Prevention of Postmenopausal Bone Loss at Lumbar Spine and Upper Femur With Tibolonecolon; A Two-Year Randomised Controlled Trial

摘要

Tibolone is a synthetic steroid having weak estrogenic, androgenic, and progestational activity. Administered orally, it has been shown to be an effective and safe treatment for climacteric symptoms and does not stimulate the endometrium. Tibolone also inhibits enzymes involved in estradiol synthesis in human breast cancer cells. Its effects on bone have now been examined in a 2-year randomized trial of 47 healthy postmenopausal women aged 50 to 57 years who entered an osteoporosis screening study. All had bone mineral density (BMD) above the 25th centile for the normal population in the lumbar spine and femur. None of the subjects had used hormone replacement therapy for at least 6 months. Participants received either 2.5 mg of tibolone daily or no treatment and were reviewed at 12-week intervals for 8 years. BMD was estimated by dual-energy x-ray absorptiometry.Tibolone-treated patients had significantly increased BMD from 6 months onward in the lumbar spine (Fig. 1) and from 72 weeks onward in the trochanter (Fig. 2). Untreated women had no significant changes in BMD at the trochanter site, but bone density declined significantly in the lumbar spine, femoral neck, and Ward’s triangle. Significant differences between the tibolone-treated and control women began emerging at week 72. Six women withdrew from tibolone therapy, and three in the untreated group dropped out of the study. No tibolone-related side effects were regarded as severe; only one woman withdrew because of vaginal bleeding. Most often vaginal spotting ceased within the first 6 months of treatment.Fig. 1. Median percentage change in lumbar spine bone mineral density (interquartile range).Fig. 2. Median percentage change in femoral neck bone mineral density (interquartile range).Tibolone may be an effective means of forestalling bone loss in postmenopausal women and seems to be well tolerated. One qualification is that this study failed to demonstrate increased bone density at the femoral neck and Ward’s triangle, both clinically important sites.Br J Obstet Gynaecol 1999;106:678–683