Perception about benefits and risks related to combined hormonal contraceptives use in women with Lynch syndrome.

OBJECTIVE: Lynch syndrome (LS) is a hereditary condition associated with an increased risk of colorectal and endometrial cancer. This study aimed to assess the knowledge, attitudes, and beliefs of women with LS regarding combined hormonal contraceptive (CHC) use compared to a control group of healthy women. METHODS: Pre-menopausal women with LS (n = 43) and an age-matched control group of healthy women (n = 128) participated in this prospective, cross-sectional study (NCT05909410). Participants completed an electronic questionnaire evaluating perceptions of CHC use and its impact on various cancers, medical conditions, and symptoms. Statistical analysis compared responses between the two groups, with reported p-values. RESULTS: Women with LS were less likely to use CHCs compared to the control group (p = 0.03) and had a more negative perception of CHCs' impact on colorectal cancer (p = 0.023) and endometrial cancer (p = 0.028). Limited knowledge was observed in both groups regarding the protective effects of CHCs against colorectal and ovarian cancer. Perceptions of CHC use and its impact on symptoms and chronic diseases did not significantly differ between the groups (p > 0.05). CHC use was not associated with greater awareness of the protective effect against colorectal (p = 0.89) and endometrial cancer (p = 0.47), but it was associated with a desire for contraception (OR 21.25; 95% CI 1.16 to 388.21; p = 0.039). CONCLUSION: This study highlights contrasting perceptions of CHCs and their implications in oncology between women with LS and healthy women. Tailored counselling and support strategies are crucial for empowering women with LS to make informed decisions about their gynaecologic health.

This study illuminates divergent perceptions of combined hormonal contraceptives and their oncological implications between women with Lynch syndrome and healthy women.Tailored counseling and supportive strategies are essential for empowering women with Lynch syndrome to make informed decisions regarding their gynecologic health.

Steroids Used to Treat Acne Vulgaris: A Review of Efficacy, Safety, and Clinical Considerations.

Acne vulgaris is prevalent among adolescents and adults worldwide and can significantly impact patients' quality of life. Steroidal molecules, including oral and intralesional corticosteroids, combined oral contraceptives (COCs), oral spironolactone, and topical clascoterone, are an important part of the acne treatment armamentarium. The recommended use, mechanism of action, and available evidence supporting the use of steroids for acne treatment are reviewed, and differences in acne clinical presentation and treatment approaches based on patient characteristics relevant to the selection of an appropriate steroid are also discussed. Steroid-based approaches target the systemic or local hormones (ie, testosterone and androgens) and inflammation that contribute to acne pathogenesis. Oral corticosteroids are primarily used as a short-term adjunctive therapy early in treatment, whereas intralesional corticosteroid injections are used for individual acne lesions. COCs and oral spironolactone are limited to female patients who wish to avoid pregnancy. Topical clascoterone can be used by female and male patients 12 years of age and older. Patients' characteristics (including age and patients with darker skin color) and preferences for the route of administration can impact treatment response and adherence, respectively. Overall, healthcare providers must be aware of the differences among steroidal acne treatments and use shared decision-making to select the optimal therapy. J Drugs Dermatol. 2024;23(6):404-409.     doi:10.36849/JDD.7846.

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

High-dose oral contraceptives induce hyperinsulinemia without altering immune activation in diet-induced obesity which persists even following a dietary low-fat diet intervention.

Combined oral contraceptives (COCs) are known to cause weight gain and alter metabolic and immunological pathways. However, modifications in arterial or venous thrombotic risk profiles of women of reproductive ages on COC remain unclear. The study aimed at assessing the impact of COC on immune activation in diet-induced obesity. We further established whether the dietary intervention of switching from a high-fat diet (HFD) to a low-fat diet (LFD) attenuates immunological responses. Twenty (n=20) five-week-old female Sprague Dawley rats were randomly divided into two diet groups of HFD (n=15) and LFD (n=5) and were monitored for eight weeks. After eight weeks, animals in the HFD group switched diets to LFD and were randomly assigned to receive high-dose COC (HCOC) or low-dose COC (LCOC) for six weeks. Animals on HFD significantly gained weight and had a higher lee index when compared to the LFD group (p < 0.05). Moreover, the triglyceride-glucose index, insulin, and other metabolic parameters also increased in the HFD group compared to the LFD group (p < 0.001). Consistently, the levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), were elevated in the HFD group when compared to the LFD group (p < 0.05). Upon switching from a high-fat to a low-fat diet, insulin levels persistently increased in animals receiving HCOC treatment compared to the LFD and HFD/LFD groups (p < 0.05). Thus, in a rat model of HFD-feeding, short-term HCOC treatment induces long-term metabolic dysregulation, which persists despite dietary intervention. However, further studies are recommended to confirm these findings.

Combined estrogen-progestin oral contraceptives and female sexuality: an updated review.

INTRODUCTION: Sexual side effects of combined oral contraceptives (COCs) have not been fully understood, but increasing evidence prompts broader risk/benefit evaluation and merits inclusion in counseling on contraceptive options. OBJECTIVES: The study sought to explore the impact of combined estrogens-progestin oral contraceptives on components of female sexuality, including sexual desire, anatomic genitourinary changes, lubrication, orgasm, provoked vestibulodynia, well-being, body image, partner preference, and relationship stability. METHODS: A literature review was performed between April 2023 and January 2024 exploring the association between combined oral contraceptive pills and sexual health. RESULTS: Although COCs decrease free testosterone, it is unclear if COCs affect sexual function, including desire. Antiandrogenic COCs do seem to have a negative effect on sexual arousal, lubrication, and orgasm. Provoked vestibulodynia may be related to early onset of COC use, low-estrogen pills, and antiandrogenic progestins. Emotional and sexual side effects are strong predictors of COC discontinuation. Longitudinal data indicate that using COCs when meeting and selecting a partner has implications on sexual satisfaction and relationship length. Analysis of data is complicated by various doses and forms of estrogen and progestin in COCs, which have changed over time. CONCLUSION: Lack of randomized placebo-controlled studies and heterogenicity in study design hampers generalized statements about the effects of COCs on sexual function. Despite these challenges, consideration of sexual dysfunction when presenting and prescribing hormonal contraception is essential for informed consent, shared decision making, and ensuring reliable contraceptive choices.

Health benefits of combined oral contraceptives - a narrative review.

PURPOSE: This review presents an update of the non-contraceptive health benefits of the combined oral contraceptive pill. METHODS: We conducted a literature search for (review) articles that discussed the health benefits of combined oral contraceptives (COCs), in the period from 1980 to 2023. RESULTS: We identified 21 subjective and/or objective health benefits of COCs related to (i) the reproductive tract, (ii) non-gynaecological benign disorders and (iii) malignancies. Reproductive tract benefits are related to menstrual bleeding(including anaemia and toxic shock syndrome), dysmenorrhoea, migraine, premenstrual syndrome (PMS), ovarian cysts, Polycystic Ovary Syndrome (PCOS), androgen related symptoms, ectopic pregnancy, hypoestrogenism, endometriosis and adenomyosis, uterine fibroids and pelvic inflammatory disease (PID). Non-gynaecological benefits are related to benign breast disease, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and porphyria. Health benefits of COCs related to cancer are lower risks of endometrial cancer, ovarian cancer and colorectal cancer. CONCLUSIONS: The use of combined oral contraceptives is accompanied with a range of health benefits, to be balanced against its side-effects and risks. Several health benefits of COCs are a reason for non-contraceptive COC prescription.

Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!).

BACKGROUND: Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic. METHODS: Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 µg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days. RESULTS: The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks - 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD. CONCLUSIONS: The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible. TRIAL REGISTRATION: Clinical trials.gov NCT04007874 . Registered 28 June 2019.

The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients.

OBJECTIVE: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. STUDY DESIGN: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. RESULTS: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. CONCLUSION: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.

Venous Thromboembolic Risk of Estradiol Valerate-Dienogest Compared with Ethinyl Estradiol-Levonorgestrel Combined Oral Contraceptives.

This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate-dienogest with those containing ethinyl E2-levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts. Crude and adjusted hazard ratios (HRs) were calculated based on the extended Cox model. The pooled data set included 11,616 E2 valerate-dienogest users and 18,681 ethinyl E2-levonorgestrel users, contributing 17,932 and 29,140 women-years of observation, respectively. A significantly decreased VTE risk in E2 valerate-dienogest COCs compared with ethinyl E2-levonorgestrel COCs was observed (propensity score-stratified HR 0.46, 95% CI, 0.22-0.98). This pooled analysis expands data from a previous postauthorization safety study and provides valuable real-world safety information on the relative safety of current COCs.

Is the multinational, surveillance PRO-E2 study informative for all countries? The Italian data on VTE and contraceptive effectiveness.

PURPOSE: To evaluate whether the thromboembolic risk and contraceptive effectiveness of NOMAC-E2 observed in the PRO-E2 study can be extended to each participating country, as lifestyle, cardiovascular risk factors and prescribing habits may differ geographically. This analysis was performed on the PRO-E2 Italian subpopulation, where smoking habit and women over 35 years were more prevalent compared with the overall study population. MATERIALS AND METHODS: Data from NOMAC-E2 or levonorgestrel-containing COCs (COCLNG) new users were descriptively analysed. Incidence rates of thrombosis (events/10,000 women-years [WY]) and the Pearl Index (pregnancies/100 WY) were calculated. RESULTS: Overall, 11,179 NOMAC-E2 and 8,504 COCLNG users were followed up to 2 years (34,869 WY). The NOMAC-E2 cohort included more women over 35 vs. COCLNG (37.7% vs. 31.8%; p = 0.001). A comparable low risk of combined deep venous thrombosis of lower extremities (DVT) and pulmonary embolism (PE) was observed in NOMAC-E2 (1.7/10,000 WY; 95% CI: 0.21-6.2) and COCLNG users (6.6/10,000 WY; 95% CI: 2.4-14.4). Similar results were obtained by considering all thromboembolic events (VTE). Unintended pregnancies did not differ between NOMAC-E2 (0.12/100 WY; 95% CI: 0.06-0.21) and COCLNG (0.15/100 WY; 95% CI: 0.08-0.26) cohorts. CONCLUSION: Despite the higher age and tobacco use, findings from the Italian subpopulation were broadly consistent with overall PRO-E2 results, confirming a similar low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 and COCLNG. SHORT CONDENSATION: This subgroup analysis of the PRO-E2 study provides comprehensive epidemiological data on the use of combined oral contraceptives in a large Italian cohort, with a higher prevalence of women over 35 years and smokers. The study confirms the low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 pill.

Comparison of estrogenic components used for hormonal contraception.

Attempts have been made over the years to replace ethinyl estradiol (EE) in combined oral contraceptives (COCs) with the less potent natural estrogen estradiol (E2), or its prodrug, E2 valerate (E2V), to improve their safety and tolerability. Recently, a COC incorporating a novel weak natural estrogen, estetrol (E4), combined with drospirenone, has become available. We present a comparative analysis of the three prevailing estrogens used in COCs, focusing on their structure-function relationships, receptor-binding affinity, potency, metabolism, pharmacokinetic parameters, and pharmacodynamics. The binding affinity of EE to estrogen receptor (ER)α is twice that of E2, whereas its affinity for ERß is about one-half that of E2. E4 has a lower binding affinity for the ERs than E2. The high potency of EE is notable in its dramatic increase in estrogen-sensitive hepatic globulins and coagulation factors. EE and E2 undergo extensive and comparable metabolism, while E4 produces only a very limited number of metabolites. E4 has the highest bioavailability among the three estrogens, with E2 having <5%. Studies demonstrate consistent ovulation inhibition, although a higher dose of E4 (15 mg) in COCs is required to achieve follicular suppression compared to E2 (1-3 mg) and EE (0.01-0.035 mg). E2 and E4 in COCs may be less stimulatory of coagulant proteins than EE. Studies with E2/dienogest suggest a comparable risk of venous thromboembolism to EE/levonorgestrel, while data assessing risk with an E4-based COC are insufficient. Nevertheless, the E4-based formulation shows promise as a potential alternative to EE and E2 due to its lower potency and possibly fewer side effects.

Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives.

ABSTRACT: The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985.

High-fat diet promotes coagulation and endothelial activation in Sprague Dawley rats: Short-term effects of combined oral contraceptives.

BACKGROUND: Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats. METHODS: Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks. RESULTS: Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p<0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p>0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals. CONCLUSION: HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. However, additional studies are required to confirm these findings, especially long-term effects of this treatment within the cardiac tissues or endothelial cells of these animals in certain conditions relating to postmenopausal state.

Intimate partner violence as a risk factor for venous thromboembolism in women on combined oral contraceptives: An international matched case-control study.

BACKGROUND: Intimate partner violence (IPV) targeting women is probably underestimated during a woman's lifetime. Venous thromboembolism (VTE) is a multifactorial disease associated with haemostasis-activating conditions. Minor injuries can trigger VTE. OBJECTIVES: We aimed to look for an association between VTE and IPV in women taking combined oral contraceptives (COCs) METHODS: We performed a multicentric, international, matched case-control study. Patients were women with a first VTE associated with COC intake. Controls were women taking COCs undergoing regular gynaecological check-ups. Patients and Controls were matched for country, age, length of COC intake and type (997 pairs). IPV was evaluated using the WAST self-administrated questionnaire. RESULTS: IPV, defined as a WAST score value at least 5, was diagnosed in 33 Controls (3.3 %) and 109 patients (10.9 %), conditional odds ratio (OR): 3.586, 95 % confidence interval (2.404-5.549), p < 0.0001. After multivariate analysis, the adjusted OR was 3.720 (2.438-5.677), p < 0.0001. Sensitivity analysis using increasing WAST score thresholds confirmed the association. CONCLUSIONS: A first VTE in women taking COCs is associated with IPV. This association can have strong human consequences but also raises significant medical issues, for instance on the haemorrhagic risk of anticoagulant treatments in abused women. Pathophysiological studies are warranted.

Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review.

Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of ∼ 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.

O câncer cervical (CC) é causado pela infecção persistente pelo papilomavírus humano de alto risco oncogênico (hr-HPV); entretanto, vários cofatores são importantes na sua carcinogênese, como tabagismo, multiparidade e uso prolongado de contraceptivos hormonais orais (COCs). No mundo, 16% das mulheres usam AOCs, enquanto no Brasil essa taxa é de ∼ 30%. A segurança e os efeitos adversos dos COCs são amplamente discutidos na literatura, incluindo o aumento do risco carcinogênico. Devido à existência de várias drogas, combinações e dosagens de COCs, é difícil ter informações uniformes em estudos epidemiológicos. Nosso objetivo foi realizar uma revisão narrativa sobre o papel do uso de COCs na carcinogênese do câncer cervical. Vários estudos populacionais têm sugerido aumento da incidência de câncer de colo uterino para aquelas que usam COCs há mais de 5 anos, mas outros estudos disponíveis chegam a resultados controversos e contraditórios quanto à ação dos COCs no desenvolvimento do CCU.

A new progestin-only pill (POP): the impact of drospirenone-only pill 4 mg 24 + 4 on coagulation markers and bleeding patterns.

PURPOSE: Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control. The aim of this study was to evaluate the impact of a new POP [4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval] on some coagulation markers (both procoagulant and fibrinolytic) and to describe its impact on bleeding patterns. MATERIALS AND METHODS: This is a prospective trial, based on serum evaluation of following coagulation markers and tests: Factor (F) X, F VIII, F V, INR, aPTT, Protein S and antithrombin III. A 'bleeding diary' was used to categorise women as having (1) unscheduled bleeding, (2) scheduled bleeding and (3) amenorrhoea. Thirty patients were followed for six 28-day intake cycles, with a follow-up at the end of the 3rd and 6th cycles. RESULTS: There was a significant decrease of F X (p = 0.03) (-5.7% at cycle 6). No significant changes have been observed for F VII, F V and INR. A significant increase in aPTT (p = 0.01 at 3 cycles), Protein S (p = 0.0006 at 3 cycles) and antithrombin III (p < 0.0001 at 3 cycles) was recorded. This non-deteriorating coagulation impact was associated with a significant and progressive reduction of days of scheduled and unscheduled bleeding in users between cycles 4 and 6 (from 1.3 ± 0.2 days at cycle 4 to 0.8 ± 0.1 days at cycle 6 and from 2.6 ± 0.4 days at cycle 4 to 0.6 ± 0.2 days at cycle 6, respectively, p < 0.0001). CONCLUSIONS: DRSP 24 + 4 use was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Contraception with DRSP 24 + 4 was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Combined oral contraceptives: update recommendations of the Latin American contraceptive association.

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users.Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety.Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'.Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman.Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.

Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal.

Importance: Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation. Objective: To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs. Design, Setting, and Participants: This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria. Exposure: COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses. Main Outcomes and Measures: Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed. Results: A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause. Conclusions and Relevance: In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.