# Aggressive Prostate Cancer After a 14-Year Gonadotropin Therapy: A Case Report

## TL;DR

A man with low testosterone developed aggressive prostate cancer decades after hormone therapy, highlighting the need for long-term PSA monitoring.

## Contribution

This case report highlights the potential for aggressive prostate cancer development despite long-term low PSA levels during hormone therapy.

## Key findings

- A patient with hypogonadotropic hypogonadism developed advanced prostate cancer 20 years after starting gonadotropin therapy.
- PSA levels initially remained low but later increased sharply, leading to a diagnosis of metastatic prostate cancer.
- Treatment with enzalutamide and radium-223 chloride reduced bone metastases and lowered PSA levels.

## Abstract

A 40-year-old man with a four-year history of infertility was referred to our department. The semen analysis revealed low motility, and the blood test showed low luteinizing hormone levels. Gonadotropin therapy was initiated upon the diagnosis of hypogonadotropic hypogonadism. During treatment, serum prostate-specific antigen (PSA) was consistently low (1.4-1.9 ng/mL). Fourteen years after the start of treatment, at 54 years old, PSA was abruptly elevated (3.5 ng/mL), and gonadotropin therapy was discontinued due to possible prostate cancer. After cessation, PSA decreased temporarily but then gradually increased to 7.6 ng/mL, but the patient requested PSA follow-up. Twenty years after discontinuation of gonadotropin therapy, PSA increased sharply to 65.9 ng/mL. A prostate biopsy revealed adenocarcinoma with a Gleason score of 4+5. A bone scan showed multiple bone metastases, leading to an advanced prostate cancer (cT4N0M1b) diagnosis. Six months after androgen deprivation therapy, PSA increased again. Under castration-resistant prostate cancer diagnosis, enzalutamide and radium-223 chloride were administered. After treatment, bone metastases were significantly reduced, and PSA decreased. Although gonadotropin and testosterone replacement therapy may not increase prostate cancer risk, patients with low testosterone levels may develop high-grade advanced prostate cancer. Therefore, PSA should be monitored regularly; if PSA levels are continuously elevated, even below 4 ng/mL, a close examination of cancer may be warranted.