Castration Levels of Testosterone Results in Atrophy of Androgen-Sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism

Nityam Rathi; Zoë Blake; Jason Hyman; Daniel R Nemirovsky; David G Gelikman; Charles Hesswani; Christopher Koller; Daniel Nethala; Neil Mendhiratta; Alexander P Kenigsberg; Jibriel Noun; William Dahut; Fatima Y Karzai; W Marston Linehan; Peter A Pinto; Baris Turkbey; Sandeep Gurram

doi:10.1016/j.urology.2024.10.006

Castration Levels of Testosterone Results in Atrophy of Androgen-Sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism

Urology. 2024 Oct 18:S0090-4295(24)00865-3. doi: 10.1016/j.urology.2024.10.006. Online ahead of print.

Authors

Nityam Rathi¹, Zoë Blake¹, Jason Hyman¹, Daniel R Nemirovsky¹, David G Gelikman¹, Charles Hesswani¹, Christopher Koller¹, Daniel Nethala¹, Neil Mendhiratta¹, Alexander P Kenigsberg¹, Jibriel Noun¹, William Dahut¹, Fatima Y Karzai¹, W Marston Linehan¹, Peter A Pinto¹, Baris Turkbey¹, Sandeep Gurram¹

Affiliation

¹ Urologic Oncology Branch National Cancer Institute, NIH 10 Center Drive Bethesda, MD 20892.

PMID: 39427924
DOI: 10.1016/j.urology.2024.10.006

Abstract

Objectives: To evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship.

Methods: Data was prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width.

Results: Thirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dl, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (p<0.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (p=0.032).

Conclusions: Androgen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.