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality

Diffuse large B-cell lymphoma and Hodgkin Lymphoma are two aggressive lymphomas often treated with doxorubicin containing chemotherapy. Doxorubicin is an anthracycline and is known to be toxic to both Leydig Cells of the testes and hormone-producing cells of the hypothalamus. Therefore, patients treated with this drug are at risk of developing hypogonadism. Standard follow-up programs do not include analysis of hormone levels or treatment of hypogonadism. With this study the aim is to investigate the effect and toxicity of treatment with exogenous testosterone in male long-term survivors of malignant lymphoma, to clarify whether it is relevant to include serum testosterone and potentially testosterone replacement therapy in standard follow-up programs.

Our Hypothesis:

Hypothesis 1: A significant proportion of long-term male survivors of HL and DLBCL have impaired quality of life (QoL) due to sexual dysfunction.

Hypothesis 2: A significant proportion of long-term male survivors of HL and DLBCL have reduced levels of testosterone.

Hypothesis 3: A significant relationship between QoL, sexual dysfunction and testosterone levels exists.

Hypothesis 4: Substitution with testosterone in carefully selected subgroups will improve sexual function and QoL.

Hypothesis 5: Treatment with testosterone in this setting is safe with acceptable toxicity.

To assess efficacy and safety of treatment with testosterone replacement therapy on hypogonadism in lymphoma patients, blood tests and questionnaires are completed throughout one year of treatment. To assess patient sexuality and quality of life, 3 questionnaires are included; the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ C30) for general quality of life, EORTC Sexual Health Questionnaire 22 (SHQ-22) for sexual health and International index of erectile function with 5 questions (IIEF-5) for sexual function.

Inclusion criteria

• Age 18-65 years at inclusion
• Male
• Verified diagnosis of de novo DLBCL or classical HL diagnosed between April 2008 and April 2018 according to World Health Organization (WHO) classification.
• Completed curative intent first line treatment with anthracycline-containing chemotherapy with or without consolidating radiotherapy, with disease in complete remission at End of Treatment (EOT) Positron Emissions Tomography / Computerized Tomography (PET/CT) at least one year prior to inclusion.
• Literate in Danish
• Serum testosterone level below threshold for age adjusted reference level used in the local laboratory at the time of inclusion.

Exclusion criteria

• Concurrent low-grade lymphoma
• Current or prior lymphoproliferative disease of the central nervous system (CNS)
• Current or prior lymphoproliferative disease of the testes
• Contraindications for the treatment with testosterone: Verified prostate cancer / Prostate Specific Antigen (PSA) > 3 ng/ml, cancer of the mammae, primary liver cancer or polycythaemia vera / Hct > 0,49.
• Mental or physical conditions that are expected to prevent the necessary "compliance" and/or "adherence" in relation to the study procedures
• Current or prior anabolic steroid drug abuse
• Treatment with second line chemotherapy or high dose therapy.
• Known allergies to additives in Testogel.