COC Use Research Articles

Targeted Cancer Therapy-on-A-Chip.

Targeted cancer therapy (TCT) is gaining increased interest because it reduces the risks of adverse side effects by specifically treating tumor cells. TCT testing has traditionally been performed using two-dimensional (2D) cell culture and animal studies. Organ-on-a-chip (OoC) platforms have been developed to recapitulate cancer in vitro, as cancer-on-a-chip (CoC), and used for chemotherapeutics development and testing. This review explores the use of CoCs to both develop and test TCTs, with a focus on three main aspects, the use of CoCs to identify target biomarkers for TCT development, the use of CoCs to test free, un-encapsulated TCTs, and the use of CoCs to test encapsulated TCTs. Despite current challenges such as system scaling, and testing externally triggered TCTs, TCToC shows a promising future to serve as a supportive, pre-clinical platform to expedite TCT development and bench-to-bedside translation.

Fraction of cancers attributable to and prevented by reproductive factors and exogenous hormones use in Italy

ObjectiveEndogenous and exogenous hormonal factors have been associated with female breast, genital, and colorectal cancer risk. The aim of the present study is to conduct an evidence-based evaluation of the fraction of cancers attributable to and prevented by exogenous hormonal (i.e., combined oral contraceptives [COC] and combined estrogen-progestogen menopausal therapy [CEPMT]) and reproductive factors (i.e., parity and breastfeeding) in Italy. Study designWe calculated the population attributable and prevented fractions combining relative risks and prevalence of exposure in Italian women. Italian cancer incidence and mortality data were extracted from national sources and used to estimate the number of cancer cases and deaths attributable to reproductive factors and exogenous hormones in Italy in 2020. For long-term effects, a 20-year latency period was considered. ResultsCOC were responsible for 4.4 % of breast and 10.9 % of cervical cancers in women aged 15–44, but also avoided 6.4 % of endometrial, 5.6 % of ovarian, and 2.9 % of colorectal cancers in women of all ages. Overall, COC use prevented 1174 cancer diagnoses and 577 cancer deaths. CEPMT caused 0.4 % of breast cancers at age 45–69. Low parity accounted for 8.1 %, 11.8 % and 15.5 % of breast, endometrial and ovarian cancers, respectively (6267 cases, 1796 deaths). Breastfeeding avoided 6.4 % of breast cancers (3775 cases, 897 deaths). ConclusionsOur analysis quantified the complex effects of hormonal and reproductive factors on cancer burden in Italian women.

Previous Use of Combined Oral Contraception in High Complexity Assisted Reproduction Treatments in Protocol with Oral Progestin – Previous use of COC and ART

Previous Use of Combined Oral Contraception in High Complexity Assisted Reproduction Treatments in Protocol with Oral Progestin – Previous use of COC and ART

Cognitive and psychoemotional changes in menopausal transition: The possibility of medical correction

The increasing of older age group in the population determines studying of age related diseases and emergence of new investigations in this area. In Female body, entering the menopausal transition is the start of «aging» of reproductive function and linked with decreasing of sex hormons levels. A direct connection between changes of estrogen, progesterone, androgen ratios and cognitive function of women was revealed. The anatomical localization of sex hormone receptors, the mechanisms of interaction of hormones with these receptors determine the ways of implementing biological effects of steroids on the CNS. Modern theories of «healthy nerve cells» and «eu-estrogenemia» explains the role of additional criteria, such as the absence of neurological diseases history and the duration of hypoestrogenia, to the outcome of menopausal hormone therapy. Additional factors that can affect to MHT action include: the composition of hormone therapy, administration methods, regimens (cyclic, continuous), duration of treatment, history of endocrine diseases, diabetes mellitus, gynecological history (parity, menarche age, COC use), heredity. The sections present the effect of menopausal transition on the development of depression, mood changes, sleep disturbances and mental disabilities. The explanation of negative effects of menopausal hormone therapy to cognitive health is also described by modern point of view. The ambivalent opinions of researchers, the potential of new reading of the results of earlier studies, confirms the necessity of continuing study of this topic.

Spironolactone Versus Oral Contraceptive Pills in the Treatment of Adolescent Polycystic Ovarian Syndrome: A Systematic Review.

Polycystic ovarian syndrome (PCOS) is a multi-system endocrinopathy that affects women of reproductive age. Due to features that coincide with puberty, it frequently remains undiagnosed in adolescent females. The lack of evidence on management alternatives has resulted in significant variation in practice. This systematic review evaluated the therapeutic advantages and adverse effects of a regularly used therapy option, combined oral contraceptive pills (COC/OCP) with spironolactone (SP), a newer alternative that may be used alone or in conjunction with other drugs to treat adolescent PCOS. A literature search was conducted using PubMed, PubMed Central, Scopus, and Google Scholar. It was restricted to studies published in English between 2021 and 2011 that discussed the management of adolescent PCOS with COC, SP, or both. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Two reviewers independently examined the content of the included studies using appropriate quality assessment tools. Four meta-analyses, four randomized controlled trials (RCTs), and one traditional review were found to be eligible. After extensive analysis, we concluded that SP, alone or in combination, is far safer than COC. However, COC treats more PCOS-associated symptoms than SP, including acne and menstrual irregularities, while also providing contraceptive benefits. However, SP monotherapy is cardioprotective and therapeutic when combined with other drugs. Long-term COC use has been linked to an increased risk of venous thromboembolism, hypertension, dyslipidemia, low-density lipoprotein (LDL) elevation, dysglycemia, and cancer in women.

The healthy female microbiome across body sites: effect of hormonal contraceptives and the menstrual cycle.

STUDY QUESTIONHow does hormonal contraceptive use and menstrual cycle phase affect the female microbiome across different body sites?SUMMARY ANSWERThe menstrual cycle phase, but not hormonal contraceptive use, is associated with the vaginal and oral but not the gut microbiome composition in healthy young women.WHAT IS KNOWN ALREADYWomen with low vaginal levels of Lactobacillus crispatus are at increased risk of pre-term birth, fertility treatment failure, sexually transmitted infections and gynaecological cancers. Little is known about the effect of hormonal fluctuations on other body site’s microbiomes as well as the interplay between them.STUDY DESIGN, SIZE, DURATIONThis study includes a cohort of 160 healthy young Danish women using three different contraceptive regimens: non-hormonal methods (n = 54), combined oral contraceptive (COC, n = 52) or levonorgestrel intrauterine system (LNG-IUS, n = 54). Samples were collected from four body sites during the menstrual cycle (menses, follicular and luteal phases) at Copenhagen University Hospital, Rigshospitalet, Denmark.PARTICIPANTS/MATERIALS, SETTING, METHODSThe oral, vaginal, rectal and faecal microbiomes were characterized by shotgun sequencing. Microbial diversity and community distance measures were compared between study groups, menstrual phase timepoints and body sites. All participants answered an extensive questionnaire on current health, lifestyle and sex life. Confounding factors such as smoking, BMI and diet were analysed by PERMANOVA. Plasma oestradiol and progesterone levels are correlated with microbiome composition.MAIN RESULTS AND THE ROLE OF CHANCEThe use of COC and LNG-IUS was not associated with the microbiome composition or diversity. However, increased diversity in the vaginal microbiome was observed during menses, followed by a subsequent expansion of Lactobacillus spp. during the follicular and luteal phases which correlated with measured serum oestradiol levels (r = 0.11, P < 0.001). During menses, 89 women (58%) had a dysbiotic vaginal microbiome with <60% Lactobacillus spp. This declined to 49 (32%) in the follicular phase (P < 0.001) and 44 (29%) in the luteal phase (P < 0.001). During menses, bacterial richness and diversity in saliva reached its lowest point while no differences were observed in the faecal microbiome. The microbiome in different body sites was on average more similar within the same individual than between individuals, despite phase or hormonal treatment. Only the vagina presented a clear cluster structure with dominance of either L. crispatus, Lactobacillus iners, Gardnerella vaginalis or Prevotella spp.LARGE SCALE DATAThe microbiome samples analysed in this study were submitted to the European Nucleotide Archive under project number PRJEB37731, samples ERS4421369–ERS4422941.LIMITATIONS, REASONS FOR CAUTIONThe cohort is homogenous which limits extrapolation of the effects of ethnicity and socio-economic status on the microbiome. We only present three defined timepoints across the menstrual phase and miss potential important day to day fluctuations.WIDER IMPLICATIONS OF THE FINDINGSThe use of hormonal contraception did not significantly associate with the microbiome composition in the vagina, faeces, rectum or saliva in healthy young women. This is a welcome finding considering the widespread and prolonged use of these highly efficient contraceptive methods. The menstrual cycle is, however, a major confounding factor for the vaginal microbiome. As such, the time point in the menstrual cycle should be considered when analysing the microbiome of women of reproductive age, since stratifying by vaginal dysbiosis status during menstruation could be misleading. This is the first study to confirm by direct measurements of oestradiol, a correlation with the presence of L. crispatus, adding evidence of a possible hormonal mechanism for the maintenance of this desirable microbe.STUDY FUNDING/COMPETING INTEREST(S)This work was partly funded by the Ferring Pharmaceuticals through a research collaboration with The Centre for Translational Microbiome Research (CTMR) at the Karolinska Institutet (L.W.H., E.F., G.E. and I.S.-K.). Ferring Pharmaceuticals also funded the infrastructure to obtain the clinical samples at Copenhagen University Hospital ([#MiHSN01], M.C.K., Z.B., and H.S.N.). This work was also supported by funding from Rigshospitalet’s Research Funds ([#E-22614-01 and #E-22614-02] to M.C.K.) and Oda and Hans Svenningsen’s Foundation ([#F-22614-08] to H.S.N.). M.C.K., L.W.H., E.F., Z.B., G.E., L.E., I.S.-K. and H.S.N., are partially funded by Ferring Pharmaceuticals, which also provided funds for the collection and processing of the samples analysed in this study. H.S.N.’s research is further supported by Freya Biosciences and the BioInnovation Institute. H.S.N. has received honoraria from Ferring Pharmaceuticals, Merck A/S, Astra-Zeneca, Cook Medical and Ibsa Nordic. A.N.A. reports no competing interests.

Analysis of modern views on the uterine fibroids and methods of its treatment

Despite a significant amount of research on the pathogenesis, diagnosis and treatment of uterine fibroids, many questions remain unanswered today. The appearance and progressive growth of this formation is the result of a whole complex of disorders in the female body: neurohumoral, genetic, inflammatory and others that suppress reproductive function and worsen the course of the disease. Given the number of key factors in the pathogenesis and pathophysiology of uterine fibroids, the treatment of this group of patients should be comprehensive, aimed at early detection, treatment of concomitant gynecological diseases and correction of hormonal disorders.In recent decades, hormone therapy has been widely used for the conservative treatment of uterine hyperplastic diseases. However, according to some data, the use of COCs or intrauterine hormonal releasing system has a slight blocking effect on fibroid growth processes. Pharmacotherapy of the disease can be both a stage for preoperative preparation on the organ, and an independent unit for stabilizing the nodes and getting rid of surgical treatment. And although the results of conservative treatments indicate their effectiveness, it should be stated that the main method of treatment of uterine fibroids is surgery.In the age of endoscopic surgery, this discussion has not exhausted itself and the modern approach to the treatment of uterine fibroids dictates the expansion of indications for organ-sparing operations. The choice of their methodology should be considered and determined by the size, location, clinical picture of the disease and the feasibility of preserving menstrual and reproductive function of women. Laparoscopic myomectomy is considered a minimally invasive and less traumatic intervention, contributes to a favorable course of the postoperative period and reduces pain. With effective organ-sparing surgical treatment of uterine fibroids in women of reproductive age, the menstrual cycle is normalized, reproductive function is restored, and pregnancies usually occur in 1,5-2 years after surgery.Endoscopic treatments are now successfully used both for planning a pregnancy and for its onset. A significant amount of patients have an uncomplicated course of pregnancy and childbirth, even in the presence of multiple and small nodes. Of course, pregnant women with fibroids can not be considered as a homogeneous group of patients, clearly recommending the preservation of pregnancy. The predominant location and size of the tumor, the degree of pathological changes in the myometrium, the duration of the disease, the state of health of the woman, the age of the woman giving birth for the first time, determine different degrees of risk of pregnancy and childbirth for mother and fetus. The division of patients into risk groups allows to differentiate the question of the feasibility of maintaining pregnancy, to carry out appropriate clinical and laboratory examinations and preventive measures to prevent complications.

MATERNAL ESTROGEN-PROGESTIN IMPROVES CARDIAC GLUCOSE-6-PHOSPHATE DEHYDROGENASE ACTIVITY BUT AGGRAVATES TRIGLYCERIDE IN GESTATIONAL GLUCOCORTICOID-EXPOSED RATS

Objective: Glucocorticoids (GCs) are used in pregnant women to treat numerous medical disorders. Oral estrogen-progestin, a means of contraception that has been associated with cardiometabolic disturbances is widely used as a method of maternal contraception. We therefore sought to investigate the effects of maternal COC on dams that were exposed to late gestational GC. Design and method: Twenty-four female rats were mated to achieve timed pregnancy and delivery. They were randomly allotted into 4 groups of 6 rats each. Dams received COC (combination of 1.0 microgram ethinylestradiol and 5.0 microgram levonorgestrel) between 3rd and 11th week maternal with or without prior exposure to GC (dexamethasone; 0.2 mg/kg) between gestational days 14–19. Plasma corticosterone and insulin were determined by using ELISA. Triglyceride (TG), was measured by standardized enzymatic colorimetric method. Plasma and cardiac levels of glucose-6-phosphate dehydrogenase (G6PD), nicotinamide adenine dinucleotide phosphate (NADPH), oxidized glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), xanthine oxidase (XO), adenosine deaminase (ADA), uric acid, FFA, lactate, lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured by spectrophotometric method using assay kit Results: Data showed that late-gestational GC exposure led to insulin resistance (IR), increased cardiac ADA, XO, lactate, LDH, and disrupted cardiac G6PD-dependent antioxidant defenses. On the other hand, maternal COC treatment in dams not exposed to gestational GC led to IR, increased cardiac XO, LDH and defective cardiac G6PD-dependent antioxidant defenses. However, maternal COC with prior gestational GC exposure led to attenuated IR, cardiac ADA, UA, LDH, and improved cardiac G6PD-dependent antioxidant defenses but worsened cardiac TG accumulation when compared with dam with gestational GC exposure without maternal COC. Circulating corticosterone was comparatively elevated in the three experimental groups compared to dam without prior GC exposure and maternal COC treatment. Conclusions: The result provides evidence that late gestational GC exposure programs IR that is accompanied with increased ADA, lactate production and defective cardiac G6PD-dependent antioxidant defense, whereas maternal COC use resulted in IR and defective cardiac G6PD-dependent antioxidant defense. The study further suggests that maternal COC improves GC-programmed cardiovascular risk factors with enhanced cardiac TG accumulation.

Segurança do uso de contraceptivos orais combinados em pacientes com enxaqueca: revisão narrativa

Objetivo: Avaliar por meio de uma revisão narrativa a segurança do uso de AOC disponíveis, com o intuito de verificar quais formulações e doses são mais seguras para mulheres que apresentam enxaqueca. Além de verificar se há maior risco de eventos cardiovasculares relacionados ao uso de AOC nessas pacientes, comparando a ocorrência de AVE. Revisão Bibliográfica: A segurança do uso de AOC em mulheres que apresentam enxaqueca vem sendo estudada a anos. Com base nos estudos, fica bem estabelecido que o uso de AOC de altas dosagens em mulheres com enxaqueca, principalmente, com aura, pode elevar o risco de acidentes cardiovasculares, sendo mais comum a ocorrência de AVE. Além disso, esse risco se eleva ainda mais quando essas mulheres estão expostas a outros fatores de risco. Acerca dos AOC de baixa dosagem, os estudos ainda não estabelecem um padrão. Considerações finais: Conclui-se que há correlação do uso de AOC e enxaqueca para ocorrências de fenômenos cardiovasculares, principalmente quando consideramos enxaqueca com aura. Além disso, o risco de AVE varia de acordo com a dose de estrogênio utilizada, sendo que nos de baixas doses não há risco significativo para a ocorrência de AVE, porém ainda é notória a escassez de dados.

Катамениальный пневмоторакс как особая форма спонтанного пневмоторакса (обзор литературы)

Spontaneous pneumothorax is a common (more than 12.5% of all urgent conditions in thoracic surgery) life-threatening condition, statistically more commonly found in men with pulmonary emphysema. However, a rare and difficult diagnostic form of spontaneous pneumothorax that develops in more than 73% of women of reproductive age with thoracic endometriosis is spontaneous catamenial pneumothorax. In the prevailing majority of patients, this pneumothorax turns out to be right-sided and recurrent in more than 70% of cases. The “gold standard” for verification of thoracic endometriosis is the visual inspection of the chest organs and biopsy using video-assisted mini-thoracotomy (VATS). The signs of thoracic endometriosis detected intraoperatively include the identification of fenestrations of the diaphragm, endometriosis of the visceral pleura, bullae of various calibers, cicatricial changes in lung parenchyma, etc. There is no consensus on the tactics of patients´ management, however, the primary importance in the treatment of thoracic endometriosis and spontaneous catamenial pneumothorax as its main manifestation should be given to surgical interventions: suturing diaphragm defects, typical (anatomical) or atypical resection of the lungs in different volumes, pleurodesis to prevent the recurrence of pneumothorax, etc. The most effective pleurodesis methods are chemical pleurodesis with sterile talc, the use of YAG-ND and CO2 lasers. Apical pleurectomy is actively used; various materials (fibrin gel, polyglycolic acid, etc.) are being studied as suture-line coverage to create aerostasis. Along with surgical methods, the use of COCs, analogues of gonadotropin-releasing hormone, danazole, progestins, and aromatase inhibitors minimizes the recurrence of spontaneous pneumothorax in patients with thoracic endometriosis.

Papillary Thyroid Cancer-Promoting Activities of Combined Oral Contraceptive Components

Background: Thyroid cancer is more common in women at reproductive age, suggesting the relationship between its high-incidence and therapeutic use of hormonal medications, such as oral contraceptives (OCPs). The aim of this study was to identify the effect of low-dose combined OCP (LD-COC) on proliferation, apoptosis, and migration of human papillary thyroid cancer (PTC) BCPAP cell line. Materials and Methods: BCPAP cells were cultured and treated with the combination of 90nM levonorgestrel (LNG) and 20nM ethinylestradiol (EE) for 48 hours. Afterward, using 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay, the proliferation of the cells was measured. Apoptosis was determined by using a Caspase-3 ELISA kit. Migratory properties of combined LNG and EE were studied through wound scratch assay. The expression levels of pro-apoptotic factor BAX, anti-apoptotic factor Bcl2, and proliferation marker Ki67 were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting. Results: Upon treatment with the combination of LNG and EE, proliferation and migration of BCPAP cells were significantly enhanced. However, LNG and EE remarkably inhibited apoptosis of these cells. Furthermore, treating PTC cells with combined LNG and EE caused a marked increase in the expression of Bcl2 and Ki67 and a considerable decrease in BAX levels (P˂ 0.05). Conclusion: Our data linked the use of COCs and the progression and aggressiveness of PTC, suggesting the role of these hormonal compounds as promoting factors for PTC tumors. Despite these observations, further investigations will be required to fully establish the pathogenic impact of these medications on PTC. [GMJ.2020;9:e1648]

Papillary Thyroid Cancer-Promoting Activities of Combined Oral Contraceptive Components.

Background: Thyroid cancer is more common in women at reproductive age, suggesting the relationship between its high-incidence and therapeutic use of hormonal medications, such as oral contraceptives (OCPs). The aim of this study was to identify the effect of low-dose combined OCP (LD-COC) on proliferation, apoptosis, and migration of human papillary thyroid cancer (PTC) BCPAP cell line. Materials and Methods: BCPAP cells were cultured and treated with the combination of 90nM levonorgestrel (LNG) and 20nM ethinylestradiol (EE) for 48 hours. Afterward, using 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay, the proliferation of the cells was measured. Apoptosis was determined by using a Caspase-3 ELISA kit. Migratory properties of combined LNG and EE were studied through wound scratch assay. The expression levels of pro-apoptotic factor BAX, anti-apoptotic factor Bcl2, and proliferation marker Ki67 were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting. Results: Upon treatment with the combination of LNG and EE, proliferation and migration of BCPAP cells were significantly enhanced. However, LNG and EE remarkably inhibited apoptosis of these cells. Furthermore, treating PTC cells with combined LNG and EE caused a marked increase in the expression of Bcl2 and Ki67 and a considerable decrease in BAX levels (P˂0.05). Conclusion: Our data linked the use of COCs and the progression and aggressiveness of PTC, suggesting the role of these hormonal compounds as promoting factors for PTC tumors. Despite these observations, further investigations will be required to fully establish the pathogenic impact of these medications on PTC.

In vitro examination of the primary stability of three press-fit acetabular cups under consideration of two different bearing couples

BackroundFor preclinical statements about the anchoring behavior of prostheses, the primary stability of the prosthesis is of special importance. It was the aim of this study to examine and compare the relevant relative micromotions of three different acetabulum prostheses by introducing three-dimensional torques. MethodsThe cups were implanted under standard conditions into an anatomical artificial bone model. Three-dimensional torques were applied to the acetabular cups. Taking into account the resulting frictional moments of two different bearing couples, ceramic-on-ceramic and ceramic-on-polyethylene, the relative micromotions of the cups were recorded as maximum total micromotion, translational and rotational micromotion, and the primary stability values of the three cups were compared. ResultsRelative micromotion of all cup models was always significantly smaller with the CoC bearing couples than with the CoP bearing couples (p < 0.001). The rotational micromotion was always lower (p < 0.001) than the translational micromotion, and the rotational as well as the translational micromotions were each always lower than the maximum total micromotion (p < 0.001, p < 0.010). The thinnest-walled cup system always showed the largest relative micromotions. ConclusionThe results of our study can be interpreted as indicating that the low relative micromotions of all cups – irrespective of the use of CoC or CoP bearing couples – are within an acceptable range favoring secondary osseointegration of the implants. Furthermore, we were able to show that the cup wall thickness and the surface quality of the cup systems have an influence on the primary stability and the elastic deformability of the examined cup systems.

Use of the IEEE Codes of Conduct to Resolve Legal Disputes

We describe an important trend: increasing use by the US judicial system of CoCs to resolve disputes. Specifically, CoCs are being used to judge, literally, the performance of non-code subscribers and unaffiliated organizations. We illustrate successful use of an IEEE CoC at arbitration, resulting in a multi-million dollar judgment against an organization having no IEEE members. Our fictionalized 'case' is a compilation of real cases – an ERP system implementation failure. Plaintiffs faced a common dilemma: an inability to determine applicable ‘standards of care.’ These disputes were won as a direct result of using the IEEE CoC to compare and contrast human and organizational behaviors. Although the implications of this factual trend are unclear, use of such a technique has reached a 'tipping point.' We hope to spark discussion leading to more beneficial outcomes for the IEEE Computer Society, the IEEE, our professional community, and for the information technology (IT), business and consulting communities.

OVARIAN RESERVE PARAMETERS IN WOMEN USING NO CONTRACEPTION, USING ORAL CONTRACEPTION OR IUCD

Background:- The Pill is one of the most popular forms of contraception ,its use is different in different countries, and among women of different ages and levels of education. Oral contraceptives may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain. The main goal of ovarian reserve testing is to identify those individuals who are at risk of decreased or diminished ovarian reserve. Objective:- To quantify endocrine and sonographic parameters of ovarian reserve in women using combined oral contraceptive pills and comparing them with IUCD users and non contraceptive users . Patients and methods:- Cross sectionl study included 100 healthy volunteer women divided into 35 COC users (all using monophasic preparations, ethinylestradiol 30&35ug and progestin, norgestimate and gestodene) and 65 non-users (35 IUCD users and 30 non contraceptive users). On day 2–5 of the menstrual cycle or during withdrawal bleeding, blood sampling to measure anti-mullerian hormone(AMH) and transvaginal ultrasonography to measure antral follicle count(AFC) and ovarian volume were performed. Results:- ovarian reserve parameters were significantly lower among COC users than non-users of hormonal contraception(IUCD users nAFC,P -.006; ovarian volume, P-.001 . Further more we found that AFC of intermediate (5–7 mm) and large (8–10 mm) size categories were significantly lower in COC users than non-users with p value .001 .while that of small ( 2–4 mm) size were increased P-.001. Also negatively linear association was observed between duration of COC use and ovarian reserve parameters. Conclusion:- This study indicates that ovarian reserve markers (AMH, AFC&ovarian volume) are lower in women using COC compared to IUCD users and non contraceptive users.

Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone.

Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed.Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e.g. acne vulgaris in some countries are allowed clinical entities for the use of these drugs). Therefore, appropriate discussions with the patient regarding this fact should performed and documented by the prescribing physicians.Independent of the off-label situation, COCs containing the newer progestogens dienogest and drospirenone with their antiandrogenic and antimineralocorticoid health benefits play an important role in the management of many diseases and their use should therefore be considered by clinician’s.This review will focus on the effects of these COCs on the endometrium, the skin, the fat tissue and the premenstrual syndrome.

Drospirenone‐containing combined oral contraceptives and the risk of arterial thrombosis: a population‐based nested case‐control study

To compare the rate of arterial thromboembolism (ATE) of drospirenone-containing COCs to that of levonorgestrel-containing COCs. Population-based cohort study. United Kingdom's Clinical Practice Research Datalink (CPRD), which contains clinical records for >11 million patients. Women aged 16-45 years prescribed a drospirenone- or levonorgestrel-containing COC between May 2002 and June 2012. We conducted nested case-control analyses using risk set sampling to randomly select up to 10 controls for each ATE case, matched on age, cohort entry year, CPRD registration year, COC user type (first-time ever, new, switcher, or prevalent users), duration of COC use, duration of progestin-only or implantable contraceptive use, pre-cohort entry duration of drospirenone and levonorgestrel use, and duration of follow up. We used conditional logistic regression to estimate hazard ratios and 95% confidence intervals (CIs), adjusted for high-dimensional propensity scores. Our cohort included 339 743 women followed over a mean 4.4 years, during which 228 ATE cases occurred: 37 myocardial infarctions, 170 strokes, and 21 other ATEs; overall rate: 1.5 events per 10 000 person-years (PYs). After adjusting for potential confounders, the hazard ratio for ATE with current use of drospirenone-containing COCs versus current use of levonorgestrel-containing COCs was 0.89 (95% CI 0.35, 2.28), corresponding to a rate difference of -0.16 events per 10 000 PYs. The overall rate of ATE in this population is low regardless of which COC was taken. We found little evidence of a difference in the rate of ATE with drospirenone- versus levonorgestrel-containing COCs. Little evidence was found of a greater incidence of arterial thrombosis with drospirenone versus levonorgestrel contraceptives.

Cannabis use, schizotypy, and attentional inhibition

Results: In aggregate, among 206 NICU with no TS, CDTP estimate = 7.4% (95% CI = 0.1%, 14.6%). The CDTP estimate is 4.0% for 413 NICU with past TS >12 months before test date (95% CI = 1.8%, 6.1%). As K–K might predict, larger CDTP estimates are seen when TS occurred during the COC onset interval (CDTP = 7.5%; 95% CI = 6.2%, 8.6%). These subgroup estimates are >10% for TS initiates with concurrent rapid-onset TD (CDTP = 11.8%; 95% CI = 3.9%, 30.4%) and for past-onset persistent TS with TD during COC onset interval (CDTP = 10.0%; 95% CI = 7.8%, 12.2%). Conclusions: In initial estimates, NICU with active TS and TD have larger CDTP, tending to support K–K ‘priming’ hypothesis. We now seek more refined NSDUH data to increase estimate precision, include other nicotine products, and clarify timelines to identify the nature of ‘nicotine pre-treatment’ in this epidemiological context. In humans, rapid-onset TD might be more important than TS pre-treatment, per se, although time from 1st to 2nd nicotine use and time from 1st to 2nd COC use deserve attention as individuallevel markers of a subject-specific reinforcing function of these compounds.

Рациональная контрацепция: как свести риск к минимуму?

The use of COCs, even low - and microdosed should be based on an individual assessment of the risk of thrombotic complications. It is advisable to combine the COC together with multivitamin complexes that affect the hemostatic system in the first place, vascular endothelial component (Duovit® for women). The therapeutic use of COCs in women high risk of VTE may together with antithrombotic drugs (heparin and LMWH).

Abstract 5575: Effects of continuous combined oral contraceptives on mouse mammary gland structure and tumor progression

Abstract The breast goes through cycles of cell growth, differentiation and regression with every estrous/menstrual cycle, driven by hormonal stimulation followed by hormone withdrawal. The number of cycles over a lifetime is positively associated with breast cancer risk. This increased risk may be the result of hormone-stimulated epithelial growth, inflammatory tissue remodeling processes during hormone withdrawal, or both. The use of cyclic combined oral contraceptives (cyclic COC), which incorporates a hormone withdrawal period in each cycle, has been associated with an increased risk of breast cancer, particularly in African American women, current COC users, and women who initiated COC use early in life. In contrast, the effect of extended-use (i.e., continuous) COC on breast cancer risk has not been evaluated. The purpose of the current study was to test the hypothesis that continuous exposure to COC is not associated with the increased risk observed with cyclic COC, and may even provide protection against breast cancer, by removal of the hormone withdrawal phase. Starting at day 50 of age (to mimic COC exposure in young women), BALB/C mice were fed liquid diets +/- supplementation with 0.0041 mg/kg ethinyl estradiol and 0.0185 mg/kg levonorgestrel (dose calculated by surface area conversion from the human COC dose of 20 µg ethinyl estradiol and 90 µg levonorgestrel). After 28 days, 10 mice per group were sacrificed and mammary glands dissected for whole mount and histologic analysis. An additional 20 mice per group were injected orthotopically with 10e5 syngeneic TM2H mammary epithelial tumor cells, and tracked for tumor latency, growth and tumor burden. The extended COC group showed 65% increase in mammary gland epithelial density compared to control. However, this increased epithelial density was associated with an increased alveolar branching and a decrease in carcinogen-sensitive terminal end buds. These results suggest that short term exposure to continuous COC can induce a more differentiated state in nonparous mouse mammary glands. In mice transplanted with tumor cells, the continuous COC group showed significantly increased tumor latency and decreased tumor burden, compared to controls. These results demonstrate that continuous COC administration, despite the higher levels of hormone exposure, can render the mouse mammary gland less susceptible to the growth of transplanted tumor cells. Mechanistic studies are ongoing. Citation Format: Evelyn Esteves, Sherin David, Dawn Bowers, Brian MacQueen, Melanie Ruszczyk, Dhruv Chachad, Rajani Marthappa Shenoy, Patricia A. Masso-Welch. Effects of continuous combined oral contraceptives on mouse mammary gland structure and tumor progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5575. doi:10.1158/1538-7445.AM2014-5575