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1.
Front Endocrinol (Lausanne) ; 15: 1362774, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904035

RESUMEN

Introduction: To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Methods: Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Results: Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Discussion: Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.


Asunto(s)
Desogestrel , Levonorgestrel , Progestinas , Ratas Wistar , Glándula Tiroides , Animales , Femenino , Ratas , Progestinas/farmacología , Progestinas/efectos adversos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Levonorgestrel/farmacología , Desogestrel/administración & dosificación , Desogestrel/farmacología , Tiroxina/sangre , Hormonas Tiroideas/sangre , Pruebas de Función de la Tiroides
2.
Front Endocrinol (Lausanne) ; 14: 1077798, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36896185

RESUMEN

Introduction: Congenital Central Hypoventilation Syndrome, a rare disease caused by PHOX2B mutation, is associated with absent or blunted CO2/H+ chemosensitivity due to the dysfunction of PHOX2B neurons of the retrotrapezoid nucleus. No pharmacological treatment is available. Clinical observations have reported non-systematic CO2/H+ chemosensitivity recovery under desogestrel. Methods: Here, we used a preclinical model of Congenital Central Hypoventilation Syndrome, the retrotrapezoid nucleus conditional Phox2b mutant mouse, to investigate whether etonogestrel, the active metabolite of desogestrel, led to a restoration of chemosensitivity by acting on serotonin neurons known to be sensitive to etonogestrel, or retrotrapezoid nucleus PHOX2B residual cells that persist despite the mutation. The influence of etonogestrel on respiratory variables under hypercapnia was investigated using whole-body plethysmographic recording. The effect of etonogestrel, alone or combined with serotonin drugs, on the respiratory rhythm of medullary-spinal cord preparations from Phox2b mutants and wildtype mice was analyzed under metabolic acidosis. c-FOS, serotonin and PHOX2B were immunodetected. Serotonin metabolic pathways were characterized in the medulla oblongata by ultra-high-performance liquid chromatography. Results: We observed etonogestrel restored chemosensitivity in Phox2b mutants in a non-systematic way. Histological differences between Phox2b mutants with restored chemosensitivity and Phox2b mutant without restored chemosensitivity indicated greater activation of serotonin neurons of the raphe obscurus nucleus but no effect on retrotrapezoid nucleus PHOX2B residual cells. Finally, the increase in serotonergic signaling by the fluoxetine application modulated the respiratory effect of etonogestrel differently between Phox2b mutant mice and their WT littermates or WT OF1 mice, a result which parallels with differences in the functional state of serotonergic metabolic pathways between these different mice. Discussion: Our work thus highlights that serotonin systems were critically important for the occurrence of an etonogestrel-restoration, an element to consider in potential therapeutic intervention in Congenital Central Hypoventilation Syndrome patients.


Asunto(s)
Desogestrel , Progestinas , Animales , Ratones , Desogestrel/farmacología , Desogestrel/uso terapéutico , Progestinas/farmacología , Serotonina , Gonanos , Dióxido de Carbono , Modelos Animales de Enfermedad , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/metabolismo , Congéneres de la Progesterona
3.
Contraception ; 119: 109925, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36535414

RESUMEN

OBJECTIVES: To synthesize published literature on POP effectiveness and efficacy. STUDY DESIGN: We searched PubMed Central, PubMed, and the Cochrane library through March 07, 2022. We included articles written in English reporting a Pearl Index or life table rate for pregnancy. We excluded articles only assessing formulations that: were never marketed globally, are only sold in combination with estrogen, are currently sold only for noncontraceptive purposes, or were not given to participants continuously. Four researchers independently extracted data and two analyzed data using Excel and R. RESULTS: We included 54 studies. Among studies at low or moderate risk of bias, the median Pearl Index rate (the failure rate during typical use) was 1.63 (range 0.00-14.20, IQR 4.03) and the median method failure Pearl Index rate (the failure rate during perfect use) was 0.97 (range 0.40-6.50, IQR 0.68). Excluding the newer formulations, Desogestrel and Drospirenone, which are closer to combined oral contraceptives in that they prevent pregnancy by inhibiting ovulation, the median Pearl Index rate is 2.00 (range 0.00-14.12, IQR 2.5) and the median method failure Pearl Index rate is 1.05 (range 0.00-10.90, IQR 1.38). CONCLUSIONS: Among studies at low or moderate risk of bias, the median Pearl Index rate during typical POP use was much lower than currently estimated (7.00), while the median perfect use rate was similar to current estimates. IMPLICATIONS: Future research should investigate the possibility that POPs may be much more effective during typical use than currently believed.


Asunto(s)
Desogestrel , Progestinas , Embarazo , Femenino , Humanos , Desogestrel/farmacología , Anticonceptivos Orales Combinados , Estrógenos , Ovulación
4.
Rom J Morphol Embryol ; 63(1): 137-144, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36074677

RESUMEN

Endometriosis is a relatively frequent pathology in gynecological practice. We performed an analysis to demonstrate the molecular changes that occur in endometriosis synthetic progestin-treated patients, hoping to sketch a possible pathophysiological pathway that will help us to better understand and treat this debilitating disease. We conducted a prospective study that included a group of 40 women, evaluated in our hospital between 2020-2021. We evaluated immunohistochemical tissue expression of estrogen receptor (ER), progesterone receptor (PR), B-cell lymphoma 2 (Bcl-2) protein, Ki-67, and serum levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in patients with ovarian endometrioma with and without progestin treatment. Our study revealed that Desogestrel treatment increases OPN serum levels, PR and Bcl-2 tissue expression and reduces VEGF serum levels and Ki-67 tissue expression. The results we have obtained are very interesting because the serum levels of OPN seem to be more influenced by progestin treatment, than by endometriosis itself. The study we have conducted gives a molecular complex view of what endometriosis represents and on how Desogestrel treatment works.


Asunto(s)
Endometriosis , Neoplasias Ováricas , Apoptosis , Proliferación Celular , Desogestrel/farmacología , Desogestrel/uso terapéutico , Endometriosis/tratamiento farmacológico , Endometriosis/patología , Femenino , Humanos , Inflamación/metabolismo , Antígeno Ki-67 , Progestinas , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-bcl-2 , Factor A de Crecimiento Endotelial Vascular
5.
Eur J Contracept Reprod Health Care ; 26(6): 454-461, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34348526

RESUMEN

Purpose: Steroid hormones in hormonal contraceptives influence a variety of metabolic parameters. Mainly, ethinyloestradiol (EE) in combined hormonal contraceptives (CHC) is a potent inducer of hepatic coagulation factors, has an impact on cholesterol and triglyceride levels and glucose tolerance. Progestins in CHC modify the oestrogen effects in different ways, depending on their pharmacologic properties. The metabolic impact of progestin-only contraceptives is generally considered low.Methods: The influence of novel drospirenone (DRSP)-only pill (4 mg DRSP in 24/4 intake) on a variety of lipid-, carbohydrate- and bone metabolic parameters and on haemostatic variables including clotting factors and D-Dimer level was evaluated in comparison to 0.075 mg desogestrel (DSG) during a multicentric, prospective, double-blind, double-dummy clinical trial with 1190 participants over nine treatment cycles.Results: For both DRSP and DSG, there was a decrease in cholesterol (total, HDL, and LDL) and triglyceride levels. No relevant influence on glucose, insulin, and c-peptide levels or bone remodelling markers were detected in both treatment groups. Considering the coagulatory parameters, there was no impact on hemostasis.Conclusions: The results confirm the beneficial properties of the drospirenone-only pill.EudraCT Number: 2011-002396-42.


Asunto(s)
Desogestrel , Progestinas , Androstenos , Anticonceptivos Orales Combinados , Desogestrel/farmacología , Etinilestradiol/farmacología , Femenino , Humanos , Laboratorios , Estudios Prospectivos
7.
Steroids ; 162: 108694, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32650000

RESUMEN

Biotransformation of an orally active contraceptive drug, desogestrel (1), with Cunninghamella elegans yielded a new metabolite, 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3,6-dione (2), along with five known metabolites, i.e., 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3ß,6ß,17ß-triol (3), 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6ß,17ß-diol-3-one (4), 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3-one (5), 13ß-ethyl-11-epoxy-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3-one (6), and 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-10ß,17ß-diol-3-one (7). The structure of new metabolite 2 was elucidated by using 1H-, 13C-, and 2D-NMR, EI-, and HREI-MS, IR, and UV spectroscopic data. Compounds 1-7 were evaluated for anti-inflammatory activities, i.e., inhibition of T-cell proliferation, and pro-inflammatory cytokine (TNF-α). Compounds 1 (IC50 = 1.12 ± 0.03 µg/mL), 2 (IC50 = 1.15 ± 0.05 µg/mL), 3 (IC50 = 1.15 ± 0.05 µg/mL), 4 (IC50 = 1.40 ± 0.03 µg/mL), 5 (IC50 = 1.78 ± 0.08 µg/mL), and 6 (IC50 = 1.36 ± 0.07 µg/mL) were identified as potent inhibitors of T-cells proliferation, in comparison to the standard drug, prednisolone (IC50 = 3.51 ± 0.03 µg/mL). Compound 7 (IC50 = 6.18 ± 0.04 µg/mL) showed a good activity. In addition, substrate 1 (IC50 ≤ 1 µg/mL), and its metabolites 2 (IC50 = 4.1 ± 0.60 µg/mL), and 6 (IC50 = 6.8 ± 0.8 µg/mL) also showed a potent inhibition of pro-inflammatory cytokine (TNF-α) production, as compared to the standards drug, pentoxifilline (IC50 = 94.8 ± 2.1 µg/mL). Whereas compounds 3 (IC50 = 57.9 ± 7.6 µg/mL), and 5 (IC50 = 27.2 ± 6.8 µg/mL) showed a moderate inhibition of TNF-α production, while compounds 4 and 7 showed no inhibition. Compounds 1-7 were found to be non-cytotoxic to 3T3 normal cell line (mouse fibroblast).


Asunto(s)
Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Anticonceptivos/metabolismo , Anticonceptivos/farmacología , Cunninghamella/metabolismo , Desogestrel/metabolismo , Desogestrel/farmacología , Antiinflamatorios/química , Biotransformación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Anticonceptivos/química , Desogestrel/química , Humanos , Relación Estructura-Actividad , Linfocitos T/citología , Linfocitos T/efectos de los fármacos
8.
Int J Gynaecol Obstet ; 147(1): 54-58, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31265128

RESUMEN

OBJECTIVE: To compare weight gain between women using etonogestrel implants and those using levonorgestrel implants 12 months after insertion. METHODS: A multicenter prospective cohort study was performed on women recruited from family planning clinics between July 2016 and August 2017. The main study outcome was mean weight gain after 12 months of insertion of the implants. RESULTS: The present study included 150 women (age range 18-45 years) using levonorgestrel implants and 167 women using etonogestrel implants. The women recruited had been using implants for less than 6 months; implants had been inserted 6-12 months after their last pregnancy. Participants were followed up until 12 months after insertion through telephone conversations. Baseline parameters were obtained from the clinic records and weight was measured within 6 weeks of the 12-month anniversary of insertion of the implants. Data were analyzed with SPSS version 23. Weight gain in the levonorgestrel group was significantly higher than in the etonogestrel group (3.16 ± 4.08 vs 0.77 ± 3.76, P = 0.013; relative risk 1.69, 95% confidence interval 1.46-1.96). There were no differences in the occurrence of menstrual irregularities and client satisfaction. CONCLUSION: Women using levonorgestrel implants were more likely to gain weight compared to those using etonogestrel implants after 12 months of insertion.


Asunto(s)
Anticonceptivos Femeninos/efectos adversos , Desogestrel/efectos adversos , Levonorgestrel/efectos adversos , Adulto , Anticonceptivos Femeninos/farmacología , Desogestrel/farmacología , Implantes de Medicamentos/uso terapéutico , Femenino , Humanos , Levonorgestrel/farmacología , Estudios Prospectivos , Factores de Tiempo
9.
Contraception ; 100(2): 152-154, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30998927

RESUMEN

OBJECTIVE: To describe contraceptive knowledge and counseling practices of postpartum nurses. METHODS: We surveyed postpartum nurses at the largest women's hospital in Rhode Island. RESULTS: We distributed 117 anonymous questionnaires and received 58 responses (response rate=50%). Twenty-three of 51 nurses (45%) reported routinely offering contraceptive advice to new mothers. Only 5/55 (9%) responded correctly that combined hormonal contraceptives were an "unacceptable health risk" in the immediate postpartum period. A minority of respondents correctly classified the progestin-only pill, depot medroxyprogesterone acetate, the etonogestrel implant, the levonorgestrel intrauterine system and the copper intrauterine device as safe to use during lactation [14/56 (25%), 24/56 (43%), 27/56 (48%), 19/55 (35%) and 9/55 (16%), respectively]. Thirty-three of 51 nurses (65%) incorrectly responded that depot medroxyprogesterone acetate decreases milk supply if started immediately postpartum. CONCLUSION: There are opportunities to improve knowledge regarding contraceptive safety and impact on lactation among postpartum nurses at our institution.


Asunto(s)
Anticoncepción/métodos , Conocimientos, Actitudes y Práctica en Salud , Lactancia/efectos de los fármacos , Enfermeras y Enfermeros , Adulto , Anticonceptivos Femeninos/farmacología , Desogestrel/farmacología , Femenino , Maternidades , Humanos , Dispositivos Intrauterinos/estadística & datos numéricos , Levonorgestrel/farmacología , Anticoncepción Reversible de Larga Duración , Acetato de Medroxiprogesterona/farmacología , Persona de Mediana Edad , Pautas de la Práctica en Enfermería , Rhode Island , Adulto Joven
10.
Reprod Biol Endocrinol ; 17(1): 26, 2019 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-30795774

RESUMEN

BACKGROUND: Hormonal contraceptives, particularly depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; however, the biological mechanisms of this risk remain poorly understood. We aimed to investigate the effects of different hormonal contraceptives on the expression of the HIV co-receptors, CXCR4 and CCR5, on female endocervical and peripheral blood T cells. METHODS: A total of 59 HIV-negative women were enrolled, including 15 initiating DMPA, 28 initiating a levonorgestrel-releasing intrauterine device (LNG-IUD) and 16 initiating an etonogestrel (ETG)-delivering vaginal ring. Peripheral blood and endocervical cytobrush specimens were collected at enrollment and 3-4 weeks after contraception initiation to analyze the expression of CXCR4 and CCR5, on CD4+ and CD8+ T cells using flow cytometry. RESULTS: Administration of DMPA increased the percentages of CD4+ and CD8+ T cells expressing CCR5 in the endocervix but not in the peripheral blood. Administration of the LNG-IUD or the ETG vaginal ring did not affect the percentages of T lymphocytes expressing CXCR4 or CCR5 in the female cervix or peripheral blood. CONCLUSIONS: Increase in the percentage of endocervical T cells expressing CCR5 upon DMPA exposure provides a plausible biological explanation for the association between DMPA use and an elevated risk of HIV infection.


Asunto(s)
Cuello del Útero/efectos de los fármacos , Anticoncepción/métodos , Desogestrel/farmacología , Levonorgestrel/farmacología , Acetato de Medroxiprogesterona/farmacología , Adulto , Cuello del Útero/citología , Cuello del Útero/metabolismo , Anticonceptivos Femeninos/farmacología , Femenino , VIH/fisiología , Infecciones por VIH/sangre , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Humanos , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Adulto Joven
11.
Cardiovasc Res ; 115(3): 637-646, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30295757

RESUMEN

AIMS: Effective stroke treatments beyond reperfusion remain scant. The natural steroid hormone progesterone has shown protective effects in experimental models of brain injury and cardiovascular disease. However, unfavourable bioavailability limits its clinical use. Desogestrel and drospirenone are new generation progestins with progesterone-like properties, developed as oral contraceptives with excellent bioavailability and safety profile. We investigated the neuroprotective properties of these progestins in vivo using transient middle cerebral artery occlusion (MCAO) and in vitro using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in primary neuronal cells. METHODS AND RESULTS: MCAO was induced in female, female ovariectomized (modelling postmenopausal females) and male mice. Treatment with the progestins resulted in less severe strokes after MCAO and less neuronal death in OGD/R. Desogestrel and drospirenone induced higher expression levels of GABAAR α4 and delta subunits within the brain, suggesting changes in GABAAR configuration favouring tonic inhibition as potential mechanism of action. Treatment with the GABAAR blocker picrotoxin abolished the protection afforded by the progestins in vivo and in vitro. CONCLUSION: For the first time, here, we delineate a potential role of desogestrel and drospirenone, both clinically approved and safe drugs in mitigating the consequences of stroke. Contraception with desogestrel and drospirenone in progestin-only preparations may be particularly beneficial for women at risk of stroke.


Asunto(s)
Androstenos/farmacología , Encéfalo/efectos de los fármacos , Desogestrel/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Progestinas/farmacología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Ratones Endogámicos C57BL , Inhibición Neural/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ovariectomía , Receptores de GABA-A/metabolismo , Filtrado Sensorial/efectos de los fármacos
12.
Steroids ; 137: 47-56, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30086356

RESUMEN

An effort with the goal of discovering single-dose, long-lasting (>6 months) injectable contraceptives began using levonorgestrel (LNG)-17-ß esters linked to a sulfonamide function purposed as human carbonic anhydrase II (hCA 2) ligands. One single analog from this first series showed noticeably superior anti-ovulatory activity in murine models, and a subsequent structure-activity relationship (SAR, the relationship between a compound's molecular structure and its biological activity) study based on this compound identified a LNG-phenoxyacetic acid ester analog exhibiting longer anti-ovulatory properties using the murine model at 2 and 4 mg dose than medroxyprogesterone acetate (MPA). The same ester function linked to etonogestrel (ENG) furnished a compound which inhibited ovulation at 2 mg for 60 days, the longest duration of all compounds tested at these doses. By comparison, MPA at the same dose inhibited ovulation for 32 days.


Asunto(s)
Anticonceptivos Femeninos/química , Anticonceptivos Femeninos/farmacología , Desogestrel/química , Desogestrel/farmacología , Ésteres/química , Levonorgestrel/química , Levonorgestrel/farmacología , Animales , Anticonceptivos Femeninos/administración & dosificación , Desogestrel/administración & dosificación , Femenino , Inyecciones Subcutáneas , Levonorgestrel/administración & dosificación , Ovulación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
13.
Exp Cell Res ; 370(2): 671-679, 2018 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-30036539

RESUMEN

The paired-like homeobox 2B gene (PHOX2B) encodes a key transcription factor that plays a role in the development of the autonomic nervous system and the neural structures involved in controlling breathing. In humans, PHOX2B over-expression plays a role in the pathogenesis of tumours arising from the sympathetic nervous system such as neuroblastomas, and heterozygous PHOX2B mutations cause Congenital Central Hypoventilation Syndrome (CCHS), a life-threatening neurocristopathy characterised by the defective autonomic control of breathing and involving altered CO2/H+ chemosensitivity. The recovery of CO2/H+ chemosensitivity and increased ventilation have been observed in two CCHS patients using the potent contraceptive progestin desogestrel. Given the central role of PHOX2B in the pathogenesis of CCHS, and the progesterone-mediated effects observed in the disease, we generated progesterone-responsive neuroblastoma cells, and evaluated the effects of 3-Ketodesogestrel (3-KDG), the biologically active metabolite of desogestrel, on the expression of PHOX2B and its target genes. Our findings demonstrate that, through progesterone nuclear receptor PR-B, 3-KDG down-regulates PHOX2B gene expression, by a post-transcriptional mechanism, and its target genes and open up the possibility that this mechanism may contribute to the positive effects observed in some CCHS patients.


Asunto(s)
Desogestrel/farmacología , Proteínas de Homeodominio/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Progesterona/genética , Factores de Transcripción/efectos de los fármacos , Núcleo Celular/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Hipoventilación/congénito , Hipoventilación/genética , Células-Madre Neurales/metabolismo , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Apnea Central del Sueño/genética , Factores de Transcripción/metabolismo
14.
J Obstet Gynaecol ; 38(7): 979-984, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29553853

RESUMEN

The use of long-acting contraceptive methods is on the rise. The aim of this study was to describe the main variables (effectiveness, tolerability, menstrual bleeding) associated with the use of subdermal contraceptive implants and to investigate the influence of age on these variables. This was a descriptive, retrospective, observational study of 221 cases of contraceptive implants inserted at a Spanish hospital between 2006 and 2015. The mean age of implant users was 31.2 ± 7.5 years. Effectiveness was 100% and good tolerability was recorded for 86.5%. Infrequent bleeding was the most common bleeding pattern, followed by amenorrhoea. Of the 221 implants inserted, 47.5% were removed. The main reasons were expiration (54.3%) and discomfort due to bleeding alterations and other adverse effects (25.7%). Nulliparity and weight gain were significantly associated with an increased probability of implant removal. This study shows that implants were highly effective, safe and well-tolerated in our population. The age of users had no influence on any of the study variables analysed. Impact Statement What is already known on this subject? Subdermal contraceptive implants are long-acting reversible contraceptives which are both safe and effective. What do the results of this study add? The age of users had no influence on any of the study variables analysed. Nulliparity and weight gain were significantly associated with an increased probability of implant removal. What are the implications of these findings for clinical practice and/or further research? Subdermal contraceptive implants were a safe and effective long-acting progestin contraceptive method for women from all age groups in our series because no significant age-related differences were observed for the tolerability, vaginal bleeding patterns, the effectiveness, the adverse effects or any other variables.


Asunto(s)
Anticonceptivos Femeninos/efectos adversos , Desogestrel/efectos adversos , Implantes de Medicamentos/efectos adversos , Levonorgestrel/efectos adversos , Anticoncepción Reversible de Larga Duración/efectos adversos , Adulto , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Desogestrel/administración & dosificación , Desogestrel/farmacología , Remoción de Dispositivos/estadística & datos numéricos , Implantes de Medicamentos/administración & dosificación , Femenino , Humanos , Levonorgestrel/administración & dosificación , Levonorgestrel/farmacología , Menstruación/efectos de los fármacos , Estudios Retrospectivos , Adulto Joven
15.
Reprod Sci ; 25(9): 1413-1423, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29237349

RESUMEN

Age-related fertility decline is hypothesized to occur mainly by the spontaneous exhaustion and deterioration of the ovarian follicle, and the accumulation of ovarian tissue damage resulting from the ovulation cycle may play roles in the process. In this study, we hypothesized that suppressing ovulation would exert protective effects against age-related fertility decline. To test this hypothesis, we established a mouse model in which oral contraceptives (OCs) were administered daily. Female C57BL/6N mice were administered OCs daily from the age of 2 months to 12 months as an ovulation suppression mouse model. Mouse fecundity was investigated by counting oocyte number after ovarian stimulation and by examining live fetuses after mating. We found that compared with control mice administered vehicle alone, 12-month-old mice administered 2-fold dose OCs used for treating humans exhibited a significantly greater average oocyte number after ovarian stimulation (8.5 ± 0.6 vs 5.9 ± 0.6, P < .01). In addition, spontaneous conception with living fetuses after mating was strikingly increased in 12-month-old mice administered OCs relative to controls (6.0 ± 1.2 vs 0.4 ± 0.3, P < .01). In the histological examination of mouse ovarian tissues, we did not detect a significant difference in ovarian follicle number, but reduced amount of brownish foamy fibrous tissues, which might reflect ovarian tissue damage, was detected in aged mice administered OCs. These results suggest the possibility that long-term OC administration might alleviate age-related fertility decline, and the improvement mechanism could be attributed to the prevention of ovarian tissue damage by suppressing ovulation.


Asunto(s)
Envejecimiento/efectos de los fármacos , Anticonceptivos Sintéticos Orales/farmacología , Desogestrel/farmacología , Fertilidad/efectos de los fármacos , Ovario/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Femenino , Fertilidad/fisiología , Peroxidación de Lípido/efectos de los fármacos , Ratones , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Ovario/metabolismo
16.
Curr Neuropharmacol ; 16(10): 1433-1454, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28721821

RESUMEN

BACKGROUND: Central alveolar hypoventilation syndromes (CHS) encompass neurorespiratory diseases resulting from congenital or acquired neurological disorders. Hypercapnia, acidosis, and hypoxemia resulting from CHS negatively affect physiological functions and can be lifethreatening. To date, the absence of pharmacological treatment implies that the patients must receive assisted ventilation throughout their lives. OBJECTIVE: To highlight the relevance of determining conditions in which using gonane synthetic progestins could be of potential clinical interest for the treatment of CHS. METHODS: The mechanisms by which gonanes modulate the respiratory drive were put into the context of those established for natural progesterone and other synthetic progestins. RESULTS: The clinical benefits of synthetic progestins to treat respiratory diseases are mixed with either positive outcomes or no improvement. A benefit for CHS patients has only recently been proposed. We incidentally observed restoration of CO2 chemosensitivity, the functional deficit of this disease, in two adult CHS women by desogestrel, a gonane progestin, used for contraception. This effect was not observed by another group, studying a single patient. These contradictory findings are probably due to the complex nature of the action of desogestrel on breathing and led us to carry out mechanistic studies in rodents. Our results show that desogestrel influences the respiratory command by modulating the GABAA and NMDA signaling in the respiratory network, medullary serotoninergic systems, and supramedullary areas. CONCLUSION: Gonanes show promise for improving ventilation of CHS patients, although the conditions of their use need to be better understood.


Asunto(s)
Gonanos/farmacología , Gonanos/uso terapéutico , Progesterona/análogos & derivados , Apnea Central del Sueño/tratamiento farmacológico , Animales , Desogestrel/farmacología , Desogestrel/uso terapéutico , Humanos , Progestinas/farmacología
18.
Nurs Womens Health ; 21(3): 186-195, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28599740

RESUMEN

Initiation of long-acting reversible contraception (LARC) in the immediate postpartum period is becoming more common, resulting in increased requests for early removal, primarily because of unpredictable bleeding patterns. Competing interests of healthful spacing of pregnancies, impact on breastfeeding, risks associated with pregnancy versus contraceptive method, potential adverse effects of LARC, and timing of informed consent make immediate postpartum initiation of LARC an important issue. Nearly 40% of women do not attend a postpartum visit at all, resulting in decreased initiation of contraception and increased risk of unplanned pregnancy. Nurses caring for women during the peripartum period can help women make informed decisions and can provide anticipatory guidance regarding this method of contraception. Evidence-based postpartum education and support can result in women's increased continuation of and satisfaction with LARC.


Asunto(s)
Anticoncepción/métodos , Madres/psicología , Atención Posnatal/métodos , Factores de Tiempo , Adulto , Lactancia Materna , Anticoncepción/normas , Contraindicaciones , Desogestrel/farmacología , Desogestrel/uso terapéutico , Femenino , Humanos , Dispositivos Intrauterinos de Cobre/normas , Educación del Paciente como Asunto/normas , Seguridad del Paciente/normas , Embarazo , Embarazo no Planeado/efectos de los fármacos , Progestinas/farmacología , Progestinas/uso terapéutico
19.
Contraception ; 95(4): 382-389, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28041992

RESUMEN

OBJECTIVE: Users of hormonal long-acting reversible contraception (LARC) report weight gain as a side effect, but few studies have assessed body composition change among LARC users. We evaluated weight and body composition of healthy women using the levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (copper IUD) or etonogestrel implant (ENG implant). We hypothesized that weight gain and body composition over 12 months would not differ between copper IUD, LNG-IUS and ENG implant users. STUDY DESIGN: We performed a prospective cohort study of a subgroup of women enrolled in the Contraceptive CHOICE Project who initiated the LNG-IUS, copper IUD or ENG implant. Inclusion criteria included lack of metabolic and eating disorders or change in body weight of more than 5% in the 6 months before enrollment. We measured changes in weight and body composition (body fat percentage, total body fat mass, total lean mass and total body mass) in women who continued their method for 12 months. RESULTS: We analyzed data from 149 participants: 85 LNG-IUS users, 31 copper IUD users and 33 ENG implant users. The mean age was 25.9 years, 56.4% were White, 82.5% had some college education and 67.6% were nulliparous. Although lean body mass increased over 12 months in LNG-IUS and copper IUD users but not in ENG implant users, changes in body weight and body composition did not differ between the groups. In the adjusted model, Black race was associated with change in total body mass (p<.05). CONCLUSIONS: Among those who continued the method for 12 months, changes in body weight and composition did not differ between copper IUD, LNG-IUS and ENG implant users. IMPLICATIONS STATEMENT: Changes in body weight and composition over 12 months did not differ between copper IUD users and LNG-IUS and ENG implant users among those with 12 months of continuous use.


Asunto(s)
Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Anticonceptivos Femeninos/farmacología , Desogestrel/farmacología , Dispositivos Intrauterinos de Cobre , Levonorgestrel/farmacología , Adulto , Análisis de Varianza , Índice de Masa Corporal , Anticoncepción/métodos , Preparaciones de Acción Retardada , Implantes de Medicamentos , Femenino , Humanos , Modelos Lineales , Estudios Prospectivos , Adulto Joven
20.
Rev. chil. obstet. ginecol ; 81(6): 489-495, dic. 2016. tab
Artículo en Español | LILACS | ID: biblio-844521

RESUMEN

Objetivo: Describir las características del patrón sangrado uterino de las adolescentes que usan el implante anticonceptivo sudérmico de etonogestrel (IASE) que concurren a un centro especializado en salud sexual y reproductiva de adolescentes en Santiago, Chile, y su asociación con variables biopsicosocial. Método: Estudio de cohorte retrospectiva de las usuarias de IASE. Los datos fueron analizados utilizando la ecuación de estimación generalizada, análisis de sobrevida de Kaplan Meier y test de log-rank. Resultados: La cohorte incluyó a 62 adolescentes. La media de edad fue de 16,2 años. Las participantes recibieron asesoramiento anticonceptivo antes de la inserción del IASE, y fueron seguidas durante tres años. Los patrones de sangrado más frecuentes durante el primer año fue el de amenorrea (40,5%) y el sangrado aceptable (27,1%), mientras que el menos frecuente fue prolongado y/o sangrado frecuente (15,8%). De acuerdo con el análisis de sobrevida, la única variable biopsicosocial asociado con patrón prolongado y/o sangrado frecuente fue condición médica previa. Cinco adolescentes (8%) se retiraron el IASE. Conclusiones: El IASE es una opción anticonceptiva segura y altamente eficaz para las adolescentes, independientemente de la paridad. La consejería es de gran importancia para fomentar la tolerancia y la adhesión al implante.


Objectives: To describe uterine bleeding patterns of adolescents using the long term etonogestrel contraceptive implant (ENG implant) attending a specialized adolescent sexual and reproductive health centre in Santiago, Chile, and test their association with bio-psychosocial variables. Methods: A retrospective cohort study of ENG implant users was conducted and data were analysed using the Generalized Estimating Equation, Kaplan Meier Survival Analysis and Log-Rank Test. Results: The cohort included 62 adolescents with and average age at inclusion of 16.2 years. Participants received contraceptive counselling prior to insertion of an ENG implant, and were followed up for three years. The most frequent bleeding patterns during the first year were amenorrhea (40.5%) and acceptable bleeding (27.1%), whilst the least frequent was prolonged and/or frequent bleeding (15.8%). According to the survival analysis, the only bio-psychosocial variable associated with prolonged and/or frequent bleeding was prior medical condition. Five adolescents (8%) withdrew from the treatment. Conclusions: The ENG implant is a safe and highly effective contraceptive option for adolescents, regardless of parity. Counselling is of great importance to foster tolerance and adherence to the ENG implant.


Asunto(s)
Humanos , Femenino , Adolescente , Adulto Joven , Anticonceptivos Orales Combinados/administración & dosificación , Desogestrel/administración & dosificación , Dispositivos Intrauterinos Medicados , Menstruación/efectos de los fármacos , Amenorrea , Anticonceptivos Orales Combinados/farmacología , Desogestrel/farmacología , Implantes de Medicamentos , Estudios de Seguimiento , Menstruación/psicología , Análisis de Supervivencia
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