Pharmacological management of polycystic ovary syndrome.

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m2). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions.

Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis.

Background: Venous thromboembolism (VTE) poses a significant global health challenge, notably exacerbated by the use of combined oral contraceptives (COCs). Evidence mainly focuses on the type of progestogen used in COCs to establish the increased risk of VTE with less data assessed on the type of estrogen used. This meta-analysis aims to assess the risk of VTE associated with COCs containing synthetic estrogens like ethinylestradiol (EE) versus natural estrogens like estradiol (E2). Methods: A systematic review and meta-analysis was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were performed in December 2023 in MEDLINE and EMBASE to identify clinical studies comparing the VTE risk between COCs containing synthetic versus natural estrogens. Studies were selected through rigorous screening, and data extraction followed standardized protocols, with statistical analyses employing a random effects model. Results: The search yielded five relevant studies, involving over 560,000 women/time, demonstrating a significant 33% reduction in VTE risk among users of natural estrogen-based COCs compared to synthetic estrogen-based COCs (OR 0.67, 95% CI 0.51-0.87). Stratification analyses using adjusted hazard ratios (HR) of the main observationnal studies showed a 49% reduced VTE risk of E2-based pills compared to EE in association with levonorgestrel. Discussion and conclusion: Despite the longstanding use of EE-based COCs, emerging evidence supports a lower thrombotic risk associated with natural estrogens. This meta-analysis substantiates the lower VTE risk associated with natural estrogen-based COCs compared to synthetic alternatives, advocating for a re-evaluation of contraceptive guidelines to prioritize patient safety and reduce thrombotic risks.

Preventing recurrence of endometriosis-related pain by means of long-acting progestogen therapy: the PRE-EMPT RCT.

Background: Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Recurrence of symptoms following an operation is common. Although hormonal treatment can reduce this risk, there is uncertainty about the best option. Objectives: To evaluate the clinical and cost-effectiveness of long-acting progestogen therapy compared with the combined oral contraceptive pill in preventing recurrence of endometriosis-related pain and quality of life. Design: A multicentre, open, randomised trial with parallel economic evaluation. The final design was informed by a pilot study, qualitative exploration of women's lived experience of endometriosis and a pretrial economic model. Setting: Thirty-four United Kingdom hospitals. Participants: Women of reproductive age undergoing conservative surgery for endometriosis. Interventions: Long-acting progestogen reversible contraceptive (either 150 mg depot medroxyprogesterone acetate or 52 mg levonorgestrel-releasing intrauterine system) or combined oral contraceptive pill (30 µg ethinylestradiol, 150 µg levonorgestrel). Main outcome measures: The primary outcome was the pain domain of the Endometriosis Health Profile-30 questionnaire at 36 months post randomisation. The economic evaluation estimated the cost per quality-adjusted life-years gained. Results: Four hundred and five women were randomised to receive either long-acting reversible contraceptive (N = 205) or combined oral contraceptive pill (N = 200). Pain scores improved in both groups (24 and 23 points on average) compared with preoperative values but there was no difference between the two (adjusted mean difference: -0.8, 95% confidence interval -5.7 to 4.2; p = 0.76). The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the combined oral contraceptive group (73 vs. 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). The mean adjusted quality-adjusted life-year difference between two arms was 0.043 (95% confidence interval -0.069 to 0.152) in favour of the combined oral contraceptive pill, although this cost an additional £533 (95% confidence interval 52 to 983) per woman. Limitations: Limitations include the absence of a no-treatment group and the fact that many women changed treatments over the 3 years of follow-up. Use of telephone follow-up to collect primary outcome data in those who failed to return questionnaires resulted in missing data for secondary outcomes. The COVID pandemic may have affected rates of further surgical treatment. Conclusions: At 36 months, women allocated to either intervention had comparable levels of pain, with both groups showing around a 40% improvement from presurgical levels. Although the combined oral contraceptive was cost-effective at a threshold of £20,000 per quality-adjusted life-year, the difference between the two was marginal and lower rates of repeat surgery might make long-acting reversible contraceptives preferable to some women. Future work: Future research needs to focus on evaluating newer hormonal preparations, a more holistic approach to symptom suppression and identification of biomarkers to diagnose endometriosis and its recurrence. Trial registration: This trial is registered as ISRCTN97865475. https://doi.org/10.1186/ISRCTN97865475. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/114/01) and is published in full in Health Technology Assessment; Vol. 28, No. 55. See the NIHR Funding and Awards website for further award information. The NIHR recognises that people have diverse gender identities, and in this report, the word 'woman' is used to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary.

Endometriosis is a condition where cells similar to ones that line the womb are found elsewhere in the body. Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Unfortunately, symptoms often return and some women will need repeat operations. Hormonal contraceptives can prevent the return of endometriosis-related pain: either long-acting reversible contraceptives (injections or a coil, fitted inside the womb) or the combined oral contraceptive pill (often called 'the pill'). We do not know which is the best option. The aim of this trial was to find out which of these two hormone treatments was more effective in terms of symptom relief, avoidance of further surgery and costs. Four hundred and five women with endometriosis, who were not intending to get pregnant, participated in a clinical trial. Half of the participants took long-acting reversible contraceptives, and the other half took the pill for 3 years following endometriosis surgery. The choice of treatment was made at random by a computer to ensure a fair comparison, although those allocated to the long-acting contraceptive could choose between injections or the coil. Participants completed questionnaires about their symptoms and life quality at intervals up to 3 years. Both treatments were equally good at reducing pain but more women using the pill had repeat operations. The pill was a little more costly overall but associated with a slightly higher quality of life. Both treatments are equally effective in reducing pain up to 3 years after surgery for endometriosis. The differences in costs are small and the choice of treatment should be based on personal preference.

Analysis of Risk Factors Associated with Gestational Diabetes Mellitus: A Retrospective Case-Control Study.

Objective: Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM. Methods: A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed. Results: The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥30 years old, body mass index (BMI) in early pregnancy≥24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥30 years old (≥30 vs <30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183-3.878, p=0.012), BMI≥24.0 kg/m2 (≥24.0 kg/m2 vs 18.5-23.9 kg/m2, OR: 1.887, 95% CI: 1.041-3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022-3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046-7.863, p=0.041) were associated with GDM. Conclusion: Age of pregnant woman ≥30 years old, BMI≥24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.

Investigating the influence of oral contraceptive pill use on multiple sclerosis risk using UK Biobank data.

OBJECTIVE: To investigate the association between oral contraceptive (OC) pill use and the risk of developing multiple sclerosis (MS), attempting to address the limitations present in previous studies that produced conflicting results. DESIGN: A population-based cohort study using data from the UK Biobank. PATIENTS: The study included 181,058 women of white ethnicity born in England between 1937 and 1970, among which 1,131 had an MS diagnosis. INTERVENTION: Oral contraceptive use, considering the self-reported age of initiation and discontinuation. The exposures of interest include the following: ever-use, current use, duration of current use in years, and age and year at initiation. MAIN OUTCOME MEASURES: Multiple sclerosis diagnosis (International Classification of Disease, 10th revision: G35) was used as an outcome of interest, and the associations with the exposures of interest were investigated using marginal structural models with a time-to-event approach. To adjust for confounding, we included in the models several variables, including MS polygenic risk score, education level, parity, smoking, fertility problems, obesity, and mononucleosis. We further aimed to evaluate the influence of parity using a mediation analysis. RESULTS: The association of both ever and current OC use did not result in a statistically significant MS hazard increase (ever vs. never-users, hazard ratio [HR] = 1.30 [95% confidence interval {CI}: 0.93,1.82]; current vs. never-users, HR = 1.35 [95% CI: 0.81, 2.25]). However, we highlighted parity as an effect modifier for this association. In nulliparous women, ever and current use resulted in a significant twofold and threefold MS hazard increase (HR = 2.08 [95% CI: 1.04, 4.17] and HR = 3.15 [95% CI: 1.43, 6.9]). These associations were supported by significant MS hazard increases for a higher duration of current use and for an earlier age at initiation. We further highlighted genetic MS susceptibility as another effect modifier, as a stronger OC-MS hazard association was found in women with a low MS polygenic risk score. CONCLUSION: Our findings highlighted how the association between OC use and MS varies on the basis of individual characteristics such as parity and genetic MS susceptibility. Importantly, current use in nulliparous women was found to be associated with a threefold increase in MS hazard. We acknowledge the need for cautious causal interpretation and further research to validate these findings across diverse populations and OC types.

Practical diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder by psychiatrists and obstetricians/gynecologists in Japan.

Aim: To investigate and compare the diagnoses and treatment of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) from the perspectives of psychiatrists and obstetricians/gynecologists (OB/GYNs) in Japan. Methods: Between December 2021 and February 2022, a web-based survey was conducted among the members of the Japanese Association of Neuro-Psychiatric Clinics. Data from 262 psychiatrists who responded to the aforementioned survey were compared with data from 409 OB/GYNs from a survey conducted in 2021 among members of the Japanese Society of Obstetrics and Gynecology. Results: Overall, 79.8% of psychiatrists and 97.3% of OB/GYNs were involved in practicing PMS/PMDD diagnosis and treatment. Most psychiatrists believed that PMS should be treated by OB/GYNs (74.4%) and PMDD by psychiatrists (75.6%). Only vague medical interviews were conducted by 86.6% of psychiatrists, and only 9.7% maintained a two-cycle symptom diary. Psychiatrists mostly prescribed selective serotonin/serotonin and noradrenaline reuptake inhibitor (SSRI/SNRI) continuous dosing (91.1%), followed by Kampo medicines, especially Kamishoyosan (73.3%); only 2.8% chose oral contraceptive pills, unlike OB/GYNs, while SSRI continuous (32.8%) and luteal phase dosing (20.6%) and Kampo medicine (42.1%) were the most common first-line treatments. Lifestyle guidance was prescribed by 63.6% of psychiatrists, followed by cognitive behavioral therapy (13.8%) and the symptom diary observation method (11.1%), which were similar to OB/GYNs' choices. Conclusions: Many Japanese psychiatrists and OB/GYNs do not base PMS/PMDD diagnoses on prospective monitoring methods using specific diagnostic criteria and therefore do not provide evidence-based treatment. Moreover, a tendency of being biased toward treatments in which the department specialized was observed.

A preliminary report comparing the effect of Asafoetida with oral contraceptive on polycystic ovarian syndrome in a double-blind randomized trial.

Objective: Polycystic ovarian syndrome (PCOS) is the most common cause of infertility and endocrine disorders in women of childbearing age. In Persian medicine, Ferula assafoetida L. (Asafoetida) was recommended for treating PCOS. The present study was conducted to compare the effect of Asafoetida with oral contraceptive tablets on PCOS patients. Materials and Methods: Patients with PCOS (n=30) were enrolled in a double-blind randomized clinical trial. On Day 5 of the menstrual cycle, patients received two periods of 21-day treatment, with 7 days rest between the two treatments. On a daily basis, half of the patients (n=15) received Asafoetida (1 g), and the rest received low dose oral contraceptive (LD; one tablet). Menstrual status, anthropometric characteristics, hematology and biochemistry parameters, ovarian ultrasound examination and hirsutism were evaluated prior to the initiation of the experiment and 14 days after the end of treatment. The occurrence of menstrual cycles and pregnancy was assessed eight months after the end of treatment. Results: The incidence of pregnancy was greater in patients who received Asafoetida compared to those who received LD (p=0.019). The time intervals between menstrual cycles became shorter in both groups (p<0.05). The occurrence of regular menstrual cycles remained longer in the Asafoetida compared to the LD group (p=0.001). Concentrations of triglycerides, cholesterol, HDL and LDL were significantly increased after treating with LD (p<0.05). Conclusion: In PCOS patients, the occurrence of regular menstrual cycles and the incidence of pregnancy were improved following treatment with Asafoetida. This medicament could be considered a safe treatment for patients with PCOS.

A 27-Year-Old Female With JAK2 Mutation: A Case of Budd-Chiari Syndrome Secondary to Prolonged Oral Contraceptive Pill Use.

Individuals with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) such as polycythemia vera and essential thrombocythemia (ET) demonstrate an increased thrombotic risk associated with JAK2 mutations. Physicians must take heed when treating these patients, to mitigate this pro-thrombotic state as much as possible. Failure to do so, or exacerbating the state, can lead to dire consequences. We present the case of a 27-year-old female with a history of ulcerative colitis (UC) and ET, currently taking estrogen-containing oral contraceptive pills (OCPs). She presented to the emergency department with rapid weight gain, jaundice, nausea, and diarrhea and was found to have obstructive jaundice and thrombotic burden that extended into the portal, mesenteric, splenic, and hepatic veins. On the second attempt, a successful transjugular intrahepatic portosystemic shunt procedure was performed, resulting in improved venous flow. This case underscores the importance of cautious medication use, especially OCPs, in patients with hypercoagulable states due to JAK2 mutations, for example, the V617F mutation in JAK2. It emphasizes the need for vigilant monitoring, individualized management, and a multidisciplinary approach to mitigate thrombotic complications. Increased awareness and continued research are crucial for optimizing treatment strategies for patients with MPNs and associated genetic mutations.

Use of Generative AI for Improving Health Literacy in Reproductive Health: Case Study.

BACKGROUND: Patients find technology tools to be more approachable for seeking sensitive health-related information, such as reproductive health information. The inventive conversational ability of artificial intelligence (AI) chatbots, such as ChatGPT (OpenAI Inc), offers a potential means for patients to effectively locate answers to their health-related questions digitally. OBJECTIVE: A pilot study was conducted to compare the novel ChatGPT with the existing Google Search technology for their ability to offer accurate, effective, and current information regarding proceeding action after missing a dose of oral contraceptive pill. METHODS: A sequence of 11 questions, mimicking a patient inquiring about the action to take after missing a dose of an oral contraceptive pill, were input into ChatGPT as a cascade, given the conversational ability of ChatGPT. The questions were input into 4 different ChatGPT accounts, with the account holders being of various demographics, to evaluate potential differences and biases in the responses given to different account holders. The leading question, "what should I do if I missed a day of my oral contraception birth control?" alone was then input into Google Search, given its nonconversational nature. The results from the ChatGPT questions and the Google Search results for the leading question were evaluated on their readability, accuracy, and effective delivery of information. RESULTS: The ChatGPT results were determined to be at an overall higher-grade reading level, with a longer reading duration, less accurate, less current, and with a less effective delivery of information. In contrast, the Google Search resulting answer box and snippets were at a lower-grade reading level, shorter reading duration, more current, able to reference the origin of the information (transparent), and provided the information in various formats in addition to text. CONCLUSIONS: ChatGPT has room for improvement in accuracy, transparency, recency, and reliability before it can equitably be implemented into health care information delivery and provide the potential benefits it poses. However, AI may be used as a tool for providers to educate their patients in preferred, creative, and efficient ways, such as using AI to generate accessible short educational videos from health care provider-vetted information. Larger studies representing a diverse group of users are needed.

Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. OBJECTIVE: To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. METHOD: From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. RESULT: Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). CONCLUSION: Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

Understanding the Interplay Between Premenstrual Dysphoric Disorder (PMDD) and Female Sexual Dysfunction (FSD).

Premenstrual dysphoric disorder (PMDD) is a severe variant of premenstrual syndrome (PMS), categorized as a mood disorder due to marked symptoms of depression and anxiety, compounded with severe physical symptoms. Female sexual dysfunction (FSD) can manifest as low libido, difficulty achieving sexual pleasure, and dyspareunia, causing functional and psychological distress. PMDD and FSD are globally prevalent conditions with postulated biological, psychological, and social associations between them. Nevertheless, sexual dysfunction in PMDD is an important aspect of women's health that has been understudied and has notable methodological limitations. In this narrative review, we summarize the existing literature on sexual function in women with PMDD and PMS, specify the distinctions between PMDD and other general symptoms of PMS, highlight the significance of understanding sexual dysfunction in the female population, and outline some available therapeutic options. Studies show that women frequently experience debilitating sexual distress during the premenstrual phase; however, there is an essential need to formulate standardized tools for definite diagnosis. Selective serotonin re-uptake inhibitors (SSRIs) and combined oral contraceptive pills (COCPs) are approved medications for PMDD, while flibanserin and bremelanotide are effective in treating FSD. However, the potential effects of these treatment modalities on the two comorbid conditions render them inconclusive. Awareness of PMDD and FSD among clinicians and society can allow the implementation of targeted interventions to alleviate the suffering of women and enhance their quality of life.

Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review.

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the use of hormonal contraception (oral contraceptives and hormonal intrauterine devices) on metabolism, muscular strength, and recovery in active females. Ovarian hormones are known to influence metabolism because estrogen is a master regulator of bioenergetics. Importantly, the menstrual cycle may impact protein synthesis, impacting skeletal muscle quality and strength. Studies investigating muscular strength in eumenorrheic women report equivocal findings between the follicular phase and luteal phase with no differences compared to oral contraceptive users. Studies examining recovery measures (using biomarkers, blood lactate, and blood flow) do not report clear or consistent effects of the impact of the menstrual cycle or hormonal contraception use on recovery. Overall, the current literature may be limited by the evaluation of only one menstrual cycle and the use of group means for statistical significance. Hence, to optimize training and performance in females, regardless of hormonal contraception use, there is a need for future research to quantify the intra-individual impact of the menstrual cycle phases and hormonal contraceptive use in active females.

A bitter pill to swallow: adjustments to oral contraceptive pill use in polycystic ovary syndrome.

INTRODUCTION: This Special Report aims to highlight the importance of tailored therapies in women with Polycystic Ovary Syndrome (PCOS), avoiding prescribing generalized or unsuitable therapies based on oral contraceptive pills (OCPs). AREAS COVERED: This article discusses the benefits and risks of OCP-based therapy, highlighting the possible undesirable effects, especially in those patients exhibiting risk factors as women with PCOS, and the importance of carefully evaluated tailored therapeutic approaches. Literature searches were performed with the use of PubMed, Google Scholar, and Web of Science between January and February 2024. EXPERT OPINION: Considering the recent re-analysis of PCOS Rotterdam Criteria by the Expert Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), the traditional Rotterdam phenotypes can be reclassified to achieve more efficacious therapy choices. Using personalized therapies that consider the specific clinical characteristics of the patient allows to improve the management of the syndrome, thus avoiding the generalized use of OCPs, which risk treating only symptoms of PCOS rather than the underlying cause. In cases when contraceptive purpose is desired, patients may benefit from combined therapy with diet or insulin-sensitizer agents, as inositol, to rebalance the metabolic profile, thus reducing the risk of developing future complications.

El papel del estetrol en la anticoncepción: una revisión integral

Esta revisión narrativa explora el papel potencial del estetrol (E4), un esteroide estrogénico natural, en la anticoncepción, analizando sus propiedades farmacológicas, su efectividad y su seguridad. Se revisaron estudios preclínicos, ensayos clínicos y evaluaciones de seguridad del E4 como anticonceptivo oral combinado (AOC). Se investigó el impacto en parámetros endocrinos, metabólicos y hemostáticos, así como su tolerabilidad. En los resultados, el E4 tiene menor afinidad por el receptor de estrógeno-α de membrana, pero mantiene la actividad agonista en los receptores nucleares. E4/DRSP (drospirenona) demostró ser un AOC eficaz, con ciclos de sangrado regulares y predecibles en la mayoría de las mujeres. La tolerabilidad fue favorable, con eventos adversos leves o moderados y bajas tasas de interrupción. El sangrado fue el evento adverso más común, y se reportaron casos raros de migrañas con aura, trombosis venosa profunda, hiperpotasemia y depresión. E4/DRSP tuvo mínimo impacto en los parámetros lipídicos, hepáticos, de globulina fijadora de hormonas sexuales y de metabolismo de hidratos de carbono, y efecto neutral o mínimo en los parámetros hemostáticos. Se concluye que E4/DRSP parece ser una opción anticonceptiva eficaz y segura, con reducido riesgo trombótico y mínimo impacto en los parámetros endocrinos y metabólicos. Se requiere más investigación para confirmar su seguridad y eficacia a largo plazo.

This narrative review explores the potential role of estetrol (E4), a natural estrogenic steroid, in contraception, analyzing its pharmacological properties, effectiveness, and safety. Preclinical studies, clinical trials, and safety assessments of E4/DRSP (drospirenone) as a combined oral contraceptive (COC) were reviewed. The impact on endocrine, metabolic, and hemostatic parameters, as well as tolerability, was investigated. In results, E4 exhibits lower affinity for estrogen transmembrane receptor-α but maintains agonistic activity on nuclear receptors. E4/DRSP proved to be an effective COC with regular and predictable bleeding cycles in most women. Tolerability was favorable with mild or moderate adverse events and low discontinuation rates. Bleeding was the most common adverse event, and rare cases of aura migraines, deep vein thrombosis, hyperkalemia, and depression were reported. E4/DRSP had minimal impact on lipid, hepatic, sex hormone-binding globulin, and carbohydrate metabolism parameters, with a neutral or minimal effect on hemostatic parameters. The conclusion is that E4/DRSP seems to be an effective and safe contraceptive option, with reduced thrombotic risk and minimal impact on endocrine and metabolic parameters. Further research is needed to confirm long-term safety and efficacy.

A Rare Case of Renal Vein Thrombosis Secondary to Oral Contraceptive Pills.

Renal vein thrombosis (RVT) is a common complication of nephrotic syndrome and renal malignancy. However, its association with oral contraceptive use has rarely been reported. We report a case of a 29-year-old female with a history of oral contraceptive use, presenting with acute flank pain. On further investigation, she was found to have unilateral RVT. Oral contraception was discontinued, and she was started on therapeutic anticoagulation, initially with low-molecular-weight heparin, and then switched to apixaban. Her symptoms improved, and she is currently doing well. This case signifies the importance of proper history-taking and how oral contraception should be considered a significant risk factor for venous thromboembolism.

Giant pedunculated hepatic hemangioma accompanied by a 10-year history of taking oral contraceptive: A case report and literature review.

Key Clinical Message: Giant pedunculated hepatic hemangiomas, mostly seen in women, are considered a rare type of giant hepatic hemangioma, with challenging diagnosis. Unlike other types of liver hemangiomas, they can manifest different kinds of symptoms, and are prone to life-threatening manifestations like rupture or torsion. Abstract: Hemangioma is the most common benign liver primary tumor. Hepatic hemangioma >4 cm (some studies suggest >10 cm) is referred to as a giant hemangioma. Although hepatic hemangioma does not manifest symptoms in most cases, a giant hepatic hemangioma can manifest different kinds of symptoms. Giant pedunculated hepatic hemangiomas are considered a rare type of giant hepatic hemangioma, with challenging diagnosis, as the thin pedicle could be hard to be detected on imaging. A 41-year-old woman was admitted to our hospital, with dull discomfort of the right upper quadrant and epigastric region and early satiety for the past 7 months, with the history of taking oral contraceptive (OCP) for 10 years. Ultrasound and computed tomography revealed a 130 × 124 × 76 mm solid mass, with central cystic lesion, located in the midline of the epigastric region, attaching to the inferior surface of the third segment of the left lobe of the liver. Due to the potential risk for torsion, and rupture of the hemangioma, the management of the patient proceeded to surgical excision. Pathological examination of the specimen confirmed the diagnosis of hepatic hemangioma. Giant pedunculated hepatic hemangioma is a rare benign tumor. It demonstrates higher incidence rate in women, as some hemangiomas have estrogen receptors, and estrogen can lead to endothelial cell proliferation and organization in vascular structure. Most hemangiomas do not express any symptoms; therefore, no treatment is needed except for the patients who manifest symptoms, or in giant pedunculated hemangiomas, as they are prone to rupture or torsion. In this review most cases were female, and most of them presented with abdominal pain, in most cases the tumor located in the left lobe of the liver. Almost all the reviewed cases underwent surgery. Giant hepatic hemangioma is a differential diagnosis of palpable mass, or other symptoms of the right upper quadrant, and epigastric region specially in women taking OCP. Imaging is needed to rule out these tumors, and most often, pedunculated hemangioma is harder to be defined on imaging. It requires surgery because of the risk of acute problems, such as torsion and rupture.

Triple whammy in a patient with portal vein thrombosis.

Infection with SARS-CoV-2 has been shown to predispose to thromboembolic events. The risk of such thromboses further increases in those with underlying inherited or acquired prothrombotic states. The authors present a 30-year-old lady who developed acute abdominal pain, three days after recovery from a mild COVID-19 infection. She was also using oral contraceptive pills. Laboratory investigations revealed elevated inflammatory markers, and a contrast-enhanced abdominal CT scan demonstrated portal vein thrombosis (PVT). Due to the unusual site of thrombosis, a thrombophilia screen was performed, which detected a heterozygous Factor V Leiden mutation (FVL). Thus, her PVT was attributed three simultaneous risk factors, namely COVID-19 infection, OCP use and FVL mutation. She was initiated on anti-coagulation, with which she improved significantly. In patients presenting with thromboses at uncommon sites, investigation for evidence of recent Covid-19 infection and screening for inherited and acquired thrombophilia should be considered, while discontinuing any offending medications.

Exploration of new models for primary dysmenorrhea treatment: low-power visible-light-activated photodynamic therapy and oral contraceptives.

Background: Primary dysmenorrhea (PD) is one of the most common reasons that affect the life quality of women during childbearing age. This research aims to explore the efficacy and curative effect characteristics of oral contraceptives and low-power visible-light-activated photodynamic therapy (PDT). Besides investigating the possible mechanism of PDT, we expected to find a treatment model with better efficacy and fewer side effects. Method: It was a multicenter, randomized, parallel-controlled study. Eligible participants were randomly assigned to three groups: placebo group, oral contraceptive (Marvelon) group, and the PDT group. They were treated continuously for three menstrual cycles and followed up for two cycles after treatment. The scores of the visual analog scale (VAS) and the concentration of pain-related small molecules in blood before and after treatment were recorded in each group, which can evaluate the therapeutic characteristics of different treatments. Result: Both Marvelon and PDT were effective. The effect of Marvelon appears quickly which can significantly relieve symptoms at the beginning, while PDT shows a relatively slow role. There was no significant difference in the final efficacy two cycles after treatment. The therapeutic effect was achieved by reducing the concentrations of prostaglandin 2 (PGE2) and endothelin (ET) in the blood. Conclusion: Marvelon and PDT are effective methods for the treatment of PD. The long-term efficacy of the two is similar, while the therapeutic characteristics and the side effects are different. Patients can choose the suitable way according to their individual needs.

Longitudinal assessment of coagulation potential before, during, and following an in vitro fertilization cycle.

INTRODUCTION: The association between estrogen and hypercoagulability is well-established but little is known about coagulation dynamics during IVF. Our goal was to measure coagulation potential prior to, during, and following an IVF cycle and to investigate differences by conception outcome. MATERIALS AND METHODS: Patients undergoing IVF with fresh embryo transfer at a single academic center using oral contraceptive pills for cycle batching underwent evaluation of thrombin generation using the calibrated automated thrombogram at multiple points during the IVF cycle. Multiple thrombin generation parameters were compared across timepoints and by IVF cycle outcome using ANOVA repeated measures analysis. RESULTS: Of the 17 patients included, 11 conceived. There was a significant increase in peak and total thrombin generation in the entire cohort between the pre-treatment natural follicular phase and following a short course of oral contraceptive pills used for cycle batching. Further increase in these parameters was seen at the time of oocyte retrieval. In the pre-treatment natural follicular phase, patients who conceived had lower peak thrombin generation. There were changes throughout the cycle for factors II, V, VIII, X, XI, XII, antithrombin, and tissue factor pathway inhibitor. Only Factor XI was distinguishable by conception status; values were lower at all visits in patients who conceived. CONCLUSION: Increases in coagulation potential are seen in patients undergoing IVF following a short course of oral contraceptive pills for cycle batching and continue during controlled ovarian hyperstimulation. Those who conceived were seen to have lower peak thrombin generation in the pre-treatment natural follicular phase.

Intestinal obstruction induced by portal vein thrombosis in a female undergoing oral contraceptive therapy: a case report with comprehensive review.

Introduction: Portal vein thrombosis (PVT) is a rare medical condition that obstructs blood flow in the portal vein, with cirrhosis as a common predisposing factor. However, its association with oral contraceptive pills (OCPs), particularly with progestins, remains inadequately explored. This case report aims to contribute to this understanding, focusing on the rare presentation of PVT-induced intestinal obstruction in a female on prolonged OCP therapy. Case presentation: A 45-year-old female presented with severe abdominal pain, vomiting, and constipation. Diagnosis revealed PVT-induced intestinal obstruction, an exceptionally rare occurrence in the context of prolonged OCP therapy. The patient's symptoms improved with conservative management, including rivaroxaban, highlighting the crucial role of early intervention. Discussion: This case brings attention to the limited literature exploring the link between OCPs and PVT. Despite the generally safe reputation of OCPs, they can induce pro-thrombotic conditions, emphasizing the need for heightened clinical awareness. In this case, the rarity of intestinal obstruction in PVT, compounded by the absence of common risk factors, underscores the diagnostic challenges associated with such presentations. Conclusion: PVT-induced intestinal obstruction in a patient on prolonged OCP therapy is exceptionally rare, emphasizing the necessity for multidisciplinary management. It provides crucial insights into suspecting, identifying, and treating this uncommon complication in non-cirrhotic individuals, contributing to the limited existing literature on the subject.