Toward optimal estrogen-replacement therapy.

Some of the many paradoxes about estrogen therapy are addressed by Ross et al. in this issue of the Journal.1 Their studies consider the optimal dose of ethinyl estradiol to promote growth, and they are relevant to a more general question: Why is the outcome of the usual estrogen therapy often less satisfactory than that of normal feminization? Many of our problems with estrogen treatment can be understood from a historical perspective. Early researchers did not have ready access to indexes more sophisticated than uterine weight. Estrogen doses that greatly stimulated uterine growth were found to inhibit somatic growth. . . .