Combined Oral Contraceptives Research Articles

Drovelis: an oral contraceptive with drospirenone and estetrol

Drovelis is a new combined oral contraceptive (COC) containing drospirenone and estetrol. This article discusses its dosing requirements, clinical trial efficacy and adverse effects.

Peculiarities of the course of genital endometriosis and its recurrence in women of reproductive age

Endometriosis remains one of the most studied pathologies in modern gynecology, as it is accompanied by such complications as constant pelvic pain, menstrual cycle disorders, and infertility. These complications not only prevent the implementation of a woman’s reproductive function, but also worsen the normal life of a woman in general. The early diagnosis and the right choice of treatment is the basis of prevention of disease recurrence. Therefore, most of the efforts of scientists are directed to this.The objective: to reduce the frequency of genital endometriosis recurrence and improve the implementation of reproductive functions based on the improved approaches to its diagnosis and treatment.Materials and methods. The study included two groups of patients. The 1st group included 60 women with a diagnosis of ovarian endometriosis, whose data were analyzed retrospectively based on the results of medical histories. The 2nd group was studied prospectively and included 60 women with a diagnosis of ovarian endometriosis.All patients had general clinical and laboratory examinations, specific laboratory and ultrasound examinations. In patients of the 2nd group tumor markers were additionally determined, in particular CA-125, HE4, CA 19-9, CA 72-4, CA 15-3, REA, and the level of anti-Müllerian hormone, magnetic resonance imaging was performed. Patients of both groups were operated and histological examination of the material obtained during the operation was performed.The difference in the management of the postoperative period in the 2nd group was that, in addition to anti-inflammatory therapy all women received hormonal therapy (gonadotropin-releasing hormone agonist (GnRH agonist) with subsequent use of combined oral contraceptives (COCs) or simultaneous use of GnRH agonist and COCs with subsequent transition in both variants for dienogest for 6 months continuously). Recurrence of the pathology was detected after 3 and 6 months on the basis of a repeated diagnosis of ovarian endometriosis.Results. The obtained data showed that in the postoperative period, 3 months after treatment 5 (8.3 %) women in the 1st group had a recurrence of ovarian endometriosis and 4 (6.7 %) patients – pelvic adhesions. Whereas in the 2nd group, there were no cases of recurrence and adhesions.In 6 months after treatment in the 1st group 11 (18.3 %) patients were diagnosed with ovarian endometriosis recurrence, and 6 (10.0 %) women were diagnosed with pelvic adhesions. In the 2nd group recurrence of ovarian endometriosis was found only in 1 (1.7 %) woman, pelvic adhesions were not detected (p<0.05). During the year after treatment the number of pregnant women among persons who wished to become pregnant and had a history of infertility was statistically higher in the 2nd group compared to the 1st group, in particular, 10 (16.7 %) and 2 (3.3 %) women, respectively (p<0.05).Conclusions. The proposed algorithm for the diagnosis and treatment of genital endometriosis minimizes the risk of its recurrence and improves reproductive function.

КОНТРАЦЕПЦИЯ ПОСЛЕ АБОРТА: ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ

It is important to choose a combined oral contraceptive (COC) after an abortion operation, since the requirements for a contraceptive prescribed during this period have their own specifics. It is necessary to stop as many negative consequences for the woman's body caused by the termination of pregnancy and, in addition, to ensure maximum safety of the prescribed drug. The relevance of this topic is due to the need to choose the safest and most effective contraceptive. A study was conducted of the effect of monophasic low-dose COCs, which is a combination of 0.15 mg levonorgestrel and 0.03 mg eeinylestradiol 0.03 mg in each tablet (PlaniGenslevo) on the state of the body and endothelial function in 22 women of reproductive age using the drug for 3 months after an artificial abortion and belonging to the first category of acceptability of COCs. As a control, the results of a test with reactive hyperemia were evaluated in 22 healthy women aged 19 to 35 years. As a result of the study, there was no increase in body mass index, blood pressure, changes in metabolic parameters in the biochemical analysis of blood, as well as an increase in the duration of menstrual bleeding, the absence of intermenstrual bleeding, as well as breast swelling, headaches, dyspeptic phenomena and other adverse events that may be caused by taking COCs in women using Women's Left within 3 months. The conducted study demonstrated the absence of adverse events on the part of the body of women taking after abortion Plani Women left. In addition, there were no statistically significant changes compared to the control group in the results of the test with reactive hyperemia, reflecting the absence of endothelial dysfunction in women using the contraceptive Plani Women left, which can serve as confirmation of the absence of a negative effect of the drug on the cardiovascular system.

Efficacy of Dienogest on Pelvic Pain and Dyspareunia: Comprehensive Meta-Analysis and Systematic Review

Introduction: Endometriosis is a severe disorder marked by endometrial tissue outside the uterus and linked to infertility, although typically manifesting as discomfort in the form of dysmenorrhea, dyspareunia, and pelvic pain. Dienogest is indicated as a first-line hormone treatment for endometriosis-related discomfort. The aim of this study is to analyze the efficacy of Dienogest on treating pelvic pain and dyspareunia compared to placebo or combined oral contraceptives (COC) in women with endometriosis. Methods: A systematic search is conducted in PubMed, ScienceDirect, and Google Scholar. The PRISMA 2020 rules were used to screen the articles that were obtained. For the review, studies that examined how using dienogest in improving endometriosis were exposed to were taken into consideration. In a meta-analysis utilizing a random-effects model, odds ratios with their 95% confidence intervals (CI) were provided. Results: Five studies that met the criteria for inclusion were determined to be pertinent to the association between using dienogest in improving endometriosis (n=711). The Dienogest group had substantially improve pelvic pain with a mean difference of 1.01 (95% CI 1.2, 0.82; p<0.00001) and dyspareunia with a mean difference of 0.58 (95% CI 1.09, 0.08; p=0.02) compared to placebo. Compared to combined oral contraceptives, COC had substantially improves dyspareunia with a mean difference of 0.99 (95% CI 0.62, 1.37; p<0.00001) and pelvic pain with a mean difference of 1.15 (95% CI 0.23, 0.83; p=0.01). Conclusion: Dienogest should be considered as an alternate treatment for endometriosis-related symptoms. In double-blind research, DNG efficacy was compared to placebo.

A Multi-Institutional Informed Consent Proposal as a Prevention Tool for Combined Oral Contraceptive Intake and Thrombotic Risk.

The review of relevant literature and international guidelines on prescription of combined oral contraceptives made it possible to create a proposal for informed consent to be used for prescribing. The several sections of our consent proposal were designed according to a rationale in order to cover all the aspects presented by worldwide guidelines: how to take, adverse effects, advertisements, extra-contraceptive benefits and effects, a checklist for condition at risk of thromboembolism, the signature of the woman. An informed consent to standardize combined oral contraceptives prescription can improve women's eligibility, mitigate thromboembolic risk, and assure legal protection to healthcare providers. In this systematic review in particular, we refer to the Italian medical-legal scenario, to which our group of researchers belongs. However, the model proposed was designed in the respect of main healthcare organization guidelines, and it could be easily used by any center in the world.

Combined oral contraceptives as victims of drug interactions.

Combined oral contraceptives (COCs) are widely used in women of reproductive age in the United States. Metabolism plays an important role in the elimination of estrogens and progestins contained in COCs. It is unavoidable that a woman using COCs may need to take another drug to treat a disease. If the concurrently used drug induces enzymes responsible for the metabolism of progestins and/or estrogens, unintended pregnancy or irregular bleeding may occur. If the concurrent drug inhibits the metabolism of these exogenous hormones, there may be an increased safety risk such as thrombosis. Therefore, for an investigational drug intended to be used in women with reproductive potential, evaluating its effects on the pharmacokinetics of COCs is important to determine if additional labeling is necessary for managing drug-drug interactions between the concomitant product and the COCs. It is challenging to determine when this clinical drug interaction study is needed, whether an observed exposure change of progestin/estrogen is clinically meaningful, and if the results of a clinical drug interaction study with one COC can predict exposure changes of unstudied COCs to inform labeling. In this review, we summarize the current understanding of metabolic pathways of estrogens and progestins contained in commonly used COCs, known interactions of these COCs as victim drugs, and discuss possible mechanisms of interactions for unexpected results. We also discuss recent advances, knowledge gaps, and future perspectives on this important topic. The review will enhance the understanding of DDIs with COCs and improve the safe and effective use of COCs. Significance Statement This minireview provides an overview of the metabolic pathways of ethinyl estradiol (EE) and progestins contained in commonly used COCs and significant drug interactions of these COCs as victims. It also discusses recent advances, knowledge gaps, and future perspectives and provides insights on potential mechanisms for unexpected results of clinical drug interaction studies of COCs. This minireview will help the reader understand considerations when evaluating the drug interaction potential with COCs for drugs that are expected to be used concurrently.

Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis.

Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.

The role of female sex hormones and oral combined contraceptives in metabolic adaptations.

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Effect of contraceptive hormonal therapy on mammographic breast density: A longitudinal cohort study

PurposeEvaluate the longitudinal relationship between mammographic density and hormonal contraceptive use in late reproductive-aged women. MethodsPatients aged 35–50 years old who underwent 5 or more screening mammograms within a 7.5-year period between 2004 and 2019 in a single urban tertiary care center were randomly selected. Patients were categorized into four cohorts based on hormonal contraceptive exposure during a 2-year lead-in period and a 7.5-year study period: 1) never exposed, 2) always exposed, 3) interval hormonal contraceptive start, and 4) interval hormonal contraceptive stop. The primary outcome was difference in BI-RADS breast density category between initial and final mammograms. ResultsOf the 708 patients included, long-term use of combined oral contraceptives or a levonorgestrel intrauterine device were not associated with an increase in breast density category over the 7.5-year study period, compared to those with no hormonal contraceptive exposure. Initiation of combined oral contraceptives was associated with an increase in breast density category (β = 0.31, P = 0.045); however, no difference in initial density category was noted between those exposed and those never exposed to combined oral contraceptives during the 2-year lead-in period, and discontinuation was not associated with a decrease in breast density category when compared to those with continuous exposure. Conclusion(s)Long-term use of combined oral contraceptives or a levonorgestrel intrauterine device was not associated with an increase in BI-RADS breast density category. Initiation of a combined oral contraceptive was associated with an increase in breast density category, although this may be a transient effect.

Perception of oral contraception – do women think differently from gynaecologists?

Purpose This study aimed to assess the experience and satisfaction with contraceptives and use of Combined Oral Contraceptives (COC) by women and compare their perceptions with those of gynaecologists. Methods This was a multicentre survey study conducted in Portugal, during April and May, 2021 with women using contraceptives and gynaecologists. Online quantitative questionnaires were carried out. Results A total of 1508 women and 100 gynaecologists were included. Cycle control was the pill non-contraceptive benefit most valued by gynaecologists and women. For gynaecologists, the main pill concern was the risk of thromboembolic events, but they believed that weight gain was the main concern for their patients. The pill was the most used contraceptive (70%) and women were largely (92%) satisfied. The pill was associated with health risks for 85% of users, mainly thrombosis (83%), weight gain (47%), and cancer (37%). The attributes of the pill most valued by women are contraceptive efficacy (82%), followed by low risk of thromboembolic events (68%), good cycle control (60%), non-interference with libido and mood (59%) and weight (53%). Conclusion Most women use contraceptive pills and are generally satisfied with their contraceptive. Cycle control was the most valued non-contraceptive benefit for gynaecologists and women, agreeing with physicians’ beliefs about women. On the other hand, contrary to physicians’ beliefs, that women’s main concern is weight gain, women are mainly concerned with risks associated with contraceptives. Thromboembolic events are women’s and gynaecologists most valued risk. Finally, this study indicates the need for physicians to better understand what COC users really fear.

Mental health, Reproductive health and contraception: pharmacological interaction, current evidence and challenges

IntroductionMental pathology is relatively prevalent in the women, and there is often a need for treatment with psychotropic drugs, with an impact on women’s reproductive health. The use of contraception is widely spread among this population and the choice between these methods must be considered carefully.ObjectivesThis review aims to present the main interactions between contraceptive methods and psychotropic therapy and its impact on psychiatric disorders, in addition to the precautions to be taken in their choice.MethodsLiterature review of relevant articles on Pubmed. Query: Contraceptive+(psychiatric disorder, depression, anxiety, schizophrenia, bipolar disorder, psychotropic drugs).ResultsBased on current evidence, no statistically significant differences regarding unplanned pregnancy rates or the psychotropic treatment outcomes were found when using combined oral contraceptives and antidepressants, benzodiazepines or atypical antipsychotics (being clozapine the exception). The impact of contraceptive methods on mood was unclear, as some articles showed an association between contraceptive use and a higher risk of beginning antidepressants and others showing no differences or even as a protective factor. Although the interactions of the aforementioned drugs are infrequent, there are cases where important interactions occur, such as clozapine, valproic acid, lamotrigine and carbamazepine, as some herbal products as the St.John’s wort. With clozapine, there is an increased serum concentrations, while the opposite occurs in the case of valproate and lamotrigine with a decrease of 32.6% and 23.4%, respectively. Treatment with valproic acid in women of childbearing age has been discouraged because of its association with polycystic ovary syndrome, elevated testosterone concentrations and menstrual irregularities, in addition to the risk of fetal malformations. In cases where this drug is prescribed, it is recommended to use highly effective methods such as subcutaneous implants or intrauterine devices. Lamotrigine and carbamazepine reduce the effectiveness of some contraceptive methods, such as oral contraceptives, transdermal patch and vaginal ring, in which case the placement of a subcutaneous implant or intrauterine device is indicated.ConclusionsThe magnitude of the impact between contraceptives, regarding depressive disorders, is unclear. The evidence shows that some women report the appearance and recrudescence of depressive symptoms, evidencing the need of further studies to identify the risk factors in these cases. The importance of clear and simple information and a shared decision on which contraception to choose is crucial, as clarification about their interactions with psychiatric treatment. The clinician must also be aware of the implications for reproductive health, in order to reduce the risks and side effects associated with some drugs.Disclosure of InterestNone Declared

Combined Hormonal Contraception - Which Pill for Which Patient?

Combined Hormonal Contraception - Which Pill for Which Patient? Abstract. Combined hormonal contraceptives (CHC) are a valuable and highly effective option in contraceptive counseling. Methods and preparations available in Switzerland are combined oral contraceptives (COC), vaginal rings and transdermal patches. All preparations contain an estrogen and a progestin component. The estrogen component mainly consists of the synthetically produced ethinylestradiol (EE), although newer COC may contain natural estrogens such as estradiol (E2) and estetrol (E4). For the progestin component, a variety of luteal body hormones are available, which enable the health care professional to prescribe a "tailored" product for the patient due to their different partial effects. The individual thromboembolism (TE) risk should always be considered and taken into account when prescribing CHC.

Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years

BackgroundMenopausal hormone therapy (MHT) can elevate venous thromboembolism (VTE) risk, but less is known about formulations and routes of exposures. ObjectiveTo estimate hormone-associated VTE risk by route and formulation in exposed and unexposed women aged 50 to 64 years in the US. MethodsIn a nested case-control study of US commercially insured women aged 50 to 64 years (2007-2019), cases were defined as incident VTE diagnoses and matched to 10 controls by date of VTE and age, excluding prior VTE, inferior vena cava filter placement, or anticoagulants. Filled prescriptions in the prior year defined hormone exposures. International Classification of Diseases and Current Procedural Terminology codes identified risk factors and comorbidities. ResultsOdds ratios (ORs) were estimated with conditional logistic regression controlling for differences between cases (n = 20,359) and controls (n = 203,590) in comorbidities and VTE risk factors. For exposures within 60 days, oral MHT risk was almost twice as high as transdermal MHT (OR = 1.92; 95% CI, 1.43-2.60); transdermal MHT did not elevate risk compared with no exposure (unopposed OR = 0.70; 95% CI, 0.59-0.83; combined OR = 0.73; 95% CI, 0.56-0.96). Risk was highest for MHT combinations with ethinyl estradiol, followed by conjugated equine estrogen (CEE) (ethinyl estradiol-CEE: OR = 1.55; 95% CI, 1.07-2.25), and lowest for estradiol (CEE-estradiol: OR = 1.33; 95% CI, 1.02-1.72). Combined hormonal contraceptives elevated risk 5 times higher than no exposure (OR = 5.22; 95% CI, 4.67-5.84) and 3 times higher than oral MHT (OR = 3.65; 95% CI, 3.09-4.31). ConclusionThe risk of VTE is much lower with MHT than combined hormone contraceptives and varies by hormone formulation and route of exposure. Transdermal MHT did not elevate risk. Oral MHT combinations with estradiol were lower risk than other forms of estrogen. Oral combined hormone contraceptives had much higher risk than oral combined hormonal MHT.

Abstract P3-03-27: Assessment of the proliferative activity of breast tissue after the administration of combined oral hormonal contraceptive, associated or not with estriol

Abstract The molecular mechanisms related to the breast cancer development are poorly understood, particularly those associated with estrogen. Evidence is mounting that developmental differences may influence the risk of cancer. However, understanding breast development, morphology and the biochemical factors that influence them is pertinent to study pre-malignant and malignant conditions that affect the breasts. Objective: To evaluate the proliferative activity of normal breast epithelium, through the c-myc expression, after the administration of combined oral hormonal contraceptive, associated or not with estriol. Retrospective double-blind study, in which the effect of combined oral contraceptives on the normal breast epithelium in women with fibroadenoma was evaluated. We analyzed 33 women In a cohort of 70 selected (37 excluded). The control group (1) received a compound containing levonorgestrel 0.15mg (LNG) and ethinylestradiol 0.03mg (EE), associated with 2mg of placebo (PLC) manufactured in the same capsule ingested daily for 21 days with an interval of 7 days, during four cycles. The study group (2) received a compound containing levonorgestrel 0.15 mg (LNG) and ethinylestradiol 0.03 mg (EE), associated with estriol 2 mg (E3) manufactured in the same capsule ingested daily for 21 days with an interval of 7 days, up to four cycles, when was proceeded the lumpectomy plus normal breast tissue sample. The UNIFESP-EPM Department of Pathology received the samples collected and fixed in 10% buffered formalin. We used an automation device to perform the Immunohistochemistry reactions, using c-myc antibodies, added DAB developer (diaminobenzidine) that provides a bright brown color that provides good contrast. We used conventional optical microscopy to read TMA slides. We considered positive the nuclei stained with dark brown in contrast to the blue negative to the c-myc reactions. We evaluated the epithelial areas at least five acinar units were present in the sample at 40X magnification. In the statistical analysis, the initial stages of consolidation as well as the analysis were performed in Software R (2020) and Rstudio (version 4.1), using the packages Tidyverse (2016), Psyco, SummaryTools, Janitor and DataExplorer. After verifying the assumptions of normality, independence and linearity, Student’s T test was performed for independent samples. An alpha of 0.05 was chosen for rejection of the null hypothesis, that is, a confidence interval of the test results of 95%. An effect size measure of the difference between the groups was also performed, called Cohen’s D; it ranges from -1 to 1, and the closer to 0, the smaller the effect size of the difference between the groups. Regarding the control group (30.30%) and the case group (69.70%). The table 2 presents the results for group 1 (COC + Placebo), while table 3 presents the results for group 2 (COC + Estriol). The T test was performed to verify a possible significant difference in the levels of cell proliferation in patients with or without Estriol. The normality was verified by the Shapiro-Wilk test, with data following a normal distribution (W = 0.901 and 0.96, p value &amp;gt; 0.3). The equitable variance was verified by the Levine test, which verified the equitable variance in both groups (F (1) = 0.24, p value = 0.62). A mean positive nucleus of 14 (SD = 10.65) was observed in the group of patients with contraceptive plus placebo and a mean of positive nuclei of 20.81 (SD = 9.88) in the group of patients with contraceptive plus Estriol. The ratio of positive nuclei to total was higher in the estriol group than in the control group. However, it was not possible to verify a significant difference in the two groups (T (14.57) = 1.3, p value = 0.215, d Cohen = 0.53). Cohen’s d pointed to a moderate difference effect (table 4). Table 2. Number of positive, negative and total normal epithelial cell nuclei in immunohistochemical investigation of c-myc antigens in Group 1 (COC + Placebo) (N = 10) Table 3. Number of positive, negative and total normal epithelial cell nuclei in immunohistochemical investigation of c-myc antigens in Group 2 (COC + Estriol) (N = 23) Table 4. Inferential results of the ratio of positive normal epithelial cell nuclei as a function of the control and case groups Citation Format: Osmar Pellegrini, Jr., Afonso Nazário, Angela Flavia L. Waitzberg. Assessment of the proliferative activity of breast tissue after the administration of combined oral hormonal contraceptive, associated or not with estriol [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-27.

Spironolactone use for acne is not associated with an increased risk of venous thromboembolism: A matched, retrospective cohort study

To the Editor: Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), and there have been concerns about whether the risk is even greater with drospirenone containing combined oral contraceptives. 1 Jick S.S. Hernandez R.K. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ. 2011; 342: d2151 Crossref PubMed Scopus (211) Google Scholar Drospirenone has antimineralocorticoid properties that may modify hemostasis leading to decreased coagulability. This provides a potential mechanism by which drospirenone containing COCs could result in an increased risk of thrombosis compared to other COCs. Since drospirenone is molecularly related to spironolactone, it is possible that spironolactone might also be associated with an increased risk for VTE. The purpose of this study was to evaluate whether patients with acne treated with spironolactone are at increased risk for VTE.

Features of diagnosis and management of patients with hepatocellular adenoma. Literature review

Hepatocellular adenoma is a solid benign neoplasm of the liver, quite rare, heterogeneous in its immunohistochemical features and can be very difficult to diagnose in the realities of modern medicine. Such a tumor is often an incidental diagnostic finding, and treatments range from observation to radical surgical tactics. The most frequent cases of detection in women of childbearing age, taking combined oral contraceptives or other hormonal drugs. This paper will consider the features of the clinical course, modern diagnostic methods and various approaches to the treatment of this type of tumor.

Sex Hormones and Calcitonin Gene-Related Peptide in Women With Migraine: A Cross-sectional, Matched Cohort Study.

Sex hormones may modulate calcitonin gene-related peptide (CGRP) release in the trigeminovascular system. We studied CGRP concentrations in plasma and tear fluid in female participants with episodic migraine (EM) and a regular menstrual cycle (RMC), female participants with EM and combined oral contraception (COC), and female participants with EM in the postmenopause. For control, we analyzed 3 corresponding groups of age-matched female participants without EM. Participants with an RMC had 2 visits: during menstruation on menstrual cycle day 2 ± 2 and in the periovulatory period on day 13 ± 2. Participants with COC were examined at day 4 ± 2 of the hormone-free interval (HFI) and between days 7 and 14 of hormone intake (HI). Postmenopausal participants were assessed once at a random time point. Plasma and tear fluid samples were collected at each visit for determination of CGRP levels with an ELISA. A total of 180 female participants (n = 30 per group) completed the study. Participants with migraine and an RMC showed statistically significantly higher CGRP concentrations in plasma and tear fluid during menstruation compared with female participants without migraine (plasma: 5.95 pg/mL [IQR 4.37-10.44] vs 4.61 pg/mL [IQR 2.83-6.92], p = 0.020 [Mann-Whitney U test]; tear fluid: 1.20 ng/mL [IQR 0.36-2.52] vs 0.4 ng/mL [IQR 0.14-1.22], p = 0.005 [Mann-Whitney U test]). In contrast, female participants with COC and in the postmenopause had similar CGRP levels in the migraine and the control groups. In migraine participants with an RMC, tear fluid but not plasma CGRP concentrations during menstruation were statistically significantly higher compared with migraine participants under COC (p = 0.015 vs HFI and p = 0.029 vs HI, Mann-Whitney U test). Different sex hormone profiles may influence CGRP concentrations in people, with current or past capacity to menstruate, with migraine. Measurement of CGRP in tear fluid was feasible and warrants further investigation.

Regulation of human endothelial cell migration by oral contraceptive estrogen receptor ligands

Ethinylestradiol (EE) and estetrol (E4) are the two main estrogenic agents used in combined oral contraceptives. These compounds have different binding affinity to and efficacy on estrogen receptors (ER) subtypes. We previously reported that treatment with estrogenic agents enhances angiogenesis via nongenomic, G protein-coupled estrogen receptor (GPER)-dependent mechanisms. However, the impact of EE and E4 on human endothelial function has been little investigated. EE and E4 (10−9– 10−7 M) significantly enhanced migration of human umbilical vein endothelial cells (HUVECs) using scratch and Boyden chamber assays. Mechanistically, both agents increased accumulation of phosphorylated protein tyrosine kinase 2 on tyrosine 397 (FAK Y397), a key player in endothelial cell motility, after 30-min treatment. Treatment with increasing concentrations of EE, but not E4, enhanced accumulation of the glycolysis activator PFKFB3. Of note, effects of EE and E4 on endothelial migration and signalling proteins were abolished by addition of the GPER antagonist G36 (10−6 M). Thus, EE and E4 induced comparable endothelial responses in vitro, suggesting no apparent alterations of vascular remodelling and regeneration capacity by oral contraceptives containing these agents.

Metabolomic study combined with the low-level light therapy of Chinese acupuncture points and combined oral contraceptives in treatment of primary dysmenorrhea: A prospective, multicenter, randomized controlled study

ObjectiveTo compare the changes of metabolites between Low-level light therapy (LLLT) and combined oral contraceptive (COC) after treatment of primary dysmenorrhea (PD), and to compare and analyze the biological and biochemical effects of the two treatments by analyzing the differences in metabolite profiles. MethodsA multicenter, double-blind, prospective, parallel, randomized controlled study was conducted on 69 women aged 16–35 years old with PD who were randomly divided into COC treatment group or LLLT treatment group. Low-level light therapy with light-emitting diodes (LED) was applied on two acupoints named “Guanyuan” (CV4) and “Qihai” (CV6). After 12 weeks of treatment intervention, blood samples were collected before and after treatment for metabolomic analysis. We used UPLC-MS/MS analysis to compare the differences in metabolite changes between LLLT and COC before and after treatment. Results76 differential metabolites were detected in the LLLT group, and 92 differential metabolites were detected in the COC group, which were up-regulated or down-regulated (p < 0.001). Prostaglandin D2 (PG D2) was down-regulated and biliverdin was up-regulated after LLLT treatment, 4a-Hydroxytetrahydrobiopterin, Prostaglandin D2, 5-Hydroxy-l-tryptophan, Cholic acid were down-regulated and cortisol was up-regulated after COC treatment, and the differences were statistically significant. Cortisol and testosterone glucuronide in LLLT group were significantly lower than those in COC group. The metabolic pathways affected were glycerophospholipid metabolism, linoleic acid metabolism and arachidonic acid metabolism in the LLLT group, and glycerophospholipid metabolism, folate biosynthesis, arachidonic-acid-metabolism, and tryptophan metabolism in the COC group. The differential metabolic pathway were linoleic acid metabolism, steroid hormone biosynthesis, and alpha-Linolenic acid metabolism after the comparison of LLLT with COC. ConclusionLLLT and COC might relieve dysmenorrhea by down-regulating PGD2, and LLLT might also relieve dysmenorrhea by up-regulating biliverdin. The level of cortisol and testosterone glucuronide after LLLT treatment was lower than that after COC treatment, which might lead to the difference in the clinical efficacy of the two treatments for dysmenorrhea.

Prevalence of Vaginal Candidiasis among women and Diagnosis of Candida species from vaginal infection in Kirkuk city

Vaginal candidiasis is a common complaint among women of different age groups in any society whether or not they are sexually active. Although it is both treatable and mild, when left untreated, The study was set to detect Candida organisms in women vaginal. A prospective study of women vaginal swabs collected from Gynecological Clinic in Azadi teaching Hospital and some privet clinical in Kirkuk city and a total of two hundred (200) women swab were analysed for microscopy and culture, from May 2014 to April 2015. Data on epidemiologic indices were collected from the patients, using structured interviewer-administered questionnaires. fifty- seven positive cultures were obtained, constituting 28.5% (n = 57) in a total of 200 women vaginal samples. A total of 28.5% (n= 57) isolates were detected which comprises four different Candida species, namely Candida albicans, C. glabrata, C. krusei and C. kefyre respectively as well as isolated Cryptococcus lorynti with frequency of occurrence of 23%, 2%, 1.5%, o.5% and 1.5% respectively. The isolates were related to age, the age range of 26-35 years had the highest incidence (35%), followed by age range of 36-45 years (29.5%) and 56-88 years had the least (2%) percentage of occurrence. The isolates were also related to used contraceptives, copper-T contraceptives and combined oral contraceptives 41.5% was the most common methods used by recurrent vaginitis patients while the male condom contraceptives users had lower cure (26.5%). The distribution of vaginal candidiasis according antibiotic using was highest in women take antibiotic with 64.4% of the total 200 cases, while the women don’t take antibiotic was recorded lowest occurrence (35.5%). The result shows that Candida species has assumed the role of the most common cause of vaginitis, with Candida albicans as the most prevalent species. vaginal candidiasis was common in the young adults o age range of 26-35 years, contraceptive , broad spectrum antibiotic users ,other diseases and operation .We therefore recommend prevention, early diagnosis and prompt treatment of vaginal candidiasis especially among the risk groups in order to avert its complications.