PSA inhibitors for contraception: insights from prostate cancer

Despite the availability of effective hormonal contraceptive methods, nearly half of pregnancies worldwide remain unintended, highlighting the urgent need for innovative, nonhormonal options. Prostate-specific antigen (PSA) is a biomarker for prostate cancer and is well established for its role in liquefying semen by hydrolyzing gel-forming proteins. Liquefaction is essential for sperm motility and fertilization, making PSA inhibition a prime candidate for novel contraceptive strategies. Advances in prostate cancer research have led to the development of PSA inhibitors for cancer therapeutic purposes, including drugs that suppress PSA activity or selectively kill PSA-expressing cells. PSA presents a unique target as it is produced in men and acts in women, making it a promising contraceptive strategy for both sexes. This opinion explores the potential adaptation of existing PSA inhibitors from the oncology field for contraceptive applications. It also highlights emerging strategies to identify effective PSA-targeted contraceptive candidates, opening new avenues for next-generation nonhormonal contraception for men and women.