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INTRODUCTION

Approximately 50% of men will develop cancer in their lifetime. Historically, the overriding focus of cancer therapy has been its cure, and concerns about the side effects of treatment have typically received less consideration during the planning and implementation of care. However, cancer as well as cancer therapies can each result in a wide range of negative downstream health effects. These unfavorable “late-term effects,” may include a wide spectrum of conditions, such as cardiac disease, pulmonary insufficiency, peripheral vascular disease, endocrine and metabolic disorders, neuropathy, cognitive deficits, musculoskeletal impairment, gastrointestinal disorders, and secondary cancers.1 As a result of these multifaceted health concerns, a new field in medicine has emerged to address the unique health issues that affect cancer survivors. “Survivorship clinics” have now been established at most tertiary care centers, in which specialists help patients manage the chronic and often debilitating health concerns that can interfere with normal function, quality of life, and longevity.

An important late-term adverse effect of cancer and/or its treatment is impaired reproductive health. Failure to consider this negative outcome of cancer treatments in the past has rendered large numbers of men permanently infertile with no option to pursue biological paternity. Numerous studies have shown that infertility often leads to anxiety and depression in the patient as well as the patient’s partner.2,3 These reproductive issues among cancer survivors have led to a formal effort, endorsed now universally by oncological professional societies, to consider future reproductive health at the time of the cancer diagnosis to facilitate fertility preservation measures before cancer treatments are initiated.4–6

EFFECTS OF CANCER ON FERTILITY

Key Points

  • Even before cancer therapy has been initiated, cancer and the body’s immune response to cancer can each impair fertility.

  • Fertility can be affected at the pretesticular (hypothalamic-pituitary-gonadal axis), testicular, or posttesticular (sperm delivery) levels.

While clinicians sometimes focus exclusively on the adverse impact of cancer treatments, cancer and the body’s response to this disease process can each disrupt the normal reproductive system, even before the initiation of any cancer therapies.

Pretesticular Effects of Cancer

Tumors involving the central nervous system (CNS) can disrupt the hypothalamic-pituitary-gonadal (HPG) axis. These effects can arise due to the growth of cancer within these structures, infiltration of these structures, or mass effect. Additionally, perturbations of normal hypothalamic-pituitary function can result from inflammatory cell– and cytokine-mediated immune responses to certain types of tumors. The cytokines and other modulators produced by the tumors themselves or by the immune system in response to the tumor can result in an anorexia–cachexia syndrome, a condition seen commonly in patients with advanced cancer.7 Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferon alpha (INF-α) have all been linked to disruption of hypothalamic-pituitary function and anorexia–cachexia syndrome. This pathophysiological mechanism might also lead to pretesticular fertility impairment in some males. Central hypogonadism is highly prevalent among patients ...

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