Beyond GnRH analogues: The renaissance of estrogens in prostate cancer management.

CONTEXT: Androgen deprivation therapy (ADT) induced by LHRH agonists or antagonists for the treatment of advanced prostate cancer induces a concomitant suppression of estradiol levels. This estrogen deficiency is responsible for significant side effects that impair patients' quality of life (QoL). The role of estrogens in prostate cancer management is currently being investigated in multiple clinical trials, either as a replacement for conventional ADT or as add-back therapy combined with standard ADT.

METHODS

A literature search was conducted on PubMed using the following keywords: androgen deprivation therapy (ADT), bone loss, estrogen deficiency symptoms, hot flushes, and transdermal estradiol (tE2), for articles published between 1970 and 2026.

RESULTS

Estrogen suppression is responsible for multiple adverse effects, including loss of bone mineral density (BMD), vasomotor symptoms, metabolic disorders, and fatigue. However, the use of tE2 remains associated with a notably higher incidence of gynecomastia compared with conventional ADT.

CONCLUSIONS

The suppression of estrogens by ADT induces multiple deleterious effects justifying the re-evaluation of controlled estrogen replacement. Available data regarding the use of transdermal estradiol or estetrol (E4) as add-on therapy are preliminary but encouraging although larger randomized trials are needed to confirm their integration into routine clinical practice.