The estrogen nobody told you about is changing hormone care — here's why it matters now

Economic Times

26-07-2025

Estrogen hormone therapy with estetrol E4: Estrogen treatments have depended on three core types: estrone, estradiol, and estriol for decades, but new on the horizon is a lesser-known natural estrogen called estetrol, or E4, that is slowly altering the process of hormone treatment, as per a report. Made by the fetal liver only during pregnancy, E4 differs from its more famous hormonal cousins and has promising advantages that may revolutionize how women treat hormone therapy, according to a Flow Space report.Unlike other estrogens, E4 acts selectively on some of the body's tissues, as per the report. Nurse practitioner Alexandra Rooker of The Lanby, a functional medicine clinic, explains that E4 selectively activates estrogen receptors in a way that may provide therapeutic benefits while minimizing stimulation of tissues like the breast and liver,' as quoted by Flow Space. This selectivity is what makes E4 potentially deliver many of the benefits of estrogen therapy, such as alleviating menopausal symptoms, without some of the dangers associated with older hormone therapies.
ALSO READ: Happy Gilmore 2 brings Adam Sandler's family back to the screen! What roles do his daughters Sadie and Sunny play in the Netflix film?Researchers are calling E4 a "Native Estrogen with Selective Tissue activity," or NEST, since it's specifically where it's needed and not overstimulating in sensitive areas, as per the Flow Space report. That specificity may render E4 a safer option for hormone replacement therapy (HRT) and birth control, particularly for women concerned about side effects such as blood clots or breast tissue stimulation, as per the report.What sets E4 apart is its source: it's made naturally during pregnancy and disappears at birth. For decades, it was a biological oddity rather than a useful drug. But new research has found that E4 acts differently than other estrogens. It selectively hits useful tissues such as bones and vaginal lining, while having less impact on the liver and breast tissue, tissues where too much estrogen activity can lead to trouble, according to Flow Space.
E4 is already incorporated in some oral contraceptives, including Nextstellis, wherein it prevents pregnancy but with fewer effects on blood clotting and liver function than usual estrogens, as per the report. Researchers are now exploring E4's ability to alleviate hot flashes and night sweats of menopause while possibly reducing risks linked to older hormone therapies, according to Flow Space.ALSO READ: Donald Trump's Scotland visit: Golfing or diplomacy? The real agenda uncovered!
According to Dr. Neha Pathak, chief physician editor at WebMD, E4 is 'Some forms of broken-down estrogen are thought to be gentler on the body, while others may be more active and possibly linked to health risks like breast cancer,' adding, 'But it's more complex than just good or bad; we still have a lot to learn about what these changes really mean for long-term health,' as quoted by Flow Space.
This approach is a huge step forward in itself, since older forms of estrogen can increase risks of strokes, heart problems, and other health concerns, particularly in older women or those with existing conditions, as per the report.Early research indicates E4 has a stable half-life that is adequate for once-daily oral administration and a milder impact on the liver, as per the report. Rooker explained, 'This may translate into a safer alternative for many women, particularly regarding clotting risks and breast tissue stimulation,' as quoted in Flow Space.According to the report, estetrol-based menopause hormone therapy is likely to be on the market as soon as 2026. This new treatment might provide more personalised and safer options for patients and physicians in controlling symptoms, as per Flow Space.Aside from menopause and birth control, scientists are also studying E4's use to treat hormone-sensitive cancers, such as some breast and prostate cancers, due to its selectivity, according to the report.
E4 is even being looked at as part of a possible male birth control pill because of its balanced hormonal effects and low impact on the liver and blood clotting, two major concerns in developing hormonal contraceptives for men, as reported by Flow Space. What is estetrol (E4)?Estetrol is a natural estrogen made by the fetal liver during pregnancy. It's now being studied for use in hormone therapy and birth control.
Is E4 safer than other types of estrogen? Early research suggests that E4 is gentler on the liver and blood clotting system, which may reduce risks like strokes and breast tissue stimulation.