Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis

BACKGROUND: Long-term post-menopausal hormone therapy (pHT) was often regarded as first-line therapy to prevent fractures in post-menopausal women, a recommendation under scrutiny given the benefit-risk profile of the Women's Health Initiative results of the estrogen-progestin combination. Apart from controlled clinical studies providing data with fractures as an end point, measures of lumbar and hip bone mineral density (BMD) may be used to assess bone-related effects of pHT. The objective of this study was to conduct a systematic review of 2-year trials, published between 1990 and December 2002, and assessing changes in BMD by any estrogen including ethinyl estradiol, any estrogen plus any progestin, or tibolone. METHODS: We searched MEDLINE, EMBASE and systematic reviews. Thirty-nine randomized, prospective, controlled 2-year trials were analysed in pre-specified groups according to the profile of the compounds. RESULTS: Virtually all pHT regimens at least maintain BMD at the lumbar spine and the hip compared with baseline; there is no apparent difference between the various estrogenic compounds. Tibolone, a synthetic progestin, appears to be as effective as any estrogen. Most trials were conducted in early post-menopausal women, fewer in women with hysterectomy and/or bilateral oophorectomy. CONCLUSIONS: The size of impact on BMD does not appear to differ between tibolone and any estrogen compound studied.     

替勃龙联合更安宁对雌性去势大鼠血管内皮细胞的保护作用

目的:观察替勃龙联合补肾中药(更安宁)在雌性去势大鼠加高脂饮食状态下,对血管内皮细胞的保护作用。方法:9月龄雌性Sprague-Dawley大鼠50只,随机分为假手术组(SHAM)、卵巢切除组(OVX)、卵巢切除后药物联合治疗组(OVX+E)、高脂血症组(OVX+HC)、高脂血症药物联合治疗组(OVX+HC+E)。在卵巢切除术后14d起,OVX组、OVX+HC组给予生理盐水灌胃,OVX+E组、OVX+HC+E组予替勃龙+补肾中药更安宁溶液灌胃,OVX+HC组、OVX+HC+E组同时喂饲高脂饮食。12周后处死大鼠,测定血浆雌二醇(E2)、高密度脂蛋白(HDL-c)、低密度脂蛋白(LDL-c)、胆固醇(Tch)、甘油三脂(TG)、一氧化氮(NO)、血管性假性血友病因子(vWF),在光镜及电镜下观察主动脉管壁结构的改变。结果:OVX+E组与OVX组相比,OVX+HC+E组与OVX+HC组相比,均表现Tch、LDL-c明显降低,HDL-c明显升高,血浆NO含量增加;OVX组存在轻度动脉粥样硬化坏死,OVX+HC组动脉管壁损伤严重,伴随vWF明显升高;OVX+E组与OVX+HC+E组动脉管壁结构正常。结论:替勃龙联合补肾中药更安宁治疗能保护血管内皮细胞,对抗高脂血症对动脉管壁的损伤。     

Use of hormone therapy for menopausal symptoms and quality of life in breast cancer survivors. Safe and ethical?

Breast cancer is the most prevalent cancer in women and presently, the breast cancer survivors are an important group of women that faced the several consequences of estrogen deficiency, which is especially common in women after chemotherapy. The most bothersome is the vasomotor symptoms, which are effectively relieved by hormonal therapy (HT). Also, the increased risk of osteoporosis and coronary artery disease is major problem to be resolved in pos of maintaining a good quality of life. Fearing cancer recurrence, most physicians do not offer HT to women with a history of breast cancer. Over this issue reviews the available evidence of the use of HT and tibolone in women treated for breast cancer.     

The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP). DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements. SETTING: The Leiden University Medical Center. SUBJECTS: Postmenopausal women with type III HLP (aged < or = 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L(-1). MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels. RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L(-1) and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L(-1), respectively (both P < 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P < 0.05). CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.     

替勃龙治疗去势大鼠骨质疏松症的研究

OBJECTIVE To explore the curative effect of Tibolone on osteoporosis of castration rats.METHODS Forty female wistar rats about 3 months old were divided into 4 groups by body weight randomly.The 4 groups were false operation group,model group,Tibolone gro     

替勃龙对大鼠神经细胞Bcl-2、Bax表达的影响

目的探讨雌激素对去势大鼠脑缺血再灌注后神经细胞Bcl-2、Bax表达的影响和替勃龙的神经保护作用。方法 30只雌性成年SD大鼠,随机分为假手术组,手术对照组,替勃龙组,每组10只;采用大鼠大脑中动脉闭塞制成局灶性脑缺血模型。在缺血2h、再灌注24h后立即断头取脑,应用TTC染色观察脑梗死体积,TUNEL法检测凋亡细胞,链酶菌抗生物素蛋白过氧化物酶(SP)法检测抗凋亡基因Bcl-2、细胞凋亡诱导因子Bax的表达。结果替勃龙用药组较手术对照组脑梗死体积显著缩小(P<0.05),TUNEL阳性细胞数少(P<0.01),Bcl-2阳性细胞增多(P<0.01),Bax阳性细胞减少(P<0.01)。结论替勃龙可抑制去卵巢大鼠局灶性脑缺血再灌注时神经细胞凋亡,具有神经保护作用。     

Pharmacotherapeutic approaches to treating depression during the perimenopause

ABSTRACT

Introduction: Although postnatal depression is now well recognized, there is also a risk of depressive symptoms during perimenopause. The mechanisms underlying perimenopausal depression are still poorly understood; however, there are available treatment options.

Areas covered: This review describes: the current pharmacotherapeutic approaches for perimenopausal depression, their strengths and weakness, and provides recommendations on how current treatment can be improved in the future. An electronic search identified specific guidelines for the treatment of perimenopausal depression released in 2018, as well as recent clinical studies on the subject.

Expert opinion: The 2018 guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) as front-line medications for perimenopausal depression, but SSRIs and SNRIs are not always effective. The efficacy of estrogen in perimenopausal depression is well documented, but estrogen is not FDA-approved to treat mood disturbances in perimenopausal women. Clinical practice guidelines currently recommend to restrict hormone therapy to the symptomatic treatment of menopause (not for the prevention of chronic diseases). Research with new estrogenic compounds is under way to improve their benefit/risk ratio in perimenopausal depression.     

New findings with old drugs for osteoporosis

Background: Postmenopausal osteoporosis is common and is associated with stooped posture, loss of height, back pain and fractures. Objectives/methods: This evaluation is of clinical outcome trials with tibolone (Long-Term Intervention of Fractures with Tibolone) and strontium ranelate (Spinal Osteoporosis Therapeutic Intervention) in postmenopausal osteoporosis. Results: Although the Long-Term Intervention of Fractures with Tibolone trial established that tibolone decreased the incidence of vertebral and non-vertebral fractures in postmenopausal osteoporosis, it also showed that tibolone caused a small increase in the incidence of stoke. The Spinal Osteoporosis Therapeutic Intervention trial established that strontium ranelate decreased the incidence of vertebral fractures, but had little effect on the incidence of non-vertebral fractures. Conclusions: As some of the bisphosphonates (alendronate, risedronate, zoledronic acid) have been shown to prevent hip fractures without increasing the incidence of stroke, they should be preferred to tibolone and strontium in the treatment of postmenopausal osteoporosis.     

Treatment of menopausal symptoms post-Women’s Health Initiative: refinement of existing treatments and development of new therapies

Menopause is a normal life transition for women. More than 80% of women experience some symptoms at menopause and > 25% of women in western countries seek treatment for a variety of symptoms that accompany this transition. In addition, there are certain chronic disease processes that accelerate after the menopausal transition. Hormone replacement therapy (HRT) with various combinations of oestrogen and progesterone compounds has been the mainstay of treatment for menopausal symptoms, as well as theoretical reduction in acceleration of certain chronic diseases after menopause. After the publication of the results of the Women’s Health Initiative study in June 2002, the safety of HRT, as well as its effectiveness in decreasing various chronic diseases, was challenged. New formulations of hormone therapy, as well as new treatments, are evolving to aid the reduction of menopausal symptoms and long-term risks of common chronic disease processes that accelerate after the menopause.