Busulfan Tibolone is also efficacious on bone in elderly wom
Tibolone is also efficacious on bone in elderly women and induces a clear reduction in bone turnover markers , . Rymer et al. showed that, after 10 years of treatment with tibolone, the difference in bone mineral density compared with a placebo group was more than 12% for both lumbar spine and femoral neck .
Comparing treatments and their effects on bone Good head-to-head, randomized studies comparing the effects of various treatments on bone are limited and are usually of short duration and involve only a small numbers of patients. Unfortunately, reliable comparisons are difficult to obtain from the literature due to differences in study design, methodology and use of supplements. This latter point is particularly important as calcium alone has a positive effect on bone . Lippuner et al. failed to find a significant difference between tibolone and oral or transdermal 17β-estradiol 50μg per day combined with dydrogesterone for 12 days with regard to changes in bone mineral density . Prelevic et al. compared the effects of tibolone, transdermal Busulfan and oral sequential CEE plus norgestrel after 3 years of treatment . The mean percentage change in spine bone mineral density was significantly increased in tibolone users when compared with baseline, whilst the increase with the other two treatments did not reach statistical significance. Thiebaud et al. confirmed the significant effects of tibolone on bone mineral density in a comparative study against CEE plus MPA in early postmenopausal women (Table 2) in which tibolone had a much more marked effect on spine and total hip bone mineral density than CEE plus MPA . This was also reflected in the greater reduction in the bone turnover markers, osteocalcin and hydroxyproline/creatinine. In contrast, a 2-year study comparing the effects of estradiol plus NETA with two doses of tibolone (1.25 and 2.5mg) showed that bone mineral density values were significantly higher in the estradiol plus NETA group than in the two tibolone groups . These two investigations ,  indicate that NETA may add something extra to bone compared with the other progestogens, although this may be deduced only from comparative trials using MPA and NETA. Direct comparisons between estrogens and SERMs are rare, although it has been suggested that raloxifene may have less marked effects than estrogens on bone mineral density . A head-to-head comparative study between tibolone and raloxifene is currently lacking. However, in order to compare tibolone, raloxifene and estradiol plus NETA as reliably as possible, data has been assessed from three independent studies with similar design (duration and supplementation) and methodology , , . Two of the three studies were conducted by the same group. Table 3 shows the effects on bone mineral density in the lumbar spine and total hip and on bone turnover markers. After 2 years of treatment, tibolone appears to have had a more marked effect than raloxifene on bone mineral density at both the spine and hip. Bone turnover markers were also decreased less with raloxifene, indicating that bone turnover is more strongly influenced by tibolone. Estradiol plus NETA was also more effective than raloxifene, whilst the effects of tibolone and estradiol plus NETA appear to be comparable.
Effects on other tissues: the pros and cons The recent publication of the WHI study  outcome has changed the opinion of many prescribers and consumers. However, this study was performed with CEE plus MPA and it is doubtful whether the same result would have been obtained with other combinations. The CEE preparation consists of a mixture of estrogenic and non-estrogenic compounds, whilst MPA differs from progestogens such as NETA and norgestrel. From this review we may conclude that all treatments have a positive effect on bone. However bone loss is not the symptom from which peri- and early menopausal women suffer the most; hot flushes and vaginal atrophy are the first symptoms of estrogen deficiency. It is well established that estrogens efficiently prevent hot flushes in the majority of women, as does tibolone , whilst raloxifene and tamoxifen may even induce such symptoms . In the first study assessing the effects of tibolone on bone , in addition to a beneficial effect on menopausal complaints there was also a positive effect on mood. A finding that was later confirmed by other studies . The fact that tibolone is more effective than estrogens in improving mood and sexual function is probably due to its androgenic activity. Beneficial effects of tibolone on the vagina are also likely to contribute to improvements in sexual well being , . In contrast to tibolone, SERMs have no effect on mood or sexuality.