Endocrine, Sexual Function, and Infertility Side Effects of Immune Checkpoint Inhibitor Therapy for Genitourinary Cancers

Akshay Sood, Daniel Cole, Firas Abdollah, Ben Eilender, Zade Roumayah, Mustafa Deebajah, Ali Dabaja, Shaheen Alanee

Immune checkpoint therapy has grown in prominence in the last few decades and is being increasingly utilized in treatment of advanced cancers. Although information on toxicities of these drugs is forthcoming, not much is known regarding the toxicity profile of these drugs from a sexual function standpoint. We undertook the current review to appraise the literature for endocrine/sexual side effects of anti-PD-1/PD-L1 and anti-CTLA-4 therapy. Our review included 32 articles and focused primarily on the programmed death (PD) pathway. We found that endocrine side effects after anti-PD-1/PD-L1 therapy are relatively rare, with hypothyroidism (range < 1 to 40%) and hypophysitis (range < 1 to 10%) being the two most common. None of the studies specifically commented on the infertility or sexual side effects of these drugs. However, two studies evaluating biochemical profiles of patients undergoing therapy with ipilimumab (a CTLA-4 inhibitor) or combination therapy (CTLA-4 + PD-1/PD-L1 inhibitors) noted that about < 1 to ~ 60% of the patients developed hypogonadotropic hypogonadism. None of the studies provided information regarding clinically meaningful sexual health endpoints such as libido, erectile function assessments, or sexual function-related quality of life. Endocrine side effects, although uncommon, are important and unique side effects of immune checkpoint therapy because they are often complex and can be life threatening. While side effects on sexual health may not be life threatening, they are lifestyle limiting. Thus, long-term follow-up, post-marketing surveillance, and future studies will need to elucidate the true rates of endocrine/sexual side effects and the mechanisms underlying them. This will aid in better counseling of the patients, as more of them undergo these novel immune checkpoint inhibitor therapies.