Risk of Estrogen-Driven Malignancies in Females on 5-alpha Reductase Inhibitors

Risk of Estrogen-Driven Malignancies in Females on 5-alpha Reductase Inhibitors | 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 Short Report Risk of Estrogen-Driven Malignancies in Females on 5-alpha Reductase Inhibitors Thomas Rohan, Grace Turchetta, Sherry Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4810414/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Importance: It is hypothesized that 5α-reductase inhibitors (5aRI) increase aromatase-mediated conversion of testosterone to estrogen, which may facilitate development of estrogen-driven malignancy. Previous studies in male patients receiving 5aRI treatment failed to demonstrate an increased risk of breast cancer; however, similar data in females are lacking. Methods We utilized the TriNetX Global Collaborative Network, which provides access to electronic medical records from ~ 145 million patients. Both cohorts included females with an ICD-10 diagnosis of androgenetic alopecia (AGA), non-scarring hair loss, or cicatricial alopecia and excluded patients with prior diagnoses of estrogen-driven malignancies. The study cohort included patients with at least 6 months of finasteride of dutasteride use, while the control cohort excluded any-time use of these medications. A 1:1 matched propensity score analysis was performed for confounding risk factors. Results After matching, there were 5,156 patients in each cohort (median age 57.8 ± 14.3). Ten years after first medication use, patients taking 5aRI had a 27.6% decreased risk of having a breast cancer diagnosis compared to controls (95% CI: 0.532–0.985, p = 0.0389). The study cohort had a 31.9% decrease in lifetime breast cancer risk compared to the control patients (95% CI: 0.503–0.923; p = 0.0126). Between the 5aRI and control groups, there was no significant difference in risk of developing ovarian or endometrial cancer (95% CI: 0.317–1.605; p = 0.4126 and 95% CI; 0.025–1.13; p = 0.09367 respectively). Conclusions The data show that there is no increased risk of estrogen-driven malignancies for women taking 5aRI for alopecia, and that 5aRI use may be protective against breast cancer. 5-alpha reductase inhibitors alopecia hair loss breast cancer ovarian cancer uterine cancer Background Alopecia subtypes are broadly classified as either scarring (cicatricial) or nonscarring, with the latter being more prevalent. 1 Androgenetic alopecia (AGA) is the most common form of non-scarring alopecia in the United States, affecting an estimated 50% of males and females depending on age. 2 AGA is characterized by decreased hair growth secondary to androgen receptor activation by dihydrotestosterone (DHT), which shortens the anagen growth phase and leads to thin, short hair formation and miniaturization. 3 The 5α-reductase enzyme present in hair follicles and other regions of the body is primarily responsible for conversion of testosterone to its more potent form, DHT. Inhibition of this enzyme by medications like finasteride or dutasteride can reduce serum and scalp DHT concentrations by 60–70%, resulting in prevention and reversal of hair follicle miniaturization that drives AGA. 4,5 DHT inhibitors have also been used in cicatricial alopecia to salvage surrounding non-scarred follicles. Adverse effects of 5α-reductase inhibitors (5αRI) are well described in men; however, it is unclear if these effects are a result of decreased DHT levels or a relative increase in estradiol via shunting of testosterone through the aromatase pathway. 6 This potential increase in estradiol has led researchers to evaluate if males on 5αRI therapy are at an increased risk of estrogen-driven malignancies, namely breast cancer. 7 Prior works have failed to demonstrate an increased risk in male patients on 5aRI therapy for AGA or benign prostatic hyperplasia (BPH). 6, 7, 8 However, the risk of estrogen-driven malignancies following use of 5αRI is poorly described in female patients. 9 This study aims to clarify the relationship between estrogen-driven malignancies and 5αRI use in women with nonscarring and scarring alopecia. Methods Setting The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline was followed for the reporting of this cohort study. The data used in this study was queried between 5/20/2024 and 6/14/2024 from the TriNetX Global Collaborative Network, which provides access to deidentified electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 145 million patients across 120 healthcare organizations. Cohorts Both the study and control populations included female patients over 18 years old (n = 66,094,652) with androgenic alopecia (ICD-10: L64, n = 90,687), cicatricial alopecia (L66, n = 446,437), or other nonscarring hair loss (L65, n = 935,626) of at least 6 months duration diagnosed on two separate occasions. The study population consisted of patients who received either dutasteride or finasteride after their hair loss diagnosis, while the control population consisted of those without any exposure to these medications at any point in time. Both cohorts excluded patients with ICD-10 diagnosis for breast (C50, n = 1,390,144), endometrial (C54.1, n = 193,614), and/or ovarian cancers (C56, n = 179,879) prior to onset of hair loss diagnosis (Supplementary Fig. 1). Covariates We performed 1:1 propensity score matching according to age at alopecia diagnosis, race, body mass index (BMI), comorbidities, alcohol-related disorders (F10), nicotine dependence (F17), hormone-related medications, and family history of estrogen-driven malignancies. Comorbidities/diagnoses included endometriosis (N80), ovarian dysfunction (E28), polycystic ovarian syndrome (E28.2), incidental pregnant state (Z33.1), encounter for assisted reproductive fertility procedure cycle (Z31.83), and type 2 diabetes mellitus (E11). Matched medications included systemic contraceptives, progestins, and estrogens. The outcomes included were breast, ovarian, and/or endometrial cancers. Adjusted relative risks were stratified for each outcome by time since the index event. Statistical analysis was performed in the TriNetX database with a level of significance defined as α = 0.05 and associated 95% confidence (CI) intervals. Results Baseline Patient Characteristics There were 826,976 females ≥ 18 years old with the hair conditions of interest; 29,317 were excluded due to having a prior estrogen-driven malignancy, 616,402 more were excluded for not having at least 6 months of diagnostic follow-up, and 176,098 were excluded for not having been prescribed 5aRI therapy. There were 5,159 patients that met study criteria, with 5,156 ultimately included after matching. The baseline patient characteristics between the two cohorts are shown in Table 1 . The age at index after matching was 57.8 ± 14.3 for the case cohort and 58 ± 14.4 for the control cohort. Table 1 Baseline patient characteristic before and after propensity score matching Before Matching After Matching Characteristic Cases (n = 5,159) Controls (n = 164,071) p-value Cases (n = 5,156) Controls (n = 5,156) p-value Age at index, mean (SD) 57.8 ± 14.3 49.3 ± 17.5 < 0.0001 57.8 ± 14.3 58 ± 14.4 0.3465 Race, n (%) White 3,928 (76.1) 99,898 (60.9) < 0.0001 3,928 (76.2) 3,946 (76.5) 0.6765 Black 357 (6.9) 23,196 (14.1) < 0.0001 357 (6.9) 352 (6.8) 0.8457 Asian 182 (3.5) 6,865 (4.2) 0.0046 182 (3.5) 176 (3.4) 0.7469 Unknown race 333 (6.5) 20,268 (12.4) < 0.0001 333 (6.5) 337 (6.5) 0.8730 Diagnoses, n (%) Nicotine dependence 242 (4.7) 13,381 (8.2) < 0.0001 242 (4.7) 222 (4.3) 0.3421 Alcohol-related disorder 119 (2.3) 3,400 (2.1) 0.4468 119 (2.3) 119 (2.3) 1.0000 Ovarian dysfunction 313 (6.1) 8,670 (5.3) 0.0704 313 (6.1) 275 (5.3) 0.1066 Endometriosis 118 (2.3) 4,623 (2.8) 0.0074 118 (2.3) 118 (2.3) 1.0000 Type 2 Diabetes 665 (12.9) 20,608 (12.6) 0.7632 665 (12.9) 636 (12.3) 0.3897 Hormone replacement therapy 306 (5.9) 3,466 (2.1) < 0.0001 306 (5.9) 268 (5.2) 0.1026 Polycystic ovarian syndrome 186 (3.6) 5,987 (3.6) 0.5020 186 (3.6) 163 (3.2) 0.2104 Pregnant state, incidental 70 (1.3) 8,404 (5.1) < 0.0001 70 (1.4) 64 (1.2) 0.6019 Encounter for assisted reproductive fertility procedure cycle 10 (0.2) 270 (0.2) 0.6935 10 (0.2) 10 (0.2) 1.0000 Medications, n (%) Contraceptives, systemic 663 (12.9) 29,693 (18.1) < 0.0001 663 (12.9) 623 (12.1) 0.2332 Estrogens 1,343 (26) 22,524 (13.7) < 0.0001 1,343 (26) 1,318 (25.6) 0.5737 Progestins 744 (14.4) 25,070 (15.3) 0.0055 744 (14.4) 692 (13.4) 0.1391 Family History of Estrogen-Driven Cancer, n (%) Family history of malignant neoplasm of breast 378 (7.3) 8,020 (4.9) < 0.0001 378 (7.3) 360 ( 7 ) 0.4917 Family history of malignant neoplasm of ovary 82 (1.58) 1,300 (0.8) < 0.0001 82 (1.6) 66 (1.3) 0.1853 BMI, n (%) BMI - At least 30 kg/m 2 1,375 (26.7) 44,718 (27.3) 0.0105 1,375 (26.7) 1,371 (26.6) 0.9290 Incidence of Breast Cancer There was no significant difference in risk of breast cancer after 1 and 5 years of finasteride or dutasteride use (Table 2 ). Ten years after first medication use, patients taking 5aRI had a 27.6% decreased risk of having a breast cancer diagnosis compared to those who have not taken a 5aRI (Table 2 ) (95% CI: 0.532–0.985; p = 0.0389). Similarly, there was a 31.9% decrease in lifetime breast cancer risk compared to control patients (95% CI: 0.503–0.923; p = 0.0126). Incidence of Ovarian Cancer There were fewer than 10 patients in the 5aRI group who developed ovarian cancer at any point following the start of medications (Table 2 ). In the control cohort, 14 patients had ovarian cancer at some point following their alopecia diagnosis; there was no significant difference in risk between the populations (95% CI: 0.317–1.605; p = 0.4126). Incidence of Endometrial Cancer Similar to the ovarian cancer analysis, less than 10 5aRI users developed endometrial cancer at any point following the initiation of finasteride or dutasteride for alopecia (Table 2 ). Nineteen of the patients in the control cohort developed endometrial cancer at some point following alopecia diagnosis (Table 2 ). There was no significant difference in risk between the two populations (95% CI: 0.025–1.13; p = 0.09367) Table 2 Incidence of breast, ovarian, and endometrial cancer among female case and control cohorts (after propensity score matching). Patients with Outcome Case Cohort Risk Control Cohort Risk Risk Ratio 95% Confidence Interval Case Cohort Control Cohort Breast Cancer 1 year 15 18 0.292% 0.351% 0.831 (p = 0.5951) (0.419,1.647) 3 years 41 47 0.798% 0.918% 0.87 (p = 0.5117) (0.573,1.32) 5 years 58 69 1.129% 1.347% 0.838 (p = 0.3179) (0.592,1.186) 10 years 69 95 1.343% 1.855% 0.724 (p = 0.0389) (0.532,0.985) Lifetime 69 101 1.343% 1.972% 0.681 (p = 0.0126) (0.503,0.923) Ovarian Cancer 1 year < 10 < 10 0.194% 0.194% 0.999 (p = 0.9986) (0.416, 2.399) 3 years < 10 < 10 0.194% 0.194% 0.999 (p = 0.9986) (0.416, 2.399) 5 years < 10 12 0.194% 0.233% 0.833 (p = 0.6682) (0.36, 1.926) 10 years < 10 13 0.194% 0.252% 0.769 (p = 0.5299) (0.337, 1.751) Lifetime < 10 14 0.194% 0.272% 0.714 (p = 0.4126) (0.317, 1.605) Endometrial Cancer 1 year < 10 < 10 0.194% 0.194% 0.999 (p = 0.9983) (0.416, 2.398) 3 years < 10 11 0.194% 0.214% 0.908 (p = 0.8254) (0.386, 2.137) 5 years < 10 16 0.194% 0.311% 0.624 (p = 0.2377) (0.284, 1.375) 10 years < 10 19 0.194% 0.369% 0.526 (p = 0.0937) (0.245, 1.13) Lifetime 11 21 0.215% 0.411% 0.524 (p = 0.0765) (0.245, 1.13) Discussion By inhibiting the 5aR-mediated conversion of testosterone to DHT, finasteride and dutasteride can theoretically result in increased production of estradiol via the aromatase pathway, which in turn may contribute to estrogen-driven malignancies. However, previous studies in male patients have shown that 5aRI have only mild (25%) increases in blood testosterone and no increase in estradiol levels. 10 Large-scale clinical studies have similarly failed to demonstrate an increased risk of male breast cancer following 5aRI use for benign prostatic hypertrophy or AGA. 7,8 Our data demonstrates that 5-alpha reductase inhibitor use for alopecia in females does not increase the risk of ovarian or endometrial cancers and may even protect against breast cancer development after 10 years of use. To the best of our knowledge, this is the first large-scale study to evaluate this risk in females utilizing administrative data. 6, 7, 9 The limitations of this study are consistent across many administrative claims-based projects, including potential inaccuracies in diagnosis coding, lack of longitudinal follow up, inability to verify medication dosage and compliance, and failure to capture outcomes occurring at non-reporting institutions. Despite the substantial size of our patient population, one notable limitation specific to our study is the low number of outcomes of interest in both our case and control cohorts. One possibility for this is that patients seeking medical treatment for alopecia may be more likely to follow preventative care guidelines. Future works could measure serum estrogen and testosterone levels in female patients taking 5aRI therapy to evaluate for biochemical changes. Declarations Funding sources: None Author Contribution T.Z.R. and S.Y. conceived the study. All authors contributed to its design. T.Z.R. and G.T. performed data collection. T.Z.R. and G.T. wrote the manuscript with edits and revisions by S.Y, and T.Z.R. and G.T. created the tables and figure. S.Y. supervised the study. References Vañó-Galván S, Saceda-Corralo D, Blume-Peytavi U et al (2019) Frequency of the Types of Alopecia at Twenty-Two Specialist Hair Clinics: A Multicenter Study. Skin Appendage Disorders 5(5):309–315. 10.1159/000496708 Ho CH, Sood T, Zito PM (2024) Androgenetic Alopecia. In: StatPearls . StatPearls Publishing; Accessed May 25, 2024. http://www.ncbi.nlm.nih.gov/books/NBK430924/ Trüeb RM (2002) Molecular mechanisms of androgenetic alopecia. Exp Gerontol 37(8):981–990. 10.1016/S0531-5565(02)00093-1 Drake L, Hordinsky M, Fiedler V et al (1999) The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol 41(4):550–554. 10.1016/S0190-9622(99)80051-6 Bayne EK, Flanagan J, Einstein M et al (1999) Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp. Br J Dermatol 141(3):481–491. 10.1046/j.1365-2133.1999.03042.x Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (2016) Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review. J Clin Aesthet Dermatol 9(7):56–62 Wang J, Zhao S, Luo L, Li E, Li X, Zhao Z (2018) 5-alpha Reductase inhibitors and risk of male breast cancer: a systematic review and meta-analysis. Int Braz J Urol 44(5):865–873. 10.1590/S1677-5538.IBJU.2017.0531 Hagberg KW, Divan HA, Fang SC, Nickel JC, Jick SS (2017) Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Epidemiol 9:83–91. 10.2147/CLEP.S124674 Rozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture M (2019) Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat 174(1):15–26. 10.1007/s10549-018-4996-3 Amory JK, Wang C, Swerdloff RS et al (2007) The Effect of 5α-Reductase Inhibition with Dutasteride and Finasteride on Semen Parameters and Serum Hormones in Healthy Men. J Clin Endocrinol Metabolism 92(5):1659–1665. 10.1210/jc.2006-2203 Additional Declarations No competing interests reported. Supplementary Files 5aRIFigure.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 Aug, 2024 Editor assigned by journal 30 Jul, 2024 Submission checks completed at journal 30 Jul, 2024 First submitted to journal 26 Jul, 2024 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4810414","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":336303348,"identity":"f7ee1019-864c-4388-9dc8-5d5736197c2d","order_by":0,"name":"Thomas Rohan","email":"","orcid":"","institution":"Sidney Kimmel Medical College, Thomas Jefferson University","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Rohan","suffix":""},{"id":336303349,"identity":"653a9bad-9467-4530-9cd6-c902f750412a","order_by":1,"name":"Grace Turchetta","email":"","orcid":"","institution":"Sidney Kimmel Medical College, Thomas Jefferson University","correspondingAuthor":false,"prefix":"","firstName":"Grace","middleName":"","lastName":"Turchetta","suffix":""},{"id":336303350,"identity":"5e313220-6d3e-4da9-94d7-5d1658c418c1","order_by":2,"name":"Sherry Yang","email":"data:image/png;base64,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","orcid":"","institution":"Thomas Jefferson University","correspondingAuthor":true,"prefix":"","firstName":"Sherry","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-07-26 23:24:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4810414/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4810414/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63248759,"identity":"d32db7c8-d8bf-43ce-af11-81dddff6b298","added_by":"auto","created_at":"2024-08-26 06:37:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":551869,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4810414/v1/ec750152-f953-40ca-a5ec-14abab4a6818.pdf"},{"id":63248758,"identity":"bda6a223-95df-49d2-9a77-11d6de850c7f","added_by":"auto","created_at":"2024-08-26 06:37:39","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":234191,"visible":true,"origin":"","legend":"","description":"","filename":"5aRIFigure.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4810414/v1/e717c886539c7f8996533814.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk of Estrogen-Driven Malignancies in Females on 5-alpha Reductase Inhibitors","fulltext":[{"header":"Background","content":"\u003cp\u003eAlopecia subtypes are broadly classified as either scarring (cicatricial) or nonscarring, with the latter being more prevalent.\u003csup\u003e1\u003c/sup\u003e Androgenetic alopecia (AGA) is the most common form of non-scarring alopecia in the United States, affecting an estimated 50% of males and females depending on age.\u003csup\u003e2\u003c/sup\u003e AGA is characterized by decreased hair growth secondary to androgen receptor activation by dihydrotestosterone (DHT), which shortens the anagen growth phase and leads to thin, short hair formation and miniaturization.\u003csup\u003e3\u003c/sup\u003e The 5α-reductase enzyme present in hair follicles and other regions of the body is primarily responsible for conversion of testosterone to its more potent form, DHT.\u003c/p\u003e \u003cp\u003eInhibition of this enzyme by medications like finasteride or dutasteride can reduce serum and scalp DHT concentrations by 60\u0026ndash;70%, resulting in prevention and reversal of hair follicle miniaturization that drives AGA.\u003csup\u003e4,5\u003c/sup\u003e DHT inhibitors have also been used in cicatricial alopecia to salvage surrounding non-scarred follicles. Adverse effects of 5α-reductase inhibitors (5αRI) are well described in men; however, it is unclear if these effects are a result of decreased DHT levels or a relative increase in estradiol via shunting of testosterone through the aromatase pathway.\u003csup\u003e6\u003c/sup\u003e This potential increase in estradiol has led researchers to evaluate if males on 5αRI therapy are at an increased risk of estrogen-driven malignancies, namely breast cancer.\u003csup\u003e7\u003c/sup\u003e Prior works have failed to demonstrate an increased risk in male patients on 5aRI therapy for AGA or benign prostatic hyperplasia (BPH).\u003csup\u003e6, 7, 8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHowever, the risk of estrogen-driven malignancies following use of 5αRI is poorly described in female patients.\u003csup\u003e9\u003c/sup\u003e This study aims to clarify the relationship between estrogen-driven malignancies and 5αRI use in women with nonscarring and scarring alopecia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSetting\u003c/h2\u003e \u003cp\u003e The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline was followed for the reporting of this cohort study. The data used in this study was queried between 5/20/2024 and 6/14/2024 from the TriNetX Global Collaborative Network, which provides access to deidentified electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 145\u0026nbsp;million patients across 120 healthcare organizations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCohorts\u003c/h2\u003e \u003cp\u003eBoth the study and control populations included female patients over 18 years old (n\u0026thinsp;=\u0026thinsp;66,094,652) with androgenic alopecia (ICD-10: L64, n\u0026thinsp;=\u0026thinsp;90,687), cicatricial alopecia (L66, n\u0026thinsp;=\u0026thinsp;446,437), or other nonscarring hair loss (L65, n\u0026thinsp;=\u0026thinsp;935,626) of at least 6 months duration diagnosed on two separate occasions. The study population consisted of patients who received either dutasteride or finasteride after their hair loss diagnosis, while the control population consisted of those without any exposure to these medications at any point in time. Both cohorts excluded patients with ICD-10 diagnosis for breast (C50, n\u0026thinsp;=\u0026thinsp;1,390,144), endometrial (C54.1, n\u0026thinsp;=\u0026thinsp;193,614), and/or ovarian cancers (C56, n\u0026thinsp;=\u0026thinsp;179,879) prior to onset of hair loss diagnosis (Supplementary Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCovariates\u003c/h2\u003e \u003cp\u003eWe performed 1:1 propensity score matching according to age at alopecia diagnosis, race, body mass index (BMI), comorbidities, alcohol-related disorders (F10), nicotine dependence (F17), hormone-related medications, and family history of estrogen-driven malignancies. Comorbidities/diagnoses included endometriosis (N80), ovarian dysfunction (E28), polycystic ovarian syndrome (E28.2), incidental pregnant state (Z33.1), encounter for assisted reproductive fertility procedure cycle (Z31.83), and type 2 diabetes mellitus (E11). Matched medications included systemic contraceptives, progestins, and estrogens. The outcomes included were breast, ovarian, and/or endometrial cancers. Adjusted relative risks were stratified for each outcome by time since the index event. Statistical analysis was performed in the TriNetX database with a level of significance defined as α\u0026thinsp;=\u0026thinsp;0.05 and associated 95% confidence (CI) intervals.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Patient Characteristics\u003c/h2\u003e \u003cp\u003eThere were 826,976 females\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;18 years old with the hair conditions of interest; 29,317 were excluded due to having a prior estrogen-driven malignancy, 616,402 more were excluded for not having at least 6 months of diagnostic follow-up, and 176,098 were excluded for not having been prescribed 5aRI therapy. There were 5,159 patients that met study criteria, with 5,156 ultimately included after matching. The baseline patient characteristics between the two cohorts are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The age at index after matching was 57.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3 for the case cohort and 58\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4 for the control cohort.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patient characteristic before and after propensity score matching\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBefore Matching\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAfter Matching\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCases\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;5,159)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eControls\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;164,071)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eCases\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;5,156)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eControls\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;5,156)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at index, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e58\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3465\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRace, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,928 (76.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99,898 (60.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3,928 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3,946 (76.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.6765\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e357 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23,196 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e357 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e352 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e182 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6,865 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e182 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e176 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.7469\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e333 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20,268 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e333 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e337 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8730\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnoses, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNicotine dependence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e242 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13,381 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e242 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e222 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3421\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol-related disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,400 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4468\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e119 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e119 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvarian dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e313 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,670 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0704\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e313 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e275 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometriosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,623 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e118 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e118 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 2 Diabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e665 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20,608 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7632\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e665 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e636 (12.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3897\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHormone replacement therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e306 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,466 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e306 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e268 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolycystic ovarian syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e186 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,987 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e186 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e163 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnant state, incidental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,404 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.6019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEncounter for assisted reproductive fertility procedure cycle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedications, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContraceptives, systemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e663 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29,693 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e663 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e623 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2332\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstrogens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,343 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22,524 (13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,343 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,318 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5737\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgestins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e744 (14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25,070 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e744 (14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e692 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFamily History of Estrogen-Driven Cancer, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of malignant neoplasm of breast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e378 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,020 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e378 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e360 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.4917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of malignant neoplasm of ovary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (1.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,300 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e66 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1853\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI - At least 30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,375 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44,718 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,375 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1,371 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9290\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eIncidence of Breast Cancer\u003c/h2\u003e \u003cp\u003eThere was no significant difference in risk of breast cancer after 1 and 5 years of finasteride or dutasteride use (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Ten years after first medication use, patients taking 5aRI had a 27.6% decreased risk of having a breast cancer diagnosis compared to those who have not taken a 5aRI (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (95% CI: 0.532\u0026ndash;0.985; p\u0026thinsp;=\u0026thinsp;0.0389). Similarly, there was a 31.9% decrease in lifetime breast cancer risk compared to control patients (95% CI: 0.503\u0026ndash;0.923; p\u0026thinsp;=\u0026thinsp;0.0126).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eIncidence of Ovarian Cancer\u003c/h2\u003e \u003cp\u003eThere were fewer than 10 patients in the 5aRI group who developed ovarian cancer at any point following the start of medications (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In the control cohort, 14 patients had ovarian cancer at some point following their alopecia diagnosis; there was no significant difference in risk between the populations (95% CI: 0.317\u0026ndash;1.605; p\u0026thinsp;=\u0026thinsp;0.4126).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eIncidence of Endometrial Cancer\u003c/h2\u003e \u003cp\u003eSimilar to the ovarian cancer analysis, less than 10 5aRI users developed endometrial cancer at any point following the initiation of finasteride or dutasteride for alopecia (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Nineteen of the patients in the control cohort developed endometrial cancer at some point following alopecia diagnosis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There was no significant difference in risk between the two populations (95% CI: 0.025\u0026ndash;1.13; p\u0026thinsp;=\u0026thinsp;0.09367)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of breast, ovarian, and endometrial cancer among female case and control cohorts (after propensity score matching).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePatients with Outcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase Cohort Risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl Cohort Risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRisk Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Cohort\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eBreast Cancer\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.292%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.351%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.831 (p\u0026thinsp;=\u0026thinsp;0.5951)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.419,1.647)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.798%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.918%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.87 (p\u0026thinsp;=\u0026thinsp;0.5117)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.573,1.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.129%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.347%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.838 (p\u0026thinsp;=\u0026thinsp;0.3179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.592,1.186)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.343%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.855%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.724 (p\u0026thinsp;=\u0026thinsp;0.0389)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.532,0.985)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.343%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.972%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.681 (p\u0026thinsp;=\u0026thinsp;0.0126)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.503,0.923)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOvarian Cancer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.999 (p\u0026thinsp;=\u0026thinsp;0.9986)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.416, 2.399)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.999 (p\u0026thinsp;=\u0026thinsp;0.9986)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.416, 2.399)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.233%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.833 (p\u0026thinsp;=\u0026thinsp;0.6682)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.36, 1.926)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.252%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.769 (p\u0026thinsp;=\u0026thinsp;0.5299)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.337, 1.751)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.272%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.714 (p\u0026thinsp;=\u0026thinsp;0.4126)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.317, 1.605)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEndometrial Cancer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.999 (p\u0026thinsp;=\u0026thinsp;0.9983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.416, 2.398)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.214%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.908 (p\u0026thinsp;=\u0026thinsp;0.8254)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.386, 2.137)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.311%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.624 (p\u0026thinsp;=\u0026thinsp;0.2377)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.284, 1.375)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.194%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.369%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.526 (p\u0026thinsp;=\u0026thinsp;0.0937)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.245, 1.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.215%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.411%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.524 (p\u0026thinsp;=\u0026thinsp;0.0765)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(0.245, 1.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eBy inhibiting the 5aR-mediated conversion of testosterone to DHT, finasteride and dutasteride can theoretically result in increased production of estradiol via the aromatase pathway, which in turn may contribute to estrogen-driven malignancies. However, previous studies in male patients have shown that 5aRI have only mild (25%) increases in blood testosterone and no increase in estradiol levels.\u003csup\u003e10\u003c/sup\u003e Large-scale clinical studies have similarly failed to demonstrate an increased risk of male breast cancer following 5aRI use for benign prostatic hypertrophy or AGA.\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur data demonstrates that 5-alpha reductase inhibitor use for alopecia in females does not increase the risk of ovarian or endometrial cancers and may even protect against breast cancer development after 10 years of use. To the best of our knowledge, this is the first large-scale study to evaluate this risk in females utilizing administrative data.\u003csup\u003e6, 7, 9\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe limitations of this study are consistent across many administrative claims-based projects, including potential inaccuracies in diagnosis coding, lack of longitudinal follow up, inability to verify medication dosage and compliance, and failure to capture outcomes occurring at non-reporting institutions. Despite the substantial size of our patient population, one notable limitation specific to our study is the low number of outcomes of interest in both our case and control cohorts. One possibility for this is that patients seeking medical treatment for alopecia may be more likely to follow preventative care guidelines. Future works could measure serum estrogen and testosterone levels in female patients taking 5aRI therapy to evaluate for biochemical changes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding sources:\u003c/h2\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eT.Z.R. and S.Y. conceived the study. All authors contributed to its design. T.Z.R. and G.T. performed data collection. T.Z.R. and G.T. wrote the manuscript with edits and revisions by S.Y, and T.Z.R. and G.T. created the tables and figure. S.Y. supervised the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVa\u0026ntilde;\u0026oacute;-Galv\u0026aacute;n S, Saceda-Corralo D, Blume-Peytavi U et al (2019) Frequency of the Types of Alopecia at Twenty-Two Specialist Hair Clinics: A Multicenter Study. Skin Appendage Disorders 5(5):309\u0026ndash;315. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000496708\u003c/span\u003e\u003cspan address=\"10.1159/000496708\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHo CH, Sood T, Zito PM (2024) Androgenetic Alopecia. In: \u003cem\u003eStatPearls\u003c/em\u003e. StatPearls Publishing; Accessed May 25, 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/books/NBK430924/\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/books/NBK430924/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTr\u0026uuml;eb RM (2002) Molecular mechanisms of androgenetic alopecia. Exp Gerontol 37(8):981\u0026ndash;990. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0531-5565(02)00093-1\u003c/span\u003e\u003cspan address=\"10.1016/S0531-5565(02)00093-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrake L, Hordinsky M, Fiedler V et al (1999) The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol 41(4):550\u0026ndash;554. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0190-9622(99)80051-6\u003c/span\u003e\u003cspan address=\"10.1016/S0190-9622(99)80051-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBayne EK, Flanagan J, Einstein M et al (1999) Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp. Br J Dermatol 141(3):481\u0026ndash;491. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1046/j.1365-2133.1999.03042.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1365-2133.1999.03042.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (2016) Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review. J Clin Aesthet Dermatol 9(7):56\u0026ndash;62\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Zhao S, Luo L, Li E, Li X, Zhao Z (2018) 5-alpha Reductase inhibitors and risk of male breast cancer: a systematic review and meta-analysis. Int Braz J Urol 44(5):865\u0026ndash;873. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1590/S1677-5538.IBJU.2017.0531\u003c/span\u003e\u003cspan address=\"10.1590/S1677-5538.IBJU.2017.0531\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHagberg KW, Divan HA, Fang SC, Nickel JC, Jick SS (2017) Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Epidemiol 9:83\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2147/CLEP.S124674\u003c/span\u003e\u003cspan address=\"10.2147/CLEP.S124674\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture M (2019) Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat 174(1):15\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10549-018-4996-3\u003c/span\u003e\u003cspan address=\"10.1007/s10549-018-4996-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmory JK, Wang C, Swerdloff RS et al (2007) The Effect of 5α-Reductase Inhibition with Dutasteride and Finasteride on Semen Parameters and Serum Hormones in Healthy Men. J Clin Endocrinol Metabolism 92(5):1659\u0026ndash;1665. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/jc.2006-2203\u003c/span\u003e\u003cspan address=\"10.1210/jc.2006-2203\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"5-alpha reductase inhibitors, alopecia, hair loss, breast cancer, ovarian cancer, uterine cancer","lastPublishedDoi":"10.21203/rs.3.rs-4810414/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4810414/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eImportance:\u003c/h2\u003e \u003cp\u003eIt is hypothesized that 5α-reductase inhibitors (5aRI) increase aromatase-mediated conversion of testosterone to estrogen, which may facilitate development of estrogen-driven malignancy. Previous studies in male patients receiving 5aRI treatment failed to demonstrate an increased risk of breast cancer; however, similar data in females are lacking.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe utilized the TriNetX Global Collaborative Network, which provides access to electronic medical records from ~\u0026thinsp;145\u0026nbsp;million patients. Both cohorts included females with an ICD-10 diagnosis of androgenetic alopecia (AGA), non-scarring hair loss, or cicatricial alopecia and excluded patients with prior diagnoses of estrogen-driven malignancies. The study cohort included patients with at least 6 months of finasteride of dutasteride use, while the control cohort excluded any-time use of these medications. A 1:1 matched propensity score analysis was performed for confounding risk factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter matching, there were 5,156 patients in each cohort (median age 57.8\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;14.3). Ten years after first medication use, patients taking 5aRI had a 27.6% decreased risk of having a breast cancer diagnosis compared to controls (95% CI: 0.532\u0026ndash;0.985, p\u0026thinsp;=\u0026thinsp;0.0389). The study cohort had a 31.9% decrease in lifetime breast cancer risk compared to the control patients (95% CI: 0.503\u0026ndash;0.923; p\u0026thinsp;=\u0026thinsp;0.0126). Between the 5aRI and control groups, there was no significant difference in risk of developing ovarian or endometrial cancer (95% CI: 0.317\u0026ndash;1.605; p\u0026thinsp;=\u0026thinsp;0.4126 and 95% CI; 0.025\u0026ndash;1.13; p\u0026thinsp;=\u0026thinsp;0.09367 respectively).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe data show that there is no increased risk of estrogen-driven malignancies for women taking 5aRI for alopecia, and that 5aRI use may be protective against breast cancer.\u003c/p\u003e","manuscriptTitle":"Risk of Estrogen-Driven Malignancies in Females on 5-alpha Reductase Inhibitors","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 06:37:34","doi":"10.21203/rs.3.rs-4810414/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-05T17:07:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-30T04:57:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-30T04:55:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2024-07-26T23:22:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2bb90033-fc00-42cf-8f76-e8a0fbc57ebd","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-11-12T19:38:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 06:37:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4810414","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4810414","identity":"rs-4810414","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}