A 2-year prospective study was conducted on 44 early postmenopausal women to assess the effect of transdermal estradiol (TTS-E2) on vertebral bone mass. Twenty treated women and 24 untreated were studied. Treatment consisted of TTS-E2 (0.05 mg/day, 3 weeks a month) and an oral gestagen (10 days per month). At 24 months, bone mineral density, measured by Dual Photon Absorptiometry (DPA), decreased significantly in untreated women (-4.3%) (p less than 0.001), while treated women had a net gain of +5.4% (p less than 0.001). Bone turnover parameters (serum osteocalcin, urinary calcium/creatinine ratio) were significantly (p less than 0.05) reduced from the 2nd month of treatment onwards. Serum estradiol levels were sustained during the treatment and were in the range of an early follicular phase (approximately 45 pg/ml). These findings suggest that low doses of transdermal estradiol sufficient to relieve menopausal symptoms, and which, due to the association with progestogen, result in regular withdrawal bleeding, are effective in preventing postmenopausal bone loss.