Estrogen replacement therapy in a man with congenital aromatase deficiency: Effects of different doses of transdermal estradiol on bone mineral density and hormonal parameters

The effects of different doses of transdermal estradiol (TE) on bone mineral density (BMD) in a man with aromatase deficiency were evaluated. The study protocol was divided in the following four phases: phase 1, before estradiol treatment; phase 2, 50 mu g TE twice weekly for 6 months; phase 3, 25 mu g TE twice weekly for 9 months; and phase 4, 12.5 mu g TE twice weekly for 9 months. X-rays of hands, legs, and pelvis were performed, and BMD of the lumbar spine, hormonal parameters (LH, FSH, testosterone, and estradiol), and markers of bone turnover were determined during each phase. BMD in phase 1 was 0.933 g/cm(2) and increased to 1.051 and 1.173 g/cm(2) after 4 and 7 months of TE, respectively. In phase 3, BMD reached the maximum value (1.275 g/cm(2)). In phase 4, BMD decreased to 1.180 g/cm(2) and was 1.029 g/cm(2) at the end of the study protocol. A bilateral necrosis of femoral heads was also detected by x-ray films. In phase 1 serum testosterone was in the normal range, whereas serum estradiol was undetectable. During the 24-month period of treatment with TE (phases 2-4), estradiol was directly related to the amount of TE, whereas LH was inversely related to estradiol serum levels. Estradiol and gonadotropins reached optimal values only in phase 3, when FSH also was near normal; serum testosterone concentrations were normal in phases 3 and 4. This study confirms the role of estrogens in achieving and maintaining bone mineral content in the human male, providing further clinical tools useful in the management of bone loss in aromatase deficiency in the male, We suggest that the adequate substitutive dose of TE for maintaining both bone mass and normal estradiol serum levels in adult men with aromatase deficiency may be 25 mu g twice weekly (0.47 mu g/kg weekly).