Combined Oral Contraceptives Research Articles

Migraine and Hormonal Contraception in Gynecological Outpatient Care-Cross-Sectional Study among Practicing Gynecologists in Germany.

Hormonal contraception (HC) can influence the migraine burden and should be considered in the comprehensive management of women with migraine. In this study, we aim to investigate the influence of migraine and migraine aura on the prescribing behavior of combined oral contraception (COC) and progestogen monotherapy (PM) in gynecological outpatient care. From October 2021 to March 2022, we performed an observational, cross-sectional study using a self-administered online-based survey. The questionnaire was distributed by mail and e-mail among 11,834 practicing gynecologists in Germany using the publicly available contact information. A total of 851 gynecologists responded to the questionnaire, of whom 12% never prescribe COC in the presence of migraine. Further 75% prescribe COC depending on the presence of limiting factors such as cardiovascular risk factors and comorbidities. When deciding to start PM, migraine appears to be less relevant, as 82% prescribe PM without restrictions. In the presence of aura, 90% of gynecologists do not prescribe COC at all, while PM is prescribed in 53% without restrictions. Almost all gynecologists reported to be actively involved in migraine therapy by having already initiated (80%), discontinued (96%), or changed (99%) HC due to migraine. Our results reveal that participating gynecologists actively consider migraine and migraine aura before and while prescribing HC. Gynecologists appear cautious in prescribing HC in patients with migraine aura.

Progesterone and contraceptive progestin actions on the brain: A systematic review of animal studies and comparison to human neuroimaging studies

In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.

Cerebral Venous Sinus Thrombosis Following an mRNA COVID-19 Vaccination and Recent Oral Contraceptive Use

Rising concerns of cerebral venous sinus thrombosis (CVST) and other forms of venous thromboembolism have been associated with the SARS-CoV-2 vaccinations. Adverse effects with vector-based vaccines are well documented in the literature, while less is known about the mRNA vaccines. This report documents a case of CVST in a 32-year-old female patient who received her second Pfizer mRNA COVID-19 vaccination 16 days prior to hospital admission and had started oral combined contraceptives approximately 4 months beforehand. Clinicians should be cognizant of the possibility that mRNA vaccines, when combined with other risk factors like oral contraceptive pill use, may enhance one's hypercoagulable status.

The effect of combined oral contraceptives and Nexplanon on gastroesophageal reflux disease in premenopausal women: A nationwide database analysis.

Pregnancy, combined oral contraceptives (COC), and hormone replacement therapy have been reported to increase the risk of gastroesophageal reflux disease (GERD). To date, no study has evaluated the effect of Nexplanon, a commonly used progesterone-based contraceptive, on GERD. We aimed to determine the effect of Nexplanon and COC on GERD. We performed a population-based analysis using the IBM Explorys national database (1999-2021). The study group included premenopausal women, defined as women less than 50 years of age while excluding the diagnosis of menopause. The effect of Nexplanon and COC on GERD (at least 30 days after Nexplanon/COC was initiated) was assessed by comparing it to premenopausal women who were not on contraceptives. Foregut surgery, esophageal dysmotility disorders, hiatal hernia, and delayed gastric emptying were excluded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A multivariate logistic regression analysis was conducted. A total of 23,299,470 patients were identified as being premenopausal, of which 47,260 were on Nexplanon and 5480 on COCs. As compared to premenopausal women with GERD on no contraceptives (n=565,880), 690 patients developed GERD at least 30 days after being on Nexplanon (OR=0.55, 95% CI [0.51-0.59], p < 0.001) and 280 developed GERD after COC (1.93, [1.71-2.18], p < 0.001). A multivariate analysis accounting for Caucasian race, obesity, smoking, alcohol use, and NSAIDs revealed that COC is an independent risk factor for GERD (1.16, [1.12-1.20], p < 0.001), and Nexplanon was protective against GERD (0.90, [0.89-0.92], p < 0.001). Hydralazine was used as a control medication for data reliability. A total of 8420 patients developed GERD after initiating hydralazine, which was not statistically nor clinically significant (OR=1.02, 95% CI [0.99-1.04], p=0.08) when compared to those not on contraceptives. Combined oral contraceptives is an independent risk factor for GERD, while Nexplanon has a limited protective effect. Further studies are needed to confirm the different effects on GERD of these two contraceptives.

Clinical and sonographic impact of oral contraception in patients with deep endometriosis and adenomyosis at 2 years of follow-up

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 μg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.

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.

Combined oral contraceptives may activate the contact system in healthy women

BackgroundThe contact system (CAS) is part of the coagulation system, consisting of a group of plasma proteins stimulating inflammation, coagulation, and fibrinolysis when activated. CAS can be triggered by several activating surfaces, and CAS may play a potential role in thrombus formation. Combined oral contraceptives (COCs) are known to increase the risk of venous thromboembolism, and COCs induce various prothrombotic changes in the coagulation system, whereas the effect of COC on CAS has not been thoroughly investigated. ObjectivesTo investigate CAS in COC users compared with nonusers. MethodsBlood samples from 62 study subjects, 30 COC users, and 32 nonusers, were analyzed. Coagulation factor XII (FXII), prekallikrein (PK), H-Kininogen (HK), cleaved HK (cHK), C1-esterase inhibitor (C1-inh), and the endogenous kallikrein potential (EKP) were measured. ResultsCOC users had significantly higher FXII (median, 38.4 vs 28.9 mg/L) and lower C1-inh levels (0.20 vs 0.23 g/L) than nonusers. The levels of PK and HK were not significantly different. Measurement of EKP indicated an increased capacity of CAS in COC users (1860 vs 1500 nmol/L × min), and increased plasma levels of cHK (2.02 vs 1.07 μg/L) indicated an increased activity in vivo. ConclusionThis study demonstrates an increased CAS capacity in women using COC compared with nonusers and also an increased activity in vivo. The results indicate that increased contact activation may contribute to the increased thrombotic risk caused by COC.

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.

NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study

Objective To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COCLNG) in users over 40. Methods In this large, observational study, new users 1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed-up via questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/104 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight. Results Overall, 7,762 NOMAC-E2 and 6,059 COCLNG users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COCLNG; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9–13.7) vs 4 COCLNG (IR 5.9; 95% CI, 1.6–15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01–0.13) vs 5 COCLNG (PI 0.08; 95% CI, 0.03–0.18). No differential effect on mood and weight was observed between cohorts. Conclusions NOMAC-E2 can be considered a valid alternative to COCLNG in perimenopausal women.

Applicability of Lipid Ratios in the Prediction of Atherogenic Risks of Women on Combined Oral Contraceptives in North-Central Nigeria

Background: Combined Oral Contraceptive (COC) pill is associated with atherogenic and cardiovascular changes. Some service providers use individual lipid parameters to assess these changes unlike objective calculation using standard formulae. Objective: To determine and compare the atherogenic changes in women on COCs using six lipid ratios; coronary heart disease risk ratio, atherogenic index of plasma, atherogenic co-efficient, Cholesterol index, Castelli risk index I, and Castelli risk index II. Materials and Methods: A prospective, comparative study among new acceptors of contraceptives at four family planning clinics in Ilorin, North-Central Nigeria. Participants were categorized into COCs acceptors (group I, n=120) and acceptors of non-hormonal contraceptives (group II, n=120). Participants were followed up with serial lipid profiles at 0, 3 and 6 months after uptake. Atherogenic risks were calculated using six standard formulae; statistical analysis was with SPSS version 21.0 and Analysis of variance (ANOVA) was used to compare the differences of more than two means, Bonferroni Post Hoc test was used to test for specific significance within the group and p-value &lt;0.05 was considered significant. Results: A total of 225 participants (111 COC users, 114 non-COC users) aged 19 to 48 years completed the study. Serum levels of Low-Density Lipoprotein showed a statistically significant rise among the COC users over the study period (p=0.038), especially between the third and sixth months. The lipid ratios were statistically increased using all six methods despite apparently normal lipid parameters. Conclusion: Atherogenic changes may occur in the presence of apparently normal lipid parameters among COC users; therefore, serial lipid ratio using standard method formulae is recommended.

Комбинированные оральные контрацептивы как метод лечения пациенток репродуктивного возраста с обильными менструальными кровотечениями

Background: heavy menstrual bleeding (HMB) is one of the unsolved problems in gynecological practice. The frequency of HMB is exactly unknown, which can be most likely related to an individually perceived blood loss volume. Patients with HMB are at high risk of iron deficiency and anemia. The main problem remains the lack of a single treatment algorithm for the HMB in female patients of reproductive age. Medical specialists should actively and, at the same time, effectively solve this clinical problem. Aim: to evaluate the efficacy of combined oral contraceptive (COC) containing 0.03 mg of ethinylestradiol and 2 mg of chlormadinone acetate in patients of reproductive age with HMB. Patients and Methods: the study involved 87 female patients aged 22–43 y.o. with complaints of HMB. After a complete clinical and laboratory examination, all patients were prescribed COC (0.03 mg ethinylestradiol and 2 mg chlormadinone acetate) for 6 months with subsequent efficacy evaluation. The following parameters were evaluated: menstruation duration, RBC, hemoglobin and ferritin count. Results: initially, hemoglobin count was 78.4±0.5 g /L, RBC count — 2.9×1012/L, and ferritin count — less than 29 mg/dL in the setting of normal hemoglobin count were observed in 31 (35.6%) female patients. COCs prescription demonstrated efficacy in blood loss volume decrease during menstruation, which was noted by 85 (97.7%) female patients. Thus, it contributed to the iron content normalization in 29 (93.5%) of 31 patients. The frequency of side effects, which were manifested by discomfort in the mammary glands, nausea, headache, did not exceed 17%. All manifestations associated with drug intake did not require its cancellation or additional treatment. Conclusion: COC containing 0.03 mg of ethinylestradiol and 2 mg of chlormadinone acetate is an effective drug for the treatment of HMB in female patients of reproductive age, allowing to reduce the frequency of latent iron deficiency forms. KEYWORDS: combined oral contraceptives, heavy menstrual bleeding, ethinylestradiol, chlormadinone acetate, iron deficiency anemia, menstrual cycle control, hormonal contraception. FOR CITATION: Manukhin I.B., Manukhina E.I., Safaryan I.R., Ovakimyan M.A. Combined oral contraceptives as a treatment method for female patients of reproductive age with heavy menstrual bleeding. Russian Journal of Woman and Child Health. 2023;6(3):253–257 (in Russ.). DOI: 10.32364/2618-8430-2023-6-3-6.

Гормональная контрацепция в аспекте влияния на систему гемостаза

Aim: to study the hemostasis indicators in female patients with hyperandrogenism (HA) and menstrual disorders (MDs) during combined oral contraceptive (COC) intake, depending on the presence of undifferentiated connective tissue displasia (UCTD). Patients and Methods: the study results of 28 female patients with HA and MDs were divided into 2 groups: group 1 — 22 patients (mean age 22.1±3.2 years) with UCTD, group 2 — 6 patients (mean age 20.5±1.8 years) without UCTD. The content of hormones in the blood (on the 2nd–3rd day of the menstrual period), the parameters of hemostasis before and after 1 month of COCs intake, and the level of homocysteine were determined in all patients. Results: the analysis revealed an increase in the levels of platelet activation markers, coagulation link and fibrinolysis. During COCs intake, an increase in the fibrinogen content was noted in patients of both groups, which, however, did not exceed the reference values. During the correlation analysis, it was found that in groups 1 and 2, the parameters of the fibrinogen baseline, D-dimer and the corresponding indicators after 1 month of COCs intake had a strong correlation with each other (r=0.845, r=0.864). However, group 1 had higher levels of fibrinogen and fibrin degradation products (D-dimer) (p&lt;0.0001) versus those in group 2. The study on the trend of prothrombin time (PTT) and activated partial thromboplastin time (APTT) during COCs intake in female patients with HA and UCTD revealed an acceleration of indicators (p&lt;0.01) versus those before COCs intake. At the same time, the change in blood clotting markers was not realized by episodes of thrombosis in any of the patients. Conclusion: patients with UCTD had changes that characterized the activation of thrombogenesis. When planning hormonal contraception, it is necessary to single out a group of female patients with HA and signs of UCTD as the most vulnerable in relation to an increased risk of thrombogenic events. KEYWORDS: hyperandrogenism, combined oral contraceptive, thrombosis, connective tissue dysplasia, hyperhomocysteinemia. FOR CITATION: Kudinova E.G. Hormonal contraception in terms of effect on the hemostasis system. Russian Journal of Woman and Child Health. 2023;6(2):130–137 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-130-137.

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.

Investigating the risks of cardiovascular disease among premenopausal women using oral contraceptive: a protocol for a systematic review and meta-analysis

IntroductionThe use of oral contraceptives (OCs) is linked to an increased risk of cardiovascular diseases (CVDs) in women of reproductive age. CVD remain one of the top causes of death...

Pharmacological and metabolic effects of drospirenone as a progestin-only pill compared to combined formulations with estrogen.

The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-β-estradiol are used to treat climacteric symptoms. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of drospirenone, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of drospirenone, leading to a higher drospirenone exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. In addition, several metabolic alterations have been described. The impact of estetrol is less pronounced, and for 17-β-estradiol/drospirenone and drospirenone-only, decreased triglyceride and cholesterol levels were observed. Ethinylestradiol induces various pro-coagulatory factors, leading to hypercoagulability. The effect is significantly reduced with estetrol, and no influence was observed with the drospirenone-only preparation. The anti-mineralocorticoid activity of drospirenone seems to positively counteract the renin-angiotensin-aldosterone-system-activating action of ethinylestradiol. There is no influence on blood pressure with ethinylestradiol/drospirenone and estetrol/drospirenone formulations, while in clinical trials, a reduction has been observed with 17-β-estradiol/drospirenone and drospirenone-only. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.

Цифровая маммография в клинической практике гинеколога: расставляем акценты

High density of the mammary gland, determined with the digital mammography method, is an independent risk factor for mammary gland cancer (MGC). Prescription of combined oral contraceptives, menopausal hormone therapy drugs, intrauterine system with levonorgestrel, and ovulation induction may lead to an increase of mammary gland density (MGD). The latest research showed that the insulin-like growth factor is also a risk factor for mammary gland density. In the Republic of Tatarstan, out of 265,217 examined women, a high mammary gland density was diagnosed in 7%, including in patients older than 60 y. o. Notably, in the overwhelming majority of them the density did not decrease during 3 years of monitoring. This testifies to the need of prolonged monitoring of mammary glands in patients, combined with estimation and correction of risk factors for mammary gland density.