 Our recent pilot study started with a depot E2 dose of 0.2 mg; the monthly dose was then increased by 0.2 mg at successive 6-month intervals. The lowest dose 0.2 mg stimulated height velocity the most. However, it did not stimulate breast development as reliably as the larger doses 0.4 mg monthly, which were also growth stimulatory although to a lesser extent. We propose to resolve questions about whether these disparities were due to the invariable sequential administration of successively larger doses or the inaccuracy of delivery of such low doses by injection, and also to compare the effects on bone mineral density of the equivalent very low and low doses of E2 delivered by transdermal patch. Transdermal E2 delivery systems are now available for easily and reliably delivering the comparable very low doses of E2 in a form more suitable for routine patient care. The current guidelines recommend starting an E2 starting dose for the induction of puberty 5-12.5 mcg daily that is about one-tenth to one-eighth of the adult dose 100 mcg daily 8. However, these guidelines note that it is not established whether various means of patch dose fractionation e.g., administering a quarter patch overnight or daily or administering whole patches for 7-10 days per month are equivalent. 