Healthy plasma lipidomic signatures depend on sex, age, body mass index, and contraceptives but not perceived stress.

Perceived stress is thought to contribute to the pathogenesis of metabolic, vascular, mental, and immune diseases, with different susceptibilities in women and men. The present study investigated if and how perceived stress and/or demographic variables including sex, age, body mass index, regular prescription drugs, occasional analgesics, or dietary supplements manifested in plasma lipidomic profiles, obtained by targeted and untargeted mass spectrometry analyses. The study included 217 healthy women and 108 healthy men, aged 18-68 years, who were recruited in a 2:1 female:male ratio to account for women with/without contraceptives. As expected, dehydroepiandrosterone sulfate (DHEAS) and ceramides were higher in men than women, and DHEAS decreased with age, while ceramides increased. Contrary to expectations, neither DHEAS nor ceramides were associated with perceived stress (PSQ30 questionnaire), which was however, associated with BMI in men, but not in women. None of the lipid species or classes showed a similar "age X sex X BMI" interaction, but the endocannabinoid palmitoylethanolamide (PEA) correlated with BMI and hypertension. Independent of perceived stress, lysophosphatidylcholines (LPCs) were lower in women than men, whereas LPC metabolites, lysophosphatidic acids (LPAs), were higher in women. The LPA:LPC ratio was particularly high in women using oral contraceptives suggesting a strong hormone-induced extracellular conversion of LPCs to LPAs, which is catalyzed by the phospholipase D, autotaxin. The results reveal complex sex differences in perceived stress and lipidomic profiles, the latter being exacerbated by contraceptive use, but perceived stress and lipids were not directly correlated.

Systemic Estrogen Therapy and Thrombosis: A Call for Individualized Clinical Decision Making in the Acute Care Setting.

Systemic estrogen therapies (SETs) are integral to health care, playing critical roles in reproductive rights, managing heavy menstrual bleeding (HMB), alleviating menopausal symptoms, and supporting gender-affirming hormone therapy (GAHT) for transwomen. However, SETs are associated with an increased risk of venous thromboembolism (VTE), posing a challenge in the acute care setting. Here, we explore the nuanced management of SETs in patients who present with a hormone-related VTE in the acute care setting. The prevailing practice of discontinuing SETs in this setting may lead to significant adverse effects, including exacerbation of HMB, unintended pregnancy, menopausal symptoms, and psychological distress from interrupted GAHT or hormone replacement therapy. The discontinuation of SETs can severely affect patients' health, quality of life, and adherence to anticoagulation therapy in the case of HMB, increasing the risk of VTE recurrence. We challenge the practice of broadly discontinuing SETs in the acute care setting, advocating for a patient-centered approach that considers the underlying reasons for SET use, potential adverse effects of abrupt cessation, and individual patient needs. We underscore the importance of shared decision making and individualized care, particularly for historically marginalized groups in health care, cis women, transwomen, and individuals with HMB, to ensure safe, equitable, and affirming health care. A tailored approach to managing SETs in the acute care setting will enhance health care delivery and reduce health inequities. Lastly, we highlight the need for further research, particularly regarding GAHT-related VTE for transwomen.

Transnational Health and Self-care Experiences of Japanese Women who have taken Oral Contraceptives in South Korea, including Over-the-counter Access: Insights from Semi-structured Interviews.

In an increasingly globalized world, the accessibility of healthcare and medication has expanded beyond local healthcare systems and national borders. This study aims to investigate the transnational health and self-care experiences of 11 Japanese women who have resided in South Korea for a minimum of six months and have utilized oral contraceptives, including those that were acquired over-the-counter (OTC). Data were gathered through semi-structured interviews and analyzed by utilizing the NVivo software. The analysis yielded three significant thematic categories, namely (1) experiences and perceptions of obtaining and utilizing contraceptive pills, including OTC access; (2) individual and social perceptions of pills and their accessibility in Japan, insights from actual users; and (3) enhancing pill accessibility, transnational health and self-care experiences and perspectives. Participants acknowledged that oral contraceptives are a global product and experienced communication challenges with healthcare providers as a result of differing understandings of these medications. Additionally, this study identified transnational strategies, such as purchasing an adequate supply of pills just before departure and seeking pills from local families or acquaintances. This study not only highlights the implications of clinical care for transnational patients but also underscores their critical global perspectives on access to oral contraceptives. Furthermore, it proposes two models for improving accessibility within the Japanese healthcare system, even in prescription-only contexts, by introducing OTC options.

Gut Microbiota and Oral Contraceptive Use in Women with Polycystic Ovary Syndrome: A Systematic Review.

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine syndromes affecting women at reproductive age. With increasing knowledge of the role of the microbiota in the pathogenesis of PCOS, new management strategies began to emerge. However, data on the impact of established treatment regimens, such as metformin and oral contraceptive agents, on the gut microbiota composition are scarce. This study aimed to evaluate the specificity of the gut microbiota in women with PCOS before and after treatment with oral contraceptives. Methods: We have systematically searched the following databases: PubMed/MEDLINE, Scopus, Web of Science and Google Scholar. The last search was performed on 13 May 2024. We included only full-text original research articles written in English. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale. Results: The above described search strategy retrieved 46 articles. Additionally, 136 articles were identified and screened through Google Scholar. After removing duplicates, we screened the titles and abstracts, resulting in three eligible articles constituting the final pool. They were published between 2020 and 2022 and are based on three ethnically distinct study populations: Turkish, Spanish and American. The studies included a total of 37 women diagnosed with PCOS and using OCs. Conclusions: OC treatment does not seem to affect the gut microbiota in a significant way in patients with PCOS in short observation. Well-designed randomized controlled studies with adequate, unified sample size are lacking.

Are we asking the right questions? Female athletes' perspectives on the menstrual cycle in sport.

BACKGROUND: Menstrual cycle (MC) research employing qualitative and quantitative methods has recently increased in athlete populations. A move towards a participant-centered approach to help formulate questions that align with practitioners' and stakeholders' priorities in the sport environment is needed. Therefore, our study aims were to 1) understand what athletes feel is important to consider regarding their MC in sport, and 2) provide practical recommendations for coaches and practitioners to support a positive sport culture around the MC. METHODS: Participants were Canadian female athletes competing at national and international levels. Team (n = 10) and individual (n = 10) sport athletes (median age 23 years) shared their experiences and values in one-on-one semi-structured interviews. RESULTS: Three main theories were identified by constructive grounded theory analyses: 1) training and performance, 2) culture, and 3) health. Athletes expressed a desire for symptom management strategies and more evidence on MC training periodization to optimize performance. Key determinants in creating a positive culture included communication and feeling supported. Athletes also expressed challenges in balancing health with performance and felt ill-informed on how hormonal contraceptives could potentially impact performance. Practical recommendations included 1) addressing individualized, context-specific symptom impacts on the athlete's sport demands, 2) using a group-based approach to initiate MC communication topics and, 3) designate female health point-of-contact staff to facilitate MC information. CONCLUSION: Future research should continue to evaluate MC impacts on training and performance and study designs should include participants who are using hormonal contraceptives. Coaches and sport practitioners should prioritize female athlete health alongside performance goals.

Barriers and enablers to utilisation of postpartum long-acting reversible contraception in Eastern Uganda: a qualitative study.

INTRODUCTION: In Uganda, although most women wish to delay or prevent future pregnancies, uptake of postpartum family planning (PPFP) is low. We explored behavioural factors influencing the utilisation of postpartum long-acting reversible contraceptives (LARCs) in Eastern Uganda. METHODS: We conducted a qualitative study in two districts of Eastern Uganda. We conducted 20 in-depth interviews and three focus group discussions with postpartum women, male partners, midwives, and village health team members. We analysed transcripts using framework analysis, based on the COM-B framework. RESULTS: The use of immediate postpartum LARC was affected by the capabilities of women in terms of their knowledge and misconceptions. Limited capabilities of health workers to provide counselling and insert IUDs, as well as shortages of implants, reduced the physical opportunites for women to access PPFP. Social opportunities for women were limited because men wanted to be involved in the decision but rarely had time to accompany their partners to health facilities, and health workers often appeared too stressed. Men also feared that PPFP would enable their partners to be unfaithful. Motivation to take up immediate postpartum LARC included the desire to space births, preference for contraceptive implants over intra uterine devices (IUD) at the 6-week postpartum period, resumption of sex and menses, partner support, and perceived effectiveness of postpartum contraception. Participants thought that uptake of immediate postpartum LARC could be improved by health education and outreach visits, male involvement and couples' counselling in antenatal clinic appointments, and enabling switching between family planning methods (in case of side-effects) . CONCLUSION: Low uptake of PPFP was caused by inadequate knowledge and misconceptions about LARC by women and their partners, insufficient numbers of midwives trained to provide PPFP, stock-outs of PPFP methods, and few social opportunities for couples to be counselled together. These factors could be addressed by scaling up effective, low cost and innovative ways to provide health education (such as films), involving men in decision-making, as well as training more midwives to provide PPFP services, and ensuring that they have sufficient time and supplies.

The impact of the Roe v. Wade overturn on birth control prescriptions and sterilisation procedures in rural NC.

BACKGROUND/INTRODUCTION: On June 24, 2022, the Supreme Court overturned the 1973 verdict in the Roe v. Wade legal suit that had established the constitutional right to medical abortion [1]. With the right to abortion now being left to the states, many restrictions regarding abortion procedures are being established [2]. We aim to evaluate whether this has led to an increase in the number of birth control prescriptions and sterilisation procedures at Cape Fear Valley Medical Centre in rural North Carolina. METHODS: SlicerDicer program within EPIC medical records database was used to retrieve the records of all women that had an obstetrics and gynaecology appointment with Cape Fear Valley Health System between 11/01/21-12/31/2022 for contraception. The data was sorted into race/ethnicity, age, and types of birth control. Principal outcomes measured the trends in birth control prescription or sterilisation procedure appointments before and after the overturn of Roe v. Wade. RESULTS: Contraceptive pill prescriptions decreased from 51.70% to 32.40%. IUD insertions decreased from 39.40% to 11.30%. Injectable birth control remained consistent, at approximately 16%. Nexplanon implantations dropped from 20.60% to 9.70%. Lastly, sterilisation procedures increased from 6.7% to 10.7%. CONCLUSION: Majority of birth control prescriptions decreased following the overturn of Roe v. Wade, except for sterilisation, which increased by 4.0%. This may indicate that women are now looking for more permanent birth control options after the overturn of Roe v. Wade. Future research should investigate whether similar trends of increasing prevalence of sterilisation procedures is seen throughout the United States. SHORT CONDENSATION: We aim to assess the impact of the Supreme Court overturn regarding the Roe v. Wade legal suit on contraceptive decisions in rural North Carolina.

Effects of oral contraceptive pills on brain networks: A replication and extension.

Neuroimaging research has identified significant effects of oral contraceptive pills (OCPs) on brain networks. A wide variety of approaches have been employed, largely in observational samples, with few converging results. This study therefore was designed to test for replication and extend this previous work using a randomized, double-blind, placebo-controlled crossover trial of the effects of OCPs on brain networks. Using functional MRI, we focused on brain regions identified in prior studies. Our analyses did not strictly replicate previously reported effects of OCPs on functional connectivity. Exploratory analyses suggested that traditional seed-based approaches may miss broader, network-level effects of OCPs on brain circuits. We applied data-driven, multivariate techniques to assess these network-level changes, A deeper understanding of neural effects of OCPs can be important in helping patients make informed decisions regarding contraception, mitigating unwanted side effects. Such information can also identify potentially confounding effects of OCPs in other neuroimaging investigations.

Influences on ethnic minority women's experiences and access to contraception in the UK: a systematic qualitative evidence synthesis.

BACKGROUND: Accessible contraception is critical for promoting the health and well-being of women and their families. In the UK, contraception is free at the point of access, but only 55% of pregnancies are planned, with negative implications for maternal and infant outcomes. In general, women from ethnic minorities use contraceptives less than white women. Barriers to the uptake of contraceptives have been identified, including perceived poor information from healthcare professionals and concerns about side effects. However, most studies do not include representative proportions of women from ethnic minorities. Evidence suggests that ethnic minority (EM) women feel targeted and coerced by healthcare professionals regarding contraception. METHODS: A systematic search of Medline, Embase, and PsycINFO via Ovid, CINAHL, and Web of Science was conducted to identify primary qualitative and mixed-methods studies exploring ethnic minority women's experience of contraception in the UK. The data were charted using thematic analysis, using both summary and synthesis. RESULTS AND CONCLUSIONS: 16 studies met the inclusion criteria, including the perspectives of 717 participants from an ethnic minority. Four overarching themes were developed: contraceptive knowledge, beliefs, family, and services. Similar to women in general, ethnic minority women have concerns about side effects, especially infertility, value the perspectives of their peers and male partners, and express a preference for female healthcare professionals. Novel perspectives included conflicting ideas about the influence of religion and stereotyping of ethnic minority women. Culturally competent consultations and a better understanding of hormonal hesitancy are essential.

Novel Genes of the Male Reproductive System: Potential Roles in Male Reproduction and as Non-hormonal Male Contraceptive Targets.

The development of novel non-hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long-read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next-generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non-hormonal contraceptive targets. The review delves into the systematic identification and validation of male reproductive tract-specific genes, utilizing advanced transcriptomics and genomics studies with validation using novel knockout mouse models. We discuss the innovative application of small molecule inhibitors, developed through platforms like DNA-encoded chemistry technology (DEC-Tec), which have shown significant promise in preclinical models. Notable examples include inhibitors targeting serine/threonine kinase 33 (STK33), soluble adenylyl cyclase (sAC), cyclin-dependent kinase 2 (CDK2), and bromodomain testis associated (BRDT), each demonstrating nanomolar affinity and potential for reversible and specific inhibition of male fertility. This review also honors the contributions of Dr. David L. Garbers whose foundational work has paved the way for these advancements. The integration of genomic, proteomic, and chemical biology approaches, supported by interdisciplinary collaboration, is poised to transform male contraceptive development. Future perspectives emphasize the need for continued innovation and rigorous testing to bring these novel contraceptives from the laboratory to clinical application, promising a new era of male reproductive health management.

Immediate vs delayed postpartum insertion of long-acting reversible contraception methods: meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to conduct a meta-analysis of randomized trials comparing the immediate vs delayed provision of long-acting reversible contraceptives in postpartum subjects, focusing on short-interval pregnancies, utilization rates, and adverse events. DATA SOURCES: Cochrane Central, Embase, PubMed, and ClinicalTrials.gov were systematically searched from inception up to December 19, 2023, without filters or language limitation. STUDY ELIGIBILITY CRITERIA: We selected randomized controlled trials assessing the immediate insertion of long-acting reversible contraceptives in women during postpartum period in comparison with the delayed provision. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated relative risks with 95% confidence intervals to analyze the primary outcome of utilization rates and secondary endpoints, including initiation rates, pregnancy, any breastfeeding, exclusive breastfeeding, and serious adverse events. A random-effects model was employed in the R software. Moreover, we assessed the risk of bias of selected randomized controlled trials using version 2 of the Cochrane Risk of Bias Assessment Tool. RESULTS: We included 24 randomized trials comprising 2507 participants, of whom 1293 (51.6%) were randomized to the immediate insertion. Postpartum women in the immediate group had lower risk of pregnancy (relative risk 0.16; 95% confidence interval 0.04-0.71; P=.02) compared with delayed group, and higher rates of long-acting reversible contraceptives at 6 months of follow-up (relative risk 1.23; 95% confidence interval 1.09-1.37; P<.01). CONCLUSION: Inserting long-acting reversible contraceptives before hospital discharge was associated with a reduction in the risk of pregnancy, and increased rates of its utilization at 6 months of follow-up. This intervention may be an effective contraception strategy for postpartum women.

Starting the pill during adolescence: Age of onset and duration of use influence morphology of the hippocampus and ventromedial prefrontal cortex.

From adolescence, women become more likely to experience fear dysregulation. Oral contraceptives (OCs) can modulate the brain regions involved in fear processes. OCs are generally used for years and often initiated during adolescence, a sensitive period where certain brain regions involved in the fear circuitry are still undergoing important reorganization. It remains unknown whether OC use during adolescence may induce long-lasting changes in the fear circuitry. This study aimed to examine whether age of onset moderated the relationship between duration of use and fear-related brain structures. We collected structural MRI data in 98 healthy adult women (61 current users, 37 past users) and extracted grey matter volumes (GMV) and cortical thickness (CT) of key regions of the fear circuitry. Non-linear multiple regressions revealed interaction effects between age of onset and quadratic duration of use on GMV of the right hippocampus and right ventromedial prefrontal cortex (vmPFC). Among women who initiated OCs earlier in adolescence, a short duration of use was associated with smaller hippocampal GMV and thicker vmPFC compared to a longer duration of use. For both GMV and CT of the right vmPFC, women with an early OC onset had more grey matter at a short duration of use than those with a later onset. Our results suggest that OC use earlier in adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support further investigation into the timing of OC use to better comprehend how OCs could disrupt normal brain development processes.

High non-use of contraception among tribal and non-tribal women in North-Eastern India: alarming but neglected.

Limited evidence exists about the contraception uptake in indigenous tribal groups of the north-eastern region of India. This study based on the National Family Health Survey (NFHS) IV (2015-2016) reports aimed to describe the pattern and factors associated with contraceptive non-use in the tribal women of the north-eastern part of India. The study was a cross-sectional analytical study based on secondary analysis of NFHS-IV data. All women in the age group of 15-49 years from the north-eastern part of India were included. Data were extracted and analysed using modified STATA-14 software. The association of socio-demographic and economic characteristics with contraceptive non-use was assessed using logistic regression. The inter-group differences of population characteristics for non-use contraceptives were assessed by modified Blinder-Oaxaca decomposition technique using 'Fairlie decomposition'. A total of 65,941 women were included, of whom 34,936 (52.9%) were tribal women. The proportion of contraceptive non-use was higher in tribal women. Tribal women with age at marriage above 30 years, Christian community, and women from Assam and Manipur state had higher odds of contraceptive non-use. The decomposition analysis showed that geographical variations, parity, and Christian religion contributed the most to contraceptive use disparity in the population. A huge gap was observed in contraceptive non-use among tribal and non-tribal women in the north-eastern part of India. The healthcare system must involve community representatives in designing context-specific community-based initiatives to increase the uptake of contraceptive use in these remote vulnerable communities.

Prunes May Blunt Adverse Effects of Oral Contraceptives on Bone Health in Young Adult Women: A Randomized Clinical Trial.

Background: Oral contraceptives (OCs) may promote bone loss, thereby leading to suboptimal bone health later in life. Research is needed to determine whether dietary interventions can blunt OC-related bone loss; prune consumption, shown to be effective in improving bone density in previous studies, could provide a safe and inexpensive solution. Objectives: The purpose of this study was to determine whether 12 mo of consuming 50 g of prunes daily would prevent bone loss or increase bone accrual in young (18-25 y) OC users. Methods: Ninety women were randomly assigned to a control group not using OCs (non-OC), an OC group not consuming prunes (OC), and an OC group consuming 50 g prunes daily (OC+P) for 12 mo. Bone mineral density (BMD) was measured at baseline and after 12 mo via dual-energy X-ray absorptiometry (at all sites) and peripheral quantitative computed tomography (at tibia). Blood samples were collected at baseline and after 6 and 12 mo to assess biomarkers. Results: There were no significant differences between groups for dietary intake, physical activity, serum tartrate-resistant acid phosphatase-5b, or bone alkaline phosphatase concentrations. Baseline serum C-reactive protein and vitamin D concentrations were higher (P < 0.001) for OC and OC+P groups than those in the non-OC group. Serum parathyroid hormone was higher for non-OC group than OC group at both baseline (P = 0.049) and final (P = 0.032). BMD measured by dual-energy X-ray absorptiometry at all sites did not change among groups. Ultradistal radius BMD increased over time (P < 0.05) within non-OC and OC+P groups. Trabecular density of the distal tibia as measured by peripheral quantitative computed tomography decreased from baseline to 12 mo within the OC group only (P = 0.016). Conclusions: OC use tended to promote minor negative effects on bone and consuming prunes tended to provide a potential protective effect on trabecular density of the distal tibia and ultradistal radius.This trial was registered at www.clinicaltrials.gov as NCT04785131.

Oral Contraceptive Pills as a Potential Cause of Wallenberg Syndrome: A Mysterious Case.

Wallenberg syndrome, also known as lateral medullary syndrome, is a rare neurological condition caused by an ischemic stroke in the posterior inferior cerebellar artery (PICA) territory of the brainstem. Here, we present a case of Wallenberg syndrome in a relatively healthy 37-year-old woman with no known risk factors besides a history of long-term oral contraceptive pill (OCP) use without prior adverse effects. The patient presented with acute onset headache that worsened in bright light, left-sided lightheadedness, dizziness, blurry vision, and non-bloody, non-bilious emesis. A neurological exam revealed left facial numbness and left upper extremity numbness; however, strength was intact in all extremities. An MRI revealed an acute ischemic infarct in the left PICA distribution, consistent with Wallenberg syndrome. While the initial thought was that the patient's OCP use contributed to this stroke, it has been deduced that the risk of stroke with current formulations of OCPs is insignificant compared to women who do not take any OCPs. This case highlights the importance of reconsidering OCPs as the cause of stroke in young, healthy patients without significant risk factors and considering reclassification as an embolic stroke of undetermined source (ESUS).

In vitro evaluation of oral contraceptives on long-tailed macaque (Macaca fascicularis) primary ovarian cells.

Hormonal contraception has been advocated as an alternative population control method for the long-tailed macaque population, which has increased exponentially due to anthropogenic changes and incidental food subsidies from human food waste. Risks of increased zoonosis and conflict are imminent if the population growth of long-tailed macaques is unchecked. However, there's a gap in the literature about the effect of hormonal contraceptives on long-tailed macaque reproductive tissues cell line. The present study aims to investigate the effect of oral contraceptives (Nordette, Noriday, and Ella) on long-tailed macaque ovarian cells. We determine the cell viability and cytotoxicity as well as the morphological changes of the drugs on long-tailed macaque ovarian cells using the MTT assay, Acridine orange/propidium iodide double staining method, morphological examination, and the 4, 6-diamidino-2-phenylindole (DAPI) staining method. For the MTT assay, The drugs were dissolved in culture media before use to have a concentration ranging from 0.5 µg/mL, 2.5 µg/mL, 0.125 µg/mL, 0.0625 µg/mL, and 0.0315 µg/mL to have three replicates for each treatment. In contrast, the concentration of 0.0315 µg/mL was used for the morphological and histopathological analysis. The result of the study indicates that human oral contraceptives (Nordette, Noriday, and Ella) inhibit the growth of long-tailed macaque ovarian cells and induce apoptosis in a concentration- and time-dependent manner (at a concentration of 0.0315 µg/mL and an IC50 lower than 10 µg/mL), With a statistically significant value of ****P < 0.001 for each drug compared to the negative control. The result of the present study contributes toward addressing the gap in the literature on the effect of oral contraceptives in long-tailed macaque ovarian cells. Hence, we conclude that human oral contraceptives (Nordette, Noriday, and Ella) are safe and effective in long-tailed macaque ovarian cells as such could be used to develop non-invasive oral contraceptives for controlling the population of long-tailed macaques as an alternative population control method.

Improving contraceptive care for minors in Israel: practice, policy, and training gaps among OBGYNs.

BACKGROUND: Sexually active adolescents sometimes seek contraceptives without parental consent, posing challenges due to minors' confidentiality and consent regulations. This is especially the case under the un-nuanced Israeli legal scheme regarding adolescents' care. METHODS: Israeli OBGYNs were contacted through mailing lists and social media groups and asked to fill an online questionnaire regarding their experience and protocols concerning prescription of contraceptives to minors. They were also asked about their comprehension of the relevant legal obligations, the importance they ascribe to different ethical interests and considerations, as well as their training. RESULTS: Of the 177 responding gynecologists, 132 (74.58%) consulted minors about contraceptives during the past year, regardless of a vast lack of training on providing care to minors. More than a third of respondents believed that there is no legal requirement to involve parents in the process, and only 8% assumed a legal obligation for parental involvement in all minors under the age of 18. Three quarters would "almost always" prescribe contraceptives without parental knowledge, if requested, while 20% never would. No correlation was found between respondents' practices and their perception of the relevant legal obligations. Participants agreed that the risk to the health of the minor as a result of having sex without contraceptives is of utmost importance. Yet, those willing to prescribe gave greater weight to this consideration, while those who do not prescribe were more concerned with the legal ramifications of such an act. The majority identified the age of 15 as the threshold for consistently prescribing contraceptives to minors without parental involvement. CONCLUSION: This study highlights the significant gaps in both the legal framework and the training of Israeli OBGYNs, and further supports confidential prescription of contraceptives to minors 15 years and older, via Article 6 of the Israeli Legal Competence and Guardianship Law. Legislative reform, professional guidelines and education and training programs are all needed to ensure consistent and legally sound practices, that safeguard the health and rights of minors. It is imperative to guide healthcare providers, including OBGYNs prescribing contraceptives to minors, on managing the care of minors refusing parental involvement, clarifying the legal framework and ethical considerations involved.

Rapid and random-start endometrial preparation before outpatient hysteroscopic polypectomy in patients of perimenopausal age.

OBJECTIVE: This study aimed to assess the efficacy of randomly started oral dienogest/ethinylestradiol (DNG/EE) for swift endometrial preparation prior to outpatient hysteroscopic polypectomy in perimenopausal women. METHOD: A multicenter, prospective, randomized controlled trial was conducted in university hospitals. Eighty perimenopausal women scheduled for outpatient hysteroscopic polypectomy between January 2023 and March 2024 were randomly assigned to either intervention (n = 40) or control (n = 40) groups. Exclusion criteria included concomitant endometrial pathologies, recent therapy and adnexal diseases. The intervention group received oral DNG/EE 2 mg/0.03 mg/day started on any day of the menstrual cycle for 14 days. The control group underwent polypectomy between menstrual cycle days 8 and 11 without pharmacological treatment. RESULTS: Pre-procedure (p < 0.001) and post-procedure (p < 0.001) endometrial thickness were significantly reduced in the intervention group, along with a higher incidence of hypotrophic/atrophic endometrial patterns (p < 0.001). Surgical parameters also differed significantly between groups. CONCLUSION: DNG/EE treatment offers rapid, cost-effective endometrial preparation, enhancing surgical outcomes and patient satisfaction during outpatient polypectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT06316206.

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.