Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy.

INTRODUCTION: The Livial Intervention Following Breast Cancer: Efficacy, Recurrence and Tolerability Endpoints (LIBERATE: Clinical http://Trials.gov number NCT00408863), a randomized, placebo-controlled, double-blind trial that demonstrated that tibolone (Livial), a tissue-selective hormone-replacement therapy (HRT), increased breast cancer (BC) recurrence HR 1.40 (95% CI, 1.14 to 1.70; P = 0.001). A subgroup of women was entered into a study of bone mineral density (BMD). METHODS: Women with surgically excised primary BC (T1-3, N0-2, M-0) within the last 5 years, complaining of vasomotor symptoms, were assigned to tibolone, 2.5 mg daily, or placebo treatment for a maximum of 5 years. The BMD substudy enrolled 763 patients, using dual-energy X-ray absorptiometry (DXA) scanning at baseline and at 2 years. RESULTS: In the bone substudy, 699 of 763 women were eligible (345 allocated to tibolone, and 354, to placebo). After undergoing DXA scans, 300 (43%) women had normal BMD; 317 (45%), osteopenia; and 82 (11.7%), osteoporosis. Low body-mass index (P < 0.001), Asian race (P < 0.001), and late age at menarche (P < 0.04) predicted low bone mass at baseline. Tibolone increased BMD by 3.2% at the lumbar spine and 2.9% at the hip compared with placebo (both P < 0.001). The majority of fractures (55%) occurred in osteopenic patients. Women with normal BMD had increased recurrence with tibolone, 22 (15.6%) of 141 compared with placebo, 11 (6.9%) of 159 (P = 0.016), whereas no increased BC recurrence was seen in women with low BMD; 15 (7.4%) of 204 taking tibolone versus 13 (6.7%) of 195 taking placebo. CONCLUSIONS: Tibolone is contraindicated after BC treatment, as it increases BMD and BC recurrence. Risk of BC recurrence was elevated in BC women with normal BMD (compared with low) who took tibolone.

Testosterone addition to estrogen therapy - effects on inflammatory markers for cardiovascular disease.

OBJECTIVE: To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women. METHODS: Fifty surgically postmenopausal women were included in this double-blind, placebo-controlled and randomized study to receive daily oral treatment with estradiol valerate 2 mg + placebo (E/P) or estradiol valerate 2 mg + testosterone undecanoate 40 mg (E/T) for 24 weeks and then switched to the other regimen for another 24 weeks. Sex hormones, High sensitivity CRP (hsCRP), Interleukin-6 (IL-6), Tissue necrosis factor (TNF)-alpha, Insulin-like growth factor binding globulin (IGFBP-1), vascular cell adhesion molecule (VCAM)- 1, and homocysteine were analyzed at baseline and after 6 and 12 months. RESULTS: Estradiol and androgens increased as expected during the treatments. After 6 months of E/P, increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded, whereas IL-6, TNF-alpha, and homocysteine were unchanged. When testosterone was added to estrogen, the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone. However, testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6, TNF-alpha, and homocysteine. CONCLUSION: Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects. On the contrary, the estrogen-induced increase in hsCRP was suppressed.