Pharmacokinetic bioequivalence studies of a fixed-dose combination of tamsulosin and dutasteride in healthy volunteers.

Background And Objectives: The combination of dutasteride and tamsulosin may be more effective for the treatment of symptomatic benign prostatic hyperplasia than either treatment alone. We report the results of three pharmacokinetics and tolerability studies, which used a dutasteride/tamsulosin HCl (0.5 mg/0.

Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling.

It was recently demonstrated that antiestrogens prevented prostate cancer (PRCA) in men. The source of estradiol (E2) that contributes to carcinogenesis, as well as the selected estrogen receptor (ER) signaling pathway, is unknown. To evaluate estrogen's effects in carcinogenesis, we developed a new model of PRCA utilizing testosterone and E2 to stimulate PRCA.

Transient neonatal estrogen exposure to estrogen-deficient mice (aromatase knockout) reduces prostate weight and induces inflammation in late life.

Exposure of newborn male mice to estrogens is associated with age-related changes in prostate size and induction of epithelial hyperplasia and dysplasia. Whether these changes directly result from systemic estrogen administration or indirect effects of estrogens on systemic testosterone levels is unclear. We have addressed this question using aromatase-knockout (ArKO) mice that are estrogen-deficient during their lifespan but have elevated androgen levels and develop prostate enlargement and hyperplasia (McPherson SJ, Wang H, Jones ME, Pedersen J, Iismaa TP, Wreford N, Simpson ER, Risbridger GP: Endocrinology 2001, 142:2458-2467).

Direct response of the murine prostate gland and seminal vesicles to estradiol.

In the prostate, testosterone action depends on conversion to bioactive metabolites dihydrotestosterone and 17beta-estradiol (E2) via the 5alpha-reductase and aromatase enzymes, respectively. Exogenous estrogen inhibits prostate growth by indirect effects caused by suppression of pituitary gonadotropins and testicular testosterone output, but direct effects are less well known. Direct effects of estrogens were evaluated using the hypogonadal (hpg) mouse model, which has postnatal deficiency in gonadotropins and testosterone but remains hormone sensitive.

Prostate phenotypes in estrogen-modulated transgenic mice.

Estrogen-modulated transgenic mice, such as estrogen receptor-knockouts (alphaERKO and betaERKO), aromatase-knockout (ArKO) and aromatase-overexpressing (AROM+) mice, have contributed to our understanding of the roles of estrogens in male reproductive biology, including prostate growth and development. Varying pathological changes of the prostate have been described as being the result of aberrant actions of estrogen, both directly through the estrogen receptors or indirectly by altering the endocrine status of these mice. This article identifies the consequences of aberrant estrogen signaling on prostate growth and development.