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1.
Expert Rev Clin Pharmacol ; 12(10): 953-963, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31526281

RESUMO

Introduction: This is an overview of the recently FDA-approved silicone elastomer combined hormonal contraceptive vaginal ring (CVR), which is used cyclically for up to 1 year, eliminating resupply challenges. This ring requires no refrigeration, simplifying the supply chain. Developed by the Population Council, this CVR will soon be marketed in the United States as Annovera™ by TherapeuticsMD. Areas Covered: The composition of the elastomer ring and the chemical, pharmacokinetic and pharmacodynamic properties of both hormonal components are discussed. Results of the clinical trials of its efficacy, tolerability, safety, and acceptability follow. Finally, subanalyses from the clinical trials are presented to guide clinicians in counseling potential users. Expert Opinion: This CVR introduces a new progestin - segesterone acetate (SA) - that has no androgenic or estrogenic action in vitro or in vivo, but has the highest anti-ovulatory potential of all available progestins. SA is paired with EE in an intravaginal elastomer ring, that is used cyclically (21 days in place/7 days removed) to provide 12 months (13 cycles) of contraception. This once-a-month, self-applied CVR offers a convenient, rapidly reversible, year-long contraception with efficacy and side effect profiles similar to other combined hormonal methods, for women with BMI < 29 kg/m2.


Assuntos
Dispositivos Anticoncepcionais Femininos , Etinilestradiol/administração & dosagem , Contracepção Reversível de Longo Prazo , Pregnenodionas/administração & dosagem , Animais , Aprovação de Drogas , Etinilestradiol/efeitos adversos , Feminino , Humanos , Pregnenodionas/efeitos adversos , Elastômeros de Silicone/química , Estados Unidos , United States Food and Drug Administration
2.
Artigo em Inglês | MEDLINE | ID: mdl-31469652

RESUMO

Background Combined oral contraceptive (COC) use has been associated with an increased risk of insulin resistance (IR) and other adverse cardiovascular events, despite efforts to reduce the dosage and/or progestin type. COC containing drospirenone (DRSP) is an analog of spironolactone, hence its antimineralocorticoid and antiandrogenic characteristics have been deemed beneficial, although the benefits and/or negative outcome of its usage have not been fully elucidated. We therefore hypothesized that COC with DRSP component will not affect glucose regulation and circulating corticosterone. Method Ten-week-old female Wistar rats were divided into three groups: control (CON), ethinylestradiol/drospirenone COC (EE/DRSP)-treated, and ethinylestradiol/levonorgestrel COC (EE/LN)-treated rats. The treatment lasted for 8 weeks. Results Results showed that with the exception of lipid profiles, EE/LN but not EE/DRSP COC treatment affected body weight, glucose tolerance, plasma insulin, corticosterone, (IR), and pancreatic ß-cell dysfunction. Conclusion Taken together, the findings showed that the beneficial effect of EE/DRSP could possibly be through the DRSP component. The result also implies that COCs containing DRSP may be a better and safer means of contraception than those with LN with less cardiovascular risks.


Assuntos
Androstenos/efeitos adversos , Corticosterona/sangue , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Anticoncepcionais Orais/efeitos adversos , Combinação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , Insulina/sangue , Células Secretoras de Insulina/efeitos dos fármacos , Levanogestrel/efeitos adversos , Ratos
3.
Eur J Contracept Reprod Health Care ; 24(4): 322-324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30983430

RESUMO

Case: Second-generation combined oral contraceptives (COCs) are widely used and are believed to be safe for birth control and in the treatment of gynaecological diseases. No randomised controlled study has shown elevations in alanine transaminase (ALT) levels in relation to the use of a second-generation COC. We report a case of drug-induced liver injury (DILI) in a young, moderately obese woman, due to the use of a second-generation COC containing 30 µg ethinylestradiol and 150 µg levonorgestrel. COC use had been initiated 2 years prior to admission to our department. The diagnosis was based on elevated levels of ALT during COC use and was confirmed by re-challenge and a liver biopsy showing signs of former tissue damage after a 3 week break of COC treatment. Conclusions: To our knowledge, this is the first case of biopsy-proven DILI due to COC use in which a re-challenge was performed.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Anticoncepcionais Orais Combinados/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Etinilestradiol/efeitos adversos , Feminino , Humanos , Levanogestrel/efeitos adversos , Adulto Jovem
4.
Qual Health Res ; 29(10): 1519-1530, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30957638

RESUMO

In this article, I analyze women's negative experiences with the fourth generation of contraceptive pills: controversial drugs Yaz and Yasmin. Drawing on in-depth interviews with 24 contraceptive users residing in Canada, I highlight how women who have experienced deleterious side effects understand the risks of hormonal contraception and advocate for changes in health risk communication and prescription drug regulation. Findings show that interviewees did not feel they received adequate risk information prior to starting their new drug regimen nor did they think that pregnancy risks should be used as a comparison point for placing hormonal contraceptive risk into perspective. Patient views were generally underlined by a critique of professional risk/benefit assessment techniques and procedures. To illustrate how the modern complexities of health risk assessment extend to the realm of hormonal contraceptives, I here provide a detailed examination of women's negative experiences while on the pill.


Assuntos
Androstenos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Etinilestradiol/efeitos adversos , Trombose/induzido quimicamente , Adulto , Atitude Frente a Saúde , Feminino , Humanos , Entrevistas como Assunto , Educação de Pacientes como Assunto , Fatores de Risco , Adulto Jovem
5.
J Steroid Biochem Mol Biol ; 190: 54-63, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30923014

RESUMO

Oral contraception is the most commonly used interventional method in the world. However, several women employ the continuous use of these hormones to avoid pre- and menstruation discomforts. Some studies indicate that oral contraceptives are associated with disturbances in glycemia and the effects of the use of a continuous regime are poorly elucidated. Herein, we evaluated the effects of the continuous administration of a combined oral contraceptive (COC) composed by ethinyl estradiol (EE) and drospirenone (DRSP) on glucose homeostasis in female mice. Adult Swiss mice received 0.6 µg EE and 60 µg DRSP (COC group) or vehicle [control (CTL)] daily by gavage for 35 days. COC treatment had no effect on body weight or adiposity, but increased uterus weight and induced hepatomegaly. Importantly, COC females displayed normal glycemia and glucose tolerance, but hyperinsulinemia and lower plasma C-peptide/insulin ratio, indicating reduced insulin clearance. Furthermore, COC mice displayed reduced protein content of the ß subunit of the insulin receptor (IRß) in the liver. Additionally, pancreatic islets isolated from COC mice secreted more insulin in response to increasing glucose concentrations. This effect was associated with the activity of steroid hormones, since INS-1E cells incubated with EE plus DRSP also secreted more insulin. Therefore, we provide the first evidence that the continuous administration of EE and DRSP lead to hyperinsulinemia, due to enhancement of insulin secretion and the reduction of insulin degradation, which possibly lead to the down-regulation of hepatic IRß. These findings suggest that the continuous administration of COC could cause insulin resistance with the prolongation of treatment.


Assuntos
Androstenos/efeitos adversos , Anticoncepcionais Orais Combinados/efeitos adversos , Etinilestradiol/efeitos adversos , Hiperinsulinismo/induzido quimicamente , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Animais , Feminino , Glucose/metabolismo , Hiperinsulinismo/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Camundongos
6.
Nurs Womens Health ; 23(2): 172-176, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30836070

RESUMO

The U.S. Food and Drug Administration approved a new combination hormonal contraceptive in August 2018. Sold under the brand name Annovera, it is a combination of segesterone acetate and ethinyl estradiol, and it is the first multiuse vaginal contraceptive system that prevents ovulation for up to 13 menstrual cycles in a year. Although there are several combination hormonal contraceptives on the market, this is the first single system that can be repeatedly used for an entire year and does not require placement by a health care provider. This innovation gives women control over when to stop using the contraceptive, should they so desire. Annovera is stored at room temperature when not in use, allowing women living in uncontrolled-temperature climates to use one contraceptive method for an entire year.


Assuntos
Anticoncepção/instrumentação , Dispositivos Anticoncepcionais Femininos/normas , Anticoncepção/efeitos adversos , Anticoncepção/métodos , Dispositivos Anticoncepcionais Femininos/efeitos adversos , Dispositivos Anticoncepcionais Femininos/tendências , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Etinilestradiol/uso terapêutico , Humanos
7.
Ecotoxicology ; 28(2): 201-211, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30652235

RESUMO

Countless pharmaceuticals and endocrine disrupting chemicals (EDCs) exist on the market with more added each day. Many of these compounds are not removed during the wastewater treatment process and enter bodies of water in their active form. EDCs are known to have physiological and behavioral effects in exposed organisms. Exposure to the synthetic estrogen 17α-ethinylestradiol (EE2), a common EDC found in birth control pills, has been found to lead to population collapse after only a few generations in some fish species. Mechanisms identified as potential driving forces for collapse include feminization of males and altered fecundity in both sexes. However, an additional way in which EE2 could lead to population collapse is by altering courtship behavior, which could then change mating preferences and decrease mating opportunities. The current study had the following objectives: determine if exposing female Siamese fighting fish, Betta splendens, to EE2 changes mate choice in males; assess if the dose and duration of female exposure matters; and examine if exposing males to EE2 influences their mating preferences. Both unexposed and exposed males were presented with pairs of females that differed in EE2 dose and exposure duration. The results indicate that males were more responsive to EE2-exposed females than unexposed females, with males being most responsive to females exposed to the low versus high dose. Furthermore, exposed males responded less overall than unexposed males. If EE2 concentration increases in the environment, the likelihood of successful mating could decrease and, therefore, potentially lead to adverse population impacts.


Assuntos
Etinilestradiol/efeitos adversos , Preferência de Acasalamento Animal/efeitos dos fármacos , Perciformes/fisiologia , Poluentes Químicos da Água/efeitos adversos , Animais , Disruptores Endócrinos/efeitos adversos , Estrogênios/efeitos adversos , Feminino , Masculino , Reprodução/efeitos dos fármacos
8.
Eur J Gastroenterol Hepatol ; 31(3): 312-315, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30676471

RESUMO

OBJECTIVE: This study aims to assess the efficacy of hormone therapy in patients with severe gastrointestinal bleeding due to multiple angiodysplastic lesions. PATIENTS AND METHODS: Between May 2010 and July 2017, we included 12 consecutive patients with anaemia or recurrent bleeding due to angiodysplasia who had been started on hormone therapy. The therapy given was a combination of levonorgestrel (between 0.10 and 0.25 mg) and ethinylestradiol (between 0.02 and 0.05 mg). We determined the mean number of transfusions required in the 6 months before and after the start of the treatment, as well as the mean haemoglobin levels, number of admissions for anaemia due to gastrointestinal bleeding and length of hospital stay in these periods. RESULTS: The mean age of patients included was 77.83 years old and 75% were male. The follow-up period after treatment initiation was 6 months. Of the 12 patients included, only one stopped the treatment owing to it not being effective. Overall, 83.3% of the patients reported subjective improvement. Furthermore, we found significant differences comparing before and after starting treatment regarding the mean number of transfusions (7±4.8 vs. 3.4±4.6; P=0.005), the mean haemoglobin levels (9.5±1.2 vs. 10.8±2.6; P=0.034) and the mean number of admissions (1.6±1.6 vs. 0.2±0.4; P=0.024). On the contrary, differences between pretreatment and post-treatment length of hospital stay were not significant. CONCLUSION: Hormone therapy is a potentially useful therapeutic tool in patients with refractory bleeding and anaemia due to angiodysplasia.


Assuntos
Anemia/tratamento farmacológico , Angiodisplasia/tratamento farmacológico , Etinilestradiol/administração & dosagem , Fármacos Gastrointestinais/administração & dosagem , Hemorragia Gastrointestinal/tratamento farmacológico , Levanogestrel/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/etiologia , Angiodisplasia/complicações , Angiodisplasia/diagnóstico , Transfusão de Sangue , Combinação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemoglobinas/metabolismo , Humanos , Tempo de Internação , Levanogestrel/efeitos adversos , Masculino , Admissão do Paciente , Recidiva , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
9.
Sci Total Environ ; 653: 10-22, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30390549

RESUMO

The ability to restore tissue function and morphology after injury is a key advantage of many fish for a greater chance of survival. The tissue regeneration process is regulated by multiple pathways, and it can therefore be hypothesized that environmental contaminants targeting components of these signaling pathways, may disrupt the fish's capability to repair or regenerate. This could lead to higher mortality and eventually even to a decline in populations. In this study, the effects of 17α­ethinylestradiol (EE2), a synthetic estrogen, were assessed on the regenerative capacity of larval zebrafish. Zebrafish aged 2 hour post fertilization (hpf) were exposed to 1, 10, or 100 ng/L EE2, and the caudal fins were amputated at 72 hpf. It was found that EE2 exposure significantly inhibited fin regeneration and changed locomotor behavior. The transcription levels for most of the genes involved in the signaling networks regulating the fin regeneration, such as axin2, fgfr1, bmp2b and igf2b, were down-regulated in the amputated fish in response to EE2 exposure, which was in contrast to their increased patterns in the vehicle-exposed control fish. Additionally, the mRNA levels of several immune-related genes, such as il-1ß, il-6, il-10 and nf-κb2, were significantly decreased after EE2 exposure, accompanied by a lower density of neutrophils migrated into the wound site. In conclusion, the present study indicated for the first time that estrogenic endocrine disrupting chemicals (EEDCs) could inhibit the regenerative capacity of zebrafish, and this effect was speculated to be mediated through the alteration in regeneration-related signaling pathways and immune competence. This work expands our knowledge of the potential effects of EEDCs on injured aquatic organisms, and highlights the ecotoxicological significance of relationships between regenerative process and endocrine system. This study also implies the potential application of fin regeneration assay for assessing immunotoxicity in ecotoxicological risk assessment.


Assuntos
Nadadeiras de Animais/fisiologia , Disruptores Endócrinos/efeitos adversos , Etinilestradiol/efeitos adversos , Regeneração/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Peixe-Zebra/fisiologia , Nadadeiras de Animais/efeitos dos fármacos , Nadadeiras de Animais/cirurgia , Animais , Movimento Celular/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Leucócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Peixe-Zebra/cirurgia
10.
Sci Total Environ ; 649: 949-959, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30179823

RESUMO

We demonstrate how mechanistic modeling can be used to predict whether and how biological responses to chemicals at (sub)organismal levels in model species (i.e., what we typically measure) translate into impacts on ecosystem service delivery (i.e., what we care about). We consider a hypothetical case study of two species of trout, brown trout (Salmo trutta; BT) and greenback cutthroat trout (Oncorhynchus clarkii stomias; GCT). These hypothetical populations live in a high-altitude river system and are exposed to human-derived estrogen (17α­ethinyl estradiol, EE2), which is the bioactive estrogen in many contraceptives. We use the individual-based model inSTREAM to explore how seasonally varying concentrations of EE2 could influence male spawning and sperm quality. Resulting impacts on trout recruitment and the consequences of such for anglers and for the continued viability of populations of GCT (the state fish of Colorado) are explored. inSTREAM incorporates seasonally varying river flow and temperature, fishing pressure, the influence of EE2 on species-specific demography, and inter-specific competition. The model facilitates quantitative exploration of the relative importance of endocrine disruption and inter-species competition on trout population dynamics. Simulations predicted constant EE2 loading to have more impacts on GCT than BT. However, increasing removal of BT by anglers can enhance the persistence of GCT and offset some of the negative effects of EE2. We demonstrate how models that quantitatively link impacts of chemicals and other stressors on individual survival, growth, and reproduction to consequences for populations and ecosystem service delivery, can be coupled with ecosystem service valuation. The approach facilitates interpretation of toxicity data in an ecological context and gives beneficiaries of ecosystem services a more explicit role in management decisions. Although challenges remain, this type of approach may be particularly helpful for site-specific risk assessments and those in which tradeoffs and synergies among ecosystem services need to be considered.


Assuntos
Disruptores Endócrinos/efeitos adversos , Exposição Ambiental , Etinilestradiol/efeitos adversos , Truta/metabolismo , Poluentes Químicos da Água/efeitos adversos , Animais , Masculino , Modelos Biológicos , Oncorhynchus/metabolismo , Reprodução/efeitos dos fármacos , Estações do Ano , Espermatozoides/efeitos dos fármacos
11.
Eur J Clin Pharmacol ; 75(1): 41-49, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30191262

RESUMO

PURPOSE: Laquinimod is an orally dosed immuno-modulator currently under development for Huntington's disease (HD). Preclinical findings suggest potential teratogenicity of laquinimod, thus the reproductive ability of females with HD treated with laquinimod needs to be closely managed. Because combined oral contraceptives (COC) are often used in this context, the pharmacokinetics of COC containing ethinylestradiol (EE) and levonorgestrel (LNG) in combination with laquinimod (0.6 mg/day) was evaluated. METHODS: In this randomized, phase-1 single-center, double-blind, placebo-controlled, 2-way crossover drug-drug interaction (DDI) study in 48 healthy premenopausal women, COC were administered in a 28-day regimen of 21 days followed by 7 pill-free days for 4 cycles and laquinimod or placebo was administered for 28 days in cycle 1 and cycle 3 starting 7 days prior to COC administration. Blood samples for pharmacokinetic profiling of laquinimod, EE and LNG were collected on day 21 and day 22 of Cycles 1 and 3 pre-dose and multiple times post-dose. RESULTS: The ratio of geometric means and 90% confidence intervals for AUC0-24 and Cmax of EE and LNG with and without laquinimod were all within the bioequivalence range (80 to 125%). Laquinimod pharmacokinetics was consistent with those observed in previous studies. The adverse event profile was in line with the current knowledge on the safety profile of both drugs, with headache as the most frequently reported treatment-related adverse event. CONCLUSION: The combination of COC and laquinimod treatment was found to be safe, tolerable, and devoid of any noticeable pharmacokinetic interaction.


Assuntos
Anticoncepcionais Orais Combinados/farmacocinética , Etinilestradiol/farmacocinética , Fatores Imunológicos/farmacologia , Levanogestrel/farmacocinética , Quinolonas/farmacologia , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Interações Medicamentosas , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Levanogestrel/administração & dosagem , Levanogestrel/efeitos adversos , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Equivalência Terapêutica , Adulto Jovem
13.
Int J Mol Sci ; 19(11)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441863

RESUMO

The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human-A375 and murine-B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells-A375 and improved viability rates of healthy and B164A5 cells. A weak irritant potential exerted by EE and EE + LNG (10 µM) was assessed by the means of a chick chorioallantoic membrane assay. Further studies are required to elucidate the hormones' cell type-dependent antimelanoma effect and the role played by melanin in this context.


Assuntos
Anticoncepcionais/efeitos adversos , Etinilestradiol/efeitos adversos , Levanogestrel/efeitos adversos , Melanoma/etiologia , Pele/efeitos dos fármacos , Animais , Apoptose , Linhagem Celular , Linhagem Celular Tumoral , Anticoncepcionais/toxicidade , Etinilestradiol/toxicidade , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Levanogestrel/toxicidade , Melanócitos/efeitos dos fármacos , Melanócitos/efeitos da radiação , Melanoma/metabolismo , Camundongos , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos
14.
Gynecol Obstet Fertil Senol ; 46(12): 834-844, 2018 12.
Artigo em Francês | MEDLINE | ID: mdl-30385358

RESUMO

OBJECTIVES: To synthesize knowledge on cancer risks related to hormonal contraception and to propose recommendations on contraception during treatment and after cancer. METHODS: A systematic review of the literature about hormonal contraception and cancer was conducted on PubMed/Medline and the Cochrane Library. RESULTS: Overall, there is no increase in cancer (all types together) incidence or mortality among hormonal contraceptive users. Estroprogestin combined contraceptive use is associated with an increased risk of breast cancer (during use), and with a reduced risk of endometrial, ovarian, lymphatic or hematopoietic cancers that persist after discontinuation, and a decreased risk of colorectal cancer. Information on cancer risk is part of the systematic information given to patients wishing contraception. However, these data will not influence its prescription, considering the positive risk/benefit balance in women without specific cancer risk factor. Contraception is required during and after cancer treatment in every non-menopausal woman at cancer diagnosis. Specific thromboembolic, immunologic or vomiting risks due to the oncological context should be taken into account before the contraceptive choice. All hormonal contraceptives are contra-indicated after breast cancer, regardless of the delay since treatment, hormone receptor status and histological subtype. There is no data in the literature to limit hormonal or non-hormonal contraceptive use after colorectal or thyroid cancer. There was insufficient data in the literature to propose recommendations on contraceptive choice after cervical cancer, melanoma, lung cancer, tumor of the central nervous system, or after thoracic irradiation. If an emergency contraception is needed in a woman previously treated for a hormone-sensitive cancer, a non-hormonal copper intrauterine device should be preferred. CONCLUSIONS: Information on cancer risk is part of the patient's information but does not influence the prescription of contraception in the absence of any specific risk factor. Contraception should be proposed in every woman treated or previously treated for cancer. The whole context should be taken into account to choose a tailored contraception.


Assuntos
Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Anticoncepção Pós-Coito , Combinação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , França , Humanos , Dispositivos Intrauterinos de Cobre , MEDLINE , Neoplasias/induzido quimicamente , Norpregnenos/efeitos adversos , Fatores de Risco
15.
Eur J Contracept Reprod Health Care ; 23(4): 245-254, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30203681

RESUMO

PURPOSE: To identify at least one contraceptive vaginal ring that effectively inhibits ovulation and demonstrates cycle control that is non-inferior to NuvaRing® (Merck Sharp & Dohme B.V., The Netherlands) in terms of an unscheduled bleeding incidence, with a non-inferiority margin of 10%. METHODS: This was a randomised, active controlled, parallel group, multicentre, partially blinded trial in healthy women 18-35 years of age. Subjects received one of six contraceptive vaginal rings with an average daily release rate of 300 µg 17ß-estradiol (E2) and various rates of either etonogestrel (ENG; 75, 100, or 125 µg/day) or nomegestrol acetate (NOMAC; 500, 700, or 900 µg/day), or the active control NuvaRing® (ENG/ethinylestradiol 120/15 µg), for three 28-day cycles. RESULTS: Ovulation inhibition was observed in all groups as confirmed by absence of progesterone concentrations compatible with ovulation (>16 nmol/L) and absence of ultrasound evidence of ovulation. All investigational rings provided good cycle control, with the ENG-E2 125/300 µg/day group being associated with the best cycle control based on the numerically lowest incidence of unscheduled bleeding and absence of scheduled bleeding. Non-inferiority to NuvaRing® with respect to the incidence of unscheduled bleeding could not be concluded for any of the investigational ring groups. The safety profile was consistent with the known safety profile of combined estrogen/progestin contraceptives and similar across all groups. CONCLUSIONS: Contraceptive rings releasing 300 µg E2 and 75-125 µg/day of ENG or 500-900 µg/day of NOMAC provided adequate ovulation inhibition and cycle control and are generally well-tolerated. While non-inferiority to NuvaRing® was not met, among the investigational rings, the ENG-E2 125/300 ring provided the best cycle control.


Assuntos
Desogestrel/análogos & derivados , Estradiol , Etinilestradiol , Ciclo Menstrual/efeitos dos fármacos , Inibição da Ovulação/efeitos dos fármacos , Adulto , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Dispositivos Anticoncepcionais Femininos , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(8): 917-922, 2018 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-30187872

RESUMO

OBJECTIVE: To evaluate the efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproteroneand desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome (PCOS). METHODS: Women with PCOSfrom West China Second Hospital of Sichuan University enrolled between September, 2011 and August, 2013 were randomlyallocated to receive either ethinyl oestradiol/cyproterone tablets (Group A, n=355) or desogestrel/ethinyl oestradiol tablets(Group B, n=357) for a prospective observation period of 6 months. Women with insulin resistance also received metformin. Atbaseline, 3 months, and 6 months, the patients were evaluated for menstruation, acne score, body mass index (BMI), waist-tohip ratio (WHR), plasma levels of sex hormones, fasting blood glucose (FPG), HOMA-insulin resistance index (HOMA-IR), serum lipid, ovarian volume, and the number of ovarian follicles. RESULTS: All the patients had a regular menstrual cycle aftertreatments. Testosterone level, acne score, LH/FSH, ovarian volume, and the number of follicles decreased significantly afterthe treatments without significant differences between the two groups. Significant increases were noted in TG, TCh, LDL, HDL, and AIP, and HDL level in group A as compared with group B (P < 0.001). FPG decreased in both groups, and wassignificantly lower in group B at 6 months (P < 0.05). BMI and WHR decreased in all the patients with insulin resistance aftercombination treatment with metformin (P < 0.05), but increased significantly in patients without insulin resistance (P < 0.05). Ingroup A, HOMA- IR significantly increased in patientswithout insulin resistance at 3 months (P < 0.05), whereas asignificant increase was not observed until 6 months ingroup B (P < 0.05). CONCLUSIONS: Both ethinyl oestradiol/cyproterone tablets and desogestrel/ethinyl oestradioltablets can relieve the symptoms of PCOS, but it isadvisable to assess the risk of cardiovascular diseasebefore the treatments.


Assuntos
Ciproterona/uso terapêutico , Desogestrel/uso terapêutico , Etinilestradiol/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , China , Ciproterona/efeitos adversos , Desogestrel/efeitos adversos , Quimioterapia Combinada , Etinilestradiol/efeitos adversos , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Metformina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Estudos Prospectivos , Comprimidos
17.
Am J Reprod Immunol ; 80(4): e13029, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30076667

RESUMO

PROBLEM: In women, the use of progestin-based contraception may increase the risk of vaginal HIV acquisition. We previously showed in macaques that there is a significantly higher simian-human immunodeficiency virus (SHIV) acquisition rate in the luteal phase of the menstrual cycle, which presents a naturally high-progesterone state, and this may be attributable to altered expression of innate immune factors. We hypothesized that progestin-based contraception, especially depot medroxyprogesterone acetate (DMPA), would, in a similar way, affect mucosal immune factors that influence HIV acquisition risk. METHOD OF STUDY: We used a pig-tailed macaque model to evaluate the effects of two progestin-based contraceptives, DMPA, and levonorgestrel (LNG)/ethinyl estradiol (EE)-based combined oral contraceptives (COCs), on innate mucosal factors. We compared the vaginal epithelial thickness data from previous studies and used cytokine profiling and microarray analysis to evaluate contraception-induced molecular changes in the vagina. RESULTS: The administration of DMPA caused a reduction in the thickness of the vaginal epithelium relative to that of the follicular or luteal phase. DMPA also induced a significant increase in vaginal levels of the anti-inflammatory cytokine IL-10. Both DMPA- and LNG-based contraception induced a signature of gene expression similar to that of the luteal phase, only more exacerbated, including widespread downregulation of antiviral genes. CONCLUSION: The use of progestin-based contraception might engender a milieu that poses an increased risk of HIV acquisition as compared to both the luteal and follicular phases of the menstrual cycle.


Assuntos
Anticoncepção/efeitos adversos , Anticoncepcionais Femininos/efeitos adversos , Etinilestradiol/efeitos adversos , Infecções por HIV/transmissão , Levanogestrel/efeitos adversos , Acetato de Medroxiprogesterona/efeitos adversos , Progestinas/efeitos adversos , Vagina/efeitos dos fármacos , Animais , Anticoncepção/métodos , Anticoncepcionais Femininos/farmacologia , Etinilestradiol/farmacologia , Feminino , Infecções por HIV/patologia , Interleucina-10/metabolismo , Levanogestrel/farmacologia , Macaca nemestrina , Acetato de Medroxiprogesterona/farmacologia , Membrana Mucosa/metabolismo , Progestinas/farmacologia , Fatores de Risco
18.
Artigo em Inglês | MEDLINE | ID: mdl-29885532

RESUMO

Lipid metabolism involves complex pathways, which are regulated in a similar way across vertebrates. Hormonal and hypolipidemic deregulations cause lipid imbalance from fish to humans, but the underlying mechanisms are far from understood. This study explores the potential of using juvenile brown trout to evaluate the in vivo interferences caused by estrogenic (17α-ethinylestradiol - EE2), androgenic (testosterone - T), and hypolipidemic (clofibrate - CLF) compounds in lipidic and/or peroxisomal pathways. Studied endpoints were from blood/plasma biochemistry, plasma fatty acid profile, ultrastructure of hepatocytes and abundance of their peroxisomes to mRNA expression in the liver. Both T and CLF caused minimal effects when compared to EE2. Estrogenized fish had significantly higher hepatosomatic indexes, increased triglycerides and very-low density lipoproteins (VLDL) in plasma, compared with solvent control. Morphologically, EE2 fish showed increased lipid droplets in hepatocytes, and EE2 and T reduced volume density of peroxisomes in relation to the hepatic parenchyma. Polyunsaturated fatty acids (PUFA) in plasma, namely n-3 PUFA, increased with EE2. EE2 animals had increased mRNA levels of vitellogenin A (VtgA), estrogen receptor alpha (ERα), peroxisome proliferator-activated receptor alpha (PPARα), PPARαBa and acyl-CoA long chain synthetase 1 (Acsl1), while ERß-1, acyl-CoA oxidase 1-3I (Acox1-3I), Acox3, PPARγ, catalase (Cat), urate oxidase (Uox), fatty acid binding protein 1 (Fabp1) and apolipoprotein AI (ApoAI) were down-regulated. In summary, in vivo EE2 exposure altered lipid metabolism and peroxisome dynamics in brown trout, namely by changing the mRNA levels of several genes. Our model can be used to study possible organism-level impacts, viz. in gonadogenesis.


Assuntos
Estrogênios/efeitos adversos , Hipolipemiantes/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Peroxissomos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Testosterona/efeitos adversos , Androgênios/efeitos adversos , Animais , Aquicultura , Clofibrato/efeitos adversos , Etinilestradiol/efeitos adversos , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/ultraestrutura , Lipídeos/sangue , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Fígado/ultraestrutura , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Peroxissomos/metabolismo , Peroxissomos/ultraestrutura , Portugal , Distribuição Aleatória , Testes de Toxicidade Subaguda , Truta
19.
PLoS One ; 13(6): e0199107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29912934

RESUMO

Rodent pups use vocalizations to communicate with one or both parents in biparental species, such as California mice (Peromyscus californicus). Previous studies have shown California mice developmentally exposed to endocrine disrupting chemicals, bisphenol A (BPA) or ethinyl estradiol (EE), demonstrate later compromised parental behaviors. Reductions in F1 parental behaviors might also be due to decreased emissions of F2 pup vocalizations. Thus, vocalizations of F2 male and female California mice pups born to F1 parents developmentally exposed to BPA, EE, or controls were examined. Postnatal days (PND) 2-4 were considered early postnatal period, PND 7 and 14 were defined as mid-postnatal period, and PND 21 and 28 were classified as late postnatal period. EE pups showed increased latency to emit the first syllable compared to controls. BPA female pups had decreased syllable duration compared to control and EE female pups during the early postnatal period but enhanced responses compared to controls at late postnatal period; whereas, male BPA and EE pups showed greater syllable duration compared to controls during early postnatal period. In mid-postnatal period, F2 BPA and EE pups emitted greater number of phrases than F2 control pups. Results indicate aspects of vocalizations were disrupted in F2 pups born to F1 parents developmentally exposed to BPA or EE, but their responses were not always identical, suggesting BPA might not activate estrogen receptors to the same extent as EE. Changes in vocalization patterns by F2 pups may be due to multigenerational exposure to BPA or EE and/or reduced parental care received.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Etinilestradiol/efeitos adversos , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Vocalização Animal/efeitos dos fármacos , Animais , Animais Recém-Nascidos/psicologia , Feminino , Masculino , Peromyscus , Gravidez
20.
Am J Physiol Heart Circ Physiol ; 315(4): H925-H933, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29906227

RESUMO

Hypertension, obesity, and endothelial function predict cardiovascular disease in women, and these factors are interrelated. We hypothesized that hypertension and obesity are associated with endothelial dysfunction in young women and that short-term ethinyl estradiol exposure mitigates this dysfunction. We examined flow-mediated dilation (FMD) responses before and during 7 days of oral ethinyl estradiol (30 µg/day) in 19 women (25 ± 5, 18-35 yr). We divided our sample into two groups based on two criteria: blood pressure and obesity. Women were divided into normal blood pressure (NBP; mean arterial pressure range: 78-91 mmHg, n = 7) and high blood pressure (HBP; mean arterial pressure range: 95-113 mmHg, n = 9) groups. We also stratified our subjects by body composition (lean: 18-31%, n = 8; obese: 38-59%, n = 9). We evaluated brachial FMD after two distinct shear stress stimuli: occlusion alone and occlusion with ischemic handgrip exercise. Obesity was unrelated to both FMD responses. Before ethinyl estradiol administration, the HBP group had blunted ischemic exercise responses relative to the NBP group (8.0 ± 3.5 vs. 12.3 ± 3.2%, respectively, P = 0.05). However, during ethinyl estradiol administration, ischemic exercise responses increased in the HBP group (12.8 ± 6.1%, P = 0.04) but decreased in the NBP group (5.6 ± 2.4%, P = 0.01). Standard FMD did not reveal differences between groups. In summary, 1) moderate HBP predicted endothelial impairment, 2) ethinyl estradiol administration had divergent effects on FMD in women with NBP versus HBP, and 3) enhanced FMD (ischemic handgrip exercise) revealed differences in endothelial function, whereas standard FMD (occlusion alone) did not. NEW & NOTEWORTHY We are the first to show that mild hypertension is a stronger predictor of endothelial dysfunction than obesity in healthy women without overt cardiovascular dysfunction. Importantly, the standard 5-min flow-mediated vasodilation stimulus did not detect endothelial dysfunction in our healthy population; only an enhanced ischemic handgrip exercise shear stress stimulus detected endothelial impairment. Estradiol administration increased flow-mediated dilation in women with high blood pressure, so it may be a therapeutic intervention to improve endothelial function.


Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Artéria Braquial/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Etinilestradiol/administração & dosagem , Hipertensão/tratamento farmacológico , Obesidade/tratamento farmacológico , Vasodilatadores/administração & dosagem , Adiposidade , Administração Oral , Adolescente , Adulto , Anti-Hipertensivos/efeitos adversos , Artéria Braquial/fisiopatologia , Esquema de Medicação , Endotélio Vascular/fisiopatologia , Etinilestradiol/efeitos adversos , Teste de Esforço , Feminino , Força da Mão , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Isquemia/fisiopatologia , Obesidade/diagnóstico , Obesidade/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos , Adulto Jovem
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