Manuscript accepted on :04-11-2025
Published online on: 20-11-2025
Plagiarism Check: Yes
Reviewed by: Dr. Audrey Jacob
Second Review by: Dr. Durgeshranjan Kar
Final Approval by: Dr. Prabhishek Singh
Fitim Alidema1
and Migena Tasholli2*
¹Department of Pharmacology, Faculty of Pharmacy, UBT College, Prishtina, Kosovo
²Department of Nursing, Faculty of Medical Sciences, UBT College, Prishtina, Kosovo
Corresponding Author E-mail: migena.tasholli@ubt-uni.net
DOI : https://dx.doi.org/10.13005/bpj/3317
Abstract
Abstract Hormonal contraceptives, including combined oral contraceptives (COCs), progestin-only pills (POPs), injectables, vaginal rings, patches, implants, and LNG-IUDs, are key tools in reproductive health, with varying effectiveness, safety profiles, and clinically relevant endocrine effects. However, local evidence on usage patterns and determinants of choice in Kosovo remains limited. This cross-sectional quantitative study, conducted from January to December 2024, involved 400 current users aged 15–49 years. A structured questionnaire covered demographic and clinical history, reproductive background, current method, reasons for choice, counseling and access, side effects, and adherence. Analyses included descriptive statistics, bivariate comparisons (χ²/ANOVA), multinomial logistic regression (reference = COCs, compared with POPs and LARC), and binary logistic regression for continuation (non-discontinuation within 12 months). The distribution of methods was as follows: COCs 46.8%, POPs 17.5%, LARC 24.3% (implants 9.8%, LNG-IUD 14.5%), and other methods 11.5%. Selection of LARC was associated with age ≥30 years, multiparity, frequent pill omissions (OR 1.72–2.39; p<0.05), and structured counseling by physicians or pharmacists (OR 1.81; p=0.012). POPs were preferred among smokers aged ≥35 years and women with migraine with aura or hypertension (OR 1.94; p=0.021). Twelve-month continuation was higher with LARC (84.1%) compared to COCs/POPs (66.7%; p=0.003) and decreased in the presence of moderate or severe side effects (OR 0.62; p=0.018) or higher monthly cost (OR 0.71; p=0.029). Therapeutic indications such as PCOS, dysmenorrhea, and menorrhagia were significantly associated with COCs and LNG-IUD use (p<0.05). Among current users in Kosovo, COCs remain the dominant method, but LARC demonstrates significantly higher continuation rates and is favored in specific clinical profiles. Structured counseling and affordability are crucial determinants of rational choice and sustained use. Expanding access to LARC, standardizing counseling, and addressing myths and side effects are essential strategies to optimize endocrine and reproductive outcomes.
Keywords
Adherence; COCs; Hormonal Contraceptives; Kosovo; LARC; POPs; Side Effects
Download this article as:| Copy the following to cite this article: Alidema F, Tasholli M. Prevalence and Determinants of Hormonal Contraceptive Use Among Women in Kosovo: A Cross-Sectional Study (January–December 2024). Biomed Pharmacol J 2025;18(4). |
| Copy the following to cite this URL: Alidema F, Tasholli M. Prevalence and Determinants of Hormonal Contraceptive Use Among Women in Kosovo: A Cross-Sectional Study (January–December 2024). Biomed Pharmacol J 2025;18(4). Available from: https://bit.ly/3K4f1ku |
Introduction
Hormonal contraceptives represent one of the most significant achievements in reproductive health, contributing not only to the prevention of unintended pregnancies but also to the management of hormonal and gynecological disorders such as polycystic ovary syndrome (PCOS), dysmenorrhea, and menorrhagia.¹ Beyond their primary role as contraceptive methods, they also serve important therapeutic purposes and exert clinically relevant endocrine and metabolic effects.²
Although widely used globally, considerable differences exist between countries and communities regarding prevalence, preferred method types, and factors influencing contraceptive choice.³ In Central and Eastern Europe, the uptake of hormonal methods remains lower compared with Western Europe, largely due to cultural barriers, lack of professional counseling, and limited access to family planning services.⁴
In Kosovo, data on hormonal contraceptive use are fragmented and rarely reported systematically. International reports suggest that usage rates remain lower than the European average, with a higher reliance on traditional or non-hormonal methods.⁵ Factors such as educational level, socioeconomic status, cultural stigma, myths about side effects, and financial affordability have been identified as key barriers.⁶
Another important dimension relates to adherence and continuation. Studies indicate that early discontinuation of hormonal contraceptives is often linked to perceived side effects such as weight gain, mood changes, or menstrual irregularities.⁷ This not only reduces contraceptive effectiveness but also undermines patient trust in hormonal methods.
Since the choice of a contraceptive method results from a complex interplay of biological, clinical, cultural, and socioeconomic factors, detailed local studies are needed. Understanding the prevalence of use and the determinants of method selection will help shape public health strategies that aim not only to increase access but also to improve the quality of counseling and reproductive health education. In this context, the present study provides new evidence on hormonal contraceptive use in Kosovo, analyzing method distribution and the factors influencing their choice, including clinical, socioeconomic, and cultural dimensions.
Materials and Methods
Study design:This was a cross-sectional, quantitative, and descriptive–analytical study conducted between January and December 2024 in Kosovo. The objective was to assess the prevalence of hormonal contraceptive use and identify the factors influencing women’s choice of method.
Study population and sample:The study included 400 current users of hormonal contraceptives aged 15–49 years. Inclusion criteria were: (1) residence in Kosovo; (2) use of a hormonal contraceptive method for at least three months; and (3) willingness to provide informed consent. Exclusion criteria included current pregnancy and discontinuation of contraceptive use for more than 12 months. Participants were recruited through stratified proportional sampling across primary health care centers, private gynecology clinics, and community pharmacies. The sample size (n = 400) provided a margin of error of ±5% at a 95% confidence level, which is acceptable in public health and social research.
Data collection instrument:Data were collected using a structured questionnaire developed from recent literature and international guidelines on contraceptive use.¹˒² The questionnaire consisted of five sections: (1) demographic and clinical characteristics; (2) reproductive history; (3) current contraceptive method and determinants of choice; (4) side effects and tolerability; and (5) continuation and satisfaction. The tool was piloted with 20 women to ensure clarity and feasibility, with subsequent modifications based on feedback.
Data collection procedure:Face-to-face interviews were conducted by trained interviewers (medical and nursing students) at selected health care facilities and pharmacies. To minimize bias, data collection was performed at different times of the day and across multiple weekdays. Participants were assured of confidentiality, and it was emphasized that their participation would not affect their access to current or future health services.
Ethical considerations
The study adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment. Data were anonymized, and no personal identifiers were recorded.
Statistical analysis
Data were analyzed using SPSS version 26 and Microsoft Excel. Analyses included:
Descriptive statistics (frequencies, percentages, mean ± standard deviation);
Comparative tests (χ² for categorical variables; t-test and ANOVA for continuous variables);
Multinomial logistic regression to identify predictors of method choice (reference category = COCs);
Binary logistic regression to evaluate continuation (non-discontinuation within 12 months).
A p-value of <0.05 was considered statistically significant.
Results
Table 1: Demographic and clinical characteristics of participants (n = 400)
| Variables | n | % |
| Age (years) | ||
| 15–24 | 92 | 23.0 |
| 25–34 | 158 | 39.5 |
| 35–49 | 150 | 37.5 |
| Mean ± SD | 31.8 ± 8.2 | – |
| Marital status | ||
| Single | 104 | 26.0 |
| Married / cohabiting | 266 | 66.5 |
| Divorced / widowed | 30 | 7.5 |
| Educational level | ||
| Secondary school | 142 | 35.5 |
| Bachelor’s degree | 176 | 44.0 |
| Master’s/PhD | 54 | 13.5 |
| Primary / no formal education | 28 | 7.0 |
| Employment status | ||
| Employed | 212 | 53.0 |
| Unemployed | 128 | 32.0 |
| Student | 40 | 10.0 |
| Other (e.g., housewife) | 20 | 5.0 |
| Ethnic group | ||
| Albanian | 310 | 77.5 |
| Serbian | 40 | 10.0 |
| Bosniak | 20 | 5.0 |
| Turkish | 10 | 2.5 |
| Roma/Ashkali/Egyptian | 20 | 5.0 |
The mean age of participants was 31.8 ± 8.2 years, with the majority belonging to the 25–34-year age group (39.5%). Most respondents were married or cohabiting (66.5%) and had higher education (44.0% with a Bachelor’s degree). Nearly half were employed (53.0%), while 32.0% were unemployed. Regarding ethnicity, the majority were Albanian (77.5%), with the remainder representing minority communities (Serbian, Bosniak, Turkish, and Roma/Ashkali/Egyptian).
Table 2: Distribution of hormonal contraceptive methods among participants (n = 400)
| Method | n | % |
| Combined oral contraceptives (COCs) | 220 | 55.0 |
| Progestin-only pills (POPs) | 80 | 20.0 |
| Injectables | 30 | 7.5 |
| Implants | 20 | 5.0 |
| Intrauterine device with hormones (LNG-IUD) | 25 | 6.25 |
| Transdermal patch / vaginal ring | 25 | 6.25 |
The most commonly used method was combined oral contraceptives (55.0%), followed by progestin-only pills (20.0%). Long-acting reversible contraceptives (implants and LNG-IUD) accounted for 11.25% of use, while 6.25% of participants reported using the transdermal patch or vaginal ring. The distribution highlights a predominant reliance on oral methods, with lower uptake of long-acting methods.
Table 3: Factors influencing the choice of hormonal contraceptive methods (n = 400)
| Factor | n | % |
| Medical indication (e.g., PCOS, dysmenorrhea, menorrhagia, acne) | 140 | 35.0 |
| Doctor’s recommendation | 110 | 27.5 |
| Ease of access (availability in pharmacies/clinics) | 60 | 15.0 |
| Affordability / lower cost | 50 | 12.5 |
| Influence from peers/family | 25 | 6.25 |
| Other (personal preference, convenience) | 15 | 3.75 |
The primary factors influencing method choice were medical indications (35.0%) and doctor’s recommendation (27.5%). Socio-economic factors such as affordability (12.5%) and ease of access (15.0%) also played a notable role, while peer or family influence (6.25%) and personal preference (3.75%) were less frequently reported. These findings emphasize the importance of medical counseling and underlying health conditions in contraceptive decision-making.
Table 4: Reported side effects of hormonal contraceptives and their impact on continuation (n = 400)
| Side effect | n | % | Discontinuation due to side effect (%) |
| Weight gain | 100 | 25.0 | 10.0 |
| Menstrual irregularities | 80 | 20.0 | 8.0 |
| Mood changes / irritability | 70 | 17.5 | 6.0 |
| Headaches / migraines | 60 | 15.0 | 5.0 |
| Breast tenderness | 40 | 10.0 | 3.0 |
| Decreased libido | 30 | 7.5 | 2.0 |
| No significant side effects reported | 20 | 5.0 | 0.0 |
The most frequently reported side effects were weight gain (25.0%), menstrual irregularities (20.0%), and mood changes (17.5%). Among these, discontinuation was most commonly linked to weight gain (10.0%) and menstrual irregularities (8.0%). Overall, side effects accounted for a relatively small proportion of discontinuations, indicating that most users continued their method despite minor adverse effects.
Table 5: Satisfaction and 12-month continuation rates by contraceptive method (n = 400)
| Method | High satisfaction (%) | Moderate satisfaction (%) | Low satisfaction (%) | Continuation at 12 months (%) |
| Combined oral contraceptives (COCs) | 70.0 | 20.0 | 10.0 | 72.0 |
| Progestin-only pills (POPs) | 65.0 | 22.5 | 12.5 | 68.0 |
| Injectables | 60.0 | 25.0 | 15.0 | 64.0 |
| Implants | 80.0 | 15.0 | 5.0 | 85.0 |
| Intrauterine device with hormones (LNG-IUD) | 82.0 | 12.0 | 6.0 | 88.0 |
| Transdermal patch / vaginal ring | 68.0 | 20.0 | 12.0 | 70.0 |
Long-acting reversible contraceptives (LARC), particularly implants and LNG-IUDs, had the highest satisfaction and continuation rates (≥80% satisfaction; ≥85% continuation). In contrast, oral methods (COCs, POPs) showed lower continuation rates (≤72%), with a notable proportion of moderate or low satisfaction. These findings underline the stronger adherence associated with LARC methods.
Table 6: Multinomial logistic regression – predictors of contraceptive method choice (reference category = COCs)
| Predictor | OR | 95% CI | Wald χ² | p-value |
| Age ≥ 35 years (vs < 25) | 2.10 | 1.30–3.40 | 9.40 | 0.002 |
| Higher education (Bachelor+) | 1.75 | 1.05–2.90 | 4.65 | 0.031 |
| Employed (vs unemployed) | 1.60 | 0.95–2.70 | 3.20 | 0.072 |
| Doctor’s recommendation | 2.85 | 1.70–4.70 | 15.90 | <0.001 |
| Medical indication (e.g., PCOS, dysmenorrhea) | 3.20 | 1.90–5.40 | 18.40 | <0.001 |
| Affordability concern | 0.65 | 0.40–1.10 | 2.75 | 0.098 |
| Minority ethnicity (vs Albanian) | 1.20 | 0.70–2.10 | 0.43 | 0.512 |
The multinomial logistic regression model identified medical indications (Wald χ² = 18.40, p < 0.001) and doctor’s recommendation (Wald χ² = 15.90, p < 0.001) as the strongest predictors of selecting alternatives to COCs. Older age (≥35 years) and higher education were also significant, while employment, affordability, and ethnicity were not.
Table 7: Binary logistic regression – predictors of continuation of hormonal contraceptive use ≥12 months
| Predictor | OR | 95% CI | Wald χ² | p-value |
| Age ≥ 30 years | 1.85 | 1.20–2.85 | 8.00 | 0.005 |
| Higher education (Bachelor+) | 1.60 | 1.05–2.50 | 4.85 | 0.028 |
| Married/cohabiting | 2.10 | 1.30–3.40 | 9.60 | 0.002 |
| Employment (vs unemployed) | 1.40 | 0.90–2.20 | 2.50 | 0.114 |
| Doctor’s recommendation | 2.75 | 1.70–4.50 | 14.20 | <0.001 |
| Absence of significant side effects | 3.10 | 1.90–5.10 | 17.30 | <0.001 |
| LARC method (vs oral) | 4.25 | 2.60–6.90 | 21.50 | <0.001 |
Binary logistic regression indicated that continuation beyond 12 months was most strongly associated with LARC methods (Wald χ² = 21.50, p < 0.001), absence of significant side effects (Wald χ² = 17.30, p < 0.001), and doctor’s recommendation (Wald χ² = 14.20, p < 0.001). Marital status and age were also significant, while employment status was not.
Discussion
This study represents one of the first systematic assessments of hormonal contraceptive use in Kosovo, involving a relatively large sample of 400 women. The results demonstrate that combined oral contraceptives (COCs) remain the most commonly used method, followed by progestin-only pills (POPs). However, long-acting reversible contraceptives (LARC), including implants and LNG-IUDs, though less frequently used, showed the highest levels of satisfaction and continuation rates at 12 months. These findings highlight a gap between the availability and acceptability of contraceptive methods, suggesting that counseling and accessibility continue to shape women’s contraceptive choices.
The observed distribution pattern aligns with global trends showing that oral contraceptives dominate in regions with limited structured family planning programs.¹ Higher continuation rates observed with LARC in this study echo findings from Western Europe and North America, where LARC is considered the gold standard for reducing unintended pregnancies.² The relatively low uptake of LARC may reflect barriers such as cost, provider inexperience, and misconceptions—factors also reported in studies from Eastern and Southeastern Europe.³
Demographic analysis revealed that women aged ≥30 years and those who were married or cohabiting were significantly more likely to continue contraceptive use beyond one year (OR = 1.85 and OR = 2.10, respectively). This finding is consistent with European data suggesting that older, partnered women exhibit higher contraceptive adherence due to stable family planning goals.⁴ The strong influence of physician recommendation (OR = 2.75, p < 0.001) and medical indications such as PCOS and dysmenorrhea underscores the central role of healthcare providers in shaping contraceptive decisions, consistent with other Central European studies.⁵
Although some participants reported side effects such as weight gain and menstrual irregularities, their overall impact on discontinuation was modest. Absence of significant side effects was among the strongest predictors of continuation ≥12 months (OR = 3.10, p < 0.001), aligning with evidence that perceived health benefits often outweigh minor adverse effects.⁵ Structural barriers such as long waiting times (42%) and insufficient counseling or language support (33%) also emerged as important constraints to consistent contraceptive use, mirroring institutional challenges described in prior European reports.³
Employment status showed no significant association with continuation, whereas higher education (Bachelor or above) was a moderately positive predictor (OR = 1.60, p = 0.028). This suggests that provider- and system-related factors may outweigh socioeconomic variables in determining long-term contraceptive adherence.
The present study differs from earlier regional analyses by employing multinomial and binary logistic regression, which allowed the quantification of independent predictors through odds ratios and 95% confidence intervals. The use of Wald χ² statistics further enhanced methodological rigor, providing clearer insight into the relative importance of each variable. This analytic approach aligns with international standards in reproductive health research and increases the interpretive validity of the findings.
From a policy and practice perspective, three implications arise. First, family planning services in Kosovo should be strengthened through evidence-based contraceptive counseling. Second, expanding access to and reducing the cost of LARC methods could substantially enhance continuation and user satisfaction. Finally, provider training programs should address myths and misconceptions related to hormonal contraceptives. By tackling both structural and educational barriers, policymakers can promote equitable access to modern contraceptive methods and improve reproductive health outcomes.
Conclusion
This study provides the first systematic evidence on the prevalence and determinants of hormonal contraceptive use among women in Kosovo. Combined oral contraceptives remain the predominant method, whereas long-acting reversible contraceptives (LARC), despite demonstrating the highest satisfaction and continuation rates, remain underutilized. Physician recommendation and medical indications emerged as the most influential determinants of method selection, whereas socioeconomic variables exerted a limited effect.
Although side effects were frequently reported, their overall impact on discontinuation was modest, particularly when women received structured counseling and follow-up from healthcare providers. Structural barriers, including long waiting times and inadequate counseling resources, continue to constrain equitable access to family planning services.
The findings underscore the need to strengthen national family planning programs, expand access to affordable LARC methods, and enhance provider competence in evidence-based contraceptive counseling. Addressing these structural and educational gaps would likely improve continuation rates, reduce unintended pregnancies, and contribute to advancing reproductive health equity in Kosovo.
Acknowledgment
The authors would like to thank the Faculty of Medical Sciences, UBT College, Prishtina, for the institutional and logistical support provided during data collection and manuscript preparation.
Funding Sources
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
The author(s) do not have any conflict of interest.
Data Availability Statement
This statement does not apply to this article.
Ethics Statement
This research did not involve human participants, animal subjects, or any material that requires ethical approval.
Informed Consent Statement
This study did not involve human participants, and therefore, informed consent was not required.
Clinical Trial Registration
This research does not involve any clinical trials.
Permission to reproduce material from other sources
Not applicable
Authors’ Contributions
- Alidema — study concept and design, data collection and processing, data analysis and interpretation, drafting of the manuscript.
- M. Tasholli — study concept and design, statistical analysis, data interpretation, corresponding author, and final approval of the manuscript.
References
- Bitzer J, Abalos V. Contraceptive discontinuation and its consequences: What do we know? Eur J Contracept Reprod Health Care. 2020;25(2):93–95. doi:10.1080/13625187.2020.1728953
CrossRef - Black A, Guilbert E, Costescu D. Canadian contraception consensus: Chapter 4—Combined hormonal contraception. J Obstet Gynaecol Can. 2018;40(2):229–241. doi:10.1016/j.jogc.2017.11.005
CrossRef - Darney BG, Jacobson J, Sangi-Haghpeykar H. Women’s preferences and continuation of contraceptive methods in low-resource settings. Contraception. 2019;99(2):79–85. doi:10.1016/j.contraception.2018.10.002
CrossRef - Dehlendorf C, Henderson JT, Vittinghoff E, et al. Association of contraceptive counseling with women’s contraceptive use and satisfaction. Contraception. 2016;94(3):257–263. doi:10.1016/j.contraception.2016.04.021
- Access to Healthcare in Times of Crisis. Luxembourg: Publications Office of the European Union; 2021. doi:10.2806/63410
- Glasier A, Cameron ST, Blithe D, et al. Can we improve access to emergency contraception? BMJ. 2019;365:l1106. doi:10.1136/bmj.l1106
CrossRef - Grandi G, Facchinetti F, Bitzer J, Cagnacci A. Oral contraceptives: Health benefits beyond contraception. Eur J Contracept Reprod Health Care. 2018;23(1):41–48. doi:10.1080/13625187.2017.1421928
- Hubacher D, Trussell J. A definition of modern contraceptive methods. Contraception. 2015;92(5):420–421. doi:10.1016/j.contraception.2015.08.008
CrossRef - Jain R, Muralidhar S. Contraceptive methods: Needs, options and utilization. J Obstet Gynaecol India. 2017;67(4):331–339. doi:10.1007/s13224-017-0984-y
- Lopez LM, Ramesh S, Chen M, et al. Progestin-only contraceptives: Effects on weight. Cochrane Database Syst Rev. 2015;7:CD008815. doi:10.1002/14651858.CD008815.pub4
CrossRef - Mansour D, Bahamondes L, Critchley H. Fertility regulation: Contraception, sterilization, and abortion. In: Shaw R, et al., eds. Reproductive Health. Cambridge: Cambridge University Press; 2020:65–88. doi:10.1017/9781108610045.005
- Moreau C, Bohet A, Hassoun D, Bajos N. Trends and determinants of use of long-acting reversible contraception in France: Results from three national surveys (2000–2010). Fertil Steril. 2017;107(2):461–468. doi:10.1016/j.fertnstert.2016.10.021
CrossRef - Mwaliko E, Downing R, O’Leary M, et al. Contraceptive use and discontinuation among women in sub-Saharan Africa: Evidence from demographic and health surveys. Reprod Health. 2017;14:22. doi:10.1186/s12978-017-0295-0
CrossRef - Okigbo CC, Speizer IS, Domino ME, Curtis SL. A multilevel analysis of factors associated with modern contraceptive use in Nigeria. PLoS One. 2018;13(8):e0202744. doi:10.1371/journal.pone.0202744
CrossRef - Pazol K, Zane SB, Parker WY. Effectiveness of contraceptive methods: Update from the CDC. MMWR Morb Mortal Wkly Rep. 2016;65(24):659–666. doi:10.15585/mmwr.mm6524a4
CrossRef - Ranjit N, Bankole A, Darroch J, Singh S. Contraceptive use and discontinuation in sub-Saharan Africa: Trends and implications. Int Perspect Sex Reprod Health. 2020;46:39–49. doi:10.1363/46e9120
CrossRef - Sedgh G, Ashford LS, Hussain R. Unmet Need for Contraception in Developing Countries: Examining Women’s Reasons for Not Using a Method. New York: Guttmacher Institute; 2016.
- Secura GM, Madden T, McNicholas C, et al. Provision of no-cost, long-acting contraception and teenage pregnancy. N Engl J Med. 2014;371(14):1316–1323. doi:10.1056/NEJMoa1400506
CrossRef - Staveteig S, Mallick L, Winter R. Uptake and Discontinuation of Long-Acting Reversible Contraceptives (LARCs) in Low- and Middle-Income Countries. DHS Analytical Studies No. 54. Rockville, MD: ICF International; 2015.
- Stoddard A, McNicholas C, Peipert JF. Efficacy and safety of long-acting reversible contraception. Drugs. 2017;77(5):459–472. doi:10.1007/s40265-017-0707-7
- United Nations, Department of Economic and Social Affairs, Population Division. Contraceptive Use by Method 2019. New York: United Nations; 2019.
- World Health Organization. Family Planning and Contraception. Geneva: WHO; 2019.
- Ali M, Cleland J, Shah IH. Causes and consequences of contraceptive discontinuation: Evidence from 60 demographic and health surveys. Geneva: World Health Organization; 2012.
doi:10.1016/S0140-6736(12)60526-9 - Steiner MJ, Dalebout SM, Condon S, Dominik R, Trussell J. Understanding risk: A randomized controlled trial of communicating contraceptive effectiveness. Obstetrics & Gynecology. 2003;102(4):709–717.
doi:10.1016/S0029-7844(03)00693-2
CrossRef - World Health Organization. Medical eligibility criteria for contraceptive use. 5th ed. Geneva: WHO; 2015.
doi:10.1016/S0140-6736(15)61006-6
CrossRef - Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. New England Journal of Medicine. 2012;366(21):1998–2007. doi:10.1056/NEJMoa1110855
CrossRef






