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Before any prescription agent is introduced, the triggering factors are removed: topical corticosteroids, heavy face creams, fluorinated toothpaste, occlusive sunscreens, and any other product that may be sustaining the inflammatory cycle

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That is the strongest class of evidence there is for a side effect: measured in randomized, controlled approval trials

Pediatr Endocrinol Rev 2 (Suppl 1): 8692 Tschop M et al

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Binding of 3 H-labeled 17--estradiol to Hs578 cells containing empty vector was considered as non-specific and the counts were subtracted from the counts obtained with ER-expressing cells