Prostate cancer increases its incidence with age after men in their fifth decade as the ratio of estrogen to androgen rises. Epidemiological studies indicat that high levels of estrogens are associated with increased risk for prostate cancer. Therefore, estrogens may be involved in prostatic carcinogenesis. Unlike breast cancer, which often grows under the influence of estrogen, prostate cancer is not so straightforward. Some prostate cancers will stop growing when estrogen is blocked with the drug tamoxifen, but others will not. In most studies, androgen (male) hormones are the culprit, not estrogen (female) hormones. And when estrogen is given, these androgen-driven cancers will stop growing.

For over 50 years urologists have used androgen ablation therapy to reduce normal and abnormal growth of the prostate. However, only limited attention has been given to the role of blocking estrogens in controlling the pathobiology of the prostate. A paradigm shift in our understanding of the importance of estrogens and how they may be regulated as both preventive and therapeutic agents in the control of prostate cancer, benign prostatic hyperplasia (BPH), and prostate inflammation is now occurring.

Historically, urologists have focused only on one edge of estrogens’ double-edged sword. It was well known that estrogens strongly inhibited prostate growth by markedly lowering serum testosterone through blocking the hypothalamic-pituitary axis from releasing luteinizing hormone—a hormone essential for stimulating production of testosterone by the Leydig cells in the testes. In contrast, however, in the presence of androgens, estrogens strongly enhance abnormal growth of the prostate.

In a classic study, Patrick C. Walsh and Jean D. Wilson  administered both androgens and estrogens to castrate dogs and observed a massive overgrowth of the prostate to 4 times its normal size in non-castrated control animals. This estrogen-androgen synergy was confirmed and extended in a much larger study at Johns Hopkins. The massive overgrowth was produced by the combination of dihydrotestosterone (DHT) and estradiol. Estrogen increased the androgen receptor and induced inflammation and focal atrophy. A similar type of lesion, proliferative inflammatory atrophy (PIA), is now observed in human prostates and is proposed to be the first premalignant lesion that gives rise to prostatic intraepithelial neoplasia (PIN).

In a study conducted at the Hormone Biochemistry Laboratory, University Medical School, Palermo, Italy, growth of LNCaP human prostate cancer cells were stimulated by estradiol and halted with administration of antiestrogens. The growth of these same cells were unaffected by administration of the anti androgen drug Casodex.

A study published by the Graduate School of Biomedical Sciences demonstrated that anti estrogens  4-hydroxytamoxifen, raloxifene, phytoestrogens & resveratrol, but not estrogens (17β-estradiol and diethylstilbestrol), inhibit growth of prostate cancer DU145 cells while PC-3 cells showed growth inhibition in response to estrogen and antiestrogen treatments. It was concluded that activation of the estrogen receptor ER-8 by antiestrogen and phytoestrogen induced cell growth inhibition in prostate cancer cells.