RESUMEN

In this case series, we discuss 10 cases of norethindrone-induced transaminitis and conduct a literature review of this rare adverse event. A retrospective chart review was conducted on 10 patients (median age: 33 years) with diverse endometriosis phenotypes who received norethindrone and subsequently developed transaminitis, which is defined as elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels. This condition was diagnosed in both asymptomatic and symptomatic patients, either during the work-up of acute symptoms or incidentally through routine lab tests. Our objective was to assess and characterize a case series of transaminitis associated with norethindrone use in endometriosis patients, detailing clinical presentations, management strategies, and outcomes. All cases exhibited normalization of liver function tests after discontinuation, occurring within one to 12 months with varying intervals of liver function testing. Patients receiving higher dosages (10 mg daily) demonstrated quicker resolution (average: four months). The reported adverse effects included nausea, vomiting, headache, rash, polyarthralgia, and abnormal uterine bleeding. Vigilant management, including prompt discontinuation, consistently resulted in the resolution of transaminitis. This study underscores the importance of continuous monitoring of liver function, even in asymptomatic patients on norethindrone therapy. Further investigations are imperative to identify specific groups susceptible to this adverse event.

RESUMEN

During pregnancy, the primary function of the uterus is to be quiescent and not contract, which allows the growing fetus to develop and mature. A uterine muscle layer, myometrium, is composed of smooth muscle cells (SMCs). Before the onset of labor contractions, the uterine SMCs experience a complex biochemical and molecular transformation involving the expression of contraction-associated proteins. Labor is initiated when genes in SMCs are activated in response to a combination of hormonal, inflammatory and mechanical signals. In this review, we provide an overview of molecular mechanisms regulating the process of parturition in humans, focusing on the hormonal control of the myometrium, particularly the steroid hormone progesterone. The primary reason for discussing the regulation of myometrial contractility by progesterone is the importance of the clinical problem of preterm birth. It is thought that the hormonal mechanisms regulating premature uterine contractions represent an untimely triggering of the normal events occurring during term parturition. Yet, our knowledge of the complex and redundant hormonal pathways controlling uterine contractile activity leading to delivery of the neonate remains incomplete. Finally, we introduce recent animal studies using a novel class of drugs, Selective Progesterone Receptor Modulators, targeting progesterone signaling to prevent premature myometrial contractions.

Asunto(s)

Trabajo de Parto , Nacimiento Prematuro , Recién Nacido , Embarazo , Animales , Femenino , Humanos , Progesterona/farmacología , Progesterona/metabolismo , Miometrio/metabolismo , Parto/fisiología , Trabajo de Parto/fisiología , Receptores de Progesterona/metabolismo

RESUMEN

Background Medical management of atypical endometrial hyperplasia (AEH) includes oral or intrauterine progestins. This study aims to evaluate the oncological and reproductive outcomes of these patients and the predictive factors for disease regression, as well as to compare the treatment efficacy of different forms of progestins. Methodology This retrospective study was conducted at KK Women's and Children's Hospital, Singapore. Women diagnosed with AEH on endometrial biopsy between January 2015 to October 2017 and treated with at least eight weeks of the same progestin were included for analysis. Results Of the 42 patients who met the inclusion criteria, 37 were treated with oral progestins and five with the levonorgestrel intrauterine device (LNG-IUS). In total, 28 (66.6%) patients achieved complete regression (CR), but eight recurred with AEH or endometrial carcinoma. Four (9.5%) progressed to grade 1 endometrioid adenocarcinoma. Patients under 39 years old were 9.75 times more likely (95% confidence interval (CI) = 1.12-85.16, p = 0.04) to achieve CR compared to those who were 40 years old and above. In multivariate analysis, older age and higher mean body mass index had a significantly lower chance of CR. The probability of CR plateaued at nine months at 0.63 (95% CI = 0.47-0.79). There was no significant difference in time to regression, chance of regression, and risk of recurrence between oral progestin and LNG-IUS. Nine patients were trying to conceive. The clinical pregnancy rate was 44.4% (n = 4), and the live birth rate was 22.2% (n = 2). Conclusions Younger patients, especially those below 39 years old, are more likely to achieve CR. The value of medical treatment beyond nine months needs to be re-evaluated. There was no difference in treatment outcomes between oral progestins and LNG-IUS.

RESUMEN

INTRODUCTION: Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients. AREAS COVERED: This clinical opinion provides a summary of recent studies exploring risk factors for the development of malignant endometrial pathology including obesity, PCOS, and T2DM. Studies assessing efficacy of fertility-sparing treatment of malignant endometrial pathology are reviewed, and a potential new adjunct treatment approach to LNG-IUD is explored. EXPERT OPINION: There is an unmet-need for a personalized treatment approach in cases of first-line progestin treatment failure. Glucagon-like peptide 1 receptor agonists are a class of anti-diabetic agents, but may have a role in fertility-sparing treatment of obese patients with malignant endometrial pathology by reducing weight, decreasing inflammation, and decreasing insulin resistance; these changes may also improve chances of subsequent pregnancy. This hypothesis warrants further exploration.

Asunto(s)

Diabetes Mellitus Tipo 2 , Neoplasias Endometriales , Preservación de la Fertilidad , Síndrome del Ovario Poliquístico , Embarazo , Humanos , Femenino , Adulto , Progestinas/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/uso terapéutico , Levonorgestrel/efectos adversos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/inducido químicamente , Neoplasias Endometriales/tratamiento farmacológico

RESUMEN

BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity. OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade. SEARCH STRATEGY: We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases. SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded. DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures. MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%. CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.

Asunto(s)

Neoplasias Endometriales , Progestinas , Femenino , Humanos , Progestinas/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología

RESUMEN

Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.

Asunto(s)

Hiperplasia Endometrial , Neoplasias Endometriales , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/patología , Neoplasias Endometriales/etiología , Neoplasias Endometriales/patología , Endometrio/patología , Femenino , Humanos , Progestinas/uso terapéutico , Factores de Riesgo

RESUMEN

Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in women who are younger than 40 years old. The survival rate in these cases is 99%; therefore, uterine-sparing management could be considered under strict criteria selection and the strong desire of the woman to preserve uterus and fertility. Diagnosis should be performed after a hysteroscopic biopsy instead of dilatation and curettage. The highest remission rate was achieved after combining a hysteroscopic resection with hormonal therapy compared to single hormonal treatment. The most common regiments are the following progestins: megestrol acetate (MA) and medroxyprogesterone acetate (MPA) taken orally with a daily dosage of 160 mg-320 mg for MA and 250 mg-600 mg for MP. Evaluations at three and six months could be performed by office endometrial biopsy and/or hysteroscopic directed biopsy especially in the presence of levonorgestrel intrauterine system, and in cases of remission, either a pregnancy attempt or maintenance therapy should be considered. After childbearing, hysterectomy with bilateral salpingo-oophorectomy is recommended, whereas ovarian preservation could be considered depending on the patient's age and whether they fulfil the strict criteria selection.

Asunto(s)

Hiperplasia Endometrial , Neoplasias Endometriales , Preservación de la Fertilidad , Adulto , Antineoplásicos Hormonales/uso terapéutico , Hiperplasia Endometrial/cirugía , Neoplasias Endometriales/patología , Femenino , Humanos , Histeroscopía , Levonorgestrel , Embarazo , Útero/patología

RESUMEN

•A subset of patients with uterine carcinosarcoma will have ER/PR positive disease.•Hormone receptor expression may serve as a therapeutic target in high-grade endometrial tumors.•Hormonal therapy and SBRT may have benefit in the management of recurrent uterine carcinosarcoma.

RESUMEN

BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.

Asunto(s)

Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma Endometrioide/metabolismo , Neoplasias Endometriales/metabolismo , Receptor alfa de Estrógeno/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Receptores de Progesterona/metabolismo , Anciano , Anciano de 80 o más Años , Inhibidores de la Aromatasa/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Antagonistas de Estrógenos/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Progestinas/uso terapéutico , Supervivencia sin Progresión , ARN Mensajero/metabolismo , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tamoxifeno/uso terapéutico

RESUMEN

Women with primary ovarian insufficiency rarely ovulate and even more rarely achieve a spontaneous pregnancy. A patient with primary ovarian insufficiency who had only 13 follicle development cycles during 13 years, but had 2 live births resulting from intrauterine inseminations is reported. She was diagnosed with primary ovarian insufficiency at 19 years of age and started infertility treatment at 23 years of age. During 10 of the 13 years that she was not pregnant and not breastfeeding, she underwent cyclic estrogen and progestin therapy with biweekly monitoring of follicle development. She delivered the first and second child at 30 and 37 years of age, respectively. This case report suggests that continuous follicle monitoring may increase the probability of having a child in a subset of patients with primary ovarian insufficiency and desired fertility, although the validity and efficacy of such management has not been established.

Asunto(s)

Nacimiento Vivo , Insuficiencia Ovárica Primaria , Niño , Femenino , Fertilización In Vitro , Humanos , Inseminación , Folículo Ovárico , Inducción de la Ovulación , Embarazo

RESUMEN

Approximately fifty percent of premenopausal women who smoke cigarettes or on nicotine replacement therapy are also on hormonal contraceptives, especially oral estrogen-progestin. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR) which causes lipid influx into non-adipose tissue and impairs Na+/K+ -ATPase activity, especially in the heart and kidney. However, the effects of nicotine on excess lipid and altered Na+/K+ -ATPase activity associated with the use of estrogen-progestin therapy have not been fully elucidated. This study therefore aimed at investigating the effect of nicotine on cardiac and renal lipid influx and Na+/K+ -ATPase activity during estrogen-progestin therapy. Twenty-four female Wistar rats grouped into 4 (n = 6/group) received (p.o.) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 µg ethinyl estradiol and 5.0 µg levonorgestrel) and estrogen-progestin only daily for 6 weeks. Data showed that estrogen-progestin treatment or nicotine exposure caused IR, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, reduced bilirubin and circulating estradiol. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase activity while nicotine did not alter Na+/K+-ATPase activity but increased plasma and tissue cotinine. Renal Na+/K+-ATPase activity was not altered by the treatments. However, all these alterations were reversed following combined administration of oral estrogen-progestin therapy and nicotine. The present study therefore demonstrates that oral estrogen-progestin therapy and nicotine exposure synergistically prevents IR-linked cardio-renotoxicity with corresponding improvement in cardiac and renal lipid accumulation, oxidative stress, inflammation and Na+/K+-ATPase activity.

Asunto(s)

Anticonceptivos Orales Combinados/farmacología , Estrógenos/farmacología , Etinilestradiol/farmacología , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Levonorgestrel/farmacología , Miocardio/enzimología , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Progestinas/farmacología , Animales , Anticonceptivos Orales Combinados/toxicidad , Citoprotección , Combinación de Medicamentos , Sinergismo Farmacológico , Estrógenos/toxicidad , Etinilestradiol/toxicidad , Femenino , Mediadores de Inflamación/metabolismo , Riñón/enzimología , Riñón/patología , Levonorgestrel/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Miocardio/patología , Nicotina/toxicidad , Agonistas Nicotínicos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Progestinas/toxicidad , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismo

RESUMEN

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m2, respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39-4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11-0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83-7.89; class I-II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09-3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40-3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P = .033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005). CONCLUSION: Our study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.

Asunto(s)

Hiperplasia Endometrial/complicaciones , Hiperplasia Endometrial/tratamiento farmacológico , Dispositivos Intrauterinos Medicados , Levonorgestrel/administración & dosificación , Obesidad Mórbida/congénito , Progestinas/administración & dosificación , Adulto , Femenino , Humanos , Progestinas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

Genitourinary syndrome of menopause is a condition describing the hypoestrogenic effects on the female genitals and lower urinary tract leading to symptoms such as vaginal dryness, vulvar and vaginal burning, dyspareunia and dysuria. Genitourinary syndrome of menopause is experienced by over half of postmenopausal women, and is even more pervasive in women with cancer. Due to treatments such as surgery, chemotherapy, radiation, and hormonal therapy, women may experience early menopause resulting in earlier and more severe symptoms. Understanding the scope of this issue in female breast and gynecologic cancer survivors and identifying treatment options for this complex patient population are paramount. Tailored patient treatments include nonhormonal therapies (vaginal moisturizers, lubricants, pelvic floor physical therapy, dilator therapy, counseling), systemic and local hormonal therapies. Consensus recommendations by medical societies and associated evidence are reviewed, with emphasis on safety and efficacy of local vaginal hormonal therapies, and management variations noted depending on cancer type and characteristics. With knowledge and understanding of the unmet need associated with under-recognition and under-treatment of genitourinary syndrome of menopause, providers caring for women with cancer are in a position to improve the quality of life of their patients by providing safe and effective treatments.

Asunto(s)

Neoplasias de la Mama , Terapia de Reemplazo de Estrógeno/métodos , Enfermedades Urogenitales Femeninas/terapia , Neoplasias de los Genitales Femeninos , Menopausia , Administración Intravaginal , Anestésicos Locales/uso terapéutico , Supervivientes de Cáncer , Dispareunia/terapia , Disuria/terapia , Femenino , Humanos , Terapia por Láser , Lidocaína/uso terapéutico , Lípidos/uso terapéutico , Lubricantes/uso terapéutico , Selección de Paciente , Diafragma Pélvico , Modalidades de Fisioterapia

RESUMEN

BACKGROUND/AIM: Endometrial hyperplastic polyps (EHP) may progress to endometrial carcinoma (EC) if left untreated. We aimed to prospectively investigate the efficacy of the low-dose levonorgestrel intrauterine system (LNG-IUS) as therapy for EHP with malignant potential. PATIENTS AND METHODS: In total, 37 women with EHP underwent therapy with LNG-IUS containing 13.5 mg levonorgestrel for six months or 4-10 weeks depending on whether the EHP was characterized (by D-score analysis) as low- to medium-risk (n=33) or high-risk (n=4) of coexistent or future EC. Therapy response was defined as complete clearance of hyperplastic glands in post-therapy endometrial biopsy. RESULTS: All women with low- to medium-risk EHP obtained therapy response, whereas only 1 out of 4 with high-risk EHP responded to therapy. None of the women were diagnosed with EC during the study and no serious adverse events occurred. CONCLUSION: Low-dose LNG-IUS represents a promising therapy for selected women with EHP.

Asunto(s)

Antineoplásicos Hormonales/administración & dosificación , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/patología , Pólipos/patología , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Progestinas/administración & dosificación , Adulto , Anciano , Biomarcadores , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Progestinas/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento

RESUMEN

The present study investigated the effects of oral ethinylestradiol-levonorgestrel (EEL) on hepatic lipid and glycogen contents during high fructose (HF) intake, and determined whether pyruvate dehydrogenase kinase-4 (PDK-4) and glucose-6-phosphate dehydrogenase (G6PD) activity were involved in HF and (or) EEL-induced hepatic dysmetabolism. Female Wistar rats weighing 140-160 g were divided into groups. The control, EEL, HF, and EEL+HF groups received water (vehicle, p.o.), 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel (p.o.), fructose (10% w/v), and EEL plus HF, respectively, on a daily basis for 8 weeks. Results revealed that treatment with EEL or HF led to insulin resistance, hyperinsulinemia, increased hepatic uric acid production and triglyceride content, reduced glycogen content, and reduced production of plasma or hepatic glutathione- and G6PD-dependent antioxidants. HF but not EEL also increased fasting glucose and hepatic PDK-4. Nonetheless, these alterations were attenuated by EEL in HF-treated rats. Our results demonstrate that hepatic lipid accumulation and glycogen depletion induced by HF is accompanied by increased PDK-4 and defective G6PD activity. The findings also suggest that EEL would attenuate hepatic lipid accumulation and glycogen depletion by suppression of PDK-4 and enhancement of a G6PD-dependent antioxidant barrier.

Asunto(s)

Etinilestradiol/administración & dosificación , Etinilestradiol/farmacología , Fructosa/efectos adversos , Glucógeno/deficiencia , Levonorgestrel/administración & dosificación , Levonorgestrel/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Administración Oral , Animales , Antioxidantes/metabolismo , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Etinilestradiol/uso terapéutico , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , Hiperinsulinismo/tratamiento farmacológico , Resistencia a la Insulina , Levonorgestrel/uso terapéutico , Peroxidación de Lípido/efectos de los fármacos , Proteínas Quinasas/metabolismo , Ratas , Ratas Wistar , Ácido Úrico/metabolismo

RESUMEN

Background: The aim was to assess the effect of estrogen-progestin therapy (EPT) on serum levels of uric acid (SUA) and its precursors xanthine (X) and hypoxanthine (HX), and on uric acid (UA) renal excretion in hypertensive postmenopausal women treated with an angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic (HCTZ) (ClinicalTrials.gov identifier: NCT03921736, registered 19 April 2019). Methods: Postmenopausal women with untreated essential hypertension were recruited to the study. The control group consisted of 40 postmenopausal women with normal blood pressure. Hypertensive women were randomized to two groups: hydrochlorothiazide (n = 50) or perindopril (n = 50) and to a group receiving or not receiving EPT (EPT+/EPT-) due to vasomotor symptoms. The follow-up period was one year. Blood pressure measurements as well as blood tests for SUA and its precursors X and HX were performed at baseline and after 12 months. Results: In hypertensive women, baseline serum X and HX were significantly higher when compared to the group of normotensive women. Treatment with HCTZ led to a statistically significant increase in SUA in the subgroup of EPT- women. In this group concentrations of X and HX increased significantly after 12 months. UA/X significantly decreased after treatment with HCTZ. Lack of EPT resulted in a decrease of renal plasma flow in the HCTZ group. However, in the HCTZ and EPT + group, SUA decreased significantly when compared to baseline. None of these unfavorable effects was observed in the ACEI group regardless of EPT. Conclusions: 1) EPT prevents the development of hyperuricemia during antihypertensive treatment with thiazide diuretics. 2) Arterial hypertension and menopause cause impairment of UA excretion and increase the levels of SUA and its precursors X and HX. 3) EPT reduces the risk of hyperuricemia in postmenopausal women.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Terapia de Reemplazo de Estrógeno , Hidroclorotiazida/efectos adversos , Hipertensión/tratamiento farmacológico , Ácido Úrico/sangre , Femenino , Humanos , Hipertensión/sangre , Hiperuricemia/prevención & control , Persona de Mediana Edad , Posmenopausia

RESUMEN

The issue of cardiovascular and cognitive health in women is complex. During the premenopausal phase of life, women have healthy blood pressure levels that are lower than those of age-matched men, and they have less cardiovascular disease. However, in the postmenopausal stage of life, blood pressure in women increases, and they are increasingly susceptible to cardiovascular disease, cognitive impairments, and dementia, exceeding the incidence in men. The major difference between pre- and postmenopausal women is the loss of estrogen. Thus, it seemed logical that postmenopausal estrogen replacement therapy, with or without progestin, generally referred to as menopausal hormone treatment (MHT), would prevent these adverse sequelae. However, despite initially promising results, a major randomized clinical trial refuted the benefits of MHT, leading to its falling from favor. However, reappraisal of this study in the framework of a "critical window," or "timing hypothesis," has changed our perspective on the benefit-to-risk ratio of MHT, and this review discusses the historical, current, and future approaches to MHT.

Asunto(s)

Enfermedades Cardiovasculares/prevención & control , Demencia/prevención & control , Terapia de Reemplazo de Estrógeno/efectos adversos , Estradiol/administración & dosificación , Estradiol/efectos adversos , Estradiol/uso terapéutico , Terapia de Reemplazo de Estrógeno/métodos , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. The only medicinal therapy currently recommended to prevent PTB is prophylactic progestin therapy in the form of micronized progesterone (P4) administered daily via vaginal suppository from the 24th to the 34th week of gestation or 17α-hydroxyprogesterone caproate in oil administered weekly from the 16th to the 36th week of gestation via an intramuscular injection. These therapies decrease the risk of PTB in women with an elevated risk of PTB indicated by a history of PTB or by a short cervix measured by sonography at mid-gestation. The mechanism by which progestin therapy prevents PTB in some women is not clear but may involve non-progestin mechanism and/or supplementation of localized progestin deficiency. Advances in understanding the molecular biology and physiology of P4 signaling via the P4 receptor isoforms in uterine cells reveal novel therapeutic targets; this may improve the effectiveness of progestin therapy to prevent PTB in the majority of pregnancies by targeting key steps in the pathway leading to inflammation-induced parturition.

Asunto(s)

Caproato de 17 alfa-Hidroxiprogesterona/administración & dosificación , Nacimiento Prematuro/prevención & control , Progestinas/administración & dosificación , Caproato de 17 alfa-Hidroxiprogesterona/farmacología , Administración Intravaginal , Medición de Longitud Cervical , Ensayos Clínicos como Asunto , Femenino , Humanos , Inyecciones Intramusculares , Hipófisis/efectos de los fármacos , Hipófisis/embriología , Embarazo , Nacimiento Prematuro/metabolismo , Progestinas/farmacología , Útero/efectos de los fármacos

RESUMEN

BACKGROUND/AIM: Progestin therapy has been accepted as therapy for low- and medium-risk endometrial hyperplasia. The aim of this study was to investigate the efficacy of the low-dose levonorgestrel-impregnated intrauterine system (LNG-IUS) 13.5 mg (Jaydess®, Bayer Pharmaceuticals, Berlin, Germany) as therapy for endometrial hyperplasia. PATIENTS AND METHODS: A total of 21 women with histologically-verified endometrial hyperplasia were prospectively treated with LNG-IUS Jaydess. Therapy duration was 6 months (n=16) or 3-6 weeks (n=5) depending on individual risk (low- and medium-risk versus high-risk) for co-existent or future endometrial carcinoma. Paired endometrial biopsies were sampled prior to and after therapy and classified according to the WHO94 classification system and D-score. RESULTS: All women with low- and medium risk endometrial hyperplasia had-therapy response. In the group of women with high-risk endometrial hyperplasia only 40% (two out of five) obtained a therapy response. CONCLUSION: Low-dose LNG-IUS Jaydess was proven to be an excellent therapy option for low- and medium-risk endometrial hyperplasia. For patients with high-risk endometrial hyperplasia hysterectomy or LNG-IUS therapy under close surveillance is advised.

Asunto(s)

Anticonceptivos Femeninos/administración & dosificación , Hiperplasia Endometrial/tratamiento farmacológico , Dispositivos Intrauterinos Medicados , Levonorgestrel/administración & dosificación , Adulto , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Lesiones Precancerosas/tratamiento farmacológico , Estudios Prospectivos

RESUMEN

Endometrial cancer is the most common gynecologic cancer in the United States. It is typically diagnosed in postmenopausal women. However, given the increasing incidence of risk factors such as obesity and diabetes in younger women, it is becoming a more prevalent problem in this age group. When endometrial cancer is diagnosed in patients of reproductive age, the standard surgical option of hysterectomy and bilateral salpingo-oophorectomy may not be ideal for women interested in future fertility. Hence, conservative options for select patients should be discussed along with the associated outcomes of each approach. A number of studies have shown that in patients with complex atypical endometrial hyperplasia and grade I endometrial carcinoma, a conservative approach is safe and feasible. The aim of this review is to summarize published evidence of fertility-sparing options such as hormonal therapy, hysteroscopic resection of focal lesions, and the role of intrauterine devices. We will also provide the latest updates on ongoing prospective trials that explore strategies for conservative management in women with medical comorbidities or those interested in fertility preservation.

Asunto(s)

Antineoplásicos Hormonales/uso terapéutico , Carcinoma Endometrioide/terapia , Tratamiento Conservador , Neoplasias Endometriales/terapia , Preservación de la Fertilidad/métodos , Carcinoma Endometrioide/patología , Tratamiento Conservador/métodos , Neoplasias Endometriales/patología , Femenino , Humanos , Selección de Paciente , Resultado del Tratamiento