Testing a Fetal Form of Estrogen for Prostate Cancer Treatment


Estetrol may provide the same testosterone suppression with less adverse effects.

Estetrol (E4), a natural form of estrogen produced in the fetal liver and found in the bloodstream of their mothers during pregnancy, may have use in the treatment of prostate cancer. Results of a study that made the backed the hypothesis were presented at ENDO 2017 in Orlando, the annual meeting of the Endocrine Society.

Hormone therapy is effective because testosterone stimulates prostate cancer cells to grow, but it obviously creates side effects. E4, given its presence in fetuses, “is expected to be less harmful for the cardiovascular system,” according to Yvette Zimmerman (pictured) of Netherlands-based Pantarhei Oncology, also pointing to menopause-like side effects including hot flashes, sleep and cognitive disturbances, and osteoporosis.

Zimmerman presented the findings of a single-center, double-blind, placebo controlled trial of 45 healthy men between the ages of 40 and 70. Split into three cohorts with a 2:1 treatment-to-control ratio, one group received 20mg E4 daily, another 40mg, and the last with 60mg. Studies of the first two are completed, while the 60mg cohort is ongoing.

Compared with the placebo group, all three groups treated with E4 saw a sizable and dose-correspondent drop in total testosterone levels from baseline at 4 weeks -3.74nmol/L, -11.0nmol/L, and -13.88nmol/L, respectively, or a 28% decrease in the 20mg group, a 60% decrease in the 40mg group, and a 76% decrease in the 60mg group.

While such drops are noticeable, they were perhaps the most expected results of the study: side effects are a major concern, and in the duration the researchers found no changes in vital signs like blood pressure or body weight, bringing them to conclude that E4 was well tolerated. Naturally, with massive decreases in testosterone, there were observed effects, including decreased libido and nipple tenderness.

Zimmerman reiterated that E4 was anticipated to be a less harmful element of hormone therapy, but that the work is early and the team is looking to conduct a proof of concept study in patients with advanced prostate cancer. Some of her confidence in E4’s safety comes from studies done in women for other applications, noting that her company, Pantarhei, is also working to develop it as a breast cancer treatment, and that a Belgian company is currently in the process of developing an E4-based drug for contraception and menopausal therapy.

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