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PURPOSE: To support doctors in counselling women with genetic predisposition for breast or gynecologic cancers on endocrine interventions. METHODS: Evidence on the safety of endocrine interventions for fertility treatment, contraception, hormone replacement therapy after risk-reducing salpingo-oophorectomy (RRSO) or treatment of symptoms during peri- and postmenopause was analysed for carriers of probably pathogenic and pathogenic variants in BRCA1 or BRCA2 (BRCA1/2-pV), in other breast and ovarian cancer genes and the Lynch Syndrome. Cancer risks were compared with data on risks for the general population. RESULTS: Data on risk modulation of endocrine interventions in women with genetic predisposition is limited. Ovarian hyperstimulation for fertility treatment may be performed. Oral contraceptives should not be used to reduce ovarian cancer risk in BRCA1/2-pV carriers. Premenopausal BRCA1/2-pV carriers and carriers of pV in Lynch Syndrome genes should be offered hormone replacement therapy (HRT) after RRSO, to prevent diseases caused by estrogen deficiency. CONCLUSION: Effect direction and strength of risk modulation by endocrine interventions is similar to the general population. Participation of individuals at risk in prospective registries is recommended.

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Background: The acceptance of telemedicine in the German health care system is growing. This also extends to gynecological applications such as the prescription of contraceptives. This study investigates the contraceptive use and adherence of patients using a direct-to-consumer (DTC) prescription platform for oral contraception. Methods: A retrospective cross-sectional study was conducted using anonymized data obtained from a DTC prescription platform between May 2021 and March 2023. The patient-reported outcome was evaluated after 3 months through a follow-up questionnaire. Results: In total, 8,065 patient records were available and 1,008 patients responded to the follow-up questionnaire. Patients were mostly taking combined oral contraceptives (COCs) and only 6% were taking a progestin-only pill (POP). Even in patient populations at higher risk, such as smokers and obese women, the proportion of POP users was less than 20%. Over 90% of users reported that they took the pill without any intake errors, with the main intake error being forgotten intake. Overall, 23% of patients reported adverse events while taking the pill, with POP users reporting more adverse events than COC users (36.7% vs. 22.2%). Over 70% of patients regularly attended cervical screening. Conclusions: Users of a DTC prescribing platform exhibit strong adherence, with over 90% successfully taking oral contraceptive pills. The platform effectively identifies absolute contraindications but could enhance recommendations for contraceptives in the presence of relative contraindications. For healthy women familiar with pill usage, DTC platforms offer a viable and convenient alternative to traditional doctor's office prescriptions.

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Background: Oral contraceptives (OCs) are an essential medicine used by millions of people every day. Given the widespread usage of these medicines, even a small increase in psychiatric risk could be of clinical significance. Although mood-related side effects are a common reason for OC hesitancy and discontinuation, studies investigating psychiatric responses to OC treatment have had inconsistent results. Summary: While OCs are beneficial for most users, there is evidence that a subgroup of users is susceptible to mood side effects. Randomized controlled trials have generally failed to find differences in mood symptoms between OC and placebo users, but observational studies comparing OC users to non-users have reported increases in symptoms of depression, anxiety, and eating disorders. Additionally, observational evidence suggests that OC users may be more likely to use prescription psychotropic medications and to attempt or die by suicide. However, responses to OC treatment are highly heterogeneous, and some users report mood improvement. A variety of factors may increase the likelihood of negative psychiatric side effects, including younger age, previous experience of side effects from OCs, and preexisting psychiatric disorders. Progestin-only pills may confer a higher psychiatric risk than combination pills. Key Messages: Further research investigating factors that contribute to susceptibility to the mood-related side effects of OCs is clearly warranted. Genomic approaches may provide insight as to why some users experience side effects while others do not. Research elucidating who is most at risk and why will be essential to addressing prevalent concerns about the psychiatric risk of OCs.

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Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor α receptor 2 (sTNFR2), in the Nurses' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors, and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average 30.4% (-53.6, 4.4) with every 5 years since initial IUD use (P-trend=0.03), while CRP increased an average 9.9% (95% CI: 5.7, 14.3) with every 5 years of use of OC (P-trend<0.0001) as well as differences by BMI and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time.

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Oral contraceptive pills, of all types, are used by approximately 151 million women worldwide; however, a clear understanding of the concentrations of endogenous and exogenous hormones across a 28-day combination monophasic oral contraceptive pill pack is not well described. In our study of 14 female participants taking various combination monophasic oral contraceptive pills, we found significant fluctuations in endogenous and exogenous hormone levels throughout the pill cycle. Our analysis revealed significantly greater levels of ethinyl estradiol on the 20th and 21st days of active pill ingestion, compared with days 1-2 (active) and days 27-28 (inactive pill ingestion). Conversely, estradiol concentrations decreased during active pill consumption, while progestin and progesterone levels remained stable. During the 7 days of inactive pill ingestion, estradiol levels rose sharply and were significantly higher at days 27-28 compared with the mid and late active phase time points, while ethinyl estradiol declined and progestin did not change. These findings challenge the previous assumption that endogenous and exogenous hormones are stable throughout the 28-day pill cycle.NEW & NOTEWORTHY The results from this study have wide-ranging implications for research and treatment in women's health including considerations in research design and interpretation for studies including women taking oral contraceptives, the potential for more precise and personalized methods of dosing to reduce unwanted side effects and adverse events, and the potential treatment of a variety of disorders ranging from musculoskeletal to neurological with exogenous hormones.

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Introduction: The evolution of contraception has been crucial for public health and reproductive well-being. Over the past 60 years, combined oral contraceptives (COCs) have remained an important part of the contraceptive landscape worldwide; continued development has worked toward maintaining efficacy and improving safety. Methods: Seven global experts convened to discuss the clinical relevance of the oestrogen in COCs, focusing on the impact of the new oestrogen, oestetrol (E4). Participants then commented through an online forum on the summary content and other participants' feedback. We prepared this report to describe the experts' views, their follow-up from the open forum and the evidence supporting their views. Results: Ethinylestradiol (EE) and oestradiol (E2) affect receptors similarly whereas E4 has differential effects, especially in the liver and breast. Adequate oestrogen doses in COCs ensure regular bleeding and user acceptability. EE and E4 have longer half-lives than E2; accordingly, COCs with EE and E4 offer more predictable bleeding than those with E2. Oestrogen type and progestin influence VTE risk; E2 poses a lower risk than EE; although promising, E4/DRSP VTE risk is lacking population-based data. COCs alleviate menstrual symptoms, impact mental health, cognition, libido, skin, and bone health. Conclusion: Oestrogens play an important role in the contraceptive efficacy, bleeding patterns, and overall tolerability/safety of COCs. Recent studies exploring E4 combined with DRSP show promising results compared to traditional formulations, but more definitive conclusions await further research.

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PURPOSE: This study aimed to explore the relationship between oral contraceptive use and blood pressure values and in a national cohort of women adolescents and to investigate the level of coexistence of the high blood pressure levels, dyslipidemia or insulin resistance. METHODS: This is a retrospective cohort study that evaluated data form 14,299 adolescents aged 14 to 17 years. Crude and race-and age-adjusted analyses were performed using Poisson regression to estimate the prevalence ratios. Data clustering analysis was performed using machine learning approaches supported by an unsupervised neural network of self-organizing maps. RESULTS: We found that 14.5% (n = 2076) of the women adolescents use oral contraceptives. Moreover, an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance (all P < 0.001) was observed among adolescents who use oral contraceptives as compared to those who do not. Our analysis also showed that 2.3% of adolescents using oral contraceptives had both high blood pressure levels and dyslipidemia, whereas 3.2% had high blood pressure levels combined with insulin resistance (all P < 0.001). The algorithmic investigative approach demonstrated that total cholesterol, LDLc, HDLc, insulin, and HOMA-IR were the most predicted variables to assist classificatory association in the context of oral contraceptive use among women adolescents with high blood pressure. CONCLUSIONS: These findings suggest that oral contraceptives were associated with an increased prevalence of high blood pressure, dyslipidemia, and insulin resistance among women adolescents. Although the indication of this therapy is adequate to avoid unintended pregnancies, their use must be based on rigorous individual evaluation and under constant control of the cardiometabolic risk factors.

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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.

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BACKGROUND: Levels of anti-Müllerian hormone (AMH) are known to be associated with lifestyle determinants such as smoking and oral contraception (OC) use. When measuring AMH in clinical practice, it is essential to know which factors may influence circulating levels or ovarian reserve in general. OBJECTIVE AND RATIONALE: To date, there is no systematic review or summarizing consensus of the nature and magnitude of the relation between AMH and modifiable lifestyle factors. The purpose of this review was to systematically assess the evidence on association of lifestyle behaviors with circulating AMH levels. SEARCH METHODS: We performed a pre-registered systematic review of publications in Embase and PubMed on the lifestyle factors BMI, smoking, OC use, alcohol consumption, caffeine consumption, physical activity, and waist-hip ratio (WHR) in relation to circulating AMH levels up to 1 November 2023. The search strategy included terms such as 'Anti-Mullerian hormone', 'lifestyle', and 'women'. Studies were considered eligible if the association between at least one of the lifestyle factors of interest and AMH was assessed in adult women. The quality of included studies was assessed using the Study Quality Assessment Tools of the National Heart, Lung, and Blood Institute. The results were presented as ranges of the most frequently used association measure for studies that found a significant association in the same direction. OUTCOMES: A total of 15 072 records were identified, of which 65 studies were eligible for inclusion, and 66.2% of the studies used a cross-sectional design. The majority of studies investigating BMI, smoking, OC use, and physical activity reported significant inverse associations with AMH levels. For WHR, alcohol, and caffeine use, the majority of studies did not find an association with AMH. For all determinants, the effect measures of the reported associations were heterogeneous. The mean difference in AMH levels per unit increase in BMI ranged from -0.015 to -0.2 ng/ml in studies that found a significant inverse association. The mean difference in AMH levels for current smokers versus non-smokers ranged from -0.4 to -1.1 ng/ml, and -4% to -44%, respectively. For current OC use, results included a range in relative mean differences in AMH levels of -17% to -31.1%, in addition to a decrease of 11 age-standardized percentiles, and an average decrease of 1.97 ng/ml after 9 weeks of OC use. Exercise interventions led to a decrease in AMH levels of 2.8 pmol/l to 13.2 pmol/l after 12 weeks in women with polycystic ovary syndrome or a sedentary lifestyle. WIDER IMPLICATIONS: Lifestyle factors are associated with differences in AMH levels and thus should be taken into account when interpreting individual AMH measurements. Furthermore, AMH levels can be influenced by the alteration of lifestyle behaviors. While this can be a helpful tool for clinical and lifestyle counseling, the nature of the relation between the observed differences in AMH and the true ovarian reserve remains to be assessed. REGISTRATION NUMBER: PROSPERO registration ID: CRD42022322575.

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BACKGROUND: Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. OBJECTIVES: To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. METHODS: We performed a systematic literature search in four medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus-from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. RESULTS: Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = -0.06, CI: -0.66-0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (χ2 = 19.04, p =0.001, I2 = 80%), nausea (χ2 = 8.04, p =0.005, I2 = 75%), and vomiting (χ2 = 9.30, p =0.002; I2 = 72%). CONCLUSION: Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.

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BACKGROUND: Oral contraceptives (OCs) are used worldwide, including Lebanese women. However, the association between OCs use and anxiety or depression remains unclear. This study aims to assess the prevalence of anxiety and depression among Lebanese women using oral contraceptive pills and investigate the differential impact of combined oral contraceptives (COCs) versus progestogen-only pills (POPs) on mental health outcomes. METHODS: A cross-sectional study was conducted among a sample of Lebanese women using OCs between January and March 2023. Nine hundred nighty seven out of the 2051 women who took part in the survey met our criteria and were included in this study. Data on anxiety and depression were collected using validated and reliable scales, the Arabic versions of the Generalized Anxiety Disorder-7 Questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Statistical analyses, including multivariate analysis, were performed to assess the association between OCs type (COC vs. POP) and anxiety/depression. RESULTS: The prevalence of anxiety and depression among Lebanese women taking OCs was found to be 39.9% and 64.3%, respectively. Furthermore, the study revealed that POP users had 2.8 times higher odds of developing anxiety (adjusted odds ratio ORadj = 2.8 with 95% confidence interval CI of 1.770 to 4.435) p-value < 0.001 and 9.2 times higher odds of developing depression (adjusted odds ratio ORadj = 9.2 with 95% confidence interval CI of 5.790 to 14.506) p-value < 0.001 compared to COC users. CONCLUSION: The results of this study shed light on the elevated prevalence of anxiety and depression among Lebanese women using OCs and emphasized the varying effects of COCs and POPs on their mental health outcomes. Further research is needed to comprehensively understand this association, considering both the dosage and specific type of oral contraceptive to improve the overall well-being of women using these contraceptives.

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Despite the evidence of altered emotion processing in oral contraceptive (OC) users, the impact of hormonal intrauterine devices (IUD) on emotional processing remains unexplored. Our study aimed to investigate how behavioural performance and event-related potentials (ERPs) linked with emotion reactivity and its regulation are associated with hormonal profiles of women using different types of hormonal contraception and naturally cycling women. Women using OCs (n = 25), hormonal IUDs (n = 33), and naturally cycling women in their early follicular (NCF, n = 33) or mid-luteal (NCL, n = 28) phase of the menstrual cycle were instructed to view emotional pictures (neutral, low and high negativity) and use cognitive reappraisal to up- or down-regulate negative emotions, while their electroencephalogram was recorded. Participants rated perceived negativity after each picture and their emotional arousal throughout the task. Saliva samples were collected to assess levels of 17ß-estradiol, progesterone, and testosterone. As expected, emotional arousal increased throughout the task and correlated positively with perceived negativity. Perceived negativity and the amplitudes of the middle (N2/P3) and later (LPP) latency ERP components increased with increasing stimuli negativity. Emotion regulation modulated perceived negativity and the amplitudes of very late ERP components (parietal and frontal LPP). Moreover, IUD-users showed a higher negative amplitude of the frontal N2 in comparison to all three other groups, with the most consistent differences during up-regulation. Finally, testosterone correlated positively with the N2 peak in IUD-users and NCL women. Overall, our findings suggest that IUD-use and testosterone might be related to altered preconscious processing during the emotion regulation task requiring attention to the stimulus. The study underscores the need for additional research into how different hormonal contraceptives are linked to socio-emotional functioning.

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[This corrects the article DOI: 10.3389/frph.2023.1254953.].

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Introduction: Multipurpose prevention technologies (MPTs) combining contraception with HIV prevention offer a promising solution to uptake and adherence challenges faced with oral pre-exposure prophylaxis (PrEP). The Dual Prevention Pill (DPP), which combines oral PrEP with an oral contraceptive pill (OCP), could address unmet need for family planning (FP) and HIV prevention. This study aimed to identify barriers and motivators for DPP uptake to inform the development of a DPP demand generation strategy and broader introduction efforts for MPTs. Materials and methods: Qualitative, ethnographic research employing human-centered design techniques was conducted in Kenya, South Africa, and Zimbabwe. A research consortium conducted 45 immersions, 34 key informant interviews, and 12 friendship circles with potential end users, male romantic partners, healthcare providers (HCPs), and cultural commentators. Creative concepts were subsequently co-created and validated in workshops with end users, male partners, and HCPs. Results: Four major themes emerged. Women struggled to balance personal motivations with societal expectations. Relationship goals strongly influenced sexual and reproductive health decisions, particularly related to financial security and social status. Negative experiences, such as untrustworthy partners, were significant triggers for OCP and PrEP use. Lastly, male partners were concerned about the DPP upending gender norms but held more positive individual attitudes. Five initial audience segments for the DPP were identified: women seeking enjoyment outside of their primary relationship; new mothers adhering to social norms; women wanting to maintain romantic relationships; women at risk of unintended pregnancy; and women with unfaithful partners. Segments informed the development of three communication themes, with the preferred route highlighting the DPP as a tool to prepare for life's unpredictability. Discussion: To effectively generate demand for the DPP, several strategies should be considered. Connecting with women's diverse identities and goals and celebrating their individuality is crucial. Linking the DPP to relationship goals reframes it as a means to protect relationships rather than a risk. Leveraging negative triggers through targeted media campaigns empowers women to take control of their sexual health during challenging moments. A balance in channel placement is necessary to raise public awareness while using more discrete channels for potentially controversial messages with male partners and wider communities.

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Introduction: Women are significantly more likely to develop Alzheimer's disease and related dementias (ADRD) than men. Suggestions to explain the sex differences in dementia incidence have included the influence of sex hormones with little attention paid to date as to the effect of hormonal contraception on brain health. The aim of this scoping review is to evaluate the current evidence base for associations between hormonal contraceptive use by women and non-binary people in early adulthood and brain health outcomes. Methods: A literature search was conducted using EMBASE, Medline and Google Scholar, using the keywords "hormonal contraception" OR "contraception" OR "contraceptive" AND "Alzheimer*" OR "Brain Health" OR "Dementia". Results: Eleven papers were identified for inclusion in the narrative synthesis. Studies recruited participants from the UK, USA, China, South Korea and Indonesia. Studies included data from women who were post-menopausal with retrospective data collection, with only one study contemporaneously collecting data from participants during the period of hormonal contraceptive use. Studies reported associations between hormonal contraceptive use and a lower risk of ADRD, particularly Alzheimer's disease (AD), better cognition and larger grey matter volume. Some studies reported stronger associations with longer duration of hormonal contraceptive use, however, results were inconsistent. Four studies reported no significant associations between hormonal contraceptive use and measures of brain health, including brain age on MRI scans and risk of AD diagnosis. Discussion: Further research is needed on young adults taking hormonal contraceptives, on different types of hormonal contraceptives (other than oral) and to explore intersections between sex, gender, race and ethnicity. Systematic Review Registration: https://doi.org/10.17605/OSF.IO/MVX63, identifier: OSF.io: 10.17605/OSF.IO/MVX63.

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Objectives: The oral contraceptive pill (OCP) is the most used contraceptive worldwide; nevertheless, discontinuation rates are relatively high. While advantages of the OCP, like pregnancy prevention and planned parenthood, result in autonomy and independence, side effects and other aspects play a role in the decision to (dis)continue usage. Informed and deliberate decision-making is of importance to prevent adverse effects in health and quality of life. Therefore, the present study aimed to explore how women in the Netherlands decide to (dis)continue the OCP. Study design: This paper reports a qualitative study using four focus groups, conducted online or face-to-face, with 20 women of different educational background aged between 18 and 23. The topic guide was based on relevant theory and literature, and focused on personal beliefs, experiences and social interactions about the OCP. The study is reported according to SRQR guidelines. Results: The main themes that were found the influence decision-making were effects, side effects, towards alternatives, interpersonal communication with peers, interpersonal communication with the general practitioner, and online information seeking. Feeling responsible emerged as a relevant additional theme, embedded in the decision-making process, and influencing other themes. Some educational differences emerged. Conclusions: The decision to start the OCP is a highly normalized process in the Netherlands. However, women who feel a strong sense of responsibility for pregnancy prevention may be less open to considering alternative contraception methods. Results imply that women can be better supported in the decision-making process by providing balanced information on effects and side effects of a wide range of contraceptives, as well as restoring the balance in both sexual partner's responsibility for contraception. Implications for practice and suggestions for further research on the concept of responsibility, its influence, and underlying mechanisms are provided.

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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.

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INTRODUCTION: Estetrol (E4) is a native estrogen produced only by the fetal liver during pregnancy. E4 is the first new estrogen to be used in hormonal contraception since the introduction of oral contraceptives in 1960. Ethinyl estradiol, the most commonly used estrogen in oral contraceptives today, increases the risks of thromboembolism and has other significant hepatic impacts, which induce important drug-drug interactions. On the other hand, Phase 2 E4 characterization studies demonstrated that E4 has negligible impacts on liver, breast, and vascular endothelium due to its distinct tissue selectivity. Combined with drospirenone (DRSP), E4 offers an improved safety profile for oral contraception. AREAS COVERED: This paper briefly highlights the unique pharmacokinetic and pharmacodynamic features of E4. The efficacy, safety, and tolerability results from the Phase 2 and 3 studies of the E4/DRSP pill are discussed to provide the reader with a thorough understanding of E4 and information to use when counseling potential users. EXPERT OPINION: The estetrol/drospirenone oral contraceptive is effective and well tolerated and provides good cycle control. In the future, estetrol may be the estrogen of choice if subsequent evidence verifies that it reduces the risks associated with current estrogens, such as venous thromboembolism and drug-drug interactions.

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OBJECTIVE: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS). DESIGN: A systematic review and meta-analysis was performed, Prospero CRD42022345640. METHODS: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials. RESULTS: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified. CONCLUSION: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS. TRIAL REGISTRATION: The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.

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Introduction: Women in sub-Saharan Africa (SSA) experience the world's highest rates of both HIV infection and unintended pregnancy. The Dual Prevention Pill (DPP) is a novel multipurpose prevention technology (MPT) that co-formulates HIV pre-exposure prophylaxis (PrEP) and combined hormonal oral contraception into a single daily pill. As a dual indication product, the DPP may be preferred by women facing these overlapping health risks. However, most SSA countries face severe healthcare resource constraints. Research is needed to assess whether, in what populations, and in what use cases the DPP would be cost-effective. Methods: We augmented an agent-based SSA HIV model with maternal health parameters including unintended pregnancy, abortion, and maternal mortality. Based on a previous market analysis, we assumed a primary DPP user population of current oral contraceptive users ages 25-49, and alternative user populations in different risk groups (age 15-24, sex workers, HIV-serodiscordant couples) and baseline product use profiles (unmet need for contraception, oral PrEP use, condom use). In three geographies (western Kenya, Zimbabwe, South Africa), we estimated HIV infections averted, pregnancies averted, disability-adjusted life-years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) over a 30-year time horizon, assuming equivalent adherence to the DPP as to oral contraceptives, higher adherence, or lower adherence. Results: The DPP is likely to be a cost-effective alternative to oral PrEP among users in need of contraception. Among women not already using PrEP, the DPP is likely to be cost-saving in sex workers and serodiscordant couples. The DPP is unlikely to be cost-effective in oral contraceptive users in the general population. Switching from oral contraception to the DPP could be net harmful in some settings and populations if it were to substantially reduces adherence to oral contraception. Results were robust to a range of time horizons or discount rates. Conclusion: The DPP has the potential to be cost-effective and cost-saving in populations at substantial HIV risk. Outcomes are sensitive to adherence, implying that effective counseling and decision-making tools for users considering the DPP will be essential. More research is needed to understand real-life adherence patterns and ensure health benefits achieved from contraception alone are not lost.