Patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol combined oral contraceptives: a questionnaire-based observational study

Patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol combined oral contraceptives: a questionnaire-based observational study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol combined oral contraceptives: a questionnaire-based observational study Yuika Yamaoka, Hiroya Okano, Shuko Murata, Tomomi Hashimoto, Akira Nakabayashi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8735703/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background In Japan, the term “low-dose estrogen–progestin (LEP)” refers to combined oral contraceptive (COC) formulations that are pharmacologically equivalent to COCs but are primarily approved for therapeutic indications rather than contraception. Although bioequivalence between brand-name and generic formulations is required, patients sometimes report subjective differences after switching. This study aimed to evaluate patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations. Methods This questionnaire-based observational study included women who switched from a brand-name to a generic drospirenone–ethinylestradiol LEP/COC formulation between October 2022 and July 2023 and completed at least three cycles of the generic product. Six subjective symptoms—gastrointestinal symptoms, nausea/vomiting, irregular bleeding, dysmenorrhea, premenstrual syndrome, and headache—were assessed as improved, worsened, or unchanged. Free-text comments and one-year continuation outcomes were also analyzed. Results Eighty-one women were included. Overall, 26 patients (32%) reported some difference after switching, whereas the majority reported no change. “No change” responses were significantly predominant for all symptoms (p < 0.01). Among patients who perceived changes, headache was the only symptom significantly more likely to worsen than improve (p = 0.03). Four patients (5%) reverted to the brand-name formulation, all reporting symptom worsening and additional negative impressions in free-text responses. Conclusions Most patients did not perceive clinically meaningful differences after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations, supporting their overall interchangeability. Perceived differences appear to be influenced largely by psychological factors rather than pharmacologic differences. Appropriate counseling and reassurance are essential when switching to generic formulations. combined oral contraceptive low-dose estrogen–progestin generic drugs drospirenone ethinylestradiol patient-reported outcomes Figures Figure 1 Introduction Generic formulations of combined oral contraceptives (COCs) are widely used because of their equivalent pharmacological components and lower cost compared with brand-name products. Regulatory approval of generic oral contraceptives is typically based on bioequivalence studies rather than on large-scale clinical outcome trials. However, even when bioequivalence is established, patients may still report differences in tolerability, perceived effectiveness, or overall satisfaction after switching. In Japan, the same COC formulations are reimbursed as low-dose estrogen–progestin products (LEP) primarily for indications such as dysmenorrhea rather than for contraception. Despite identical active ingredients, switching from brand-name to generic products can raise concerns among patients and providers regarding adverse effects or differences in “feel” or usability. Few studies have evaluated subjective patient-reported outcomes after switching between brand-name and generic COCs in clinical practice. Understanding these perceptions is clinically important because discontinuation or return to brand-name drugs increases cost and may negatively affect adherence. The objective of this study was: 1. to describe subjective symptom changes after switching from brand-name to generic COCs 2. to identify symptoms associated with return to brand-name products 3. to evaluate continuation after switching over one year Methods Study design and setting This observational study was conducted at Iidabashi Ladies Clinic, Japan. Data were collected between October 2022 and July 2023. The study protocol was approved by the institutional ethics committee (approval number: 2024-0073). Participants Women taking a brand-name drospirenone/ethinyl estradiol COC who switched to a generic product for routine clinical reasons were eligible. Patients who did not complete three full cycles of generic COC or did not respond to the questionnaire were excluded. Exposure Switching from a brand-name to a generic drospirenone/ethinyl estradiol LEP/COC formulation. Outcomes The primary subjective evaluation items were: • gastrointestinal symptoms • nausea/vomiting • irregular bleeding • dysmenorrhea • PMS • headache Responses were recorded as: • improved • worsened • unchanged A free-text section allowed additional comments on product impressions, including packaging and overall satisfaction. A structured questionnaire is provided as Supplementary File 1. Follow-up Participants were followed for 1 year after switching to determine: • continuation of generic COC • return to brand-name product Statistical analysis Participants were classified into: • no-change group • perceived-change group (improvement or worsening) Comparisons of demographic variables were performed using Student’s t-test or Mann–Whitney U test as appropriate. Distribution across improvement/worsening/unchanged categories was tested using chi-square goodness-of-fit tests. Binomial tests were used to compare: • unchanged vs changed • improvement vs worsening within changed cases p < 0.05 was considered statistically significant. Statistical analysis was performed using Statcel 4 and R (version 4.3.2). Results Participant characteristics The participant flow is shown in Figure 1. A total of 81 patients were included. The mean age was 31.1 ± 7.5 years (range 19–49 years). Based on subjective outcomes, patients were divided into a no-change group (n = 55) and a change group (n = 26). No significant differences were observed in age, anthropometric variables, marital status, or parity between the groups (Table 1). Table 1. Baseline characteristics of patients in the no-change and change groups Variable No-change group (n=55) Change group (n=26) p value Age, years 31.6 ± 7.8 30.0 ± 7.0 0.58 Height, cm 157.5 ± 5.7 158.7 ± 6.1 0.39 Weight, kg 50.4 ± 6.3 51.4 ± 6.8 0.51 BMI, kg/m² 20.3 ± 1.9 20.4 ± 2.6 0.81 Marital status 0.06 Married 14 2 Unmarried 41 24 Parity 0.08 Yes 10 1 No 45 25 Values are presented as mean ± standard deviation or number of patients. p values were calculated using Student’s t test or Mann–Whitney U test as appropriate. Subjective symptom changes Subjective changes in the six primary outcomes are summarized in Table 2. For all symptoms, “no change” responses predominated (chi-square goodness-of-fit test, p < 0.01). Table 2. Patient-reported changes in subjective symptoms after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations Symptom Unchanged Improved Worsened Gastrointestinal symptoms 75 4 2 Nausea/vomiting 74 3 4 Irregular bleeding 66 8 7 Dysmenorrhea 72 4 5 Premenstrual syndrome 72 5 4 Headache 76 0 5 All values are number of patients. Chi-square goodness-of-fit test showed significant deviation among categories for all symptoms (p < 0.01). Binomial tests confirmed that “unchanged” responses were significantly more frequent than “any change”. Among patients in the change group, improvement and worsening were evenly distributed for all symptoms except headache, which was significantly more likely to worsen (p = 0.03; Table 3). Table 3. Binomial test comparing “improved” and “worsened” symptoms among patients who reported any change after switching to a generic product Symptom n (change group) Improved Worsened Two-tailed p value Gastrointestinal symptoms 6 4 2 0.69 Nausea/vomiting 7 3 4 1.00 Irregular bleeding 15 8 7 1.00 Dysmenorrhea 9 4 5 1.00 Premenstrual syndrome 9 5 4 1.00 Headache 5 0 5 0.03 Footnotes The change group included only patients who reported any subjective difference after switching from the brand-name to generic formulation. Binomial tests were used to compare the frequency of “improved” versus “worsened” responses. A two-tailed p value < 0.05 was considered statistically significant. Free-text responses and continuation outcomes Six patients provided free-text comments. Four patients reverted to the brand-name formulation within one year; all reported symptom worsening and additional negative impressions (Table 4). Table 4. Characteristics of the four patients who returned to the brand-name product after three cycles of generic use Case Worsened symptom 1 Worsened symptom 2 Free comments regarding impressions and usability of the generic product Case 1 Headache – Felt a heaviness in the lower abdomen Case 2 Dysmenorrhea Premenstrual syndrome The package was difficult to use Case 3 Nausea/vomiting – Increased appetite Case 4 Irregular bleeding Premenstrual syndrome Felt low mood Flow diagram of participant selection and follow-up in this questionnaire-based observational study. Between October 2022 and July 2023, a total of 81 women who switched from a brand-name to a generic drospirenone/ethinylestradiol low-dose estrogen–progestin (LEP) formulation were enrolled. All participants completed at least three cycles of the generic product and were included in the analysis. After the questionnaire assessment, participants were followed for one year to evaluate continuation of the generic formulation or return to the brand-name product. No participants were excluded after switching, as all completed the required three cycles of the generic formulation and returned the questionnaire. Discussion This study provides the first Japanese data focusing on patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations. Although generics are required to demonstrate bioequivalence, subjective differences are sometimes reported in clinical practice 1) . In our cohort, most patients reported no change after switching, and among those who perceived differences, improvement and worsening were generally balanced. These findings suggest that perceived differences are unlikely to reflect systematic pharmacologic inferiority of generic formulations. Notably, only a small subset of patients reverted to the brand-name formulation. As shown in Table 4, all four of these patients reported symptom worsening and provided detailed free-text comments describing additional negative impressions, such as discomfort, mood changes, or usability issues. This pattern suggests heightened symptom awareness and sensitivity rather than isolated pharmacologic intolerance. Importantly, these cases represent a minority (5%) and do not undermine the overall tolerability of generic formulations. Psychological factors, including nocebo effects and expectations related to cost or brand perception, likely contributed to perceived changes. Previous studies have demonstrated that patients informed they are receiving generic or less expensive medications may report reduced efficacy or increased adverse symptoms despite identical pharmacologic content 2) . Headache was the only symptom more frequently reported as worsened; however, the number of affected patients was small, and most continued generic use without persistent complaints, indicating a transient or perception-driven effect. Although excipients differ between formulations, clinically significant reactions appear rare 3) . Nevertheless, clinicians should remain vigilant for hypersensitivity reactions and respond promptly if severe symptoms occur 4) . Strengths and limitations This study provides real-world patient-reported data on switching LEP formulations, an area with limited prior evidence in Japan. Limitations include the single-center design, modest sample size, lack of blinding, and reliance on subjective outcomes. Clinical implications Clinicians can reassure patients that most individuals experience no change after switching to generic LEP formulations. Explaining bioequivalence and emphasizing the option to revert if intolerable symptoms occur may reduce anxiety and unnecessary discontinuation. Future research Larger multicenter studies incorporating psychological predictors, blinded switching designs, and excipient-level analyses are warranted. Conclusions Perceived differences after switching from brand-name to generic LEP formulations are uncommon and appear to be driven primarily by psychological rather than pharmacologic factors. Clear communication and patient-centered counseling are essential to support successful generic substitution. Declarations Ethical approval This study was approved by the institutional review board (approval number: 2024-0073). Ethics approval and consent to participate This study was approved by the institutional ethics committee (approval number: 2024-0073). Informed consent was obtained from all participants in accordance with institutional policies. Competing interests The authors declare no competing interests. Funding No external funding. Authors’ contributions HO designed the study and collected the data. YY performed the statistical analysis and drafted the manuscript. HO critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript. Data availability Data are available from the corresponding author upon reasonable request. References 1. Committee on Gynecologic Practice, American College of Obstetricians and Gynecologists. Brand versus generic oral contraceptives. Obstet Gynecol. 2007;110(2 Pt 1):447–448. doi:10.1097/01.AOG.0000275284.35023.13 2. Waber RL, Shiv B, Carmon Z, Ariely D. Commercial features of placebo and therapeutic efficacy. JAMA. 2008;299(9):1016–1017. doi:10.1001/jama.299.9.1016 3. Wattanapisit A, Lertwatanachai P, Pongsawat T, Wattanapisit S, Thongruch J. Side effects of antihypertensives induced by switching to different generic medications: case reports. Prague Med Rep. 2023;124(2):172–176. doi:10.14712/23362936.2023.14 4. Tetart F, Gonde H, Hervouet C. Do generic drugs cause hypersensitivity? Eur J Dermatol. 2022;32(5):571–576. doi:10.1684/ejd.2022.4383 Additional Declarations No competing interests reported. Supplementary Files Suppl.1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8735703","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587620718,"identity":"75839dcb-e146-4fb7-83b6-70d0dc2f2e50","order_by":0,"name":"Yuika Yamaoka","email":"","orcid":"","institution":"Tokyo Women’s Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuika","middleName":"","lastName":"Yamaoka","suffix":""},{"id":587620720,"identity":"26f2fba4-4a87-4cac-aff7-f7ad5de6230d","order_by":1,"name":"Hiroya Okano","email":"data:image/png;base64,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","orcid":"","institution":"Iidabashi ladies clinic","correspondingAuthor":true,"prefix":"","firstName":"Hiroya","middleName":"","lastName":"Okano","suffix":""},{"id":587620721,"identity":"3e5291b6-fe1e-42d9-9a07-ba5a0f99e332","order_by":2,"name":"Shuko Murata","email":"","orcid":"","institution":"Tokyo Women’s Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shuko","middleName":"","lastName":"Murata","suffix":""},{"id":587620723,"identity":"fe076d53-8358-486c-a072-b7b6a5cce0b8","order_by":3,"name":"Tomomi Hashimoto","email":"","orcid":"","institution":"Tokyo Women’s Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tomomi","middleName":"","lastName":"Hashimoto","suffix":""},{"id":587620727,"identity":"379f0260-d819-4dee-ab8b-8413d3faafff","order_by":4,"name":"Akira Nakabayashi","email":"","orcid":"","institution":"Tokyo Women’s Medical University","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Nakabayashi","suffix":""},{"id":587620731,"identity":"05ec7261-fbc5-4526-80c1-46c41898a100","order_by":5,"name":"Tsutomu Tabata","email":"","orcid":"","institution":"Tokyo Women’s Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tsutomu","middleName":"","lastName":"Tabata","suffix":""}],"badges":[],"createdAt":"2026-01-30 00:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8735703/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8735703/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102239000,"identity":"7d19922c-1fbe-445d-9df5-04c7c4b5587a","added_by":"auto","created_at":"2026-02-09 16:42:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71225,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8735703/v1/86bc79fab35d97d1c34bf6c9.png"},{"id":103049395,"identity":"aa727fb9-ff1a-4601-9830-fe506aa8fbcb","added_by":"auto","created_at":"2026-02-20 07:40:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1795379,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8735703/v1/45c36e28-977c-4a11-b1d3-208e06c4f98d.pdf"},{"id":102239001,"identity":"2393f681-626c-46cd-a603-b3be0a48d222","added_by":"auto","created_at":"2026-02-09 16:42:58","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":17923,"visible":true,"origin":"","legend":"","description":"","filename":"Suppl.1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8735703/v1/936c025876cd18b70908ee8a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol combined oral contraceptives: a questionnaire-based observational study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGeneric formulations of combined oral contraceptives (COCs) are widely used because of their equivalent pharmacological components and lower cost compared with brand-name products. Regulatory approval of generic oral contraceptives is typically based on bioequivalence studies rather than on large-scale clinical outcome trials. However, even when bioequivalence is established, patients may still report differences in tolerability, perceived effectiveness, or overall satisfaction after switching.\u003c/p\u003e \u003cp\u003eIn Japan, the same COC formulations are reimbursed as \u003cb\u003elow-dose estrogen\u0026ndash;progestin products (LEP)\u003c/b\u003e primarily for indications such as dysmenorrhea rather than for contraception. Despite identical active ingredients, switching from brand-name to generic products can raise concerns among patients and providers regarding adverse effects or differences in \u0026ldquo;feel\u0026rdquo; or usability.\u003c/p\u003e \u003cp\u003eFew studies have evaluated \u003cb\u003esubjective patient-reported outcomes\u003c/b\u003e after switching between brand-name and generic COCs in clinical practice. Understanding these perceptions is clinically important because discontinuation or return to brand-name drugs increases cost and may negatively affect adherence.\u003c/p\u003e \u003cp\u003eThe objective of this study was:\u003c/p\u003e \u003cp\u003e1. to describe subjective symptom changes after switching from brand-name to generic COCs\u003c/p\u003e \u003cp\u003e2. to identify symptoms associated with return to brand-name products\u003c/p\u003e \u003cp\u003e3. to evaluate continuation after switching over one year\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThis observational study was conducted at Iidabashi Ladies Clinic, Japan. Data were collected between October 2022 and July 2023. The study protocol was approved by the institutional ethics committee (approval number: 2024-0073).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eWomen taking a brand-name drospirenone/ethinyl estradiol COC who switched to a generic product for routine clinical reasons were eligible. Patients who did not complete three full cycles of generic COC or did not respond to the questionnaire were excluded.\u003c/p\u003e\n\u003ch3\u003eExposure\u003c/h3\u003e\n\u003cp\u003eSwitching from a brand-name to a generic drospirenone/ethinyl estradiol LEP/COC formulation.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary subjective evaluation items were:\u003c/p\u003e \u003cp\u003e\u0026bull; gastrointestinal symptoms\u003c/p\u003e \u003cp\u003e\u0026bull; nausea/vomiting\u003c/p\u003e \u003cp\u003e\u0026bull; irregular bleeding\u003c/p\u003e \u003cp\u003e\u0026bull; dysmenorrhea\u003c/p\u003e\n\u003ch3\u003e• PMS\u003c/h3\u003e\n\u003cp\u003e\u0026bull; headache\u003c/p\u003e \u003cp\u003eResponses were recorded as:\u003c/p\u003e \u003cp\u003e\u0026bull; improved\u003c/p\u003e \u003cp\u003e\u0026bull; worsened\u003c/p\u003e \u003cp\u003e\u0026bull; unchanged\u003c/p\u003e \u003cp\u003eA free-text section allowed additional comments on product impressions, including packaging and overall satisfaction.\u003c/p\u003e \u003cp\u003eA structured questionnaire is provided as Supplementary File 1.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up\u003c/h2\u003e \u003cp\u003eParticipants were followed for 1 year after switching to determine:\u003c/p\u003e \u003cp\u003e\u0026bull; continuation of generic COC\u003c/p\u003e \u003cp\u003e\u0026bull; return to brand-name product\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eParticipants were classified into:\u003c/p\u003e \u003cp\u003e\u0026bull; no-change group\u003c/p\u003e \u003cp\u003e\u0026bull; perceived-change group (improvement or worsening)\u003c/p\u003e \u003cp\u003eComparisons of demographic variables were performed using Student\u0026rsquo;s t-test or Mann\u0026ndash;Whitney U test as appropriate. Distribution across improvement/worsening/unchanged categories was tested using chi-square goodness-of-fit tests. Binomial tests were used to compare:\u003c/p\u003e \u003cp\u003e\u0026bull; unchanged vs changed\u003c/p\u003e \u003cp\u003e\u0026bull; improvement vs worsening within changed cases\u003c/p\u003e \u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Statistical analysis was performed using Statcel 4 and R (version 4.3.2).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eParticipant characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe participant flow is shown in Figure 1. A total of 81 patients were included. The mean age was 31.1 \u0026plusmn; 7.5 years (range 19\u0026ndash;49 years). Based on subjective outcomes, patients were divided into a no-change group (n = 55) and a change group (n = 26). No significant differences were observed in age, anthropometric variables, marital status, or parity between the groups (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Baseline characteristics of patients in the no-change and change groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNo-change group (n=55)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eChange group (n=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e31.6 \u0026plusmn; 7.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e30.0 \u0026plusmn; 7.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.58\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHeight, cm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e157.5 \u0026plusmn; 5.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e158.7 \u0026plusmn; 6.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.39\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eWeight, kg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e50.4 \u0026plusmn; 6.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e51.4 \u0026plusmn; 6.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.51\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eBMI, kg/m\u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e20.3 \u0026plusmn; 1.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e20.4 \u0026plusmn; 2.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.81\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMarital status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.06\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026emsp; Married\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026emsp; Unmarried\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e41\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eParity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.08\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026emsp; Yes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026emsp; No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eValues are presented as mean \u0026plusmn; standard deviation or number of patients.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ep values were calculated using Student\u0026rsquo;s t test or Mann\u0026ndash;Whitney U test as appropriate.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSubjective symptom changes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSubjective changes in the six primary outcomes are summarized in Table 2. For all symptoms, \u0026ldquo;no change\u0026rdquo; responses predominated (chi-square goodness-of-fit test, p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Patient-reported changes in subjective symptoms after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSymptom\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eUnchanged\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eImproved\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eWorsened\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGastrointestinal symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNausea/vomiting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e74\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIrregular bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e66\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDysmenorrhea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e72\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePremenstrual syndrome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e72\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHeadache\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e76\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eAll values are number of patients.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eChi-square goodness-of-fit test showed significant deviation among categories for all symptoms (p \u0026lt; 0.01).\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eBinomial tests confirmed that \u0026ldquo;unchanged\u0026rdquo; responses were significantly more frequent than \u0026ldquo;any change\u0026rdquo;.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAmong patients in the change group, improvement and worsening were evenly distributed for all symptoms except headache, which was significantly more likely to worsen (p = 0.03; Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Binomial test comparing \u0026ldquo;improved\u0026rdquo; and \u0026ldquo;worsened\u0026rdquo; symptoms among patients who reported any change after switching to a generic product\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSymptom\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003en (change group)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eImproved\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eWorsened\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTwo-tailed p value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGastrointestinal symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNausea/vomiting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIrregular bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDysmenorrhea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePremenstrual syndrome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHeadache\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eFootnotes\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eThe change group included only patients who reported any subjective difference after switching from the brand-name to generic formulation.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eBinomial tests were used to compare the frequency of \u0026ldquo;improved\u0026rdquo; versus \u0026ldquo;worsened\u0026rdquo; responses.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eA two-tailed p value \u0026lt; 0.05 was considered statistically significant.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eFree-text responses and continuation outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSix patients provided free-text comments. Four patients reverted to the brand-name formulation within one year; all reported symptom worsening and additional negative impressions (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Characteristics of the four patients who returned to the brand-name product after three cycles of generic use\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" width=\"582\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCase\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eWorsened symptom 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eWorsened symptom 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eFree comments regarding impressions and usability of the generic product\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFelt a heaviness in the lower abdomen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDysmenorrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePremenstrual syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eThe package was difficult to use\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCase 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNausea/vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIncreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCase 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIrregular bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePremenstrual syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFelt low mood\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Flow diagram of participant selection and follow-up in this questionnaire-based observational study.\u003c/p\u003e\n\u003cp\u003eBetween October 2022 and July 2023, a total of 81 women who switched from a brand-name to a generic drospirenone/ethinylestradiol low-dose estrogen\u0026ndash;progestin (LEP) formulation were enrolled. All participants completed at least three cycles of the generic product and were included in the analysis. After the questionnaire assessment, participants were followed for one year to evaluate continuation of the generic formulation or return to the brand-name product.\u003c/p\u003e\n\u003cp\u003eNo participants were excluded after switching, as all completed the required three cycles of the generic formulation and returned the questionnaire.\u003c/p\u003e"},{"header":" Discussion","content":"\u003cp\u003eThis study provides the first Japanese data focusing on patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations. Although generics are required to demonstrate bioequivalence, subjective differences are sometimes reported in clinical practice\u003cstrong\u003e\u003csup\u003e1)\u003c/sup\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eIn our cohort, most patients reported no change after switching, and among those who perceived differences, improvement and worsening were generally balanced. These findings suggest that perceived differences are unlikely to reflect systematic pharmacologic inferiority of generic formulations.\u003c/p\u003e\n\u003cp\u003eNotably, only a small subset of patients reverted to the brand-name formulation. As shown in Table 4, all four of these patients reported symptom worsening and provided detailed free-text comments describing additional negative impressions, such as discomfort, mood changes, or usability issues. This pattern suggests heightened symptom awareness and sensitivity rather than isolated pharmacologic intolerance. Importantly, these cases represent a minority (5%) and do not undermine the overall tolerability of generic formulations.\u003c/p\u003e\n\u003cp\u003ePsychological factors, including nocebo effects and expectations related to cost or brand perception, likely contributed to perceived changes. Previous studies have demonstrated that patients informed they are receiving generic or less expensive medications may report reduced efficacy or increased adverse symptoms despite identical pharmacologic content\u003cstrong\u003e\u003csup\u003e2)\u003c/sup\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eHeadache was the only symptom more frequently reported as worsened; however, the number of affected patients was small, and most continued generic use without persistent complaints, indicating a transient or perception-driven effect.\u003c/p\u003e\n\u003cp\u003eAlthough excipients differ between formulations, clinically significant reactions appear rare\u003cstrong\u003e\u003csup\u003e3)\u003c/sup\u003e\u003c/strong\u003e. Nevertheless, clinicians should remain vigilant for hypersensitivity reactions and respond promptly if severe symptoms occur\u003cstrong\u003e\u003csup\u003e4)\u003c/sup\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study provides real-world patient-reported data on switching LEP formulations, an area with limited prior evidence in Japan. Limitations include the single-center design, modest sample size, lack of blinding, and reliance on subjective outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinicians can reassure patients that most individuals experience no change after switching to generic LEP formulations. Explaining bioequivalence and emphasizing the option to revert if intolerable symptoms occur may reduce anxiety and unnecessary discontinuation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFuture research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLarger multicenter studies incorporating psychological predictors, blinded switching designs, and excipient-level analyses are warranted.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePerceived differences after switching from brand-name to generic LEP formulations are uncommon and appear to be driven primarily by psychological rather than pharmacologic factors. Clear communication and patient-centered counseling are essential to support successful generic substitution.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional review board (approval number: 2024-0073).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional ethics committee (approval number: 2024-0073). Informed consent was obtained from all participants in accordance with institutional policies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHO designed the study and collected the data. YY performed the statistical analysis and drafted the manuscript. HO critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e\u003cstrong\u003e1. Committee on Gynecologic Practice, American College of Obstetricians and Gynecologists.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eBrand versus generic oral contraceptives.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eObstet Gynecol. 2007;110(2 Pt 1):447\u0026ndash;448.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003edoi:10.1097/01.AOG.0000275284.35023.13\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Waber RL, Shiv B, Carmon Z, Ariely D.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCommercial features of placebo and therapeutic efficacy.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eJAMA. 2008;299(9):1016\u0026ndash;1017.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003edoi:10.1001/jama.299.9.1016\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. Wattanapisit A, Lertwatanachai P, Pongsawat T, Wattanapisit S, Thongruch J.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSide effects of antihypertensives induced by switching to different generic medications: case reports.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePrague Med Rep. 2023;124(2):172\u0026ndash;176.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003edoi:10.14712/23362936.2023.14\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. Tetart F, Gonde H, Hervouet C.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eDo generic drugs cause hypersensitivity?\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEur J Dermatol. 2022;32(5):571\u0026ndash;576.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003edoi:10.1684/ejd.2022.4383\u003c/strong\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"combined oral contraceptive, low-dose estrogen–progestin, generic drugs, drospirenone, ethinylestradiol, patient-reported outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8735703/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8735703/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e In Japan, the term \u0026ldquo;low-dose estrogen\u0026ndash;progestin (LEP)\u0026rdquo; refers to combined oral contraceptive (COC) formulations that are pharmacologically equivalent to COCs but are primarily approved for therapeutic indications rather than contraception. Although bioequivalence between brand-name and generic formulations is required, patients sometimes report subjective differences after switching. This study aimed to evaluate patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis questionnaire-based observational study included women who switched from a brand-name to a generic drospirenone\u0026ndash;ethinylestradiol LEP/COC formulation between October 2022 and July 2023 and completed at least three cycles of the generic product. Six subjective symptoms\u0026mdash;gastrointestinal symptoms, nausea/vomiting, irregular bleeding, dysmenorrhea, premenstrual syndrome, and headache\u0026mdash;were assessed as improved, worsened, or unchanged. Free-text comments and one-year continuation outcomes were also analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eEighty-one women were included. Overall, 26 patients (32%) reported some difference after switching, whereas the majority reported no change. \u0026ldquo;No change\u0026rdquo; responses were significantly predominant for all symptoms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Among patients who perceived changes, headache was the only symptom significantly more likely to worsen than improve (p\u0026thinsp;=\u0026thinsp;0.03). Four patients (5%) reverted to the brand-name formulation, all reporting symptom worsening and additional negative impressions in free-text responses.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMost patients did not perceive clinically meaningful differences after switching from brand-name to generic drospirenone/ethinylestradiol LEP/COC formulations, supporting their overall interchangeability. Perceived differences appear to be influenced largely by psychological factors rather than pharmacologic differences. Appropriate counseling and reassurance are essential when switching to generic formulations.\u003c/p\u003e","manuscriptTitle":"Patient-reported outcomes after switching from brand-name to generic drospirenone/ethinylestradiol combined oral contraceptives: a questionnaire-based observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 16:42:53","doi":"10.21203/rs.3.rs-8735703/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5988ae12-ee88-4b03-b05c-274cd7f4df43","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-17T11:25:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 16:42:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8735703","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8735703","identity":"rs-8735703","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}