Tratamiento a largo plazo del dolor pélvico con levonorgestrel en mujeres con endometriosis que desean posponer el embarazo y preservar su fertilidad. Serie de casos / Long-term management of pelvic pain with levonorgestrel in women with endometriosis who desire to postpone a future pregnancy and preserve their fertility. Case Series

Resumen OBJETIVO: Valorar el tratamiento a largo plazo del dolor pélvico con levonorgestrel en mujeres con endometriosis que desean posponer el embarazo y preservar su fertilidad. MATERIALES Y MÉTODOS: Estudio ambispectivo, con intervención medicamentosa, longitudinal y descriptivo de serie de casos. Parámetros de estudio: medición de la intensidad del dolor a los 12, 24 y 36 meses posteriores a la colocación de un implante único de goserelina (Zoladex de 10,6 mg, AstraZeneca AB, Gärtunavägen). Al retorno de la menstruación se colocó un dispositivo intrauterino con levonorgestrel (Mirena Bayer AG, Leverkusen). La intensidad del dolor pélvico se midió con la Escala Numérica del Dolor (Escala ENA). RESULTADOS: Se estudiaron 14 pacientes de las que 5 refirieron dolor: 4 con intensidad 1 y una con intensidad 3. El resto de las pacientes no refirió dolor. Todas las pacientes refirieron alivio general subjetivo a los 12 meses de seguimiento. CONCLUSIONES: El levonorgestrel administrado por vía intrauterina puede ser una alternativa para mantener, a largo plazo, sin dolor a pacientes con endometriosis que desean posponer el embarazo. Para confirmar lo aquí encontrado hacen falta estudios controlados, con asignación al azar y con un tamaño de muestra realmente representativo.

Abstract OBJECTIVE: To assess the long-term treatment of pelvic pain with levonorgestrel in women with endometriosis who wish to postpone pregnancy and preserve their fertility. MATERIALS AND METHODS: Ambispective study, with drug intervention, longitudinal and descriptive case series. Study parameters: measurement of pain intensity at 12, 24 and 36 months after placement of a single goserelin implant (Zoladex 10.6 mg, AstraZeneca AB, Gärtunavägen). At the return of menstruation, an intrauterine device containing levonorgestrel (Mirena Bayer AG, Leverkusen) was inserted. The intensity of pelvic pain was measured with the Numerical Pain Scale (NPS). RESULTS: Fourteen patients were studied of whom five reported pain: four with intensity 1 and one with intensity 3. The rest of the patients reported no pain. All patients reported subjective general relief at 12 months follow-up. CONCLUSIONS: Levonorgestrel administered intrauterine may be an alternative for the long-term pain-free treatment of patients with endometriosis who wish to postpone pregnancy. Controlled, randomized studies with a truly representative sample size are needed to confirm the findings.

Is the expression of the components of the carotid matrix of rats influenced by estrogen, progestin and tibolone? / A expressão dos componentes da matriz carotídea de ratos é influenciada pelo estrogênio, progestagênio e tibolona?

Abstract Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by realtime polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.

Resumo Objetivo Analisar os efeitos do estrogênio isolado ou em combinação com progestogênios e tibolona (TIB) na expressão das metaloproteinases 2 e 9 da matriz extracelular (MMP-2 e MMP-9), da perlecan e da heparanase (HPSE) das paredes vasculares das artérias carótidas. Métodos Trinta ratas Wistar ovariectomizadas com 250 dias de idade foram tratadas oralmente por 5 semanas com: a) 1 mg/kg de benzoato de estradiol (EB); b) EB + 0,2 mg/kg de acetato de medroxiprogesterona (MPA); c) EB + 0,2mg/kg de acetato de noretisterona (NETA); d) EB + 2 mg/kg de didrogesterona (DI); e) 1 mg/kg de TIB; f) placebo (CTR). Após o tratamento, a expressão de mRNA para MMP-2, MMP- 9, e HPSE foi analisada por reação em cadeia da polimerase (RCP) em tempo real, e a expressão de MMP-2, MMP-9, inibidor tecidual de metaloproteinase 2 (TIMP-2), e de perlecan foi quantificado por imunohistoquímica em artérias carótidas. Resultados Os grupos apresentaram diferenças significativas na expressão do mRNA HPSE (p = 0,048), sendo maiores nos grupos EB, EB + MPA e TIB. Não houve diferença estatisticamente significativa nas expressões de mRNA MMP-2 ou MMP-9. A expressão imunohistoquímica de MMP-2, TIMP-2, MMP-9, HPSE e perlecan não mostrou diferenças entre os grupos. Conclusão O estradiol isolado ou associado ao tratamento com MPA e TIB pode aumentar a expressão de mRNA HSPE nas paredes das artérias carótidas em ratas ovariectomizadas.

Comparison of the Efficacy of Tibolone and Transdermal Estrogen in Treating Menopausal Symptoms in Postmenopausal Women

OBJECTIVES: This study aimed to compare the efficacy of tibolone and transdermal estrogen in treating menopausal symptoms in postmenopausal women with an intact uterus.METHODS: Overall, 26 women consumed tibolone orally and 31 women received transdermal estrogen gel mixed with progestogen. The menopause rating scale (MRS) was used to assess their menopausal symptoms at their first outpatient visit and 6 months later.RESULTS: The transdermal estrogen group showed significant improvements in more items of the MRS questionnaire. There was a favorable change in body weight in the transdermal estrogen group compared with that in the tibolone group. Depressive mood, irritability, physical and mental exhaustion, sexual and bladder problems, and joint and muscular discomfort improved only in the transdermal estrogen group, whereas heart discomfort and vaginal dryness improved only in the tibolone group. Nevertheless, the intergroup differences in each item were insignificant after adjusting for body mass index and hypertension, which differed before treatment.CONCLUSIONS: Both the therapeutic options improved menopausal symptoms within 6 months of use. However, transdermal estrogen appeared to be more effective in preventing weight gain in menopausal women than tibolone.

Sangrado y terapia hormonal en la menopausia (THM) / Bleeding during menopause hormone therapy (MHT)

La definición de sangrado ginecológico anormal durante terapia hormonal de la menopausia es aquel sangrado no programado durante el uso de la terapia. Este artículo es un pauteo que describe: 1) cuándo diagnosticar unsangrado anormal, ya que difiere según el tipo de esquema hormonal utilizado; 2) eldiagnóstico diferencial del origen del sangrado anormal; 3) los métodos de evaluación para diagnosticar el origen del sangrado. Se destacan los aspectos principales para el diagnóstico diferencial entre patología orgánica versus disrupción endometrial debida al tratamiento hormonal. Además, se describen los ajustes posibles para resolver el sangrado cuando éste se debe a disrupción del endometrio.

Abnormal bleeding related to menopausal hormone therapy is defined as unscheduled bleeding during the use of the therapy. This article outlines when to diagnose an abnormal bleeding -as this differs according to the type of hormonal scheme used-, the differential diagnosis of the origin of abnormal bleeding, and the methods of evaluation to assess the origin of the bleeding. The main aspects are highlighted on the differentiation of organic pathology versus disruption of the endometrium due to treatment. Also, treatment adjustments to resolve bleeding when it is due to disruption of the endometrium are outlined.

Effect of tibolone on the survival of early stage cervical adenocarcinoma patients

OBJECTIVE: Gynecologic oncologists are uncertain about the safety of tibolone application in cervical adenocarcinoma (AC) patients. This study examined the possible adverse effects of tibolone on the survival of cervical AC patients. METHODS: Medical records of 70 cervical AC patients with International Federation of Gynecology and Obstetrics stages IA to IB were reviewed. A bilateral salpingo-oophorectomy was performed in all patients, and survival outcomes between tibolone users (n=38) and non-users (n=32) were compared. RESULTS: A comparison of the tibolone users with non-users revealed similar clinicopathological variables. Progression-free survival (P=0.34) and overall survival (P=0.22) were similar in the users and non-users. The risks of progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 0.46–6.37; P=0.43) and death (HR, 1.59; 95% CI, 0.06–45.66; P=0.79) were also similar in both groups. CONCLUSION: Tibolone has no adverse effect on the survival of cervical AC patients and can be administered safely to this population. These findings may be helpful in improving the quality of life of cervical AC patients.

Calidad de vida en posmenopáusicas tratadas con tibolona / Quality of life in postmenopausal women treated with tibolone

Comparar la calidad de vida (CV) en mujeres posmenopáusicas antes y después del tratamiento con Tibolona atendidas en la consulta ginecológica de la Maternidad "Dr. Armando Castillo Plaza", Maracaibo, Venezuela. Métodos: Investigación comparativa y aplicada, con diseño no experimental, y prospectivo, que incluyo una muestra de 100 pacientes posmenopáusicas, evaluadas antes y después de 6 y 12 meses de recibir la terapia de reemplazo hormonal con Tibolona oral (2,5mg/día) por medio del cuestionario Menopause Rating Scale (MRS).Resultados: 94 mujeres completaron el protocolo de estudio, determinándose que antes de comenzar el tratamiento la mayoría presentaba síntomas somáticos, psicológicos y genitourinarios severos, mientras que al cabo de 12 meses de tratamiento hubo una mejoría significativa en todos los síntomas estudiados (P= 0.000). Asimismo, se evidenció una mejora significativa en la CV luego del tratamiento con Tibolona, expresada por una regresión de las mediasen las puntuaciones alcanzadas con el MRS entre la medición inicial, a los 6 y a los 12 meses; con un porcentaje de cambio en la CV de las pacientes participantes de -38,33% y -82.20% después de 6 y 12 meses de la intervención farmacológica, los cuales resultaron de relevancia clínica y significancia estadística (P= 0.000). Conclusión: La terapia hormonal sustitutiva con Tibolona mejora la CV de las pacientes posmenopáusicas en todas sus dimensiones, sobre todo en cuanto a la disminución de los síntomas somáticos.Palabras clave: calidad de vida, menopausia, terapia de reemplazo hormonal, tibolona(AU)

To compare the quality of life (QOL) in postmenopausal women before and after treatment with Tibolone attending at the gynaecological consultation in the "Maternidad Dr. Armando Castillo Plaza", Maracaibo, Venezuela. Methods: Comparative and applied research with quasi experimental and prospective design, which included a sample of 100 postmenopausal women, evaluated before and after 6 and 12 months receiving hormone replacement therapy with oral Tibolone (2,5mg/day) through the questionnaire Menopause Rating Scale (MRS). Results: 94 women completed the study protocol, it was found that before treatment the majority had most somatic, psychological and severe genitourinary, while after 12 months of treatment there was a significant improvement in all symptoms studied (P = 0.000 .) We also demonstrated a significant improvement in QOL after treatment with Tibolone, expressed by a regression of the means of the scores obtained with the MRS between the initial measurement, at 6 and 12 months, with a percentage change in the CV of the patients participating -38.33% -82.20% and after 6 and 12 months of pharmacological intervention, which were of clinical relevance and statistical significance (P = 0.000). Conclusion: Hormone replacement therapy with Tibolone improves QOL of the postmenopausal patients in all its dimensions, especially in terms of reduction in somatic symptoms(AU)

Tibolone combined with alendronate on curative effect of osteoporosis of women in perimenopausal and postmenopausal women / 中国生化药物杂志

Objective To study the analysis of tibolone combined with alendronate on curative effect of osteoporosis of women in perimenopausal and postmenopausal women. Methods 126 cases of perimenopausal and postmenopausal women with osteoporosis were selected from April 2015 to October 2016 in our hospital. The subjects were randomly divided into the control group and the experimental group, with 63 patients in each group. The control group were treated with oral compound amino acid chelated calcium treatment, the patients in the experimental group of tibolone combined with alendronate sodium. The treatment time of the experimental group and the control group was in December. The therapeutic effects of the experimental group and the control group were compared and analyzed. Results After the corresponding treatment, 63 patients in the experimental group, 16 patients were invalid, and 47 patients were effective. Of the 63 patients in the control group, 58 patients were ineffective, and 5 patients were treated effectively. The effective rate of treatment in the experimental group (92.1%) was significantly higher than that in the control group (74.6%), with statistical difference (P<0.05). In the experimental group, 4 patients had side effects, and 3 cases in the control group had side effects. There was no significant difference in the incidence of adverse reactions between the two groups, and there was no statistical difference. Conclusion Tibolone combined with alendronate sodium in the treatment of the clinical effect of women with osteoporosis in perimenopausal and postmenopausal women, high treatment efficiency, high safety, has clinical significance.

Clinical efficacy of Kuntai capsules combined with tibolone for treating menopausal syndrome / 中国生化药物杂志

Objective To investigate the efficacy of Kuntai capsules combined with tibolone in treating menopausal syndrome. Methods 80 cases of gynaecology patients from January 2014 to December 2016 were selected and randomly divided into the treatment group and the control group, 40 cases in each group. The treatment group was given Kuntai capsules combined with tibolone, the control group was given tibolone. Results After treatment,the Kupperman scores of the two groups were better than before treatment (P<0.05), the total effective of the treatment group was significantly higher than that of the control group (P<0.05). The number of women who reduced dosage of tibolone in the treatment group was more than in the control group (P<0.05). Conclusion Kuntai capsules combined with tibolone is better in treating menopausal syndrome than tibolone treatment.

Influence of tibolone on postoperative effect of osteoporosis patients with bone cementless type artificial total hip replacement / 中国基层医药

Objective To discuss the influence of tibolone on near and long-term postoperative effect of osteoporosis patients with bone cementless type artificial total hip replacement effect.Methods 136 patients with hip fracture by bone cementless type artificial total hip replacement were selected.According to the situation of osteoporosis,all patients were divided into osteoporosis group and control group.The osteoporosis group received tibolone treatment,followed up for 12 weeks.The intraoperative blood loss,operating time were analyzed.Enzyme-linked immunosorbent assay was used to determine serum bone alkaline phosphatase(sBAP),osteocalcin(sOC),C-terminal peptide collagen cross-linking Ⅰ type(sCTx).Harris hip score was applicated to evaluate hip function.Before and after treatment,lumbar vertebra bone mineral density(BMD) was detected by dual-energy X-ray absorption metry method.Results The intraoperative blood loss,operating time between the two groups had no significant differences(all P>0.05).The serum sBAP and sOC levels of the osteoporosis group were (28.41±6.13)U/L,(22.74±5.87)g/L,which were significantly lower than those of the control group[(35.18±7.21) U/L,(27.42±6.38)g/L],the serum sCTx level[(0.56±0.21)ng/mL]was higher than that of the control group[(0.42±0.11)ng/mL].The differences were statistically significant(tsBAP=5.36,tsOC=6.62,tsCTx=6.71,all P0.05).Conclusion The type of bone cement after total hip arthroplasty patients with osteoporosis bone metabolism and bone mineral density in osteoporosis patients are poor in the hip joint function recovery is poorer,postoperatively for drug resistance to osteoporosis treatment can effectively avoid further loss of bone mass,it is worthy of further clinical promotion.

Tibolone combined with alendronate on curative effect of osteoporosis of women in perimenopausal and postmenopausal women / 中国生化药物杂志

Objective To study the analysis of tibolone combined with alendronate on curative effect of osteoporosis of women in perimenopausal and postmenopausal women. Methods 126 cases of perimenopausal and postmenopausal women with osteoporosis were selected from April 2015 to October 2016 in our hospital. The subjects were randomly divided into the control group and the experimental group, with 63 patients in each group. The control group were treated with oral compound amino acid chelated calcium treatment, the patients in the experimental group of tibolone combined with alendronate sodium. The treatment time of the experimental group and the control group was in December. The therapeutic effects of the experimental group and the control group were compared and analyzed. Results After the corresponding treatment, 63 patients in the experimental group, 16 patients were invalid, and 47 patients were effective. Of the 63 patients in the control group, 58 patients were ineffective, and 5 patients were treated effectively. The effective rate of treatment in the experimental group (92.1%) was significantly higher than that in the control group (74.6%), with statistical difference (P<0.05). In the experimental group, 4 patients had side effects, and 3 cases in the control group had side effects. There was no significant difference in the incidence of adverse reactions between the two groups, and there was no statistical difference. Conclusion Tibolone combined with alendronate sodium in the treatment of the clinical effect of women with osteoporosis in perimenopausal and postmenopausal women, high treatment efficiency, high safety, has clinical significance.

Clinical efficacy of Kuntai capsules combined with tibolone for treating menopausal syndrome / 中国生化药物杂志

Objective To investigate the efficacy of Kuntai capsules combined with tibolone in treating menopausal syndrome. Methods 80 cases of gynaecology patients from January 2014 to December 2016 were selected and randomly divided into the treatment group and the control group, 40 cases in each group. The treatment group was given Kuntai capsules combined with tibolone, the control group was given tibolone. Results After treatment,the Kupperman scores of the two groups were better than before treatment (P<0.05), the total effective of the treatment group was significantly higher than that of the control group (P<0.05). The number of women who reduced dosage of tibolone in the treatment group was more than in the control group (P<0.05). Conclusion Kuntai capsules combined with tibolone is better in treating menopausal syndrome than tibolone treatment.

Solubility and dissolution studies of tibolone polymorphs

ABSTRACT Different solid forms of an active pharmaceutical ingredient can have distinct chemical and physical characteristics. In this work, we studied the solubility and dissolution properties of the described tibolone polymorphic forms (I and II). Both forms were successively recrystallized and characterized by powder X-ray diffraction and attenuated total reflection infrared spectroscopy. Equilibrium solubility and dissolution profiles were performed for both forms. Solubility studies demonstrated that form II is statistically more soluble in water, 0.01 mol L-1 HCl and pH 4.5 acetate buffer. The solubility of forms I and II were explained in terms of crystal packing. Dissolution tests of tablets showed a lower release of polymorphic form II than form I from tablets. The results showed an impact of polymorphism on the quality of tibolone tablets and suggest that tibolone forms I and II can show distinct interactions with pharmaceutical excipients used in tablets. Therefore, only form I is acceptable for the preparation of tablet forms. Based on our results, we propose the quality control on tibolone raw materials using X-ray diffraction analysis and attenuated total reflection infrared spectroscopy.

Systematic Review of Efficacy of Tibolone Tablet in the Treatment of Senile Vaginitis / 中国药房

OBJECTIVE:To systematically review the clinical efficacy of Tibolone tablet in the treatment of senile vaginitis, and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,Medline,CJFD,CBM,VIP and Wangfang Database,randomized controlled trials(RCT)about Tibolone tablet in the treatment of senile vaginitis were collct-ed. Meta-analysis was performed by using Rev Man 5.2 software after data extract and quality evaluation. RESULTS:Totally 10 RCTs were enrolled,involving 909 patients. Results of Meta-analysis showed Tibolone tablet can significantly improve the cure rate of senile vaginitis [RR=1.46,95%CI(1.32,1.61),P<0.001],maturation vaginal cell index score [SMD=1.83,95%CI(1.65, 2.01),P<0.001] and vaginal health score [SMD=1.56,95%CI(1.21,1.92),P<0.001],reduce recurrence rate [RR=0.07,95%CI (0.02,0.18),P<0.001] and vaginitis score [SMD=-1.44,95%CI(-1.79,-1.08),P<0.001]. CONCLUSIONS:Tibolone tablet has good clinical efficacy in the treatment of senile vaginitis,it can improve the vaginal mucosa estrogen and vaginal environment, reduce recurrence rate.

Efeitos da tibolona sobre o parênquima mamário: estudo experimental / Effects of tibolone on the breast parenchyma: experimental study

OBJETIVO: Avaliar o efeito da terapia hormonal com tibolona, em três períodos de tempo diferentes, sobre o tecido mamário de ratas castradas. MÉTODO: Foram utilizadas 60 ratas Wistar adultas e virgens, submetidas à ooforectomia. Após 21 dias de pós-operatório (PO), confirmado o hipoestrogenismo, os animais foram divididos aleatoriamente em 6 grupos: tibolona 1 (n=10) recebeu tibolona 1 mg/dia por 23 dias, tibolona 2 (n=10), por 59 dias, tibolona 3 (n=10), por 118 dias; os subgrupos controle 1 (n=8), controle 2 (n=7) e controle 3 (n=10) receberam a água destilada por 23, 59 e 118 dias, respectivamente. Após o tratamento, foram ressecados seis pares de mamas, destinados à análise histológica pela coloração de hematoxilina e eosina (HE); o procedimento seguiu de eutanásia. Os parâmetros histológicos avaliados foram: hiperplasia epitelial e atividade secretora (AS). As variáveis foram submetidas à análise estatística, adotando-se como significante p<0,05. RESULTADOS: Foram observadas alterações histológicas em 20/55 ratas, sendo: hiperplasia epitelial leve (HEB1) em 7/55, hiperplasia epitelial moderada (HEB2) em 5/55, hiperplasia alvéolo-nodular (HAN) em 7/55, atipia sem proliferação epitelial em 1/55, não sendo encontrada hiperplasia severa (HEB3). Encontrou-se AS em 31/55 das ratas. A AS foi significativamente maior no grupo tibolona (T), em todos os tempos avaliados (p=0,001). As alterações histológicas analisadas não foram significantes comparando (p>0,05) os grupos controle (C) e T. A variável tempo de exposição à droga não apresentou significância, quando comparados os três períodos avaliados. CONCLUSÃO: Não foi verificada relação entre as alterações histológicas e a terapêutica com tibolona em curto, médio e longo prazo. .

OBJECTIVE: To assess the effect of tibolone on mammary tissue of castrated rats over 3 different periods of time. METHODS: Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days after surgery, with hypoestrogenism confirmed, the experimental rats were randomly assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days, tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for 23, 59 and 118 days, respectively. After treatment, all six pairs of mammary glands were removed and stained with hematoxylin and eosin (HE) for histological analysis after euthanasia. The histological parameters evaluated were: epithelial cell proliferation and secretory activity. The variables were analyzed statistically, with the level of significance set at 0.05. RESULTS: Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in 7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in 7/55, atypia without epithelial proliferation in 1/55, and no cases of severe epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats. The secretory activity was significantly higher in the tibolone groups compared to control at all the time points assessed (p=0,001). The histological changes were did not show significance when the control and tibolone groups were compared. The time of exposure to tibolone did not show significance when the three different periods of evaluation were compared. CONCLUSION: No relation between histological modification and tibolone treatment was verified after short-, medium- and long-term treatment. .

Alternatives to Hormone Replacement Therapy in Postmenopausal Women.

Substantial number of postmenopausal women suffers in silence. They experience vasomotor symptoms, sleep disturbances, atrophic changes in the genital and urinary systems and lack of sexual desire. The fear, side effects and contra indications of oestrogen discourage hormone replacement therapy. Life style modification with change in dietary habit, regular exercise, cessation of alcohol and smoking can help them immensely. Tibolone, Selective oestrogen receptor modulators (SERMs), Antidepressants like Venlafaxine, th Alpha 2 agonists like clonidine, carbapentine and various supplements are frequently prescribed. Available alternatives and their merits are discussed.

Yikunning Granules Combined with Tibolone and Paroxetine in the Treatment of 75 Cases of Menopausal Syndrome / 中国药师

Objective:To explore the clinical effect and safety of Yikunning granules combined with tibolone and paroxetine in the treatment of female patients with menopausal syndrome. Methods:Totally 150 female patients with menopausal syndrome were randomly divided into the control group (75 cases) and the study group (75 cases). The control group was orally given tibolone (2. 5mg,po,qd) and paroxetine tablets (20mg,po,qd), and the study group was treated with Yikunning granules additionally (3g,po,tid). After 3-month treatment, the modified Kupperman score was used to evaluate the clinical symptoms, radioimmunoassay was used to detect the serum lev-els of estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and progesterone (P), and the adverse reactions were recorded. Results:After the treatment, most of the indices in the modified Kupperman score were improved in the two groups (P0. 05). The improvement of E2, LH and FSH in the study group was better than that in the control group (P<0. 05). There was no significant difference in the adverse reactions between the two groups (P<0. 05). Conclusion:Yikunning granules combined with tibolone and paroxetine show good effectiveness in the treatment of menopausal syndrome with improved clinical symptom and sex hormone levels, which is worthy of promotion.

The Effect of Conventional Hormone Therapy and Tibolone on Tear Composition and Function in Postmenopausal Women.

Objective: To compare the effects of conventional hormonal therapy (HT) and tibolone on tear composition and tear function. Material and methods: Prospective randomized study in 60 postmenopausal women who received conventional HT versus tibolone for postmenopausal symptoms. Response assessed on Kupperman index, eye symptoms and qualitative and quantitative tests for tears at six months follow-up. Quantitative data analyzed using Student’s t-test, ANOVA test, Fisher’s exact test and qualitative data by using McNemar-Bowker test with Bonferroni correlation and Kappa test. Results: There was a significant improvement in the mean Kupperman scores with conventional HT and tibolone (p < 0.01). Tibolone effectively reduced foreign body sensation but there was no appreciable change in other eye symptoms with both therapies. P value did not show any significant change in quantitative tests (Schirmer’s I and II) and qualitative tests (break-up time) for tear secretion. Tear immunoglobulin A level was significantly elevated with both therapies. Conclusion: Conventional HT or tibolone did not have any significant beneficial effect on tear composition and tear function. A larger study can be undertaken using systemic or topical estrogen or androgen containing preparation for further evaluation for dry eye symptoms.

Efeito da tibolona na morfologia do músculo esquelético, nas enzimas hepáticas e no nível sérico de glicose em ratas castradas / Effect of tibolone on the morphology of skeletal muscle, liver enzymes and blood glucose level in castrated female rats

INTRODUÇÃO: O fígado é uma estrutura de elevada complexidade e é fundamental entender como determinadas substâncias podem afetar sua estrutura e suas funções. OBJETIVO: Analisar a influência da tibolona no metabolismo hepático por meio da avaliação de enzimas e metabólitos comumente utilizados em provas de função hepática. MÉTODOS: Foram utilizadas dez ratas Wistar, divididas em dois grupos: controle (n = 4) e tibolona (n = 6), em status de menopausa cirúrgica. A tibolona (1 mg) foi administrada diariamente por gavagem durante 20 semanas, com avaliação periódica do peso corporal. Após sedação, efetuou-se coleta de sangue para avaliação bioquímica de albumina (Alb) sérica, fosfatase alcalina (FA), transaminases (aspartato aminotransferase e alanina aminotransferase [AST/ALT]), gama-glutamiltranspeptidase (GGT) e glicose, mediante espectrofotometria. O músculo esquelético da coxa foi avaliado por histomorfometria em cortes histológicos corados com hematoxilina e eosina (HE). RESULTADOS: Os animais do grupo tibolona mostraram menor peso corporal, alterações musculares esqueléticas e discretas alterações bioquímicas. Além disso, AST e FA estavam diminuídas e GGT estava mais elevada, porém sem significância estatística. A histomorfometria do músculo revelou uma tendência de menor volume celular nesse grupo. CONCLUSÃO: A tibolona, administrada em alta dose e por tempo prolongado, não interfere de forma significativa nas funções metabólicas e de síntese hepáticas, bem como na permeabilidade da membrana celular, entretanto parece modular a expressão genômica da GGT. A tibolona apresenta influência sistêmica associada a menor peso e diminuição da massa muscular e aumento significativo no peso relativo do fígado, além de alteração da glicogenólise hepática e muscular, da gliconeogênese hepática e dos níveis de glicose circulante.

INTRODUCTION: The liver is a highly complex structure and it is essential to understand how certain substances may affect its structure and functions. OBJECTIVE: Analyze the influence of tibolone on hepatic metabolism by assessing metabolites and enzymes commonly used in liver function tests. METHODS: Ten Wistar rats in surgical menopausal status were divided into two groups: control (n = 4) and tibolone (n = 6). Tibolone (1 mg) was administered by gavage daily for 20 weeks and body weight was periodically assessed. After sedation, blood sampling was performed for biochemical evaluation of serum albumin (Alb), alkaline phosphatase (ALP), transaminases (aspartat aminotranferase and alanine aminotranferase [AST/ALT]), gamma glutamyltranspeptidase (GGT) and glucose by spectrophotometry. Hematoxylin and eosin-stained histological sections of the skeletal thigh muscle were assessed by histomorphometry. RESULTS: The animals in the tibolone group showed lower body weight, skeletal muscle alterations and slight biochemical changes. In the tibolone group, AST and ALP were decreased GGT was higher, but without a statistically significant difference. The muscle histomorphometry showed that the tibolone group tended to present a lower cell volume. CONCLUSION: Tibolone administered in high doses and for a prolonged period does not interfere significantly neither with liver metabolic functions nor liver synthesis, nor with cell membrane permeability. However, it seems to modulate the genomic expression of GGT. Tibolone has systemic influence on lower body weight, reduced muscle mass, and significant increase in relative liver weight. Additionally, liver and muscular glycogenolysis, liver gluconeogenesis and circulating glucose levels are altered.

The Effect of Tibolone and Estradiol-based Hormone Therapy on Bone Mineral Density and Serum Lipid Profiles / 대한골다공증학회지

OBJECTIVES: To investigate the differences between the effect of tibolone and estradiol (E2)-based hormone therapy (HT) on bone mineral density (BMD) and serum lipid profiles in postmenopausal Korean women. MATERIALS AND METHODS: A retrospective study was conducted with 65 postmenopausal women receiving tibolone or E2-based hormone therapy in university hospital. BMD at lumbar spine (LS) and proximal femur was measured before and after 1 year of therapy and serum total cholesterol, triglyceride (TG) and high-density lipoprotein (HDL) was determined by enzymatic methods. RESULTS: BMD at LS increased after 1 year of tibolone (mean change: 3.0%) or E2-based HT (mean change: 1.6%), and the changes were significant (P=0.002 and 0.04, respectively). In E2 group, serum total cholesterol has decreased significantly after 1 year of therapy (P=0.02). Moreover, the change of HDL level was statistically significant in tibolone group compared to E2 group (P=0.01). The changes of levels of total cholesterol, TG and HDL has demonstrated negative relationship of BMD changes at femur neck and trochanter in tibolone group, whereas only the HDL changes were significantly related to the change of trochanter BMD in E2 group. CONCLUSIONS: Both tibolone and E2-based hormone therapy increased BMD at lumbar spine. The changes of serum lipid levels may be associated with the BMD changes in both groups although the relationships were different according to the regimen.

Avaliação do glicogênio hepático correlacionado com glicose sérica em ratas castradas sob tratamento com tibolona / Evaluation of hepatic glycogen correlated with serum glucose in castrated rats under tibolone treatment

INTRODUÇÃO: O glicogênio representa a forma de armazenamento de açúcares na célula animal, sendo estocada naturalmente no hepatócito. Em sua dinâmica metabólica ocorre participação de receptores, hormônios e enzimas que mantêm e equilibram os níveis séricos desse componente. OBJETIVO: O presente estudo investigou a influência da tibolona no metabolismo glicídico hepático por meio de avaliação da presença do glicogênio hepático e níveis séricos de glicose. MATERIAL E MÉTODOS: Utilizamos ao todo 14 ratas Wistar, em menopausa cirúrgica comprovada citologicamente, tratadas diariamente com tibolona (n = 9) ou com placebo (n = 5) durante 20 semanas. Efetuou-se avaliação dos pesos do animal e do fígado e dos níveis de glicose sérica. O estudo morfológico foi realizado em cortes histológicos de tecido hepático, corados com hematoxilina e eosina (HE) e com ácido periódico de Schiff (PAS), com e sem amilase salivar. Para avaliação do glicogênio no fígado, utilizou-se grade de estudo morfológico (GEM), que delineia as regiões metabólicas e circulatórias do lóbulo hepático. RESULTADOS: O peso dos animais foi menor no Grupo Tibolona, com glicose sérica em níveis mais baixos; já o peso relativo do fígado foi significativamente maior (p < 0,001). No Grupo Controle o glicogênio apresentou distribuição heterogênea em três diferentes padrões e o Grupo Tibolona mostrou glicogênio uniforme em toda a estrutura lobular. CONCLUSÃO: A tibolona, administrada em alta dose e por tempo prolongado, determina perda de peso por deficiência alimentar, que leva a alterações nas funções hepáticas, podendo influir na glicogenólise e na gliconeogênese, com modificações do glicogênio hepático e da glicose circulante.

INTRODUCTION: Glycogen serves as glucose storage in animals and it is naturally found in hepatocytes. Receptors, hormones and enzymes, which maintain and balance serum levels of this component, participate in its metabolic dynamics. OBJECTIVE: This study investigated the influence of tibolone on the hepatic glycemic metabolism by assessing the presence of liver glycogen and serum glucose. MATERIAL AND METHODS: Fourteen castrated Wistar rats, cytologically validated as surgical menopause models, were treated with tibolone (n = 9) or placebo (n = 5) for 20 weeks. Their body and liver weight and serum glucose levels were assessed. The morphologic study was performed in histological sections of liver tissue stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS), with and without salivary amylase. For liver glycogen analysis, a morphological study grid (MSG), which outlines the metabolic and circulatory areas in the liver lobule, was applied. RESULTS: The animals' weight was lower in the Tibolone Group, with serum glucose at lower levels, whereas the relative liver weight was significantly higher (p < 0.001). The Control Group showed heterogeneous glycogen distribution in three different patterns. The Tibolone Group presented uniform glycogen throughout the lobular structure. CONCLUSION:Tibolone administration in high doses and for a long period determines weight loss by dietary deficiency, which leads to liver function changes. Thus, it may affect glycogenolysis and gluconeogenesis with changes in liver glycogen and circulating glucose.