“E4, a steroid produced by the human fetal liver during pregnancy only, is a potential candidate for the treatment of advanced prostate cancer, both as a single entity and for combination treatment with hormone therapy,” said Ellen Dutman, MSc, clinical research associate at Pantarhei Oncology BV in Zeist, The Netherlands, and lead researcher of a recent study investigating E4 treatment to lower testosterone.

The suppression of testosterone is crucial in the treatment of prostate cancer, as testosterone encourages prostate cancer tumor growth. “An important advantage of E4 is expected to be the avoidance of the hypoestrogenic side effects that occur with other types of testosterone-suppressing hormone therapy, including hot flushes and sweating, arthralgia, mood, sleep and cognition disturbances, and bone loss and fractures,” said Ms Dutman.

Researchers conducted a double-blind randomized placebo-controlled study in 45 healthy men between age 40 and 70 years. The men were divided into 3 groups corresponding to 3 E4 doses: 20 mg, 40 mg, and 60 mg. For every 15 men, 10 received E4 treatment and 5 received a placebo for 28 days.

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The level of total and free testosterone decreased in all groups. The absolute change in total testosterone in each group was −3.74 nmol/L, −11.0 nmol/L, and −13.88 nmol/L, respectively. The absolute change in free testosterone in each group was −0.059 nmol/L, −0.095 nmol/L, and −0.163 nmol/L, respectively. Follicle-stimulating hormone (FSH) and estradiol (E2) levels also declined. The levels of luteinizing hormone (LH) remained steady and sex hormone-binding globulin (SHBG) levels increased. All E4 doses were well tolerated, with no change in body weight or safety parameters, but libido decreased and nipple tenderness was reported.

“E4 treatment may not be as expensive as recently developed new prostate cancer therapies,” said Ms Dutman. “We expect that in the future, patients with advanced prostate cancer will have the opportunity to choose to be treated with E4, especially in combination with their current therapy.”


1. Dutman AE, Zimmerman Y, Bennink HJTC. The effects of the human fetal estrogen estetrol (E4) in healthy men to estimate its potential use for the treatment of prostate cancer. Poster presented at: ENDO 2017, the annual scientific meeting of the Endocrine Society; April 1-4, 2017; Orlando, FL. Abstract SAT 171.