Hormone replacement therapy (HRT) is considered the mainstay for postmenopausal osteoporosis prevention. However, at the standard doses, HRT preparations can induce bothersome hormone-related side-effects, in both sequential and continuous combined regimens. Lower-dose HRT schedules are reported to be highly effective in the relief of climacteric symptoms, inducing minimal endometrial stimulation with very low rates of unscheduled bleeding. Moreover, low-dose HRT associated with an adequate calcium supplement can spare bone by preventing the increase in bone turnover and the resultant bone loss in postmenopausal women. Low-dose regimens may be considered as a starting dose not only in elderly subjects, but also in early postmenopausal women to allow for adjustment to HRT. In older women, these may minimize the occurrence of side-effects and improve compliance, while preventing the long-term consequences of estrogen deprivation.