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Slim and toned with 2-hydroxy-estradiol

An inactive metabolite of estradiol, 2-hydroxy-estradiol, probably helps post-menopausal women to become slim and more muscled, write endocrinologists at Washington University in Maturitas. Or is it the other way round? Do slim women synthesise large amounts of 2-hydroxy-estradiol?

Enzymes convert estradiol in the body into compounds such as 'good' 2-hydroxy-estradiol [structural formula below] and 'bad' 16-hydroxy-estradiol. The former has hardly any oestrogenic characteristics, but animal studies show that it boosts fat burning and glucose uptake by muscle cells. If you give fat rats 2-hydroxy-estradiol for six months, they lose a quarter of their bodyweight in this period. [J Pharmacol Exp Ther. 2001 Dec; 299(3): 973-7.] 2-Hydroxy-estradiol is probably an AMPK-booster. [Obesity (Silver Spring). 2008 Jun;16(6):1284-8.]

The other estradiol metabolite, 16-hydroxy-estradiol, on the other hand is an active oestrogen, and is also capable of damaging DNA. If a cell doesn't repair the damage, it can mutate into a cancer cell.

Ergo: the more estradiol your body converts into 2-hydroxy-estradiol, the better. The more estradiol it converts into 16-hydroxy-estradiol, the worse. This is probably the reason why a diet with lots of soya and cabbage-like vegetables reduces the risk of developing hormone-related cancer types. Soya and cabbage contain substances that speed up the conversion of estradiol into 2-hydroxy-estradiol. By the way, physical exercise and a high-protein/low-carb diet have the same effect.

The researchers wanted to see whether they could demonstrate the interesting effects of 2-hydroxy-estradiol in humans too, so they measured the blood hormone levels and body composition of almost one hundred post-menopausal women aged between 49 and 80.

The researchers divided the women into three equal-sized groups, tertiles, according to the amount of 2-hydroxy-estradiol in their blood. The first tertile was the women with the lowest concentration; the third had the highest. They also divided the women into tertiles based on the ratio of 2-hydroxy-estradiol to 16-hydroxy-estradiol.

When the researchers then looked at whether there was a relationship between hormone levels and body composition, the figure below emerged. The slimmer the women's waist measurement, the more 2-hydroxy-estradiol there was in their blood, and the better the ratio between 2-hydyroxy-estradiol and 16-hydroxyestradiol.

Slim and toned with 2-hydroxy-estradiol

Slim and toned with 2-hydroxy-estradiol

A low fat mass is associated with a higher concentration of 2-hdyroxy-estradiol and a better ratio of 2-hydroxy-estradiol to 16-hydroxy-estradiol. And a higher lean body mass shows the same correlations.

The research does not divulge what is cause and what is effect, however. Are women who synthesise more 2-hydroxy-estradiol slimmer and more muscular? Or is it the other way round? And does a slim and toned body have more enzymes that convert the estradiol into 2-hydroxy-estradiol?

The researchers pin their hopes on the first option. "These observations may suggest that perhaps increasing estrogen metabolism to the 2-hydroxyl pathway may have some beneficial effects on body weight", they write. "Data from animal studies indicate that administration of 2-hydroxy-estradiol reduces body weight and improves metabolic profile. Its potential usefulness in human subjects remains undetermined and deserves investigation."

Maturitas. 2012 May;72(1):66-71.

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