Vitamin D effects on androgen levels in men

Background. Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system. Considering the potential link between vitamin D and human fertility, authors performed this review summarizing current literature on vitamin D and possible mechanisms explaining the link of vitamin D with androgen metabolism in men. The purpose of this review was to provide an overview on the effects of vitamin D on androgen metabolism in men. Methods. Author performed a systematic literature search in PubMed for relevant English language publications published from January 2011 until September 2021. Results. The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues. In men, vitamin D status has been associated with androgen levels and hypogonadism. Further, there is some evidence for a favorable effect of vitamin D supplementation on testosterone concentrations, although others failed to show a significant effect on testosterone levels. Vitamin D might play an important role in androgen metabolism. Existing evidence from available trials evaluating the effect of vitamin D supplementation on androgen levels in men is insufficient to recommend measurement of 25(OH)D levels or vitamin D supplementation in hypogonadal men. We cannot exclude vitamin D effects on androgen levels in men with low TT levels or in men with severe vitamin D deficiency. This question remains to be answered in future investigations. Conclusions. Vitamin D deficiency is associated with adverse fertility outcomes including hypogonadism, but the evidence is insufficient to establish causality. High-quality trials are needed to further evaluate the effects of vitamin D supplementation on androgen levels in men.

Hormonal Therapy for Prostate Cancer

Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation, to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with non-metastatic advanced prostate cancer, as well as frankly metastatic disease. Today’s standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g. leuprolide), 2 nd-generation non-steroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today’s standard of care will require an accounting of an individual’s androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.