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PURPOSE: To evaluate the initial impact of a combined oral contraceptive (COC) containing norgestimate (NGM) on female sexuality and on circulating androgen levels in users. MATERIALS AND METHODS: Six months modification in the McCoy Female Sexuality Questionnaire (MFSQ) and testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) serum levels in women starting a monophasic pill containing ethinyl-estradiol (EE) 35 µg and NGM 0.250 mg. RESULTS: The study was completed by 36 subjects. There was a significant increase in MFSQ during treatment (p < 0.0001) (and its domains with the exclusion of vaginal lubrication domain) with concomitant decreases in T (-4.45%, p < 0.0001) and DHEAS (-19.41%, p < 0.0001) serum levels. CONCLUSIONS: Contraception with EE/NGM was associated with a short term non-deteriorating effect on sexuality despite the evident decrease in androgen levels. Female sexuality during COC use is a complex topic and is not only linked with changes in serum androgen levels.
EE/NGM treatment has a short term non-deteriorating effect on sexuality despite the evident decrease in androgen serum levels.
Assuntos
Anticoncepcionais Orais Combinados , Etinilestradiol , Testosterona , Humanos , Feminino , Projetos Piloto , Etinilestradiol/farmacologia , Etinilestradiol/administração & dosagem , Adulto , Testosterona/sangue , Anticoncepcionais Orais Combinados/farmacologia , Sulfato de Desidroepiandrosterona/sangue , Androgênios/sangue , Sexualidade/efeitos dos fármacos , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Inquéritos e Questionários , Adulto Jovem , Norgestrel/análogos & derivadosRESUMO
BACKGROUND: The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control. PURPOSE: To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women's needs. RESULTS: All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation. CONCLUSION: Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women's needs and preferences.
For contraceptive pills physicians can choose among different oestrogens, besides many progestins. Natural oestrogens have less metabolic impact vs EE, while EE and E4 seem to provide a better cycle control. Knowing the different oestrogen characteristics is crucial for adjusting pill prescription to women's needs and desires.
Assuntos
Anticoncepcionais Orais Combinados , Estrogênios , Humanos , Feminino , Anticoncepcionais Orais Combinados/farmacologia , Estrogênios/farmacologia , Estradiol/farmacologia , Estetrol/farmacologia , Tromboembolia Venosa/prevenção & controle , Etinilestradiol/farmacologia , Etinilestradiol/efeitos adversosRESUMO
Military training increases tibial density and size. Female sex hormones may influence the adaption of bone to loading, but it is unknown if women using different hormonal contraceptives adapt similarly to military training. One hundred and sixteen women (57 women not using hormonal contraceptives [non-users], 38 combined oral contraceptive pill [COCP] users, 21 depot medroxyprogesterone acetate [DMPA] users) completed this study. Tibial volumetric bone mineral density (vBMD) and geometry were measured by peripheral quantitative computed tomography (4 %, 14 %, 38 %, and 66 % sites) at the start (week 1) and end (week 14) of British Army basic training. Circulating markers of bone and calcium metabolism were measured at weeks 1, 2, 4, 6, 10, and 14. Training increased trabecular vBMD at the 4 % site, periosteal perimeter at the 14 % and 66 % sites, and total area, cortical area, cortical thickness, and bone strength at all sites (0.1 to 1.6 %, p ≤ 0.009), with no differences between hormonal contraceptive groups (p ≥ 0.127). Trabecular vBMD increased at the 14 % site in non-users (0.8 %, p = 0.005), but not in COCP or DMPA users (p ≥ 0.205). Periosteal perimeter increased at the 38 % site in COCP (0.4 %, p < 0.001) and DMPA (0.5 %, p < 0.001) users, but not in non-users (p = 0.058). Training had no effect on periosteal perimeter at the 4 % site or cortical vBMD or endosteal perimeter at any site (p ≥ 0.168). ßCTX decreased and PINP increased during training with no difference between hormonal contraceptive groups. Training increased iPTH in non-users, but not COCP or DMPA users. Hormonal contraceptives may exert site-specific effects on the mechanobiology of bone, with higher endogenous oestradiol promoting trabecularisation and inhibiting periosteal expansion in non-users compared with hormonal contraceptive users.
Assuntos
Anticoncepcionais Orais Combinados , Acetato de Medroxiprogesterona , Militares , Feminino , Humanos , Densidade Óssea/fisiologia , Estudos de Coortes , Anticoncepcionais Orais Combinados/farmacologia , Acetato de Medroxiprogesterona/farmacologiaRESUMO
OBJECTIVES: Endocrinal variations within an individual impact the electrolyte composition, pH, and flow-rate (FR) of saliva. The aim of this study was to evaluate the gender-specific differences and the effect of combined estrogen-progestin oral contraceptives (COCs) on FR, pH, and electrolyte concentrations in the parotid saliva (PS) of a group of healthy adults. MATERIAL AND METHODS: Stimulated PS was collected from 20 healthy adults using a Lashley cup; 11 males, 8 females, and 1 female undertaking combined contraceptive therapy (levonorgestrel/ethinyloestradiol 0.1 mg + 0.02 mg). FR and pH were recorded for each saliva sample. Electrolytes concentrations (Na+ , Ca2+ , K+ , Mg2+ ) were measured using inductively coupled plasma optical emission spectrometer (ICP-OES). Statistical analysis was performed, and the significance level was set at p < .05. RESULTS: PS FR varied from 0.13 to 0.42 mL/min in females not taking any medication and from 0.08 to 0.5 mL/min in males not taking any medication. PS pH of females and males not taking any medication ranged from 6.23 to 7.50 and from 6.15 to 7.55. PS pH and FR of the female taking COCs were 6.5 and 0.1 mL/min. PS pH, FR, and electrolytes concentrations (Ca2+ , Na+ , K+ , Mg2+ ) were not statistically significantly different between females and males not taking any medication. PS concentrations of Ca2+ and Na+ were significantly higher in the females taking COCs than in the females not taking any medication. Whereas, concentrations of K+ and Mg2+ did not differ significantly between the females taking COCs and the females not taking any medication. CONCLUSIONS: There are no significant gender-specific differences in PS flow rate, pH, and electrolyte concentrations of Na+ , Ca2+ , Mg2+ , and K+ . Combined hormonal oral contraceptive has a significant effect on PS flow rate, pH, Ca2+ , and Na+ concentrations. Whereas the PS concentration of K+ and Mg2+ are not influenced by COCs. These results warrant further investigation.
Assuntos
Anticoncepcionais Orais Combinados , Progestinas , Adulto , Masculino , Feminino , Humanos , Anticoncepcionais Orais Combinados/farmacologia , Saliva , Estrogênios , Eletrólitos , Concentração de Íons de HidrogênioRESUMO
Hormonal contraceptives are among the most widely used drugs by young healthy women to block ovulation and avoid pregnancy. They reduce the ovarian secretion of estradiol and progesterone, hormones that also modulate neuronal plasticity, cognitive functions, emotions and mood. Cannabis is the most commonly used illicit drug worldwide and its use is increasing among young women, many of which regularly take the "pill". Despite evidence of a bidirectional interaction between the endocannabinoid system and gonadal hormones, only very few studies have examined the consequences of cannabis consumption in young females under hormonal contraceptives treatment. To fill this gap, this study evaluated the behavioral effects of co-exposure to chronic 1) hormonal contraceptives, i.e., ethinyl estradiol (EE) plus levonorgestrel (LNG), one of the synthetic estrogen-progestin combinations of hormonal contraceptives, and 2) cannabinoid receptor agonist, i.e., WIN 55,212-2 (WIN), on motor activity, emotional state and cognitive functions in young adult female rats (8-11/experimental group). Hormonal and cannabinoid treatment started at post-natal day (PND) 52 and 56, respectively, while behavioral testing occurred between PND 84-95. The results show that chronic EE-LNG treatment, at doses (0.020 and 0.060 mg/rat, respectively) known to drastically reduce plasma progesterone levels, and the contextual exposure to WIN, at a dose (12.5 µg/kg/infusion) known to be rewarding in the rat, alters the hormonal milieu but does not cause further changes in locomotor activity compared to EE-LNG or WIN alone, and does not modify anxiety-like state (as measured by the elevated plus maze and the marble burying tests) and cognitive abilities (as measured by the novel object recognition and the prepulse inhibition tests) in young adult female rats. Although exposure to EE-LNG and WIN tends to increase the duration of immobility and to reduce the time spent swimming in the forced swimming test, there was not a significant additive effect suggestive of a depressive-like state. These findings allow deepening the current knowledge on the interaction between cannabinoid agonists and hormonal contraceptives and suggest that low, rewarding doses of cannabinoids do not significantly alter the motor and cognitive skills and do not induce anxiety or depressive-like states in females that use hormonal contraceptives.
Assuntos
Canabinoides , Progesterona , Adulto Jovem , Feminino , Ratos , Humanos , Animais , Progesterona/farmacologia , Anticoncepcionais Orais Combinados/farmacologia , Canabinoides/farmacologia , Estradiol , EstrogêniosRESUMO
Hormonal contraceptives (HC) are widely used among women in reproductive ages. In this review, the effects of HCs on 91 routine chemistry tests, metabolic tests, and tests for liver function, hemostatic system, renal function, hormones, vitamins and minerals were evaluated. Test parameters were differently affected by the dosage, duration, composition of HCs and route of administration. Most studies concerned the effects of combined oral contraceptives (COC) on the metabolic, hemostatic and (sex) steroids test results. Although the majority of the effects were minor, a major increase was seen in angiotensinogen levels (90-375â¯%) and the concentrations of the binding proteins (SHBG [â¼200â¯%], CBG [â¼100â¯%], TBG [â¼90â¯%], VDBP [â¼30â¯%], and IGFBPs [â¼40â¯%]). Also, there were significant changes in levels of their bound molecules (testosterone, T3, T4, cortisol, vitamin D, IGF1 and GH). Data about the effects of all kinds of HCs on all test results are limited and sometimes inconclusive due to the large variety in HC, administration routes and dosages. Still, it can be concluded that HC use in women mainly stimulates the liver production of binding proteins. All biochemical test results of women using HC should be assessed carefully and unexpected test results should be further evaluated for both methodological and pre-analytical reasons. As HCs change over time, future studies are needed to learn more about the effects of other types, routes and combinations of HCs on clinical chemistry tests.
Assuntos
Hemostáticos , Laboratórios Clínicos , Feminino , Humanos , Globulina de Ligação a Hormônio Sexual , Anticoncepcionais Orais Combinados/farmacologia , Hormônios Esteroides Gonadais , Testosterona , Proteínas de TransporteRESUMO
The most prevalent endocrine and metabolic condition in women of reproductive age are polycystic ovary syndrome (PCOS) with significant risk factors such as circadian rhythm and melatonin disruption. The aim of this study is to assess the effect of vitamin E in combination with a combined oral contraceptive (COC) on continuous light-induced PCOS using hormonal measures, oxidative stress (OS) indicators, and the inhibin beta-A (INHBA) gene, which targets the melatonin protein kinase C (PKC) pathway. An in silico technique anticipated INHBA's binding affinity for vitamin E and COC. For the in vivo investigation (IAEC/240/2021), female SD rats were divided into six groups and subjected to a 16-week induction period, followed by a 2-month test drug treatment with drospirenone (DRSP) as a standard. Serum testosterone, FSH, melatonin, and OS were calculated as hormonal markers. The expression of the INHBA gene was studied to see if it could be linked to the circadian rhythm and OS via the melatonin PKC pathway. According to the in silico study, vitamin E and DRSP had higher binding energy for the INHBA (-8.6 kcal/mol and -8.4 kcal/mol, respectively). When compared to the control group, in vivo results showed a substantial decrease in testosterone levels (p = .05), as well as changes in FSH (p = .78) and melatonin (p = .13). IHNBA gene expression has also dramatically increased, stimulating FSH production in the pituitary gland. Vitamin E and COC concomitantly are beneficial against PCOS because it modulates OS, which in turn influences circadian rhythm and the melatonin PKC pathway.
Assuntos
Melatonina , Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Ratos , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Combinados/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Melatonina/farmacologia , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ratos Sprague-Dawley , Hormônio Foliculoestimulante , TestosteronaRESUMO
INTRODUCTION: Drospirenone/estetrol (DRSP/E4) is a combined oral contraceptive (COC) recently approved in several countries. It is composed of 15 mg of E4, a natural estrogen produced by human fetal liver throughout pregnancy, and 3 mg of DRSP, the first synthetic progestin used in oral contraception derived from 17-α-spirolactone. E4 and DRSP synergistically prevent pregnancy by inhibiting ovulation. E4 differs from 17-ß-estradiol or ethinylestradiol because it represents a native estrogen with selective action in tissues (NEST), therefore it displays both agonist and antagonist estrogenic effects in different tissues. AREAS COVERED: In this paper, we reviewed the scientific literature published in English prior to April 2023 and gathered information on the pharmacodynamics and pharmacokinetics of DRSP, E4 and their combination for contraception. We also proposed possible clinical applications based on the characteristics of the components of this COC. EXPERT OPINION: E4/DRSP-based COC has shown high tolerability, safety and satisfaction and may represent a viable choice in young girls in need of oral contraception and pill users who suffer from high cholesterol, breast tenderness or water retention. Moreover, this new COC shows higher scheduled bleeding rate compared to other pills containing natural estrogens. All the data are reassuring, permitting long-term use.
Assuntos
Androstenos , Anticoncepcionais Orais Combinados , Estetrol , Gravidez , Feminino , Humanos , Anticoncepcionais Orais Combinados/farmacologia , Estetrol/efeitos adversos , Etinilestradiol/farmacologia , EstrogêniosRESUMO
Background: Endogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake. Objective: We investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network. Methods: We recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users' salivary ethinyl estradiol (EE) were assessed using liquid chromatography - tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods. Results: Compared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs. Discussion: Our results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.
Assuntos
Anticoncepcionais Orais Combinados , Etinilestradiol , Adulto , Feminino , Humanos , Masculino , Anticoncepcionais Orais Combinados/farmacologia , Etinilestradiol/farmacologia , Congêneres da Progesterona , Medo , Encéfalo/diagnóstico por imagemRESUMO
Rates of tobacco and alcohol use in women are rising, and women are more vulnerable than men to escalating tobacco and alcohol use. Many women use hormonal birth control, with the oral contraceptive pill being the most prevalent. Oral contraceptives contain both a progestin (synthetic progesterone) and a synthetic estrogen (ethinyl estradiol; EE) and are contraindicated for women over 35 years who smoke. Despite this, no studies have examined how synthetic contraceptive hormones impact this pattern of polysubstance use in females. To address this critical gap in the field, we treated ovary-intact female rats with either sesame oil (vehicle), the progestin levonorgestrel (LEVO; contained in formulations such as Alesse®), or the combination of EE+LEVO in addition to either undergoing single (nicotine or saline) or polydrug (nicotine and ethanol; EtOH) self-administration (SA) in a sequential use model. Rats preferred EtOH over water following extended EtOH drinking experience as well as after nicotine or saline SA experience, and rats undergoing only nicotine SA (water controls) consumed more nicotine as compared to rats co-using EtOH and nicotine. Importantly, this effect was occluded in groups treated with contraceptive hormones. In the sequential use group, both LEVO alone and the EE+LEVO combination occluded the ability of nicotine to decrease EtOH consumption. Interestingly, demand experiments suggest an economic substitute effect between nicotine and EtOH. Together, we show that chronic synthetic hormone exposure impacts nicotine and EtOH sequential use, demonstrating the crucial need to understand how chronic use of different contraceptive formulations alter patterns of polydrug use in women.
Assuntos
Nicotina , Ovário , Feminino , Humanos , Animais , Ratos , Nicotina/farmacologia , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Combinados/uso terapêutico , Estradiol , Progestinas/farmacologia , Hormônio Foliculoestimulante , Etanol/farmacologia , Água/farmacologiaRESUMO
The oral contraceptive pill, 'the pill', was introduced in the starting of the 1960s. Presently, worldwide about 100 million women are current users of combined hormonal contraceptives (COC) most frequently used in the western world. The most frequently used agents are a combination of drugs containing both the estrogen and progesterone. This combination is considered to be highly efficacious, generally considered 99.9% and a use effectiveness of 97.0% to 98.0%. This study was done to evaluate the changes of Body Mass Index (BMI) and Blood pressure ( BP) in combined oral contraceptive pill users in comparison to non- users. This cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2021 to June 2022. Total number of 120 reproductive aged women, age ranged from 15-55 years was included in this study. Among them, sixty (60) combined oral contraceptive pill users subjects were taken as study group (Group II) and sixty (60) age matched oral pill non users subjects were taken as control group (Group I). Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test and Pearson's correlation coefficient test. The mean±SD of BMI of control group (Group I) and study group (Group II) were 22.50±1.50 kg/m² and 27.64±1.28 kg/m² respectively. In study group (Group II) BMI was increased. Result is statistically highly significant (p<0.001). The mean±SD of systolic blood pressure of control group (Group I) and study group (Group II) were 111.17±8.51 mm of Hg and 127.50±6.14 mm of Hg respectively. In this study the mean±SD of diastolic blood pressure of control group (Group I and study group (Group II) were 75.58±5.05mm of Hg and 87.00±4.89 mm of Hg respectively. In study group (Group II) diastolic blood pressure was increased. Result is statistically highly significant (p<0.001). So the assessment of this parameter is important for early detection and prevention of complication related to combined oral contraceptive pill use for leading a healthy life.
Assuntos
Anticoncepcionais Orais Combinados , Estrogênios , Feminino , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Anticoncepcionais Orais Combinados/farmacologia , Índice de Massa Corporal , Pressão Sanguínea , Estudos TransversaisRESUMO
Oral contraceptives (OCs) are one of the most common forms of hormonal birth control. A small literature suggests that OC use may affect visuospatial ability, episodic memory, and executive control. However, previous studies have been criticized for small sample sizes and the use of different, single cognitive tests. We investigated the degree to which biological sex and OC use might affect individual mental rotation, episodic memory, and executive control in a large sample of healthy, young adults (N = 155, including 52 OC users, 53 naturally cycling females, and 50 males) tested individually over videoconference. To measure cognition, we used a set of neuropsychological tasks inspired by Glisky and colleagues' two-factor episodic memory and executive control battery, from which two composite scores (based on principal component analysis) were derived for each participant. Our pre-registered analysis revealed a clear female advantage in episodic memory, independent of OC use. In an exploratory analysis, gist memory was elevated in OC users. Interestingly, we found no significant sex-related differences nor effects of OC use on mental rotation or executive control. Duration of OC use was also not related to any of our cognitive measures. These results suggest that the use of combined, monophasic OCs does not lead to many significant changes in cognition in young adults, although young females overall may have better episodic memory than young males. Additional studies, including longitudinal designs and looking in more detail at the menstrual cycle and OC use history, will further clarify the effects of different types of OCs and their duration of use on different aspects of cognition.
Assuntos
Memória Episódica , Masculino , Adulto Jovem , Humanos , Feminino , Anticoncepcionais Orais Combinados/farmacologia , Cognição , Testes NeuropsicológicosRESUMO
STUDY QUESTION: Does an estradiol-based combined oral contraceptive (COC) have a milder effect on the serum proteome than an ethinylestradiol (EE)-based COC or dienogest (DNG) only? SUMMARY ANSWER: The changes in serum proteome were multifold after the use of a synthetic EE-based COC compared to natural estrogen COC or progestin-only preparation. WHAT IS KNOWN ALREADY: EE-based COCs widely affect metabolism, inflammation, hepatic protein synthesis and blood coagulation. Studies comparing serum proteomes after the use of COCs containing EE and natural estrogens are lacking. STUDY DESIGN, SIZE, DURATION: This was a spin-off from a randomized, controlled, two-center clinical trial. Women (n = 59) were randomized to use either EE + DNG, estradiol valerate (EV) + DNG or DNG only continuously for 9 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were healthy, young, white volunteer women. Serum samples were collected before and after 9 weeks of hormonal exposure. Samples from 44 women were available for analysis (EE + DNG n = 14, EV + DNG n = 16 and DNG only n = 14). Serum proteins were analyzed by quantitative, discovery-type label-free proteomics. MAIN RESULTS AND THE ROLE OF CHANCE: Altogether, 446 proteins/protein families with two or more unique peptides were detected and quantified. The number of proteins/families that altered over the 9-week period within the study groups was 121 for EE + DNG and 5 for EV + DNG, while no changes were detected for DNG only. When alterations were compared between the groups, significant differences were detected for 63 proteins/protein families, of which 58 were between the EE + DNG and EV + DNG groups. The most affected functions during the use of EE + DNG were the complement system, acute phase response signaling, metabolism and the coagulation system. The results were validated by fetuin-B and cortisol-binding globulin ELISA and sex hormone-binding globulin immunoassay. LARGE SCALE DATA: Data are available via ProteomeXchange with identifiers PXD033617 (low abundance fraction) and PXD033618 (high abundance fraction). LIMITATIONS, REASONS FOR CAUTION: The power analysis of the trial was not based on the proteomic analysis of this spin-off study. In the future, targeted proteomic analysis with samples from another trial should be carried out in order to confirm the results. WIDER IMPLICATIONS OF THE FINDINGS: The EE-based COC exerted a broader effect on the serum proteome than the EV-based COC or the DNG-only preparation. These results demonstrate that the effects of EE in COCs go far beyond the established endpoint markers of estrogen action, while the EV combination is closer to the progestin-only preparation. The study indicates that EV could provide a preferable option to EE in COCs in the future and signals a need for further studies comparing the clinical health outcomes of COCs containing EE and natural estrogens. STUDY FUNDING/COMPETING INTEREST(S): Funding for this researcher-initiated study was obtained from the Helsinki University Hospital research funds, the Hospital District of Helsinki and Uusimaa, the Sigrid Juselius Foundation, the Academy of Finland, the Finnish Medical Association, the University of Oulu Graduate School, the Emil Aaltonen Foundation, the Swedish Cultural Foundation in Finland, the Novo Nordisk Foundation, Orion Research Foundation and the Northern Ostrobothnia Regional Fund. The funders had no role in study design, data collection and analysis, publishing decisions or manuscript preparation. T.P. has received honoraria for lectures, consultations and research grants from Exeltis, Gedeon Richter, MSD, Merck, Pfizer, Roche, Stragen and Mithra Pharmaceuticals. O.H. occasionally serves on advisory boards for Bayer AG and Gedeon Richter and has designed and lectured at educational events for these companies. The other authors have nothing to disclose. O.H. occasionally serves on advisory boards for Bayer AG and Gedeon Richter and has designed and lectured at educational events for these companies. The other authors have nothing to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02352090. TRIAL REGISTRATION DATE: 27 January 2015. DATE OF FIRST PATIENT'S ENROLMENT: 1 April 2015.
Assuntos
Etinilestradiol , Proteoma , Feminino , Humanos , Etinilestradiol/farmacologia , Levanogestrel/farmacologia , Progestinas , Proteômica , Estradiol/farmacologia , Anticoncepcionais Orais Combinados/farmacologia , EstrogêniosRESUMO
Millions of women around the world use combined oral contraceptives (OCs), yet surprisingly little is known about their central nervous system (CNS) effects. This article provides a short overview of the basic pharmacology of OCs, emphasizing features that may be relevant to understanding their effects in the CNS. Historical and recent findings from studies of cognitive function, mood, and negative affect (depressive changes under OC use) are then reviewed. We also present data from an archival dataset from our own laboratory in which we explore dysphoric changes in women using four generations of contraceptive progestins. Current data in the field are consistent with a modest effect of OC use on CNS variables, but conclusions based on current findings must be made very cautiously because of multiple methodological issues in many published studies to date, and inconsistencies in the findings. Directions for future research over the next 10 years are suggested. (150 words).
Assuntos
Anticoncepcionais Orais Combinados , Progestinas , Feminino , Humanos , Anticoncepcionais Orais Combinados/farmacologia , Sistema Nervoso CentralRESUMO
Combined oral contraceptives (containing synthetic forms of estradiol and progestins) are one of the most commonly used drugs among females. However, their effects on the gut-brain axis have not been investigated to a great extent despite clear evidence that suggest bi-directional interactions between the gut microbiome and endogenous sex hormones. Moreover, oral contraceptives are prescribed during adolescence, a critical period of development during which several brain structures and systems, such as hypothalamic-pituitary-gonadal axis, undergo maturation. Considering that oral contraceptives could impact the developing adolescent brain and that these effects may be mediated by the gut-brain axis, further research investigating the effects of oral contraceptives on the gut-brain axis is imperative. This article briefly reviews evidence from animal and human studies on the effects of combined oral contraceptives on the brain and the gut microbiota particularly during adolescence.
Assuntos
Anticoncepcionais Orais Combinados , Etinilestradiol , Feminino , Adolescente , Humanos , Anticoncepcionais Orais Combinados/farmacologia , Etinilestradiol/farmacologia , Saúde Mental , Eixo Encéfalo-Intestino , Hormônios Esteroides GonadaisRESUMO
The consumption of progestins has increased considerably in recent decades, as has their disposal into the environment. These substances can negatively affect the reproduction, physiology, and behavior of non-target organisms, such as fish. We aimed to evaluate the effects of exposure to environmentally relevant concentrations of levonorgestrel-control birth based (1.3, 13.3, 133, and 1330 ng/L) on the development and behavior of zebrafish (Danio rerio) in terms of mortality, hatching, spontaneous movement, and larval and adult behavioral tests. Exposure caused anxiogenic-like behavior in larvae, which persisted in adults, as demonstrated by the light-dark test. In contrast, it caused anxiolytic-like behavior in the novel tank test. There was a high mortality rate at all tested concentrations and increases in the hormone cortisol at 13.3 ng/L that affected the sex ratio. These changes may lead to an ecological imbalance, emphasizing the risk of early exposure to progestins in the environment.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Humanos , Animais , Feminino , Peixe-Zebra/fisiologia , Levanogestrel/toxicidade , Progestinas/toxicidade , Larva , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepção , Poluentes Químicos da Água/toxicidade , Embrião não MamíferoRESUMO
INTRODUCTION: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. MATERIAL AND METHODS: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). CLINICAL TRIAL REGISTRATION: NCT02352090. RESULTS: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. CONCLUSIONS: Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.
Assuntos
Anticoncepcionais Orais Combinados , Nandrolona , Adolescente , Adulto , Anticoncepcionais Orais Combinados/farmacologia , Estradiol , Estrogênios , Etinilestradiol/farmacologia , Feminino , Fibrina , Humanos , Levanogestrel , Nandrolona/farmacologia , Progestinas , Trombina , Tromboplastina , Adulto JovemRESUMO
AIM: This meta-analysis was conducted to compare the effect and safety of oral contraceptive pills (OCP) plus orlistat with OCP alone in clinical, hormonal, and lipid metabolism outcomes in patients with polycystic ovary syndrome (PCOS) and overweight/obesity. METHODS: Pubmed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and SinoMed were systematically reviewed. A random-effects or fixed-effects model was used to pool the estimate. RESULTS: Eight studies were included in this meta-analysis. Significant reductions in BMI, WHR, and waist circumference were observed in combination group as compared with OCP alone group. Regarding the hormonal outcome, T, SHBG, FAI, LH, DHEAS, FSH, and E2 levels were significantly improved in combination group compared with OCP alone group. However, the TT and FT did not change significantly between the two groups. Regarding the lipid metabolism outcomes, TC, LDL-C, and TG levels were reduced and HDL-C level was increased in the combination group. Regarding the insulin metabolism outcomes, FINS and HOMA-IR levels were reduced in combination group than in OCP group. The ovulation rate, pregnancy rate, and overall effective rate were significantly higher in combination group than in OCP alone group. Fewer complications were observed in the combination group than in OCP group, and the difference between them was significant. CONCLUSION: This combination treatment of OCP and orlistat was more effective than OCP alone in reducing the weight, hormonal, lipid, and insulin metabolism profiles, as well as improving the ovulation rate, pregnancy rate, and overall effective rate, as compared with OCP alone.