874 D3000 new imprint Word template Vol 13, No 1 (2025) ISSN 2167-8677 (online) DOI 10.5195/d3000/2025.874 http://dentistry3000.pitt.edu Oral Contraceptives Are Associated with a Higher Risk of Dental In- flammatory and Bleeding Disorders Asmaa Sami Jawad1 1College of Den*stry, University of Babylon, Babylon, Iraq Abstract Objec0ve: Oral contracepDve pills (OCPs) are a prevalent form of contracepDon, yet their associaDon with potenDal impacts on gingival and periodontal health remains a subject of interest. Prolonged uDlizaDon of OCPs, aSributable to elevated pro-inflammatory cytokines and prostaglandins, has been demonstrated to heighten the risk of developing periodontal disease. This heightened risk is hypothesized to result from the presence of hormone recep- tor-posiDve cells within gingival Dssue. Methods: The cross-secDonal study was conducted from January 2023 to March 24. Drug-naïve controls (n = 50) were parDcipants who had not received any pharmaceuDcal therapy, whereas cases were parDcipants who had received just OCPs (ethinyl estradiol 0.03 mg or levonorgestrel 0.15 mg) for at least six months. Results: Women aged 20–45 were referred to the denDst for a check-up. There were no differences (p > 0.05) between the control and case groups for BMI, blood glucose, fasDng, or kidney funcDon tests. However, there were differences (p < 0.05) in cholesterol and liver enzyme levels. According to the study, 30% of cases had localized or chronic periodonDDs, while 60% of the parDcipants had a widespread aggressive disease. AddiDonally, research found higher but not staDsDcally significant amounts of plaque, gingiviDs, and bleeding in the case group. Compared to non-users, case women had average probing depths that were deeper. Conclu- sion: The study found that young women with aggressive gum disease, especially those with generalized aggressive periodonDDs, tended to use the pill. These women also had higher levels of plaque. Open Access Cita%on: Jawad AS. (2025) Oral Contracep%ves Are Asso- ciated with a Higher Risk of Dental Inflammatory and Bleeding Disorders. Den%stry 3000. 1:a001 doi:10.5195/d3000.2025.874 Received: March 5, 2025 Accepted: April 26, 2025 Published: June 9, 2025 Copyright: ©2025 Jawad AS. This is an open access ar%- cle licensed under a Crea%ve Commons AYribu%on Work 4.0 United States License. Email: dent.asmaa.sami@uobabylon.edu.iq Introduc)on Oral contraceptive pills (OCPs) are a widely utilized and convenient method of contra- ception. Their utilization has been associated with potential impacts on the progression of gingival and periodontal diseases in women [1]. The impact of oral contraceptives on gin- gival microvasculature is well-documented. Human gingiva contains progesterone and oestrogen receptor-positive cells, and prolonged use of hormonal contraceptives has been shown to increase the risk of perio- dontal disease. Elevated levels of pro-inGlam- matory cytokines and prostaglandins result- ing from prolonged use and elevated dosage have been identiGied as key factors in this in- creased risk [2]. Hormonal contraceptives have been demon- strated to heighten the likelihood of alveolar osteitis in the aftermath of tooth extraction, concomitantly augmenting the prevalence of the Candida species within the oral environ- ment. These medications also exert an inGlu- ence on the periodontium, manifesting in the recurrent emergence of gingivitis, yet do not induce alterations in the composition of the salivary microbiome [3,4]. Hormonal intrau- terine devices (IUDs), which have seen a surge in popularity following the introduc- tion of Mirena® in 2001 [5], consist of poly- dimethylsiloxane for controlled release and 52 mg of levonorgestrel in a T-shaped form. Oral ContracepDves Are Associated with a Higher Risk of Dental Inflammatory and Bleeding Disorders Vol 13, No 1 (2025) DOI 10.5195/d3000/2025.874 http://dentistry3000.pitt.edu 2 This non-abortive technique works by stop- ping conception and lasts for at least Give years [6]. The increasing utilization of hormonal con- traceptives among women emphasizes the need for a systematic evaluation, as do their possible effects on the oral mucosa. This study's goal was to compile data regarding the possible oral symptoms that these con- traceptive methods may cause in women of reproductive age. Material and Methods The Department of Obstetrics and Gynecol- ogy at the University of Kufa gave its ap- proval for the cross-sectional study, which took place between January 2023 and March 24 [No. f (BORS-Gynecological Science, Res/KU/15-10, 2023-6479)]. The partici- pants provided informed written consent. It has been established that cases of periodon- tal destruction diagnosed in obstructive and gynecology clinics have led to patients being referred to general dental clinics for further examination. The purpose of this referral is to conGirm and validate the diagnosis of ag- gressive periodontitis through a specialized assessment and evaluation. Furthermore, the collaboration between these clinics en- sures a multidisciplinary approach to patient care, addressing both oral health and sys- temic conditions effectively. Participants with normal menstrual periods, normo-an- drogenic traits (no alopecia, acne, or acan- thosis), and no polycystic ovaries were re- cruited from the obstetrics and gynecology clinics. Drug-naı̈ve controls (n = 50) were subjects not receiving any pharmaceutical therapy, whereas cases (n = 50) were sub- jects who had received just OCPs (ethinyl es- tradiol 0.03 mg or levonorgestrel 0.15 mg) for at least six months. The thyroid, liver, and kidneys of every woman were functioning normally. The ex- clusion criteria included coronary artery dis- ease, diabetes, thyroid dysfunction, hy- perprolactinemia, androgen-producing tu- mors, non-classic adrenal hyperplasia, Cush- ing's syndrome, pregnancy, breastfeeding, coagulation disorders, medication history, and smoking status. Multivariate regression analysis was per- formed to adjust for potential confounders. All statistical tests were two-tailed, and con- Gidence intervals (CIs) were calculated at the 95% level. Data visualization was conducted using graphs and charts generated in GraphPad Prism 8.1 to facilitate interpreta- tion of the Gindings. Results Using the provided referral screening form, general dentists identiGied female patients between the ages of 20 and 45 and referred them for a thorough periodontal examina- tion. The data relating to the basic clinical characteristics of the control subjects and the OCP-treated cases are shown in Table 1 and Figure 1. We found that there were insig- niGicant differences (p > 0.05) when com- pared the control BMI and blood glucose, fasting, renal function test (creatinine, blood urea) with case group, while signiGicant dif- ferences (p < 0.05) were found in cases as compared to controls for lipid proGile (cho- lesterol, TG), and liver enzymes (SGPT and SGOT). Most cases of generalized aggressive disease were observed in patients with the condition (60%), compared to 30% of people who have chronic or localized severe periodontitis. The case group tended to have higher levels of bleeding, plaque, and gingivitis. This dis- parity did not, however, reach statistical sig- niGicance. In comparison to non-users, case women had mean probing depths that were deeper (3.3–1.0 versus 2.7–0.5 mm) (P = 0.04) (Table 2 and Figure 2). Discussion A plethora of studies have been conducted on the utilization of OCPs as a primary form of birth control, yielding a substantial body of evidence that supports this approach. A notable Ginding from these studies is that women who have used OCPs exhibit elevated average lipid levels in comparison to those who have not used them. Moreover, there is a higher likelihood of abnormally high total cholesterol and TG levels among users of OCPs [7,8]. Age explained 34% of the observed variance, according to the analysis. However, because of the study population's extremely narrow age range, this result was determined to be statistically inconsequential. The current re- search has important ramiGications for coun- seling young female patients with advanced periodontitis who are thinking about using contraceptives [9,10]. Preshaw et al.'s result that oral contraceptives had no effect on gin- gival response might not apply to the current cohort because a signiGicant percentage of research participants had been using contra- ceptives for a long period. Further research is required, especially in light of Preshaw et al.'s Ginding that there were no discernible differences in gingival inGlammation be- tween pill users and non-users during a brief period of time [11]. According to Taichman and Ekland's re- search, there is no correlation between using oral contraceptives and a higher incidence of periodontitis or gingivitis. Their Gindings, which were based on data from 4,930 premenopausal women in NHANES I and 5,001 in NHANES II, suggested a slight pro- tective advantage of contraceptive medica- tion. This research disproves previous theo- ries on the damaging effects of oral contra- ceptives on the periodontium [12]. Conclusions The study found that a lot of young women with aggressive periodontal disease, espe- cially those diagnosed with generalized ag- gressive periodontitis, were using the pill. These women also had high levels of plaque. References 1. Prachi S, Jitender S, Rahul C, Jitendra K, Pri- yanka M, Disha S. Impact of oral contracep- tives on periodontal health. Afr Health Sci. 2019;19(1):1795-800. 2. Mistry S, Bhowmick DC. Oral contraceptive pill induced periodontal endocrinopathies and its management: A case report. European Journal of Dentistry. 2012;6(03):324-9. 3. Rojo MG, Lloret MRP, Gironés JG. Oral manifes- tations in women using hormonal contracep- tive methods: a systematic review. Clin Oral Investig. 2024;28(3):184. 4. Hassan SM, al-Jaf ANA, Hussien YA, Awad SM, Hadi NR. The potential antiviral activity of a novel pyrimidine derivative against Herpes Simplex Virus type-1 (HSV-1). Rev Pharm. 2020;11:795-806. 5. Hsia JK, Creinin MD, editors. Intrauterine con- traception. Seminars in reproductive medi- cine; 2016: Thieme Medical Publishers. 6. Blumenthal PD, Edelman A. Hormonal contra- ception. Obstetrics & Gynecology. 2008;112(3):670-84. 7. Hashemi SJ, Khezri R, Saki N, Nasehi N, Hos- seini SA, Harizi M, Rahimi Z. Association be- tween oral contraceptives with lipid prodile: results from Hoveyzeh cohort study (HCS). BMC Womens Health. 2023;23(1):552. 8. Abbas Al-Huseini LM, Al-Mudhaffer RH, Has- san SM, Hadi NR. DMF ameliorating cerebral ischemia/ reperfusion injury in Male Rats. Systematic Reviews in Pharmacy. 2019;10(1):206-13. 9. Abbas SN, Alwan TS, Hassan SM. Correlation between Diabetes Mellitus and Dyslipidemia Incidence in Center of Iraq. 2023. 10. Ahjel SW, Hassan SM, Hussein SF, Hadi NR, Awad SM. Antineoplastic Effect of New Syn- thesized Compounds of 2-Thiouracil Sulfona- mide Derivatives against Ovarian and Breast Carcinoma Cells" In Vitro Study". Systematic Reviews in Pharmacy. 2020;11(4). 11. Preshaw PM, Knutsen MA, Mariotti A. Experi- mental gingivitis in women using oral contra- ceptives. J Dent Res. 2001;80(11):2011-5. 12. Taichman LS, Eklund SA. Oral contraceptives and periodontal diseases: rethinking the asso- ciation based upon analysis of National Health and Nutrition Examination Survey data. J Per- iodontol. 2005;76(8):1374-85. Oral ContracepDves Are Associated with a Higher Risk of Dental Inflammatory and Bleeding Disorders Vol 13, No 1 (2025) DOI 10.5195/d3000/2025.874 http://dentistry3000.pitt.edu 3 Parameters Mean ± SD (Con- trols) Mean ± SD (Cases) P value significant Age 34.32 ± 1.83 35.16 ± 1.86 0.932 No BMI (kg/m2) 22.51 ± 3.71 23.61 ± 3.53 0.911 No Blood glucose fasting (mg/dl) 97.90 ± 10.98 99.82 ± 5.84 0.845 No Cholesterol (mg/dl) 153.40 ± 10.2 189.24 ± 9.85 0.002 Yes Triglycerides (mg/dl) 111.32 ± 13.78 163.58 ± 12.89 0.000 Yes S. Creatinine (mg/dl) 0.88 ± 0.15 0.96 ± 0.50 0.981 No Blood Urea (mg/dl) 31.42 ± 4.60 27.71 ± 5.95 0.707 No SGPT (IU/L) 20.92 ± 4.06 59.15 ± 3.21 0.001 Yes SGOT (IU/L) 26.09 ± 3.54 57.56 ± 2.43 0.003 Yes Table 1. The anthropometric and biochemical parameters of the controls (i.e. those not previously exposed to the drug) and cases (i.e. those treated with OCP) were analyzed. Figure 1. Anthropometric and biochemical parameters of the control and case groups have been presented as mean values with standard devia- Dons (SD). Parameters Mean ± SD (Con- trols) Mean ± SD (Cases) P value significant Generalized Aggressive (n) 40 60 0.010 Yes Localized Aggressive (n) 70 30 0.000 Yes Plaque % 30.1 ± 4.2 69.9 ± 4.0 0.000 Yes Gingivitis % 20.7 ± 9.12 79.3 ± 9.18 0.000 Yes BOP % 53.5 ± 5.34 44 ± 5.31 0.173 No Mean Probing Depth (mm) 2.7 ± 0.5 3.3 ± 1.0 0.021 Yes Table 2. A different type of periodonDDs that can be used to refer paDents to the denDst for treatment. Age BMI (k g/m 2) Blood glucose fa stin g (m g/dl) Cholesterol (m g/dl) Trig lycerid es (m g/dl) S. C reatin ine (m g/dl) Blood Urea (m g/dl) SGPT (IU /L) SGOT (IU /L) 0 50 100 150 200 250 The anthropometric and biochemical parameters co nc en te ra tio n Control Case # # # # ✱ ✱ ✱✱ * significant # insignificant Oral ContracepDves Are Associated with a Higher Risk of Dental Inflammatory and Bleeding Disorders Vol 13, No 1 (2025) DOI 10.5195/d3000/2025.874 http://dentistry3000.pitt.edu 4 Figure 2. PeriodonDDs assessments. Generalize d Aggressive (N ) Localize d Aggressive (N ) Plaque % Gingivitis % BOP % Mean Probing Depth (m m) 0 20 40 60 80 Periodontal disease assessment ✱ ✱ ✱ ✱ ✱ # Control Case * significant # insignificant