Related Experiment Video
Updated: Feb 8, 2026

Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen Screen Optimized for the Undergraduate Teaching Laboratory
Published on: January 1, 2018
A Dose-Escalating Study With the Fetal Estrogen Estetrol in Healthy Men
Herjan J T Coelingh Bennink1, Yvette Zimmerman1, Carole Verhoeven1
1Pantarhei Oncology, AL Zeist, Netherlands.
Context:
Luteinizing hormone-releasing hormone (LHRH) agonists have replaced estrogens for endocrine treatment of advanced prostate cancer (PC) because of cardiovascular side effects. The fetal estrogen estetrol (E4) may be safer for PC treatment and is expected to decrease testosterone (T) and prevent estrogen deficiency.
Objective:
To investigate the safety and T-suppressive effect of E4 in healthy men.
Design:
Double-blind, randomized, placebo-controlled, dose-escalating study.
Setting:
The study was conducted at a phase I clinical unit (QPS, Netherlands).
Participants:
Healthy male volunteers aged 40 to 70 years.
Intervention(S):
Three treatment cohorts of 15 volunteers with placebo (n = 5) and E4 (n = 10). Estetrol doses tested were 20, 40, and 60 mg/d. Subjects were treated for 4 weeks.
Main Outcome Measures:
Subjective side effects, pharmacodynamic effects on hemostatic variables, lipids, glucose, bone parameters, and endocrine parameters related to T metabolism.
Results:
Total and free T decreased dose-dependently and significantly. Nipple tenderness occurred in 40% and decrease of libido occurred in 30% of E4-treated men. The unwanted estrogenic effects on hemostasis were small, dose dependent, and in some cases significant. Lipid and bone parameters showed a favorable trend.
Conclusion:
The effect of E4 on testosterone levels is insufficient for standalone PC treatment. Taking all clinical and pharmacodynamic variables into consideration, a daily dose of 40 mg E4 seems safe for further evaluation of endocrine PC treatment in combination with LHRH analogs.
Related Concept Videos
Bioavailability Study Design: Healthy Subjects Versus Patients
Bioavailability Study Design: Single Versus Multiple Dose Studies
Fetal Circulation
Two umbilical arteries transport blood from the fetus to the placenta. At the placenta, the blood absorbs oxygen and nutrients while simultaneously eliminating waste products. This oxygen-enriched and nutrient-rich blood then returns to the fetus through one...
Dose Size and Dosing Frequency: Determination Methods
Determination of Multiple Dosing Parameters: Loading and Maintenance Doses
Rational Dosage Regimen: Maintenance Dose and Loading Dose
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...

