Estetrol review: profile and potential clinical applications.

In this review paper, the existing information on the human fetal steroid estetrol (E4) has been summarized. In the past, E4 was considered as a weak estrogen and interest disappeared. However, recent new research has demonstrated that E4 is a potent, orally bioavailable, natural human fetal selective estrogen receptor modulator, since it acts in the rat as an estrogen on all tissues investigated except breast tumor tissue, where it has estrogen antagonistic properties in the presence of estradiol.

First human exposure to exogenous single-dose oral estetrol in early postmenopausal women.

Objective: To evaluate the safety, tolerability, pharmacokinetics and effect on gonadotropins of a single escalating dose of estetrol (E(4)).

Methods: A first-in-human study with E(4) was performed in healthy early postmenopausal women. Four single doses of 0.

Estrogenic uterovaginal effects of oral estetrol in the modified Allen-Doisy test.

Objective: To evaluate the effect of estetrol (E(4)) on vaginal cornification and uterine wet weight in the ovariectomized rat.

Methods: Adult female rats served as experimental animals. Six groups of ovariectomized rats (eight per group) were treated orally once daily for 7 days as follows: vehicle (negative) control; E(4): 0.

Preventive effect of oral estetrol in a menopausal hot flush model.

Objective: To evaluate the efficacy of estetrol (E(4)) in alleviating hot flushes in an experimental animal model considered representative for menopausal vasomotor symptoms.

Methods: Recording of the thermal responses in the tail skin of morphine-dependent ovariectomized rats after morphine withdrawal by administration of naloxone. Six groups of rats were treated orally for 8 days as follows: vehicle (negative) control; E(4): 0.