Estrone

Estrone (E1) is a relatively weak endogenous estrogen that serves primarily as a precursor and long-term reservoir for the more potent estradiol, and its elevation with age is a key driver of estrogen-driven diseases. 2 Ray Peat emphasized that estrone and estradiol are perfectly interchangeable through enzymatic action, a fact that was obscured for decades by the dogmatic focus on genetic receptor theory. 3 He noted that while estradiol is considered about ten times as potent as estrone, their effects depend on overall health and progesterone levels, and a larger dose of estrone will have exactly the same effect as estradiol. 4 Georgi Dinkov has written that estrone sulfate (E1S) is the most reliable biomarker of total-body estrogenic reserves, serving as a long-lasting derivative that tissues can convert into active estradiol through the process of intracrinology. 2

The clinical significance of estrone lies in its paradoxical behavior with aging. While estradiol levels plummet after menopause, leading to the mainstream diagnosis of estrogen "deficiency," estrone and estrone sulfate actually rise with age, correlating strongly with disease. 2 Dinkov has argued that estrone is produced mostly by fatty tissue via the aromatase enzyme, meaning that higher body fat and aging both increase estrone production, making it a much more relevant marker for breast and prostate cancer prognosis than estradiol. 2 Peat explained that the apparent disappearance of estrogen from blood tests in aging is an artifact of measurement; as progesterone declines, estrogen increasingly stays inside cells, intensifying its activity while remaining undetectable in serum. 4 Administering progesterone can mobilize this tissue-bound estrogen back into the blood in a detoxified form, revealing the true estrogen load. 4

Estrone sulfate functions as the body's long-term estrogen reserve, with a half-life measured in weeks, allowing any tissue to draw upon it and convert it to active estradiol as needed. 5 Dinkov has stated that high E1S is a reliable indicator of high estrogenic reserves and is typically elevated in overweight individuals, those with low testosterone or DHEA, or those with insulin resistance. 7 He has recommended that E1S, prolactin, and CO2 are the three biomarkers that give the most information for the least amount of money regarding overall health. 2 Peat's enzymological perspective showed that progesterone activates enzymes that inactivate estrogen, while turning off those that activate it, making the estrone-estradiol interchange a central point where thyroid, stress hormones, and nutrition intersect. 3

The medical establishment's near-exclusive focus on estradiol has been criticized as a major oversight. Dinkov has documented cases where doctors were unaware of estrone or refused to test it, despite E1S being the best-known prognostic biomarker for developing and dying from breast, colon, and prostate cancer. 6 He has also noted that while a study found low androgens increased cardiovascular disease risk in women, low estrone did not show the same protective relationship; he suspects that if estrone sulfate had been measured instead, the relationship with cardiovascular disease would have been positive and contributing rather than inverse. 8 Dinkov maintains that estradiol remains the actual declared tumor carcinogen by both the CDC and WHO, and that high estrone synthesis signals elevated aromatase activity, which is itself one of the best predictors of cancer death. 9 Substances including vitamin E, aspirin, progesterone, and pregnenolone can lower E1S levels. 7