<h4>Objective</h4>To show the effectiveness of cycle applications in both areas of application-contraception and intended pregnancy.<h4>Methods</h4>A systematic review based on the PubMed and Google Scholar databases, with the addition of a hand search, was conducted from May 11, 2023, through April 11, 2024, to objectively answer this question. Of 1539 sources with matching search terms, 19 sources remained after checking for inclusion criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses scheme. These were analyzed according to an evaluation scale regarding their quality in various areas. The average quality ratings and pregnancy probabilities of the studies were compared.<h4>Results</h4>Comparability within and between the subquestions was hardly possible owing to different presentation of results, bias risks, and mostly uncontrolled study designs. Applications for those wishing to become pregnant provided better quality ratings in some cases. There were indications that cycle applications shorten the time to achieving a desired pregnancy in cases of reduced fertility. In addition, some seem to have a similar contraceptive safety as the contraceptive pill but require significantly more compliance.<h4>Conclusion</h4>Independent, controlled studies with a diverse clientele of test subjects are necessary for a scientific classification. In addition, social, structural, and political adjustments are needed to enable individuals to make informed decisions about the use of cycle and fertility applications. 6 However, according to Frank-Herrmann et al, 7 an approval of some contraceptive applications by Conformité Européenne (European Conformity) classification, Technische Überwachungsverein (Technical Inspection Association) seal, or US Food and Drug Administration is not a guarantee of their safety of use. This is because these organizations do not test their effectiveness in their own studies; instead, they rely on the information and documents provided by the manufacturers. Furthermore, numerous applications are not designed for contraceptive purposes but are used for this function based on the stated fertile period. 26 Primary factors contributing to this were potential bias resulting from the use of CycleBeads being explained to study participants during interviews and only 37% of the 185 participants used CycleBeads for contraception, as well as the short study duration of 3 months. The second lowest quality rating was found in the study by Koch et al, 27 which was retracted. 29 A further 4 studies reported mixed ratings with more negative ones. Of the 8 studies included in this article that address the application Natural Cycles, 5 studies assessed the contraceptive effectiveness of this application. A mere 3 studies yielded positive averages, led by Pearson et al, 42 but as already mentioned, the quality was still poor (see General issues encountered during the course of the evaluation section). A comparison of the values described as the contraceptive effect was only possible for 5 sources with Pearl Index (PI) information. The 4 sources referring to Natural Cycles 36 , 37 , 39 , 42 reported similar typical-use PI between 7.0 and 6.1, with different quality scores ranging from 0.35 to 0.24. As with the other studies with poor quality, the results had to be excluded because only 37% of the 185 participants used CycleBeads for contraception and the duration of this study was only 3 months. Jennings et al 30 described the perfect-use failure rate (ie, the proportion of probands with unplanned pregnancies) as 1%, whereas in typical use, it was 5.8%. However, only 24% of the cycles were reported as perfect-use cycles. This lacks generalizability and reports the low inherent effectiveness of these methods of contraception because the discrepancy between typical and perfect use is obvious owing to possible errors in use. The low percentage of perfect-use cycles documented in the included studies indicates that there is a significant degree of 50 For example, the Standard Days Method on which the Dot and CycleBeads applications are based, in which unprotected sex is avoided from the 8th to 19th day of the cycle, reported a perfect-use PI of 4.75 for regular cycles. 51 This number is likely to be considered a high probability of pregnancy by many users. However, the typical-use PI was even much higher at a PI of 11.96. 51 According to Trussel and Grummer-Strawn, 52 only the influence of imperfect use on the contraceptive effect shows the forgiveness of usage errors by the method without unintended pregnancies occurring. The typical-use values of methods with little room for maneuver for the user (eg, copper or hormone intrauterine devices and hormone implants) are significantly closer to the perfect-use values because there is a high inherent effectiveness owing to the reduction of error factors. In contrast, natural contraceptive methods sometimes show large differences in this aspect. 52 Even if we disregard the questionable quality of these studies, the difference between the typical-use and perfect-use PI values of these publications ranged between 4.1 and 6.5 and between 9.3 and 5.6 when considering the worst-case typical-use PI. This indicates a lower inherent effectiveness of the methods. Moreover, if the quality of the included studies had been high enough to produce results of stronger evidence, the influence of imperfect use on the number of unintended pregnancies would be roughly comparable with the values described by Trussel 50 for hormonal contraceptive methods that must be used regularly by the users themselves, for example, contraceptive pill or NuvaRing (perfect-use PI of 0.3 vs typical-use PI of 8.0). In contrast, the inherent effectiveness is higher for the usage of hormonal or copper intrauterine devices because of the reduced likelihood of application errors, that is, less user compliance is required to ensure safe use.

<h4>Background</h4>Hormonal contraceptives are widely used, however, their safety among women with underlying medical conditions, particularly cardiometabolic disorders such as hypertension, diabetes mellitus, and obesity, remains a key clinical concern. As the prevalence of these conditions increases globally among women of reproductive age, updated evidence is required to support risk-stratified contraceptive decision-making.<h4>Objective</h4>To evaluate the cardiometabolic, glycaemic, and metabolic safety of hormonal contraceptive use among women with underlying medical conditions.<h4>Methods</h4>A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, and Scopus were searched for English-language human studies published between 2015 and 2025. Eligible studies included randomized controlled trials, cohort studies, case-control studies, and comparative observational designs. Data were synthesized descriptively due to heterogeneity in study populations, exposure characteristics, and outcome measures. Methodological limitations included English-language restriction, lack of protocol registration, and inconsistent reporting of contraceptive dose, formulation, and duration.<h4>Results</h4>A total of 44 studies were included, with combined estrogen-containing contraceptives being the most frequently evaluated (79.5%, 35/44). Progestin-only methods 18.2% (8/44); long-acting reversible contraceptives 18.2% (8/44); mixed hormonal exposure 13.6% (6/44). Hypertension was the most commonly reported comorbidity, followed by diabetes mellitus and obesity. Lipid and metabolic parameters were reported in 31.8% (14/44) of studies, blood pressure outcomes in 25.0% (11/44), and glycaemic outcomes in 15.9% (7/44). No notable short-term changes were observed however, modest increases in systolic blood pressure, triglycerides, and insulin resistance were identified in selected high-risk populations.<h4>Conclusion</h4>Hormonal contraceptive u Long-acting reversible contraceptives, such as levonorgestrel-releasing intrauterine systems, hormonal intrauterine devices, and subdermal implants, were also reported in 18.2% of studies and were commonly examined in the context of long-term use and specialized clinical populations. Mixed hormonal Long-term exposure was primarily reported in large population-based cohorts and registry studies using person-years, multi-year datasets, or lifetime exposure, with follow-up extending up to a decade. Medium-term exposure was commonly evaluated in prospective cohort and interventional or comparative studies. Short-term exposure included recall-based designs, cycle-based assessments, and short experimental or crossover studies. Cross-sectional and survey-based studies assessed contraceptive use at a single time point without defined longitudinal exposure, limiting causal interpretation. Short-term exposure (<3 months) accounted for 13.6%, while prescription- or record-based estimates were used in 9.1%. Exposure duration was not reported in 15.9% of studies. Cardiometabolic Outcomes Associated with Hormonal Contraceptive Use Cardiometabolic outcomes were evaluated across three domains, including blood pressure, glycaemic control, and lipid/metabolic profiles ( Table 8 ). Blood pressure outcomes were assessed in 11 studies (25.0%). 5 studies reported no significant change, 4 studies reported increases in systolic blood pressure, and 2 studies reported reductions or lower baseline values. Domains assessed include bias due to confounding (D1), selection of participants (D2), classification of interventions (D3), deviations from intended interventions (D4), missing data (D5), measurement of outcomes (D6), and selection of the reported result (D7). Green indicates low risk, yellow indicates moderate risk, and red indicates serious risk. Table showing ROBINS-I risk of bias assessments across studies for seven domains and overall judgment. The table lists 44 individuals with assessments across eight columns: D1 to D7 and Overall. Most entries have 'low' ratings across all columns. Discussion This systematic review synthesizes evidence on the cardiometabolic, glycemic, and metabolic safety of hormonal contraceptive use among women with underlying medical conditions. While no uniform pattern of harm is observed, the findings vary by contraceptive type, population risk profile, exposure duration, and outcome domain. The current finding revealed that hypertension was the most frequently reported comorbidity, followed by diabetes mellitus and obesity. This finding indicates the growing global prevalence of cardiometabolic risk factors among women of reproductive age. Moreover, dose reporting across the included studies was inconsistent and frequently incomplete, a limitation that has been widely acknowledged in global contraceptive safety literature. Many large observational studies categorized exposure simply as use versus non-use, without specifying hormonal dose, formulation, or regimen. This approach facilitates large-scale analyses, it obscures potential dose–response relationships and limits mechanistic interpretation. 62 Where dose data were reported, most combined oral contraceptives contained low-to-moderate doses of ethinylestradiol, reflecting contemporary prescribing practices. Residual confounding and observational bias : A large proportion of studies were observational and relied on administrative or self-reported data, increasing vulnerability to residual confounding, exposure misclassification, and selection bias. Conclusion This systematic review demonstrates that the cardiometabolic, glycemic, and metabolic safety of hormonal contraceptive use varies across contraceptive type, population risk profile, exposure duration, and outcome measures. While most studies report no clinically significant adverse effects in the general population, important variations emerge in women with underlying cardiometabolic conditions.