Use Of Combined Oral Contraceptives Research Articles

The use of combined oral contraceptives in patients with endometriosis

Endometriosis is a benign inflammatory hormone-dependent disease characterized by pain and infertility. It seriously affect women’s health., endometriosis is a chronic disease it requires long-term treatment. Currently, hormonal drugs are most widely used for the treatment of endometriosis, which is based on the endocrine mechanisms of its pathogenesis. Key points are estrogen dependence and progesterone resistance, which provide implantation of ectopic endometrial cells, reduce apoptosis and increase oxidative stress, inflammation and neuroangiogenesis. the pain and infertility is explained by hormonal and inflammatory changes, as well as the systemic diseases and psychiatric disorders often associated with endometriosis. Hormonal treatment of endometriosis is aimed at suppressing ovulation through inhibition of the hypothalamic-pituitary-ovarian axis, as well as directly on endometrioid implants. Gonadotropin-releasing hormone (GnRH) agonists and antagonists, progestins, combined oral contraceptives (COCs) are now offcially approved for use to relieve the symptoms of endometriosis. The review provides information on the current possibilities of hormonal therapy for endometriosis, based on an understanding of the pathogenesis of the disease.

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.

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.

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.

PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a "two-hit" theory. This refers to a stepwise process in which the first "hit" is an inborn congenitally programmed predisposition, while the second "hit" arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21-45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2-3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard.

Clinical and Morphological Study of Cervical Squamous Intraepithelial Lesions.

Squamous intraepithelial lesions (SILs) are cancer precursors targeted by secondary prevention of cervical cancer programs that are sometimes difficult to grade accurately. Mena is an actin regulatory protein involved in membrane protrusion, cell motility, in tumor invasion and metastasis. We studied retrospectively 68 cases of patients diagnosed with squamous intraepithelial lesions that received expedited treatment (treatment without colposcopic biopsy). We analyzed demographic, behavioral data, obstetrical and medical history, from the patients' medical charts and we studied the cervical fragments or cones harvested after the excisional procedure. Our study failed to identify a correlation between SILs and risk factors such as low socioeconomic status, combined oral contraceptive use, intrauterine device use, parity, gravity, except for the tobacco smoking habit that proved to be related to the cervical lesions' development. Mena was expressed in most of the analyzed SILs and its expression was correlated with lesions' grade in terms of both area and intensity, suggesting that Mena stains especially abnormal cells and that its expression intensity correlates with the risk of malignant transformation. Further studies are needed to validate Mena as an early stage of cervical carcinogenesis marker.

Acute pulmonary embolism associated with acute thrombosis of the deep venous system

The purpose of the study was to present a clinical case of pulmonary embolism in a young patient of 26 years, with a brief review of the literature. The particularity of the presented case with the pulmonary embolism was the association with the acute thrombosis of the deep venous system venous system on background of combined oral contraceptives use.

The potent contraceptive gestodene exerts insulinotropic effects through its a-ring reduced metabolites with intrinsic estrogen-like activity in pancreatic β-cells.

The contraceptive gestodene is a potent synthetic progestin used in several low-dose contraceptive formulations. Clinical studies reported a relationship between long-term use of combined oral contraceptives containing gestodene (GDN) and profound alterations in glucose metabolism in women. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether GDN may induce estrogen-like effects, even though GDN does not interact with estrogen receptors. The aim of this study was to investigate whether GDN affect pancreatic β-cell activity, directly or through its conversion to other bioactive metabolites. The effects of GDN and its two derivatives 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN on insulin 2 (Ins II) and glucokinase (Gk) expression and glucose-stimulated insulin secretion were determined in pancreatic islets from female rats. Gestodene did exert significant effects on islet β-cells activity. The most striking finding was that 3β,5α-tetrahydro-GDN and 3α,5α-tetrahydro-GDN had greater stimulatory effects on Ins II and Gk expression than that observed with GDN, consistent with their effects on glucose-stimulated insulin secretion. The effects on gene expression induced by GDN-derivatives were abolished by ICI 182,780 and MPP. In addition, the presence of inhibitors of androgen and progestin-metabolizing enzymes eliminated gene expression induced by GDN. These results indicated that GDN is metabolized to A-ring reduced metabolites with estrogen-like activities and through this mechanism, GDN may affect β-cell activity. Altogether, the data suggest that 19-nortestosterone-derived contraceptives such as GDN, possess insulinotropic effects through their conversion into metabolites with intrinsic estrogen-like activity in pancreatic β-cells.

Effect of combined oral contraceptives with estrogen identical to natural estrogen on the metabolic profile and body composition in females during the menopausal transition

Aim. To study the effect of combined oral contraceptives (COC) with estrogen identical to natural estrogen on the metabolic profile and body composition in females during the menopausal transition.&#x0D; Materials and methods. Females in the menopausal transition who needed contraception were divided into two groups. Group 1 (19 patients) received COCs containing estradiol valerate/dienogest (E2V/DNG) with a dynamic dosing regimen; Group 2 (19 patients) received monophasic COCs containing 17-estradiol/nomegestrol acetate (E2/NOMAC) for 6 months. Blood pressure (BP), parameters of carbohydrate and lipid metabolism, leptin, adiponectin, C-reactive protein, uric acid, and body composition by dual-energy X-ray absorptiometry were assessed initially and after the 6 months of therapy.&#x0D; Results. No significant changes in weight and body composition after 6 months of COC use were found in both groups. COCs with E2V/DNG had no significant effect on BP and all assessed metabolic parameters. Females taking COCs with E2/NOMAC showed increased fasting glucose of 4.85 (0.43) and 5.30 (0.37) mmol/L (p=0.002), insulin of 4.97 (2.35) and 8.82 (4.67) U/mL (p=0.012), NOMA index of 1.06 (0.54) and 1.88 (0.75); p=0.010 compared to baseline. However, the parameters remained within the reference values.&#x0D; Conclusion. COCs containing estrogens identical to natural estrogens do not affect body composition and have no significant adverse effect on BP and metabolic parameters in females during the menopausal transition, indicating that the use of these agents is acceptable from the perspective of their metabolic effects in this group of patients.

Estetrol: a new estrogen component in combined oral contraceptives: A review

Estetrol (E4) is a steroid hormone found in the urine of pregnant women in 1965. E4 is produced only during pregnancy and enters the maternal bloodstream through the placenta. Its concentration in maternal human plasma increases during pregnancy, reaching a maximum by the end of pregnancy (1 ng/mL). The pharmacological properties of E4 make it a promising agent for hormonal therapy and contraception. To date, phase II and III studies have shown promising results with the combination of 15 mg of E4 and 3 mg of drospirenone: this combined oral contraceptive has shown a good effect with a neutral metabolic effect. However, evidence is scarce about the effect of the new combination on the breast and bone tissue. Further studies are needed to consolidate the available data and to investigate possible side effects of prolonged use of E4-containing combined oral contraceptives compared to known ethinylestradiol and estradiol-containing combinations.

New approaches for developing biomarkers of hormonal contraceptive use

To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC–MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users’ saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.

The role of combined oral contraceptive use on the serotonin 2A receptor brain architecture in healthy women

The role of combined oral contraceptive use on the serotonin 2A receptor brain architecture in healthy women

Antithrombin Deficiency: Frequency in Patients with Thrombosis and Thrombophilic Families

Purpose: Antithrombin (AT) deficiency is a well-known inherited risk factor for venous thromboembolism (VTE). However, F V Leiden and F II20210a mutations have drawn much more attention in the recent years. Therefore, we have decided to analyze the frequency of antithrombin deficiency in different cohorts of patients and tried to formulate indications for its testing. Results: Antithrombin deficiency was found in 4% of patients with recurrent VTE ≤ 50 years of age with, in 1% of patients with splanchnic vein thrombosis and in 2% of cases associated with combined oral contraceptives (COC) use or pregnancy. In patients with central venous thrombosis, antithrombin deficiency was not found. Recommendation: We consider antithrombin testing useful in patients with thrombosis occuring up to 45 years of age without any risk factors. Namely, females with VTE in pregnancy and puerperium should be tested as well as females with thrombosis on COC, if VTE occurred within the first year of their use. Conclusion: In spite of degressive interest in thrombophilia work up, we still consider antithrombin testing useful in defined clinical situations.

Лікування стрес індукованих розладів у жінок з лейоміомою матки на фоні гормонотерапії у військовий час

The purpose of the study was to assess psychosomatic changes and determine clinical and laboratory indicators in women with uterine fibroids under the conditions of using hormonal therapy and a drug with anxiolytic effect. Materials and methods. The study analyzed the results of 60 women with uterine fibroids who had anxiety disorder symptoms. The patients were divided into two groups: Group I – patients with uterine fibroids who took combined oral contraceptives (n=30); Group II – patients with uterine fibroids who took the anxiolytic medication fabomotizole concurrently with combined oral contraceptives (n=30). Results and discussion. The research established that patients with uterine fibroids had a change in their psycho-emotional state with a tendency to a high level of anxiety and depression. Treatment with combined oral contraceptives and fabomotizole demonstrated a more stable emotional background as compared to patients who took only combined oral contraceptives. The percentage of patients with the low level anxiety increased and the percentage of patients with the high level anxiety decreased. Among women who were treated with combined oral contraceptives only, there was still a considerable proportion of patients with high levels of anxiety and depression. It was found that the use of combined oral contraceptives in combination does not result in changes regrading the size of the tumor compared to the indicators of patients who did not take the drug with an anxiolytic effect. However, this group of patients demonstrated a tendency to stabilize the growth of nodes, to decrease clinical manifestations in the form of pain and intermenstrual bleeding in the first months of taking combined oral contraceptives. It should be noted that in patients who were not administered fabomotizole, the studied indicators remained at a lower level compared to the indicators of patients who were prescribed this drug. Probably, restoration of the psycho-emotional state in women with uterine fibroids under the influence of fabomotizole increases the effectiveness of hormonal therapy. Conclusion. The patients of both studied groups were shown to have developed pronounced anemia, which was confirmed by low values of hemoglobin in the blood, and the levels of ferritin and transferrin in the blood serum decreased. An increase in the studied indicators was observed after combined oral contraceptive treatment, and specifically after treatment with a combination of combined oral contraceptives and fabomotizole. However, the levels of ferritin and transferrin remained at a lower level compared to normal values

Management of Premenstrual Dysphoric Disorder: A Scoping Review.

Premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) refer to physical, cognitive, or affective symptoms that arise in the late luteal phase and remit with menses. The present work is a clinically focused scoping review of the last twenty years of research on treatment for these disorders. A search of key terms using the PubMed/Medline, the Cochrane Library, Embase, and Web of Science databases was performed, and 194 studies of adult women met initial inclusion criteria for review. Research studies concerning medications, pharmacological and non-pharmacological complementary and alternative medicine treatments, and surgical interventions with the most available evidence were appraised and summarized. The most high-quality evidence can be found for the use of selective serotonin reuptake inhibitors (SSRIs) and combined oral contraceptives (COCs), with gonadotropin releasing hormone (GnRH) agonists and surgical interventions showing efficacy for refractory cases. While there is some evidence of the efficacy of alternative and complementary medicine treatments such as nutraceuticals, acupuncture, and yoga, variability in quality and methods of studies must be taken into account.

Smoking and combined oral contraceptives should be considered as an independent variable in sex and gender-oriented studies

The influence of sex combined with smoking and combined oral contraceptives (COC) use on atherogenic indexes is scarcely studied. Thus, traditional lipid parameters were measured, and non-traditional atherogenic indexes were calculated in a young and healthy population of men, COC-free women, and COC users.Total cholesterol (TChol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and HDL/LDL ratio were lower in men, while triglycerides (TG)/HDL ratio, atherogenic index of plasma (AIP), Castelli's Risk Index I (CRII) and CRI-II, atherogenic coefficient (AC), creatinine, creatinine clearance, and estimated glomerular filtration rate (eGFR) were higher in men. The use of COC modified TChol, HDL, TG, TG/HDL, and AIP which had significantly higher values in COC users. In addition, TG were also increased in COC users in comparison with men.Smoking reduced sexually divergent parameters: BMI, TG, HDL/LDL, TG/HDL, AIP, CRII, CRI-II, and AC became similar among the three cohorts, losing the reported sex differences.Smoking also reduced differences in TChol, HDL, TG, and AIP between COC-free women and COC users, but it does not affect CRII, CRI-II, creatinine, creatinine clearance, and eGFR, underlining that COC users and COC-free women have to be considered two different populations.Our results represent a complex landscape suggesting that for both sexes smoking should be an independent variable in medical studies. Moreover, in women, the use of COC evidenced two different cohorts. Thus, more variables should be considered during a single study indicating that sex, smoking, and COC should be studied together to get a picture of the real-life context.

Pilot label comprehension study for an over-the-counter combined oral contraceptive pill in the United States.

A growing body of evidence supports over-the-counter access to oral contraceptives in the United States. An important consideration for over-the-counter approval is consumers' ability to understand key package label messages related to safety and effectiveness without clinician involvement. We developed a prototype over-the-counter Drug Facts Label for a combined oral contraceptive pill and conducted a pilot label comprehension study to evaluate consumer understanding of key messages for use. In November-December 2020, we conducted interviews with 163 adults and teens in the United States who were aged 12-49 years and identified as female or another gender but had a uterus and the ability to become pregnant. We developed 11 primary endpoints based on assessment of clinical risks that could occur if consumers fail to heed them, including messages about contraindications and directions for use; 11 secondary endpoints represented additional important information but with lower potential for clinical consequences if not understood. We evaluated endpoint comprehension by computing frequencies, percentages, and 2-sided Exact (Clopper-Pearson) 95% confidence intervals for observed proportions. Ten of the 11 primary endpoints and 10 of the 11 secondary endpoints were each understood by ≥95% of participants. The remaining primary endpoint on use with prior blood clots was understood by 89% of participants. The remaining secondary endpoint on the product being designed for "people who have the ability to become pregnant" was understood by 83% of participants. Participants understood the key label information required for safe and effective combined oral contraceptive use without clinician involvement.

Robotic-Assisted Laparoscopic Treatment of Diaphragmatic Endometriosis

<h3>Study Objective</h3> To demonstrate the surgical technique used for a robotic-assisted diaphragm endometriosis treatment. <h3>Design</h3> Case report illustrated with a video. <h3>Setting</h3> Patient is placed in the semi-gynecological position, left lateral decubitus and proclivity. Robotic side docking set for upper abdomen using da Vinci Si platform. <h3>Patients or Participants</h3> A 34-year-old woman reports dysmenorrhea and pain in her right shoulder during menstruation for 5 years, ceased after combined oral contraceptive use. When she stopped the contraceptive, symptoms recurred. On MRI, hematic foci were identified in the right subphrenic space, suggesting endometrial implants. <h3>Interventions</h3> A 12 mm incision is performed in the umbilicus for endoscope port. Other two 8mm robotic ports and a 5 mm accessory laparoscopic trocar were placed. Patient's cart side docking enters obliquely through patient's left shoulder. Inspection shows superficial and deep typical endometriotic lesions on right diaphragmatic surface, falciform ligament is sectioned for better liver mobilization. Most superficial lesions are removed before accessing thoracic cavity. For deeper lesions, the diaphragm is opened, showing pleural involvement of endometriosis. No pulmonary lesions were identified. Diaphragm is repaired carried out by a double-layered barbed suture. Before first layer closure, a laparoscopic suction tip is introduced into the thoracic cavity and the aspiration of the pneumothorax is done concomitantly with the forced Valsalva maneuver. <h3>Measurements and Main Results</h3> Patient was discharged in the second postoperative day, showing great evolution in respiratory physical therapy and normal chest X-ray. Painful shoulder symptoms have completely resolved. <h3>Conclusion</h3> Diaphragm endometriosis has been gaining more attention in the practice of gynecologist surgeons. Robotic system improves access to the subdiaphragmatic space due to the articulated instrument movements and 3D high-definition static vision. Excision of diaphragmatic lesions is a standardized feasible procedure that allows complete treatment and good clinical results.

Obesity and contraceptive use: impact on cardiovascular risk.

Obesity and oestrogen containing contraceptive products are well-known independent cardiovascular risk factors. However, a significant number of obese women continue to receive prescriptions of hormonal products that contain oestrogens for their contraception. We have conducted a narrative review to discuss the latest evidence, ongoing research, and controversial issues on the synergistic effect of obesity and contraceptive use, in terms of cardiovascular risk. There is compelling evidence of an interplay between obesity and contraception in increasing cardiovascular risk. Women who present both obesity and use of combined oral contraceptives (COCs) have a greater risk (between 12 and 24 times) to develop venous thromboembolism than non-obese non-COC users. Data here discussed offer new insights to increase clinicians' awareness on the cardiovascular risk in the clinical management of obese women. The synergistic effect of obesity and COCs on deep venous thrombosis risk must be considered when prescribing hormonal contraception. Progestin-only products are a safer alternative to COCs in patients with overweight or obesity. Obese women taking contraceptives should be viewed as an 'at risk' population, and as such, they should receive advice to change their lifestyle, avoiding other cardiovascular risk factors, as a form of primary prevention. This indication should be extended to young women, as data show that COCs should be avoided in obese women of any age.