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LETTER TO THE EDITOR |
-hydroxyl metabolic pathway of steroids, and sex hormones in blood and urine
Department of Nutrition and Health
Research Institute of Child Nutrition
Heinstück 11
Dortmund 44225
Germany
E-mail: remer{at}fke-do.de
Dear Sir:
In a recent article in the Journal, Napoli et al (1) reported cross-sectional data in healthy postmenopausal white women, which suggested that a higher calcium intake from dietary sources may be associated with a shift in estrogen metabolism toward the active 16
-hydroxyl metabolic pathway and with greater bone mineral density. This study addresses the important field of steroid hormone metabolomics and underscores that steroid metabolite profiling in 24-h urine specimens allows one to uncover physiologically relevant shifts in hormone metabolism, which is usually not possible with the same physiologic plausibility if only single blood measurements are performed. Accordingly, the serum estradiol measurements made by Napoli et al showed no differences between the 3 diet groups under study.
This closely corresponds to what cross-sectional blood measurements tell us about the developmental process of adrenarche, ie, the period during which the adrenal glands of healthy children begin to secrete increasing amounts of androgenic hormones. The many blood measurements of the major adrenarchal steroid hormone dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS), until recently performed, suggest that adrenarche begins at approximately the age of 6–7 y (2). However, specific steroid profiling in 24-h urine samples in healthy children of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study showed that the physiologic increase in adrenal androgen secretion must already start several years before midchildhood (3).
As in the study by Napoli et al, these changes were not detectable by measuring only one key hormone [DHEA(S)], but they became unmasked after the major 16-hydroxylated downstream metabolites of DHEA, ie, 16-hydroxy-DHEA and 3β,16,17β-androstenetriol, were additionally profiled (3). The 16-hydroxylation described by Napoli et al for estrogens in postmenopausal women is also a major metabolic pathway for adrenal androgens, and that pathway obviously lowers the circulating concentrations of the primary adrenal androgen DHEA(S) efficiently in early childhood. Thus, the sole measurement of DHEA(S) in preschool children does not reflect its increasing formation and especially not the rise in its activated 16-hydroxylated downstream metabolites occurring after age 3 y (3).
Unfortunately, some relevant aspects of the postmenopausal metabolism of estrogen in women may have been overlooked by Napoli et al.
-hydroxy-DHEA to 16-hydroxy-estrone (after a preceding enzymatic 3β-hydroxysteroid dehydrogenase step) (6). Given this strong interaction between the adrenal gland and peripheral estrogen production, the findings of Napoli et al might have been somewhat more specific if they had also excluded from their study those women with glucocorticoid medication use at a dose <5 mg/d of prednisone (or the equivalent). Whether women with a more pronounced adrenarche during childhood and adolescence may also have higher estrogen production after menopause is unknown, but it appears plausible given the high tracking of adrenal androgens (7, 8). 
2-fold higher. It can thus not be excluded that the higher bone mineral density observed in the latter 2 groups was primarily due to a higher protein intake (9). Additionally, a varying protein intake may have altered the urinary estrogen profile (10). Taken together, it remains questionable whether it is really the calcium that is responsible for the observed shift in estrogen metabolism. ACKNOWLEDGMENTS
The author had no conflict of interest related to this letter.
REFERENCES
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