Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA treatment in postmenopausal women with female sexual dysfunction.

OBJECTIVES: To compare the incidence of vaginal spotting/bleeding events and breast pain between therapy with tibolone 2.5 mg and continuous combined transdermal estradiol (E(2))/norethisterone acetate (NETA) 50 microg/140 microg after 24 weeks of treatment. METHODS: A double-blind, double-dummy, randomized, controlled trial was performed and assessments were performed at baseline, week 12 and week 24. Bleeding/spotting events were recorded in a daily diary. Breast signs and symptoms were collected as adverse events. RESULTS: A total of 403 women (mean age 56 years) were randomized. Bleeding/spotting events during weeks 1-12 with tibolone and E(2)/NETA were experienced by 16% and 56% of women, respectively (p < 0.001). The corresponding percentages during weeks 13-24 were 12% and 51%, respectively (p < 0.001). E(2)/NETA was significantly more likely than tibolone to be associated with vaginal hemorrhage (11% vs. 0%; p < 0.001) and breast signs and symptoms (11% vs. 4%; p = 0.015). Early discontinuations resulting from adverse events were significantly more common in the E(2)/NETA group than in the tibolone group (20% vs. 12%), primarily related to withdrawal due to vaginal hemorrhage (8% vs. 0%). CONCLUSIONS: Tibolone has a significantly better tolerability profile than transdermal E(2)/NETA as measured by vaginal bleeding, breast pain and treatment continuation.

Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women.

UNLABELLED: A randomized trial was conducted in osteopenic postmenopausal women to compare the efficacy of tibolone versus raloxifene on BMD of the lumbar spine and hip. Tibolone increased lumbar spine and total hip BMD to a statistically significantly greater extent than raloxifene after two years of treatment. INTRODUCTION: Both tibolone, a selective tissue estrogenic activity regulator (STEAR), and raloxifene, a selective estrogen receptor modulator (SERM), are known to prevent postmenopausal bone loss. However, no head-to-head studies to compare the efficacy on bone have been performed. METHODS: A double-blind, randomized trial was conducted in osteopenic postmenopausal women aged 60-79 years to compare the effects of tibolone 1.25 mg/day to raloxifene 60 mg/day on bone mineral density (BMD). Serum osteocalcin and serum type I collagen C-telopeptides were measured as biochemical markers of bone metabolism. RESULTS: Three hundred and eight subjects were allocated to treatment. Both treatments significantly increased lumbar spine BMD, however the increase was significantly larger after tibolone treatment than after raloxifene treatment (at year 1: 2.2% versus 1.2%, p<0.01 and at year 2: 3.8% versus 2.1%, p<0.001). After 2 years of treatment, the increase in total hip BMD in the tibolone group was significantly larger than in the raloxifene group (p<0.05). Both treatments significantly reduced type I collagen C-telopeptides and osteocalcin levels when compared to baseline. CONCLUSIONS: Tibolone 1.25 mg/day for 2 years prevents postmenopausal bone loss in older women and results in a larger increase of BMD both at the lumbar spine and hip than raloxifene.

Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.

OBJECTIVES: The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. DESIGN: A randomised, double-blind, double-dummy, group comparative intervention trial. SETTING: Multicentre study executed in 32 centres in 7 European countries. SAMPLE: Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years. METHODS: Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks. MAIN OUTCOME MEASURES: Prevalence of vaginal bleeding, hot flushes and adverse events. RESULTS: The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001). CONCLUSION: Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.

Effects of tibolone and raloxifene on health-related quality of life and sexual function.

OBJECTIVES: Study to compare the effects of tibolone and raloxifene on health-related quality of life, sexuality and vaginal atrophy. METHODS: A double-blind, randomized study was conducted in 308 osteopenic, but otherwise healthy, postmenopausal women (mean age 66 years) who received tibolone 1.25mg/day or raloxifene 60 mg/day for 2 years. Health-related quality of life was assessed by the women's health questionnaire (WHQ), sexual function by the McCoy female sexuality questionnaire (MFSQ) and vaginal atrophy by assessing the karyopycnotic index (KI) and vaginal maturation (VM). RESULTS: At week 104, the tibolone group showed a trend towards an improved health-related quality of life (HRQoL) mean score in eight out of nine WHQ domains. HRQoL scores approximated values for premenopausal women, being pre-defined as "clinically relevant". The raloxifene group showed a trend to a diminished HRQoL mean score from baseline to week 104. No difference could be assessed between the tibolone and raloxifene group in mean total score and separate domains' scores of the MFSQ, except for the vaginal lubrication domain (p=0.037). The increase in KI and VM was statistically significantly greater with tibolone than with raloxifene (for both KI and VM p<0.0001). Tibolone and raloxifene were equally well tolerated. CONCLUSIONS: In older postmenopausal women, tibolone treatment showed a trend towards an improvement in quality of life and sexuality when compared to raloxifene.

A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men.

The synthetic hexapeptide growth hormone-releasing peptide (GHRP)-2 specifically stimulates GH release in man. To determine the effects of prolonged treatment and whether response attenuation occurs in man, we administered to nine healthy subjects a daily s.c. injection of 100 microg GHRP-2 over 5 days. Every day blood samples were taken to determine GH, IGF-I, IGF-binding protein (IGFBP)-3 and osteocalcin levels. On days 1,3 and 5, GH was measured at -20,0,20,40,60,90,120 and 180 min using an immunometric and an immunofunctional assay. Mean-/+S.D). peak GH concentrations were 83+/-31, 59+/-22 and 51+/-13 microg/l on days 1, 3 and 5 respectively. Mean+/-S.D. areas under the curve for days 1, 3 and 5 were 6366+/-2514, 3987 +/- 1418 and 3392+/-1215 mU/l per min. Despite the maintained GH release, analysis of variance revealed that significant response attenuation occurred (P < 0.01). Mean serum IGF-I concentration did not increase after a 5 day treatment with GHRP-2. Mean basal levels were 22, 25,23,25,23,24 nmol/l measured on days 1 to 6. However, osteocalcin, another serum marker of GH activity in tissue, increased significantly from 3.2+/-1.0 to 4.2+/-0.4 microg/l (mean+S.D.) (P< 0.01).

Correction of a dystrophic cervicothoracic spine deformity in Recklinghausen's disease.

A case is presented of a 14-year-old boy with neurofibromatosis who had a 92 degrees dystrophic kyphosis (as measured on radiographs between C3 and C7) of the cervical spine. He was treated successfully by posterior stabilization and anterior fusion using a free vascularized fibula graft. This method appears to be an attractive alternative to an avascular fibula graft and avoids the risk of graft resorption (creeping substitution), weakening (fracture), or nonunion during the process of bony consolidation. It provides a stable and longstanding anterior strut, essential in the management of high grades of kyphosis. At 1-year followup the patient has no symptoms, is fully mobile, and shows radiographically complete incorporation of the graft with no loss of correction.