LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: a randomized controlled clinical trial

AIM: Menopause is a pro-atherogenic state with a sharp rise in the incidence of coronary artery disease. This pilot study was designed as an equivalence randomized clinical trial to explore the potential of LycoRed (containing 2000 microg lycopene) as an alternative to hormone replacement therapy (HRT) for the prevention of coronary artery disease in postmenopausal women. METHODS: Forty-one healthy postmenopausal women were randomly allocated to receive either continuous combined HRT (n = 21) or LycoRed (n = 20) for six months. Serum lipid profile, marker of lipid peroxidation (malondialdehyde), and the level of endogenous antioxidant (glutathione) were measured at the baseline, and 3 and 6 months after the intervention in both groups. RESULTS: At 6 months, HRT resulted in a significant decrease in total cholesterol (TC) level by 23.5%, low-density lipoproteins (LDL) by 19.6%, and an increase in high-density lipoproteins (HDL) by 38.9%. The LycoRed group showed similar changes in TC (-24.2%), LDL (-14.9%) and HDL (+26.1%). Triglyceride levels showed a smaller though significant increase at 6 months, but not at 3 months, in both groups. There was no significant change in the very LDL (VLDL) level in either group. Malondialdehyde levels decreased significantly by 16.3% and 13.3%, whereas glutathione levels increased significantly by 5.9% and 12.5% in HRT and LycoRed groups, respectively. CONCLUSION: Both HRT and LycoRed had a favorable effect on serum lipids and oxidative stress markers which were comparable. LycoRed can be used as an alternative to HRT to reduce the risk of atherosclerosis in postmenopausal women.     

小剂量雌激素替代治疗在子宫内膜异位症根治术后应用的疗效观察

目的 探讨倍美力对Ⅲ～Ⅳ期子宫内膜异位症根治术后（全子宫双侧附件切除）患者的激素替代作用。方法 41例内膜异位症患者根治术后并发严重围绝经期症状，用倍美力0．3mg（A组）、0．625mg（B组）、1．25mg（C组）治疗9个月，观察三组对围绝经期症状症状缓解、内膜异位症复发的影响及其副作用。结果 三组均能改善围绝经期症状，使K评分降低，提高E2水平，P〉0．05；三组间差异无显著性，副作用较小。结论 小剂量倍美力对子宫内膜异位症根治术后激素替代治疗是可行的。     

雌性去势大鼠雌激素替代治疗后大脑皮质神经元形态学变化的研究

目的 :观察雌激素替代治疗后雌性去势大鼠大脑皮质神经元形态学变化 ,探讨雌激素对中枢神经系统的有益作用。方法 :将 9月龄去势雌性SD大鼠 2 0只随机分为用药组 (去势后给予倍美力溶液 0 .2mg/kg·d- 1灌胃 )和对照组 (去势后予以生理盐水灌胃 )。 12周后测定两组血清E2 水平 ,同时对大脑额叶皮质神经元行形态学检查。结果 :(1)用药组E2 水平、脑重 /体重指数及额叶皮质神经元计数均高于对照组 (P <0 .0 1) ;用药组额叶皮质神经细胞凋亡百分率低于对照组 (P <0 .0 1)。 (2 )对照组神经元细胞超微结构显示细胞有老化、凋亡趋势 ,而用药组形态及结构基本正常 ;用药组神经元突触密度较对照组增高 ,突触前膜含神经递质的小泡较对照组多。结论 :去势大鼠应用雌激素替代治疗可延缓神经元衰老 ,减少神经细胞的凋亡和丢失     

Hormone replacement therapy in menopausal women: Past problems and future possibilities

Oral administration of conjugated equine estrogens (CEE) with and without the synthetic progestin medroxyprogesterone acetate (MPA) in postmenopausal women is associated with side-effects that include increased risk of stroke and breast cancer. The current evidence that transdermal administration of estradiol may provide a safer alternative to orally administered CEE is reviewed. Transdermally administered estradiol has been shown to be an efficacious treatment for hot flushes possibly without the increase in blood clotting that is associated with administration of oral CEE. Further, natural progesterone may have a more beneficial spectrum of physiological effects than synthetic progestins. The substantial differences between CEE compared with estradiol and estriol, as well as the differences between synthetic MPA and natural progesterone, are detailed. Estriol is an increasingly popular alternative hormone therapy used for menopausal symptoms. There is evidence that estriol, by binding preferentially to estrogen receptor-β, may inhibit some of the unwanted effects of estradiol. New clinical trials are needed to evaluate the safety and efficacy of topically or transdermally administered combinations of estradiol, estriol and progesterone. Future studies should focus on relatively young women who begin estrogen supplement use near the start of menopause.     

Effects of estrogen therapy on microalbuminuria in healthy post-menopausal women

Objective. To evaluate the impact of estrogen therapy on microalbuminuria levels in healthy post-menopausal women.

Methods. Sixty post-menopausal women were evaluated in a prospective, randomised, double-blind, placebo-controlled study. The patients were randomly allocated to one of two groups to take one pill orally per day containing either 1 mg of 17β-estradiol (E₂ group) or placebo (placebo group). Prior to initiating treatment and at the end of the sixth treatment month, microalbumin was measured in a 12-h urine sample, and lipid profile (total cholesterol, HDL, LDL and triglycerides) and fasting glucose were evaluated. Comparative intra- and inter-group analyses between the initial and final laboratory parameters were performed using the t-test for paired samples and for independent samples, respectively.

Results. Microalbuminuria levels remained within normal limits throughout the study and no statistically significant differences were found in the intra- or inter-group analyses. With respect to lipid profile, alterations characteristically encountered during use of estrogen replacement therapy were found. No statistically significant variation in glucose levels occurred during the study period.

Conclusion. Estrogen replacement therapy had no significant effect on microalbuminuria levels in healthy post-menopausal patients.     

激素补充治疗与卵巢癌

激素补充治疗(HRT)是否增加卵巢癌发生的风险尚存争议,但考虑到其潜在的致癌可能,应用时需慎重选择,并应告知患者相关风险。由于HRT能够明显改善卵巢癌患者术后的围绝经症状,提高其生存质量,且目前尚无足够证据证明HRT对卵巢癌患者的生存有不良影响,故在必要时可谨慎选用。     

Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: a randomized placebo-controlled study

OBJECTIVE: This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. STUDY DESIGN: In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS: No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3% (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5% (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)-antiplasmin complexes. CONCLUSION: Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.     

Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy

Objective.?To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk.

Methods.?The study was conducted with 44 voluntary postmenopausal women. In group I (n?=?15), the patients were treated with only intranasal estradiol (300?μg/day estradiol hemihydrate). In group II (n?=?11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n?=?18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment.

Results.?Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p?>?0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p?<?0.05).

Conclusions.?Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.     

卵巢切除和雌激素补充治疗对大鼠膀胱功能及结构的影响

目的通过对不同雌激素水平大鼠进行膀胱功能、组织形态和超微结构的比较,探讨雌激素对膀胱功能的影响及其作用机制。方法30只雌性成年SD大鼠均分为3组:OVX+E组(切除双侧卵巢后补充戊酸雌二醇0·8mg·kg-1·d-1,溶于0·5%羧甲基纤维素钠,每日灌胃1次)、OVX组(切除双侧卵巢)、正常对照组(未切除卵巢),后两组大鼠每日给予0·5%羧甲基纤维素钠灌胃1次。3组大鼠用药12周后行膀胱压力容积测定,并用切除膀胱的石蜡切片分析胶原纤维和平滑肌的面密度及两者比值,透射电镜下观察逼尿肌的超微结构。结果(1)OVX组膀胱最大容量(0·32±0·20)ml、顺应性(0·012±0·006)ml/cmH2O(1cmH2O=0·098kPa)和最大收缩力(1·4±0·4)cmH2O,相对于正常对照组[分别为(1·11±0·09)ml、(0·026±0·003)ml/cmH2O和(4·4±0·3)cmH2O]明显减少,差异均有统计学意义(P<0·05)。OVX+E组膀胱最大容量为(0·83±0·10)ml,相对于正常对照组减少(P<0·05),而膀胱顺应性(0·029±0·003)ml/cmH2O、最大收缩力(4·8±1·4)cmH2O与正常对照组比较,差异无统计学意义(P>0·05)。(2)胶原纤维面密度、胶原纤维面密度/平滑肌面密度比值,OVX组分别为0·218±0·041和0·54±0·08,相对于正常对照组(0·160±0·039、0·32±0·09)明显增加,差异有统计学意义(P<0·05);而OVX+E组(0·178±0·027、0·38±0·06)与正常对照组比较,差异无统计学意义(P>0·05)。(3)电镜观察OVX组逼尿肌超微结构出现退行性改变,其他两组无类似变化。结论大鼠切除双侧卵巢后膀胱功能明显降低,补充雌激素有利于改善膀胱功能,这一作用可能是通过抑制胶原增生,保护细胞器来实现的。     

Effect of oestrogen replacement therapy on serum lipid profile

BACKGROUND: Oestrogen deficiency in postmenopausal women alters the lipid metabolism unfavourably. AIM: To evaluate the effects of oral and transdermal oestrogen replacement therapy (ORT) on serum lipid profile. METHODS: Ninety hysterectomised and oophorectomised women were randomised into three equal groups (no hormones; oral conjugated equine oestrogen, 0.625 mg/day; transdermal oestradiol patches, 50 microg/day). Serum concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides were determined at the baseline and after 3 and 6 months of therapy. Student's t-test was used for statistical evaluation. RESULTS: Most of the hysterectomised women had abnormal serum lipid profile, especially HDL cholesterol levels (less than 40 mg/dL in 87%). A significant decline in the levels of serum cholesterol (total) as well as LDL and a significant increase in HDL cholesterol levels were observed following ORT by both modes, the response being comparatively rapid with oral route. After 3 and 6 months, the number of cases with HDL cholesterol levels above 40 mg/dL increased from initial 13 to 63% and 87% (oral) and 30 and 60% (transdermal), respectively. Serum triglyceride levels declined significantly with transdermal therapy but increased with oral ORT. CONCLUSIONS: Oestrogen replacement therapy either via oral or transdermal route has a beneficial effect on serum lipid profile of menopausal women. Whereas the oral route is more effective in increasing HDL cholesterol levels, the transdermal route is better for reducing the serum triglyceride level; hence, the latter should be the route of choice in women with high serum triglyceride levels.     

Hormone replacement therapy and successful pregnancy in a patient with premature ovarian failure

Premature ovarian failure (POF), premature ovarian insufficiency, premature menopause or hypergonadotropic hypogonadism, a serious life-changing condition that affects young women, remains an enigma and the researcher's challenge. In the present article we described a case of singleton pregnancy in a 33-year-old patient, presenting with POF and treated with hormone replacement therapy. Twenty months later this therapy led to maturation of one follicle, recruitment and fertilisation of the residual oocyte and spontaneous pregnancy ensued. A normal infant was delivered by cesarean section.     

Effect of estrogen and testosterone replacement therapy on cognitive fatigue

Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue. However, hormonal replacement studies on fatigue are rare. Therefore, we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women. Fifty women with surgically induced menopause (mean age: 54.0?±?2.9 years) were randomly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study. Neuropsychological tests and questionnaires were used to assess cognitive fatigue and psychological well-being. Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels. Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels. The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se. We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue.     

雌激素替代疗法对绝经后妇女血浆一氧化氮的影响

目的探讨雌激素替代疗法（ＥＲＴ）对绝经后妇女血浆一氧化氮（ＮＯ）含量的影响。方法测定１７例健康绝经后妇女（健康组）,２１例患高血脂症绝经后妇女（高血脂组）应用ＥＲＴ前及应用ＥＲＴ４周后血浆ＮＯ及血清雌二醇（Ｅ２）含量,并与１０例健康绝经后妇女应用安慰剂（对照组）进行对照。结果对照组应用安慰剂前后,ＮＯ含量无变化;健康组及高血脂组应用ＥＲＴ后,ＮＯ含量明显升高,健康组升高尤其明显;健康组应用ＥＲＴ４周后Ｅ２水平与ＮＯ升高有明显相关性。结论绝经后妇女补充雌激素,可通过升高ＮＯ含量发挥其对心血管的保护作用。     

Compliance with hormone replacement therapy at Songklanagarind Hospital

AIM: To determine compliance with hormone replacement therapy (HRT) over a 2-year period, reasons for discontinuing HRT and the factors associated with non-compliance. METHODS: A total of 202 women attending the menopause clinic at Songklanagarind Hospital and taking HRT were included in this retrospective study. Compliance was assessed for each 6-month interval within the first 2 years. Reasons for discontinuation were requested from women who had stopped using HRT. RESULTS: Compliance rates with HRT for the study group were 57.9% at 6 months, 42.6% at 12 months, 35.1% at 18 months and 32.7% at 24 months. The main reasons for discontinuing HRT were improvement of climacteric symptoms (20.9%), fear of cancer (16.4%) and irregular bleeding (11.9%). Logistic regression analysis revealed a significant increase in the risk of non-compliance of HRT among agriculturists or untrained workers (OR 4.7, 95% CI 1.2-18.8; reference, government employees), those with delayed onset of treatment (>1 years; OR 3.0, 95% CI 1.1-8.0; reference, 0-3 months) and those prescribed HRT for climacteric symptoms or reasons other than oophorectomy or ovarian failure (OR 18.2-41.6 depending on reasons). Agriculturists or untrained workers who delayed onset of treatment for climacteric symptoms had the highest expected non-compliance rate of 0.95%. CONCLUSION: Long-term compliance of HRT was not good at Songklanagarind menopause clinic. More attention has to be paid to the counseling of patients about HRT. Agricultural or untrained workers, late starting HRT, and presence of climacteric complaints were the significant factors for poor HRT compliance.     

Tibolone versus four estrogen replacement therapy protocols and plasma lipid levels in postmenopausal women.

OBJECTIVES: To compare tibolone therapy with four different estrogen replacement therapy protocols, with regard to the effects on plasma lipid profiles. METHODS: The plasma lipid levels of 178 postmenopausal women in five different therapy groups were compared with each other as well as their baseline levels with 6-month intervals during 2-year follow-up. Student's t-test, paired t-test and Pearson correlation analysis were utilized for statistical analysis. RESULTS: HDL cholesterol levels increased significantly from baseline in groups using oral estrogen (P<0.05) but a slight non-significant decrease was seen in tibolone therapy (P>0.05). LDL cholesterol levels significantly decreased at the end of the second year in oral estrogen and tibolone users (P<0.05). Triglyceride levels increased non-significantly with estrogen therapy (P>0.05), whilst decreased significantly in the tibolone group (P<0.05). CONCLUSION: Tibolone may be a good alternative to estrogen replacement therapy in postmenopausal women, as it has beneficial effects on LDL cholesterol and triglyceride levels, which play important role in atherosclerosis.     

Does immediate hormone replacement therapy affect the oncologic outcome in endometrial cancer survivors?

The purpose of this study was to evaluate the effect of immediate hormone replacement therapy (HRT) on oncologic outcome of patients with endometrial cancer. The patients were recruited prospectively after extensive discussion of risks and benefits of HRT. Continuous daily regimen of 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate was initiated 4-8 weeks after surgery at first postoperative visit. The patients who had the same characteristics with the HRT group were assigned as a control group. Overall, 50 patients received HRT. There was no significant difference with respect to prognosticators between the HRT users and the control group. Seven patients (14%) stopped the use of HRT. Only two patients stopped the therapy before 24 months, and all the remaining patients used HRT for at least 24 months, with a mean value of 49.1 months. Neither the patients who used HRT nor the ones who left the therapy had recurrence at the time of writing of this article. This prospective case-control study showed that immediate postoperative use of HRT did not increase the recurrence or death rates in endometrial cancer survivors.     

Effects of bilateral ovariectomy and estrogen replacement therapy on serum leptin,sex hormone binding globulin and insulin like growth factor-I levels

Studies evaluating the effect of estrogen replacement therapy (ERT) on leptin levels are contradictory. The aim of this study was to investigate effects of bilateral ovariectomy and ERT on serum leptin levels and anthropometric measurements as well as interaction among leptin, sex hormone binding globulin (SHBG), and insulin like growth factor-I (IGF-I) in premenopausal women after bilateral ovariectomy. Twenty-four premenopausal women who undergo bilateral overiectomy were divided into two groups based on whether they received hormonal treatment postoperatively. The studied parameters were evaluated in both groups preoperatively and during the fourth and eighth weeks postoperatively. Serum leptin, testosterone, prolactin, insulin, IGF-1 levels, BMI, HOMA-IR, and waist-to-hip ratio values did not change in both groups at all times. In the estradiol group, serum SHBG concentrations were significantly higher on weeks 8 compared with control group and basal values (p?=?0.03 and 0.014, respectively). Leptin levels showed a positive linear correlation with BMI in all groups and at all times evaluated (r?=?0.80, p?<?0.01 for controls and r?=?0.62, p?<?0.01 for women treated with 17β-estradiol) and with insulin in estradiol group on weeks 4 (r?=?0.755, p?<?0.05). No correlation was found between leptin and estradiol, testosterone, prolactin, SHBG, IGF-1 levels, and anthropometric variables at all times. Leptin levels do not show modification 8 weeks after bilateral ovariectomy and under ERT, suggesting that estrogens do not have a stimulatory action on leptin in humans. Although needing confirmation by a longer study, our findings suggest that IGF-I system and SHBG did not regulate leptin and vice versa and ERT do not have any effect on leptin, SHBG, and IGF-I.