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1.
J Chin Med Assoc ; 87(2): 189-195, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37882059

ABSTRACT

BACKGROUND: The objective was to elucidate the effect of tibolone vs hormone replacement therapy (HRT) on climacteric symptoms and psychological distress. METHODS: All consecutive women with climacteric symptoms were allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) plus medroxyprogesterone acetate (2.5 mg). RESULTS: The improvement in "feeling dizzy or faint" after tibolone treatment was more prominent than that after HRT (-0.7 ± 0.8 vs -0.0 ± 0.9, p = 0.004). In addition, other climacteric symptoms, including anxiety, depression, somatic symptoms, and vasomotor symptoms, and sexual function improved after tibolone and HRT, but there were no between-group differences. Psychological distress assessment demonstrated that somatic complaints, obsessive-compulsive symptoms, depressive symptoms, hostility, additional symptoms, and the General Symptom Index improved after tibolone treatment and HRT, but there were no between-group differences. Personality traits assessment revealed that neuroticism improved after tibolone treatment. CONCLUSION: Tibolone seems more beneficial than HRT in treating symptoms of dizziness and faintness. Both tibolone and HRT could improve psychological distress.


Subject(s)
Climacteric , Estrogen Replacement Therapy , Female , Humans , Norpregnenes/therapeutic use , Norpregnenes/pharmacology , Hormone Replacement Therapy , Estradiol
2.
J Neuroendocrinol ; 34(1): e13078, 2022 01.
Article in English | MEDLINE | ID: mdl-34961984

ABSTRACT

Multiple sclerosis (MS) is an immune-mediated and degenerating disease in which myelin sheaths are damaged as a result of chronic progressive inflammation of the central nervous system. Tibolone [(7α,17α)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-in-3-one], a synthetic estrogenic compound with tissue-specific actions and used for menopausal hormone therapy, shows neuroprotective and antioxidant properties both in vivo and in vitro. In the present study, we analyzed whether tibolone plays a therapeutic role in experimental autoimmune encephalomyelitis (EAE) mice, a commonly used model of MS. Female C57BL/6 mice were induced with the myelin oligodendrocyte glycoprotein MOG35-55 and received s.c. tibolone (0.08 mg kg-1 ) injection every other day from the day of induction until death on the acute phase of the disease. Reactive gliosis, Toll like receptor 4 (TLR4), high mobility group box protein 1 (HMGB1), inflammasome parameters, activated Akt levels and myelin were assessed by a real-time polymerase chain reaction, immunohistochemistry, and western blot analysis. Our findings indicated that, in the EAE spinal cord, tibolone reversed the astrocytic and microglial reaction, and reduced the hyperexpression of TLR4 and HMGB1, as well as NLR family pyrin domain containing 3-caspase 1-interleukin-1ß inflammasome activation. At the same time, tibolone attenuated the Akt/nuclear factor kappa B pathway and limited the white matter demyelination area. Estrogen receptor expression was unaltered with tibolone treatment. Clinically, tibolone improved neurological symptoms without uterine compromise. Overall, our data suggest that tibolone may serve as a promising agent for the attenuation of MS-related inflammation.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Neuritis/prevention & control , Norpregnenes/therapeutic use , Animals , Disease Models, Animal , Disease Progression , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Inflammation/pathology , Inflammation/prevention & control , Mice , Mice, Inbred C57BL , Neuritis/pathology , Neuroprotective Agents/therapeutic use , Remission Induction
3.
Biomed Pharmacother ; 140: 111769, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34058440

ABSTRACT

Traumatic brain injury (TBI) is characterized by a complex network of signals mediating inflammatory, proliferative and apoptotic processes during its acute and chronic phases. Current therapies mitigate damage and are mainly for palliative care and there are currently no effective therapies for secondary damage. This suggests a need to discover a compound with a greater spectrum of action that can control various pathological aspects of TBI. Here we used a network pharmacology approach to explore the benefits of tibolone, an estrogen and androgen receptor agonist with broader actions in cells, as a possible repurposing drug for TBI therapy. Using different databases we retrieved the targets significantly associated to TBI and tibolone, obtaining 2700 and 652, respectively. The top 10 GO enriched terms were mostly related to cell proliferation, apoptosis and inflammation. Following protein-protein functional analysis, the top connected proteins were related to kinase activity (MAPK1/14/3, AKT1 PIK3R1), apoptosis (TP53, CASP3), growth factors (EGFR), estrogen signalling (ESR1) and inflammation (IL6, TNF), with IL6 as an important signalling hub belonging to the top GO categories. Thus, we identified IL6 as a cellular node which we then validated using molecular mechanics-generalized born surface area (MMGBSA) and docking to explore which tibolone metabolite might interact with this protein. Both 3α and 3ß-OH tibolone seemed to bind better to IL6 at important sites responsible for its binding to IL6R. In conclusion, our study demonstrates key hubs involved in TBI pathology which indicates IL6 as a target molecule of tibolone as drug repurposing for TBI therapy.


Subject(s)
Brain Injuries, Traumatic/metabolism , Interleukin-6/metabolism , Norpregnenes/pharmacology , Brain Injuries, Traumatic/drug therapy , Drug Repositioning , Molecular Docking Simulation , Norpregnenes/therapeutic use , Protein Interaction Maps
4.
Pharmacol Res ; 169: 105612, 2021 07.
Article in English | MEDLINE | ID: mdl-33865986

ABSTRACT

Inconsistencies exist with regard to influence of tibolone treatment on the lipid profile. The reasons for these inconsistencies might derive from several factors, i.e., differences in baseline variables, intervention duration, participants' health status or baseline body mass index (BMI). To address these inconsistencies, based on a systematic search in Scopus, PubMed/Medline, Web of Science, and Embase for papers published until 21 December 2020, we conducted the current dose-response meta-analysis of randomized controlled trials (RCTs) to determine the impact of tibolone treatment on the lipid profile. The overall findings were derived from 26 RCTs. Tibolone administration decreased total cholesterol (TC) (weighted mean difference, WMD: -18.55 mg/dL, CI: -25.95 to -11.16, P < 0.001), high-density lipoprotein-cholesterol (HDL-C) (WMD: -9.42 mg/dL, CI: -11.83 to -7.01, P < 0.001) and triglyceride (TG) (WMD: -21.43 mg/dL, CI: -27.15 to -15.70, P < 0.001) levels. A significant reduction in LDL-C occurred when tibolone was prescribed for ≤ 26 weeks (WMD: -7.64 mg/dL, 95% CI: -14.58 to -0.70, P = 0.031) versus > 26 weeks (WMD: -8.84 mg/dL, 95% CI: -29.98, 12.29, P = 0.412). The decrease in TG (WMD: -22.64 mg/dL) and TC (-18.55 mg/dL) concentrations was more pronounced in patients with BMI ≥ 25 kg/m2versus BMI < 25 kg/m2. This systematic review and meta-analysis discovered that tibolone decreases TC, HDL-C and TG levels. LDL-C concentrations are significantly reduced when tibolone administration lasts for ≤ 26 weeks.


Subject(s)
Lipids/blood , Norpregnenes/adverse effects , Dose-Response Relationship, Drug , Estrogen Replacement Therapy/adverse effects , Female , Humans , Norpregnenes/pharmacology , Norpregnenes/therapeutic use , Randomized Controlled Trials as Topic
5.
Gynecol Obstet Invest ; 86(1-2): 170-176, 2021.
Article in English | MEDLINE | ID: mdl-33849018

ABSTRACT

OBJECTIVES: Up to 32% of women experience anatomic recurrence after conservative surgery for endometriomas, while pain recurs in 10-40% of cases. Long-term postoperative hormonal therapy is recommended to prevent disease recurrence. We evaluated the efficacy of long-term therapy with estroprogestins (EPs) or progestins (Ps) in preventing endometrioma recurrence, as identifiable cysts and subjective symptoms, after laparoscopic excision. DESIGN: This retrospective cohort study included 375 women submitted to laparoscopic endometrioma excision. Women were followed up at 6 and 12 months and then yearly after surgery. Based on postoperative medical therapy, women were divided into 4 groups: nonusers, cyclic EP users, continuous EP users, and progestogen users. Materials, Setting, Methods: Anamnestic and anthropometric characteristics were collected as well as clinical and surgical data. Gynecological examination, and transvaginal and transabdominal ultrasound scans were performed. Pain (numerical rating score >5) and endometrioma recurrence at ultrasound (ovarian cyst with typical sonographic features ≥10 mm in mean diameter) were recorded at each examination. The reoperation rate in women with recurrence was investigated. RESULTS: The median follow-up was 3.7 years with a maximum of 16.7 years. Most patients used EPs (119 cyclic and 61 continuous users), 95 used P, and 100 were nonusers. In 135 women (36%), endometriotic cyst recurrence was diagnosed, with a mean diameter of 18.7 ± 10.8 mm (range 10-55 mm). The median recurrent cyst-free time was 7.9 years (95% CI 5.8-10.8). Dysmenorrhea was the first symptom to reappear, affecting 162 patients (43.2%). Upon multivariable regression analysis, continuous users had a lower risk of relapse (OR 0.56, 95% CI 0.32-0.99), in terms of both cysts and symptom recurrence, than patients who received no medications. The reoperation rate was 16.2%. LIMITATIONS: The main limitation of this study is its retrospective design. Also, women switching therapies throughout the follow-up period were sorted into one of the study groups based on the longest treatment taken, without considering the discontinuation rates. CONCLUSIONS: Long-term EPs, administered in a continuous regimen and starting immediately after conservative surgery for endometriomas, seem to reduce the disease recurrence risk.


Subject(s)
Endometriosis/drug therapy , Ethinyl Estradiol/therapeutic use , Norpregnenes/therapeutic use , Ovarian Diseases/drug therapy , Progestins/therapeutic use , Adult , Cohort Studies , Drug Combinations , Dysmenorrhea , Endometriosis/diagnosis , Endometriosis/surgery , Female , Humans , Laparoscopy , Ovarian Cysts/diagnosis , Ovarian Cysts/drug therapy , Ovarian Cysts/surgery , Ovarian Diseases/diagnosis , Ovarian Diseases/surgery , Postoperative Period , Recurrence , Retrospective Studies , Risk Factors , Ultrasonography
6.
Gynecol Endocrinol ; 37(6): 567-571, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33150798

ABSTRACT

OBJECTIVE: Few studies have examined whether tibolone (TIB), a type of hormone replacement therapy widely used in Asia and Europe, affects dementia risk in postmenopausal women. Our study aims to investigate the association of TIB and dementia risk in Korean women aged 50-80 years. METHODS: A population-based longitudinal study was conducted using the Korean National Health Insurance Service claims database merged with national health examination data from 2002 to 2015. Among 13,110 participants, exposure to TIB was determined using the standardized defined daily dose (DDD) system from 2003 to 2007. Starting from 2007, participants were followed up for overall dementia, Alzheimer's disease (AD) and vascular dementia (VD) until 2015. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of dementia according to TIB use. RESULTS: TIB use was not significantly associated with the risk of total dementia (aHR = 1.040; 95% CI = 0.734-1.472; p = .827), AD (aHR = 0.949; 95% CI = 0.652-1.381; p = .785) and VD (aHR = 1.245; 95% CI = 0.631-2.457; p = .528). CONCLUSIONS: Our results suggest that TIB use does not have a significant association with dementia risk. Further randomized controlled trials are necessary to elucidate the role of exogenous hormones in the development of dementia.


Subject(s)
Dementia/epidemiology , Norpregnenes/therapeutic use , Administrative Claims, Healthcare/statistics & numerical data , Aged , Cohort Studies , Databases, Factual , Dementia/etiology , Estrogen Replacement Therapy/adverse effects , Estrogen Replacement Therapy/statistics & numerical data , Female , Humans , Longitudinal Studies , Middle Aged , Republic of Korea/epidemiology , Risk Factors
8.
Reprod Biol Endocrinol ; 18(1): 28, 2020 Apr 14.
Article in English | MEDLINE | ID: mdl-32290838

ABSTRACT

BACKGROUND: Chronic cyclic pelvic pain (CCPP) affects women's quality of life and pituitary downregulation is often used for symptomatic relief. However, prolonged suppression of ovarian function is associated with menopausal side effects and can lead to osteoporosis. Currently, the use of gonadotropin releasing hormone agonists (GnRHa) for treatment of CCPP is usually restricted to 6-9 months, limiting their efficacy. There is limited information regarding safety and efficacy with longer-term use. The aim of this study is to examine the safety and efficacy of long-term (24 months) pituitary down-regulation with the GnRHa (Triptorelin SR) with add-back therapy (ABT) using Tibolone for symptom relief in women with CCPP. METHODS: A single-arm, prospective clinical trial at a Tertiary University Teaching Hospital of 27 patients receiving Triptorelin SR (11.25 mg) and Tibolone (2.5 mg). Outcomes measures were the safety of treatment assessed by clinical examination, haematological markers, liver and renal function tests and bone mineral density (BMD) at 12, 18 and 24 months as well as at 6 months post-treatment. Pain and health-related quality of life (HR-QoL) assessed using the endometriosis health profile (EHP-30) and chronic pain grade (CPG) questionnaires. RESULTS: There was no evidence for any significant harmful effects on any of the measured haematological, renal or liver function tests. Although results regarding the effect on BMD are not conclusive there is an increased risk of development of osteopaenia after 12 months of treatment. Pain and HRQoL assessments showed significant improvement during medication, but with deterioration after treatment cessation. CONCLUSION: Long- term Triptorelin plus Tibolone add-back therapy in women suffering from CCPP does not appear to be associated with significant serious adverse events apart from the possibility of deterioration in the BMD that needs to be monitored. This mode of therapy appears to be effective in pain relief and in improving quality of life over a 24-month period. TRIAL REGISTRATION: Clinical trials database NCT00735852.


Subject(s)
Chronic Pain/drug therapy , Norpregnenes/therapeutic use , Pelvic Pain/drug therapy , Triptorelin Pamoate/therapeutic use , Adult , Bone Density , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Pain Measurement/methods , Prospective Studies , Quality of Life , Time Factors , Treatment Outcome
9.
BMC Fam Pract ; 21(1): 32, 2020 02 12.
Article in English | MEDLINE | ID: mdl-32050909

ABSTRACT

BACKGROUND: Among Australians aged 50 and over, an estimated 1 in 4 men and 2 in 5 women will experience a minimal trauma fracture during their remaining lifetime. Effective fracture prevention is hindered by substantial undertreatment, even of patients who clearly warrant pharmacological therapy. Poor adherence to osteoporosis treatment is also a leading cause of repeat fractures and hospitalisation. The aim of this study was to identify current osteoporosis treatment patterns and gaps in practice in Australia, using general practice data, and to explore general practitioners' (GPs') attitudes to osteoporosis treatment and their views on patient factors affecting osteoporosis management. METHODS: The study was conducted in two phases. Phase 1 was a longitudinal retrospective cohort study which utilised data from MedicineInsight - a national general practice data program that extracts longitudinal, de-identified patient data from clinical information systems (CISs) of participating general practices. Phase 2 included semi-structured, in-depth telephone interviews with a sample of MedicineInsight practice GPs. Data were analysed using an inductive thematic analysis method informed by the theory of planned behaviour. RESULTS: A diagnosis of osteoporosis was recorded in 12.4% of patients over the age of 50 years seen in general practice. Of those diagnosed with osteoporosis, almost a quarter were not prescribed osteoporosis medicines. From 2012 to 17, there was a progressive increase in the number of denosumab prescriptions, while prescriptions for bisphosphonates and other osteoporosis medicines decreased. More than 80% of patients who ceased denosumab treatment had no subsequent bisphosphonate prescription recorded. Interviews with GPs revealed beliefs and attitudes that may have influenced their intentions towards prescribing and osteoporosis management. CONCLUSIONS: This study suggests that within the Australian general practice setting, osteoporosis is underdiagnosed and undertreated. In addition, it appears that most patients who ceased denosumab treatment had no record of subsequent antiresorptive therapy, which would place them at risk of further fractures. The study supports the need for the development of clinical education programs addressing GP knowledge gaps and attitudes, and the implementation of specific interventions such as good reminder/recall systems to avoid delays in reviewing and treating patients with osteoporosis.


Subject(s)
Attitude of Health Personnel , Bone Density Conservation Agents/therapeutic use , Denosumab/therapeutic use , Diphosphonates/therapeutic use , General Practitioners , Osteoporosis/drug therapy , Osteoporotic Fractures/prevention & control , Practice Patterns, Physicians'/statistics & numerical data , Aged , Aged, 80 and over , Australia , Deprescriptions , Drug Substitution , Female , General Practice , Humans , Longitudinal Studies , Male , Middle Aged , Norpregnenes/therapeutic use , Osteoporosis/diagnosis , Raloxifene Hydrochloride/therapeutic use , Retrospective Studies , Teriparatide/therapeutic use , Thiophenes/therapeutic use
10.
Arch Med Res ; 50(4): 187-196, 2019 05.
Article in English | MEDLINE | ID: mdl-31499479

ABSTRACT

BACKGROUND: Ovarian steroid hormones are involved in modulating the growth of glioblastomas (the most common, aggressive, and lethal brain tumor) through the interaction with their intracellular receptors. Activation of sex hormone receptors is involved in glioblastomas progression. Tibolone (TIB) is a selective tissue estrogenic activity regulator widely prescribed to treat menopausal symptoms and to prevent bone lost. The effects of TIB on the growth of glioblastoma are unknown. AIM OF THE STUDY: To evaluate the effects of TIB on cell number, migration, and invasion of two derived human glioblastoma cell lines (U251 MG and U87), as well as the role of this steroid in estrogen and progesterone receptors activity and content. METHODS: U251-MG and U87 human glioblastoma cell lines were grown with different doses of TIB. The number of cells was determined and migration and invasion tests were carried out. Protein expression was performed by Western blot. RESULTS: We observed that TIB (10 nM) increased the number of cells by inducing proliferation with no effects on cell migration or invasion. The increase in cell proliferation induced by TIB was blocked by estrogen (ERs) or progesterone receptor (PRs) antagonists, ICI 182, 780 and RU 486, suggesting that these receptors mediate proliferating actions of TIB; TIB also modified the content of ERs and PRs by increasing ER-α, ER-ß, and PR-B, while decreased PR-A. CONCLUSION: Our results suggest that TIB increases cell number and proliferation of human glioblastoma cells through the regulation of ERs and PRs actions and content.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Estrogen Receptor alpha/metabolism , Glioblastoma/drug therapy , Norpregnenes/therapeutic use , Receptors, Progesterone/metabolism , Antineoplastic Agents, Hormonal/pharmacology , Cell Line, Tumor , Female , Glioblastoma/pathology , Humans , Norpregnenes/pharmacology
11.
Cas Lek Cesk ; 158(3-4): 107-111, 2019.
Article in English | MEDLINE | ID: mdl-31416316

ABSTRACT

Tibolon is the only therapeutic approach to climacteric symptoms, prevention of osteoporosis and urogenital atrophy with the same efficacy as hormone replacement therapy. Tibolon has more positive effects on sexuality and mood changes in menopausal women. It decreases the mammographic density. Its safety for breast cancer is the same as for only estrogen therapy and better than for estrogen-gestagen therapy. Tibolon is the first choice for postmenopausal women with mood and sexuality disorders, women with mastodynia and high mammographic density.


Subject(s)
Estrogen Receptor Modulators , Norpregnenes , Osteoporosis , Breast Neoplasms/chemically induced , Climate , Estrogen Receptor Modulators/adverse effects , Estrogen Receptor Modulators/therapeutic use , Estrogens , Female , Humans , Menopause , Norpregnenes/adverse effects , Norpregnenes/therapeutic use , Osteoporosis/prevention & control , Progestins
12.
J Clin Endocrinol Metab ; 104(5): 1595-1622, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30907953

ABSTRACT

OBJECTIVE: The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women. CONCLUSIONS: Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations. A consensus by the Writing Committee members was achieved for four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Denosumab/therapeutic use , Diphosphonates/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Osteoporotic Fractures/prevention & control , Absorptiometry, Photon , Accidental Falls/prevention & control , Calcitonin/therapeutic use , Calcium/therapeutic use , Clinical Decision-Making , Estrogen Receptor Modulators/therapeutic use , Estrogen Replacement Therapy , Female , Humans , Norpregnenes/therapeutic use , Osteoporosis, Postmenopausal/diagnostic imaging , Parathyroid Hormone-Related Protein/therapeutic use , Patient Preference , Raloxifene Hydrochloride/therapeutic use , Risk Assessment , Risk Reduction Behavior , Selective Estrogen Receptor Modulators/therapeutic use , Teriparatide/therapeutic use , Vitamin D/therapeutic use
13.
J Clin Endocrinol Metab ; 104(5): 1623-1630, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30907957

ABSTRACT

BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Hip Fractures/prevention & control , Osteoporosis, Postmenopausal/drug therapy , Osteoporotic Fractures/prevention & control , Selective Estrogen Receptor Modulators/therapeutic use , Spinal Fractures/prevention & control , Bone Diseases, Metabolic/drug therapy , Calcitonin/therapeutic use , Estrogen Receptor Modulators/therapeutic use , Estrogen Replacement Therapy , Female , Humans , Network Meta-Analysis , Norpregnenes/therapeutic use , Postmenopause , Vitamin D/therapeutic use
14.
Rev. chil. endocrinol. diabetes ; 12(1): 26-28, 2019. ilus
Article in Spanish | LILACS | ID: biblio-982035

ABSTRACT

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.


Subject(s)
Humans , Female , Uterine Hemorrhage/etiology , Menopause , Estrogen Replacement Therapy/adverse effects , Estrogen Receptor Modulators/adverse effects , Norpregnenes/adverse effects , Polyps/complications , Polyps/diagnosis , Endometrial Neoplasms/complications , Endometrial Neoplasms/diagnosis , Estrogen Receptor Modulators/therapeutic use , Diagnosis, Differential , Endometrial Hyperplasia/complications , Endometrial Hyperplasia/diagnosis , Endometrium/diagnostic imaging , Metrorrhagia/etiology , Norpregnenes/therapeutic use
15.
Expert Opin Pharmacother ; 19(10): 1109-1125, 2018 07.
Article in English | MEDLINE | ID: mdl-29975553

ABSTRACT

INTRODUCTION: Pharmacotherapy has a pivotal role in the management of endometriosis with long-term treatments balancing clinical efficacy (control of pain symptoms and prevention of recurrence of the disease after surgery) with an acceptable safety profile. Treatment choice is based on several factors including age and patient preference, reproductive plans, intensity of pain, severity of disease and incidence of adverse effects. AREAS COVERED: The aim of this review is to provide the reader with a complete overview of drugs that are currently available or are under investigation for the treatment of endometriosis highlighting on-going clinical trials. EXPERT OPINION: Almost all of the available treatment options for endometriosis suppress ovarian function and are not curative. Combined oral contraceptives and progestins are commonly administered to these patients in order to ameliorate pain symptoms. Gonadotropin-releasing hormone-agonists are prescribed when first-line therapies are ineffective, not tolerated or contraindicated. Aromatase inhibitors should be reserved only for women who are refractory to other treatments. Amongst the drugs under development, gonadotropin-releasing hormone antagonists have shown the most promising results. Presently, are a number of potential therapies currently in pre-clinical or early clinical studies which may alter treatment strategies in the future although further studies are necessary.


Subject(s)
Endometriosis/drug therapy , Hormone Antagonists/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aromatase Inhibitors/therapeutic use , Drug Combinations , Endometriosis/pathology , Ethinyl Estradiol/therapeutic use , Female , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Norpregnenes/therapeutic use , Pain Management , Progestins/therapeutic use
16.
J Affect Disord ; 236: 88-92, 2018 08 15.
Article in English | MEDLINE | ID: mdl-29723767

ABSTRACT

BACKGROUND: Many women with no past psychiatric history experience severe mood symptoms for the first time in their life during the menopausal transition, with debilitating long-term consequences. Women with a history of depression can experience a relapse or worsening of symptoms during the menopause transition. Traditional antidepressants, SSRIs or SNRIs, are commonly prescribed as the first line response. However, such treatment has shown only small improvements with side effects. Hormone therapies directly targeting the perimenopausal fluctuations in reproductive hormonal systems such as tibolone, have significant potential to treat perimenopausal depression. Our study investigated the use of adjunctive tibolone, selective tissue estrogenic activity regulator, to treat de-novo or relapsing depression occurring during the menopause transition period. METHODS: Women who were going through the menopause transition with depressive symptoms were invited to participate in a double-blind, 12 week randomized control trial with two arms: tibolone (2.5 mg oral/day) or oral placebo (NCT01470092). Forty-four women met inclusion/exclusion criteria; 22 were randomized to tibolone and 22 were randomized to oral placebo. Symptoms were measured with the 'Montgomery- Asberg depression rating scale' (MADRS) as the primary outcome measure. Latent growth curve analysis was used to assess the MADRS scores change over time. RESULTS: Participants in the tibolone group demonstrated a significant improvement in depression scores, as compared to the placebo group, without any significant side effects. LIMITATIONS: This trial only monitored tibolone's effects over 12 weeks. Future research should be conducted over an extended timeframe and explore whether the benefits of tibolone extend to other symptoms of perimenopausal depression. CONCLUSIONS: The use of hormone therapies such as tibolone provide exciting innovations for the treatment of depression during the menopause transition.


Subject(s)
Depression/drug therapy , Estrogen Receptor Modulators/therapeutic use , Menopause/drug effects , Norpregnenes/therapeutic use , Administration, Oral , Adult , Affect/physiology , Antidepressive Agents/therapeutic use , Double-Blind Method , Female , Humans , Menopause/psychology , Middle Aged , Treatment Outcome
17.
Mol Neurobiol ; 55(11): 8651-8667, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29582398

ABSTRACT

Previous studies have shown that estradiol reduces reactive gliosis after a stab wound injury in the cerebral cortex. Since the therapeutic use of estradiol is limited by its peripheral hormonal effects, it is of interest to determine whether synthetic estrogenic compounds with tissue-specific actions regulate reactive gliosis. Tibolone is a synthetic steroid that is widely used for the treatment of climacteric symptoms and/or the prevention of osteoporosis. In this study, we have assessed the effect of tibolone on reactive gliosis in the cerebral cortex after a stab wound brain injury in ovariectomized adult female mice. By 7 days after brain injury, tibolone reduced the number of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the number of microglial cells with a reactive phenotype in comparison to vehicle-injected animals. These effects on gliosis were associated with a reduction in neuronal loss in the proximity to the wound, suggesting that tibolone exerts beneficial homeostatic actions in the cerebral cortex after an acute brain injury.


Subject(s)
Brain Injuries/drug therapy , Cerebral Cortex/pathology , Gliosis/drug therapy , Neurons/pathology , Norpregnenes/therapeutic use , Wounds, Stab/drug therapy , Animals , Astrocytes/drug effects , Astrocytes/pathology , Brain Injuries/complications , Brain Injuries/pathology , Calcium-Binding Proteins/metabolism , Cell Count , Cell Death/drug effects , DNA-Binding Proteins , Female , Glial Fibrillary Acidic Protein/metabolism , Gliosis/etiology , Gliosis/pathology , Image Processing, Computer-Assisted , Macrophages/drug effects , Macrophages/metabolism , Mice, Inbred C57BL , Microfilament Proteins/metabolism , Microglia/drug effects , Microglia/pathology , Nerve Tissue Proteins/metabolism , Neurons/drug effects , Neurons/metabolism , Norpregnenes/pharmacology , Nuclear Proteins/metabolism , Phenotype , Wounds, Stab/complications , Wounds, Stab/pathology
18.
Gynecol Endocrinol ; 34(5): 394-398, 2018 May.
Article in English | MEDLINE | ID: mdl-29108453

ABSTRACT

Hyperandrogenism is a condition affecting 5-10% of adolescents. The aim of this study was to evaluate the efficacy of very low dose of flutamide in the treatment of hyperandrogenism in adolescence. One hundred and fifty-eight patients, presenting severe acne and/or hirsutism, received 62.5 mg/day of flutamide + ethinylestradiol + gestodene for 18 months. The patients were subjected to assessments of hepatic enzymes levels. Thirty subjects treated with drospirenone + ethinylestradiol represented the control group. After 18 months of treatment, it was obtained a decrease of hirsutism (-39.9%), an almost recovery of acne (98% of patients) with better results of those obtained in control group. Only one case of light hypertransaminasemia was recorded, regressed spontaneously. Very low dose of flutamide was successful and safe and in the treatment of hyperandrogenism in adolescence.


Subject(s)
Acne Vulgaris/drug therapy , Androgen Antagonists/therapeutic use , Flutamide/therapeutic use , Hirsutism/drug therapy , Hyperandrogenism/drug therapy , Adolescent , Androgen Antagonists/administration & dosage , Androstenes/administration & dosage , Androstenes/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/therapeutic use , Female , Flutamide/administration & dosage , Humans , Norpregnenes/administration & dosage , Norpregnenes/therapeutic use , Treatment Outcome , Young Adult
19.
Presse Med ; 46(12 Pt 1): 1199-1211, 2017 Dec.
Article in French | MEDLINE | ID: mdl-29133081

ABSTRACT

CONTEXT: Endometriosis is a chronic painful disease, for which hormone therapy is usually offered as a first line option to women not willing to conceive. OBJECTIVES: To analyse and synthesize the literature, from 2006 onwards, on pain control, and disease evolution in oemn using combined hormonal contraceptives, progestins and GnRH analogs. Data on other current and future treatment perspectives is included as well. SOURCES: Medline (Pubmed), the Cochrane Library, and endometriosis treatment recommendations published by European Society of Human Reproduction and Embryology (ESHRE), National Institute for health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), Royal College of Obstetricians and Gynaecologists (RCOG) and Société des Obstétriciens et Gynécologues du Canada (SOGC). STUDY SELECTION: Meta-analysis and clinical trials are included. RESULTS: Study quality is heterogeneous in general. Hormone therapy inconstantly allows pain relief and prevention of endometrioma and rectovaginal wall nodules recurrence. Available molecules and routes of administration as well as risk benefit balance are evaluated. Data on future perspectives are limited to date and do not allow use in routine. CONCLUSION: Hormonal treatment of endometriosis relies on combined hormonal contraceptives (using different routes of administration), progestins and particularly the levonorgestrel-releasing IUS, and GnRH analogs as a last option, in combination with an add-back therapy. Promising alternatives are currently under preclinical and clinical evaluation.


Subject(s)
Endometriosis/drug therapy , Disease Progression , Drug Combinations , Endometriosis/complications , Ethinyl Estradiol/therapeutic use , Female , Forecasting , Gonadotropin-Releasing Hormone/analogs & derivatives , Humans , Norpregnenes/therapeutic use , Pain Management , Pelvic Pain/drug therapy , Pelvic Pain/etiology , Pelvis , Progestins/therapeutic use
20.
Maturitas ; 99: 27-36, 2017 May.
Article in English | MEDLINE | ID: mdl-28364865

ABSTRACT

OBJECTIVE: Data on the effect of hormone replacement therapy (HRT) and tibolone on lipoprotein (a) [Lp(a)], an independent risk factor for cardiovascular disease, are heterogeneous and conflicting. Studies of the effect of HRT and tibolone on Lp(a) concentrations in post-menopausal women are reviewed in this meta-analysis. DESIGN AND METHODS: MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to February 10, 2017). Two researchers identified randomized controlled studies and extracted data. Potential controversies were resolved by a third reviewer. RESULTS: In 24 eligible studies, HRT caused a significant reduction in Lp(a) concentrations compared with placebo or no treatment [mean relative difference: -20.35%, 95% Confidence Interval (CI): -25.33% to -15.37%, p<0.0001], with significant heterogeneity between studies (I2=98.5%), but without evidence of publication bias. No significant effect was found for tibolone (n=7) (mean relative difference: -23.84%, 95% CI: -63.43% to 15.74%, p=0.238) (I2=98.7%, but without publication bias). Oral estrogen caused a greater reduction in Lp(a) concentrations than transdermal estrogen (n=10) (mean relative difference: 37.66%, 95% CI: 16.84% to 58.48%, p<0.0001), with significant heterogeneity between studies (I2=99%), but no evidence of publication bias. No difference was observed when continuous was compared with cyclical HRT, conventional with low-dose estrogen, and estrogen monotherapy with estrogen combined with progestogen. No difference was observed between HRT and tibolone regarding their effect on Lp(a). CONCLUSIONS: HRT significantly decreases Lp(a) concentrations, with oral being more effective than transdermal estradiol. The type of HRT, dose of estrogen and addition of progestogen do not seem to modify the Lp(a)-lowering effect of HRT.


Subject(s)
Estradiol/therapeutic use , Estrogen Receptor Modulators/therapeutic use , Estrogen Replacement Therapy/methods , Estrogens/therapeutic use , Lipoprotein(a)/blood , Norpregnenes/therapeutic use , Postmenopause/blood , Progestins/therapeutic use , Administration, Cutaneous , Administration, Oral , Cardiovascular Diseases/blood , Female , Humans , Risk Factors
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