(328) The Relationship Between Multiple Myeloma and Hypogonadism: A Systematic Review
Authors: Roth B , Hammad M , Sanford D , Barham D , Yafi F , Jenkins L 
Published: February 2024

Abstract

Introduction
Hypogonadism has been reported with substantial frequency in patients with various types of malignancies. Multiple myeloma (MM) is a cancer that affects plasma cells, a type of white blood cell responsible for producing antibodies. It is the second most common blood cancer, accounting for approximately 10% of hematologic malignancies. However, the prevalence, pathophysiology, and significance of hypogonadism as a sequela of MM or its standardized treatment regimens has not been extensively studied.

Objective
To characterize the existing literature on hypogonadism in patients with MM, including the prevalence, underlying mechanisms, and link to overall disease prognosis. Furthermore, we will examine the effects of testosterone therapy on MM and its hypogonadal symptomatology.

Methods
Relevant studies published up to November 2022 were retrieved through a search of PubMed using the keywords ‘hypogonadism’, ‘multiple myeloma’, and ‘testosterone’. Studies that reported on the presentation, management, or outcomes of patients with MM and how they were affected by a hypogonadal state were included. The search yielded 72 studies, of which 11 met the inclusion criteria.

Results
The most comprehensive assessment of the frequency of hypogonadism in a MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Further evaluation found that male patients with MM were found to have significantly lower levels of testosterone than control (p&lt;0.0001). Another assessment of hormone level differences between MM patients and controls found that male patients had higher: FSH, LH, estrogen, and E/T ratios than healthy controls. Testosterone supplementation was found to lower interleukin-6 (IL-6) levels, which could potentially contribute to the adverse effects of MM. This effect could arise from the finding that IL-6 concentration was independently associated with severe symptomatology in MM patients on multivariate analysis in a study by Wang et al. (p=0.004). Hypogonadism can occur as an adverse effect of MM treatment with immunotherapy/chemotherapy initiation. A small study by Greenfield et al. found that 65% of patients intensively treated for MM were subsequently hypogonadal. This was further supported by a study by Anderson et al. examining sexual function after autologous hematopoietic stem cell transplant (AHSCT), which saw a significant increase in erectile dysfunction at 1-month follow-up from 68.4% to 100% of all patients.

Conclusions
There appears to be a relationship between MM and hypogonadism, potentially due to the inflammatory state caused by the disease itself. This may have some association with the inflammatory cytokine IL-6. However, there is a paucity of data fully exploring this relationship, the underlying mechanisms, and the effects of testosterone therapy on MM. The true relationship is likely multifactorial, given the mixture of studies that found hypogonadism in MM at baseline as well as after systemic treatment. Future prospective and randomized studies are necessary to elucidate the true link between MM and/or its treatment and hypogonadism.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Hims & Hers Inc, Coloplast, Clarus Therapeutics, Antares Pharma, Acerus.