Diagnosis and treatment of infectious vaginitis: Proposal for a new algorithm.

Background: Vaginitis is the most common gynecologic diagnosis in primary care, and most women have at least one episode during their lives. The need for standardized strategies to diagnose and treat vaginitis, both in primary care and among gynecologists, is emphasized. The Brazilian Group for Vaginal Infections (GBIV, acronym in Portuguese) aimed to update the practical approach to affected women by reviewing and discussing recent literature, and developing algorithms for diagnosis and treatment of vaginitis. Methods: A literature search within biomedical databases PubMed and SCieLo was conducted in January 2022. The available literature was evaluated by three experienced researchers, members of the GBIV, to summarize the main data and develop practical algorithms. Results and conclusion: Detailed algorithms were developed with the main goal to improve gynecological practice considering different scenarios and access to diagnostic tools, from the simplest to the most complex tests. Different age groups and specific contexts were also considered. The combination of anamnesis, gynecological examination, and complementary tests remains the basis of a proper diagnostic and therapeutic approach. Periodic updates of these algorithms are warranted as new evidence becomes available.

Efficacy of Hormonal and Nonhormonal Approaches to Vaginal Atrophy and Sexual Dysfunctions in Postmenopausal Women: A Systematic Review.

OBJECTIVE: To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women. DATA SOURCES: We conducted a search on the PubMed, Embase, Scopus, Web of Science, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, as well as on clinical trial databases. We analyzed studies published between 1996 and May 30, 2020. No language restrictions were applied. SELECTION OF STUDIES: We selected randomized clinical trials that evaluated the treatment of sexual dysfunction in postmenopausal women. DATA COLLECTION: Three authors (ACAS, APFC, and JL) reviewed each article based on its title and abstract. Relevant data were subsequently taken from the full-text article. Any discrepancies during the review were resolved by consensus between all the listed authors. DATA SYNTHESIS: A total of 55 studies were included in the systematic review. The approaches tested to treat sexual dysfunction were as follows: lubricants and moisturizers (18 studies); phytoestrogens (14 studies); dehydroepiandrosterone (DHEA; 8 studies); ospemifene (5 studies); vaginal testosterone (4 studies); pelvic floor muscle exercises (2 studies); oxytocin (2 studies); vaginal CO2 laser (2 studies); lidocaine (1 study); and vitamin E vaginal suppository (1 study). CONCLUSION: We identified literature that lacks coherence in terms of the proposed treatments and selected outcome measures. Despite the great diversity in treatment modalities and outcome measures, the present systematic review can shed light on potential targets for the treatment, which is deemed necessary for sexual dysfunction, assuming that most randomized trials were evaluated with a low risk of bias according to the Cochrane Collaboration risk of bias tool. The present review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100488).

OBJETIVO: Avaliar a eficácia das abordagens hormonais e não hormonais para os sintomas de disfunção sexual e atrofia vaginal em mulheres na pós-menopausa. FONTES DE DADOS: Pesquisamos as bases de dados PubMed, Embase, Scopus, Web of Science, SciELO, Cochrane Central Register of Controlled Trials (CENTRAL), e Cumulative Index to Nursing and Allied Health Literature (CINAHL), assim como bancos de dados de ensaios clínicos. Foram analisados estudos publicados entre 1996 e 30 de maio de 2020. Nenhuma restrição de idioma foi aplicada. SELEçãO DOS ESTUDOS: Foram selecionados ensaios clínicos randomizados que avaliavam o tratamento das disfunções sexuais em mulheres na pós-menopausa. COLETA DE DADOS: Três autores (ACAS, APFC e JL), revisaram cada artigo com base em seu título e resumo. Os dados relevantes foram posteriormente retirados do texto completo do artigo. Quaisquer discrepâncias durante a revisão foram resolvidas por consenso entre todos os autores listados. SíNTESE DOS DADOS: Ao todo, 55 estudos foram incluídos na revisão sistemática. As abordagens testadas para tratar a disfunção sexual foram: lubrificantes e hidratantes (18 estudos); fitoestrogênios (14 estudos); deidroepiandrosterona (DHEA; 8 estudos); ospemifeno (5 estudos); testosterona vaginal (4 estudos); exercícios para os músculos do assoalho pélvico (2 estudos); oxitocina (2 estudos); laser de CO2 vaginal (2 estudos); lidocaína (1 estudo), e vitamina E vaginal (1 estudo). CONCLUSãO: Identificou-se falta de coerência na literatura quanto aos tratamentos propostos e medidas de resultados selecionadas. Apesar da grande diversidade de modalidades de tratamento e medidas de resultados, esta revisão sistemática pode lançar luz sobre alvos potenciais para o tratamento, que é considerado necessário para a disfunção sexual, assumindo que a maioria dos estudos randomizados foi avaliada com baixo risco de viés de acordo com a ferramenta de avaliação de risco de viés de Cochrane Collaboration. Esta revisão tem cadastro no International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100488).

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions.

PURPOSE: Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. METHODS: Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. RESULTS: Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. CONCLUSION: Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.

Systematic review and meta-analysis of the papillomavirus prevalence in breast cancer fresh tissues.

BACKGROUND: Although widely studied, the role of HPV in the genesis of breast carcinomas remains elusive due to the diversity of results across studies, possibly caused by the wide methodological heterogeneity, some of them with inadequate methods. OBJECTIVE: To verify the association between HPV and breast cancer through the meta-analysis of studies that used the best-recognized techniques for viral detection and tissue conservation. METHODS: A systematic review and meta-analysis restricted to studies that detected HPV by PCR in fresh and frozen tissue from breast cancer were conducted to obtain greater homogeneity. PubMed, Scopus, Science Direct, Cochrane Library, and SciELO were searched until December 14, 2019. Search terms included "breast cancer" and "HPV" without language restrictions. Eleven studies were included in the meta-analysis. The pooled relative risks and 95% confidence interval (95% CI) were calculated, and heterogeneity was assessed using the I-squared (I2). RESULTS: The selected studies had very low heterogeneity (2%). There is a 2.15 times higher combined relative risk (95% CI = 1.60-2.89) of detecting HPV in breast cancer than in cancer-free breast controls with a statistically significant p-value (p < 0.0001). CONCLUSION: Our data support the association of DNA-HPV with breast carcinomas. Further studies are needed to find out which breast cancer subtypes this association is most frequent.

Liquid-based cytology and HPV DNA test in anal specimens from women with cervical cancer.

INTRODUCTION: Cervical and anus cancers have similarities: association with HPV infection, epithelial transformation zone, and precursor lesions. However, it is still unclear whether women with cervical cancer should be screened to identify high-grade squamous intraepithelial lesions and anal cancer. We aimed to identify high-risk HPV and cytological atypia in anal samples from women diagnosed with invasive squamous cell carcinoma of the cervix. STUDY DESIGN: We conducted a cross-sectional study between July 2016 and August 2017 in reference services in oncology in the State of Ceará, Brazil. We studied 59 patients diagnosed with frankly invasive squamous cell carcinoma of the cervix (at least stages IB) and 60 women in a control group. We performed liquid-based cytology (Surepath™) and HPV test (Cobas® 4800 System Test) of anal samples. To determine statistical significance with a confidence interval of 95%, we used Fisher's exact test and Student's t-test using the GraphPad Prism 7.0 software. RESULTS: The mean age in the control group was 56.7 ± 8.5 years, while in the group of women with cervical squamous cancer, it was 54.3 ± 14.8. The liquid-based cytology results of the satisfactory cases were: negative for intraepithelial lesion or malignancy (NLM): 51 cases (85%) in the control group and 38 (64.4%) in the study group (p = .0116). The HPV test was negative more frequently in the control group (n = 56, 93.3%) than in the study group (n = 17, 31.5%) (p < .0001). HPV 16 was the most frequent type (67.6%). CONCLUSIONS: There is a higher frequency of high-risk HPV and atypical cytology in women with cervical cancer than without lesions. Thus, this group should be considered as a target population for screening.

Vaginal probiotics on the outcomes of premature rupture of membranes: a pilot randomised clinical trial.

The published literature shows that a balanced vaginal microbiota can have a favourable impact on decreasing the prevalence of premature rupture of membranes (PROM). We studied the effects of vaginal probiotics (Lactobacillus rhamnosus and L. gasseri) on the outcomes of PROM in pregnant women between 24 and 36 weeks of gestation. We performed a randomised, triple-blind, placebo-controlled study. A total of 27 participants were divided into two groups-group 1 (probiotics; n = 16) and group 2 (placebo; n = 11). Although most outcomes did not show much variation, the latency period and gestational age at delivery were higher in group 1 than in group 2. Thus, vaginal use of L. rhamnosus and L. gasseri along with standard treatment appears to increase the latency period and gestational age at delivery in women with PROM.IMPACT STATEMENTWhat is already known on this subject? Delaying delivery increases the risk of infections, but the prolongation of pregnancy allows further foetal maturation, thus reducing the risk of complications associated with premature birth. Moreover, a more extended latency period in pregnancies of <37 weeks of gestation is associated with a better neonatal prognosis.What do the results of this study add? The use of probiotics (L. rhamnosus and L. gasseri) prolongs the latency period in pregnant women with premature rupture of membranes.What are the implications of these findings for clinical practice and/or further research? Probiotics are an exciting option for extending the time to delivery in cases of premature rupture of the membrane, allowing the maturation of the foetal lung.

Potential impact of the COVID-19 in HIV-infected individuals: a systematic review Impact of the COVID-19 in HIV-Infected Individuals.

BACKGROUND: Although much has been studied about the SARS-Cov-2 virus, its effects, and the effectiveness of possible treatments, little is known about its interaction with other infectious diseases. OBJECTIVE: The aim is to study its clinical features and morbidity, and mortality outcomes of COVID-19 patients with HIV/AIDS coinfection. DATA SOURCES: MEDLINE, Web of Science, Embase, CINAHL, LILACS, Scopus, ClinicalTrials.gov, and Cochrane. STUDY ELIGIBILITY CRITERIA: Atudies in any language, published after 2019, were describing COVID-19 patients with HIV/AIDS. STUDY APPRAISAL: JBI Levels of Evidence, Joanna Briggs Institute. SYNTHESIS METHODS: As shown in the PRISMA flow diagram, two authors separately screened the search results from the obtained titles and abstracts. RESULTS: Chest CT was observed in patients with pneumonia by SARS-CoV-2 with findings of multiple ground-glass opacities (GGO) in the lungs, there is a need for supplemental oxygenation. One patient developed encephalopathy and complicated tonic-clonic seizures; four patients were transplanted (two, liver; two, kidneys), one patient developed severe SARS-CoV-2 pneumonia and 30 patients died (mortality rate, 11%). CONCLUSION: HIV did not show any relevance directly with the occurrence of COVID-19. Some studies suggest that HIV-1 infection through induction levels of IFN-I, may to some extent, stop the apparent SARS-CoV-2 infection, thus leading to undetectable RNA. Moreover, some authors suggest retroviral therapy routinely used to control HIV infection could be used to prevent COVID-19 infection.

Peritoneal lavage cytology in the diagnosis of pelvic endometriosis.

BACKGROUND: We aimed to assess the sensibility, specificity, and predictive values of cytology of the fluid sediment in patients with pelvic endometriosis diagnosed based on laparoscopic-guided biopsy. METHODS: Between January 2017 and September 2018, 71 specimens of peritoneal fluid collected by laparoscopy were evaluated. Fifty-three patients were diagnosed laparoscopically and histologically with endometriosis, and 18 were considered controls (without suspicious endometriosis lesions). We calculated the sensitivity, specificity, the positive and negative predictive value, and the accuracy of endometrial-like cells (ELC) and hemosiderin-laden macrophages (HLM) in the fluid sediment. RESULTS: Of the 50 patients with endometriosis, 32 (64%) had HLM, 9 (18%) had ELC, and 7 (14%) had both elements. Of the 18 patients without endometriosis, 3 (16%) had HLM, 2 (11%) had ELC, and 1 (5%) had both ELC and HLM. The sensitivity of the cytology of peritoneal fluid sediment for the diagnosis of endometriosis, based on the presence of ELC, was 18%, the specificity was 83%, the positive predictive value was 82%, the negative predictive value was 28.7%, and the accuracy was 36.8%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy based on the presence of HLM were 64%, 83%, 91%, 45.5%, and 69.1%, respectively. CONCLUSION: The study of peritoneal fluids obtained laparoscopically from women undergoing evaluation for endometriosis may identify patients with the disease.

Hormonal Approach for Postmenopausal Vulvovaginal Atrophy.

Menopause is a physiological and progressive phenomenon secondary to decreased ovarian follicular reserve that significantly affects the genital tract. Although postmenopausal vulvovaginal atrophy primarily affects postmenopausal women, it is also seen in premenopausal women. The hypoestrogenic condition results in hormonal and anatomical changes, with the main symptoms, are dryness, burning and genital irritation, decreased lubrication, urinary urgency, dysuria, and recurrent urinary tract infections. This review aims to update hormone therapy for urogenital atrophy, both local and systemic, and discusses the importance of understanding and the need for active treatment of this condition. The main therapeutic objective is the relief of symptoms, and hormonal therapy (HT) is still the most effective choice for treating clinical manifestations, despite the side effects of its use. HT should be used in an individualized way to the needs of the women and appropriate to the stage in which she is menopausal, perimenopausal, or after menopause.

Use of Moisturizers and Lubricants for Vulvovaginal Atrophy.

The estrogen decrease in postmenopausal women results in functional and anatomical changes in the genitourinary tract. The most prevalent and bothersome symptoms are vaginal dryness, dyspareunia, and reduced lubrication, which can significantly affect the quality of life of these women, principally those who are sexually active. Hormonal therapy with local estrogens is generally considered the "gold standard." However, there are cases in which there are clinical concerns about its use or women opt for non-hormonal options. Thus, safe and effective non-hormonal options are needed to improve symptoms in these women. Moisturizers and lubricants are first-line therapy for breast cancer survivors.

Microablative Fractional Radiofrequency as a Therapeutical Option for Genitourinary Syndrome of Menopause: Perspectives.

The genitourinary syndrome in menopause can occur at different stages of life, with different causes or triggering factors, such as prolonged use of antiestrogens, chemotherapy, radiotherapy, and extensive vaginal surgeries, which can alter vascularization, hydration, collagen quality, and tissue elasticity. Despite hormonal therapy being considered the best evidenced treatment for genitourinary syndrome of menopause (GSM), there are limitations concerning the latter. Thus, alternative, complementary, or even substitutive treatments have emerged, such as energy use, promoting thermal tissue stimulation to improve tropism. Due to its practicality and feasibility, the micro ablative fractional radiofrequency (MAFRF) has gained space among these energies. It uses high-frequency electromagnetic waves and promotes thermal micro points in the superficial and deep dermis. The safety of these energies limits thermal action laterality and depth. Laterally, it is essential for an adequate regenerative effect without scarring marks or sequelae; the appropriate depth is important for stimulating the obligatory tissue repair response with the production and reorganization of collagen, elastic fibers, increased vascularization and hydration, and the consequent improvement in tropism. In gynecology, the MAFRF is used with therapeutic indication and functional improvement; it is applied to the entire length of the vaginal walls, the vulvar vestibule, urethral meatus, labia minora, clitoris prepuce, labia majora, perineum, and perianal region. The MAFRF has been proved to be an effective and safe treatment for GSM, with long-lasting effects, significantly reducing symptoms and improving vaginal tropism. This review aims to analyze the MAFRF as a non-hormonal therapeutic option for GSM.

Genitourinary Syndrome of Menopause: Epidemiology, Physiopathology, Clinical Manifestation and Diagnostic.

Genitourinary syndrome of menopause (GSM) is a term used to define a compilation of signs and symptoms arising from decreased estrogenic stimulation of the vulvovaginal and lower urinary tract. Among 27-84% of women in postmenopausal are affected for symptoms of GSM, and these can unquestionably impair health, sexual function, consequently the quality of life of these women. The main signs and symptoms of GSM include, among others, burning, irritation, vulvovaginal dryness, dyspareunia, urinary symptoms of urgency, dysuria, or recurrent urinary tract infection. The diagnosis can be made through anamnesis, questionnaires, physical exams, and, sometimes, complementary exams. Objective vaginal assessment is essential and can be complemented by using the Vaginal Health Index (VHI), Vaginal Maturation Index (VMI), or vaginal pH measurement. The acknowledgment of this condition by health professionals is crucial for its identification and proper management and exclusion of other conditions that make a differential diagnosis with it.

Postmenopausal Vaginal Microbiome and Microbiota.

The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium, due to an increase in epithelial thickness, glycogen deposition, and influence on local immunology. The 16S rRNA gene amplification and pyrosequencing study demonstrated that healthy women have community state types (CST), classified as; type "L," with a predominance of Lactobacillus crispatus, type II, with a predominance of Lactobacillus gasseri, type III, where Lactobacillus iners predominates, and type V with a predominance of Lactobacillus jensenii. Type IV does not identify lactobacilli but a heterogeneous population of bacteria. There seems to be a relationship between increased vaginal bacterial diversity and poverty of lactobacilli with the complaining of vaginal dryness. With menopause, there appears to be a reduction in lactobacilli associated with higher serum levels of follicle-stimulating hormone (FSH) and lower estrogen levels. The evaluation of Gram-stained vaginal smears in postmenopause women must take into account the clinical-laboratory correlation. We should observe two meanly possibilities, atrophy with few bacterial morphotypes, without inflammatory, infiltrate (atrophy without inflammation), and atrophy with evident inflammatory infiltrate (atrophy with inflammation or atrophic vaginitis). The relationship between the microbiome and postmenopausal vulvovaginal symptoms seems to be related to the bacterial vaginal population. However, more robust studies are needed to confirm this impression.

Impact of SARS-CoV-2 (COVID-19) on pregnancy: a systematic review and meta-analysis protocol.

INTRODUCTION: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been growing at an accelerating rate, and has become a public health emergency. Pregnant women and their fetuses are susceptible to viral infection, and outcomes in this population need to be investigated. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, CINAHAL, Latin American and Caribbean Health Sciences Literature, clinicaltrials.gov, SCOPUS, Google Scholar and Cochrane Central Controlled Trials Registry will be searched for observational studies (cohort and control cases) published from December 2019 to present. This systematic review and meta-analysis will include studies of pregnant women at any gestational stage diagnosed with COVID-19. The primary outcomes will be maternal and foetal morbidity and mortality. Three independent reviewers will select the studies and extract data from the original publications. The risk of bias will be assessed using the Newcastle-Ottawa Scale for observational studies. To evaluate the strength of evidence from the included data, we will use Grading of Recommendation Assessment, Development, and Evaluation method. Data synthesis will be performed using Review Manager software V.5.2.3. To assess heterogeneity, we will compute the I2 statistics. Additionally, a quantitative synthesis will be performed if the included studies are sufficiently homogenous. ETHICS AND DISSEMINATION: This study will be a review of the published data, and thus it is not necessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: PROSPERO 2020: CRD42020181519.

Liquid-based cervical cytology and microbiological analyses in women using cooper intrauterine device and levonorgestrel-releasing intrauterine system.

OBJECTIVE: To assess the influence of the copper IUD and LNG-IUS on liquid-based cytology results (cellular atypia, reactive alterations, and microbiology). STUDY DESIGN: This cross-sectional study was performed between January 2012 and December 2017 in the Northeast of Brazil. Three study groups, the LNG-IUS group (n = 1179), copper IUD group (n = 519), and a control group of women not using contraception (n = 14,616) were compared. To facilitate this analysis, the LNG-IUS and IUD groups were further divided into less and more than two years of use. RESULTS: The mean age of the LNG-IUS and IUD groups was around 36 years and the control group was about 35 years (p = ns). The meantime between dispositive placement and examination was 19 ± 16 months for the LNG-IUS and 17 ± 15 months for the IUD. The frequency of epithelial atypia revealed upon cytological analysis did not differ between the groups. However, inflammatory infiltrates were significantly more frequent in the LNG-IUS and IUD (OR IUD = 1.32; OR LNG-IUS = 1.79) groups relative to control. Candida and cytolysis were more frequent in the LNG-IUS group (OR = 4.73 and 2.41, respectively) compared to both other groups. Bacterial vaginosis andActinomyces sp occurred more frequently in the IUD group (OR = 1.39 and 3352.55, respectively) compared to both other groups. Bacterial vaginosis was more common when using an IUD for more than two years than for less than two years (OR = 2.55). The Actinomyces morphotype was also observed at greater frequency after two years of IUD use than before (OR = 5.35). CONCLUSIONS: The LNG-IUS and copper IUD do not affect the incidence of cellular atypia but do interfere with the microbiota over time. Specifically, the copper IUD is associated with bacterial vaginosis andActinomyces sp infection while the LNG-IUS is associated with candidiasis and cytolysis.

Treatment of bacterial vaginosis before 28 weeks of pregnancy to reduce the incidence of preterm labor.

BACKGROUND: Controversy exists regarding the benefits of treating bacterial vaginosis (BV) during pregnancy to reduce the incidence of preterm labor (PTL). OBJECTIVES: To evaluate whether treatment of BV with vaginal clindamycin or oral metronidazole before 28 weeks of pregnancy reduces PTL incidence. SEARCH STRATEGY: PubMed, Scopus, Web of Science, Science Direct, CENTRAL, and SciELO databases were searched until December 30, 2017. Search terms included "bacterial vaginosis" and "preterm labor." No language restrictions were applied. SELECTION CRITERIA: Randomized clinical trials that evaluated treatment of BV with clindamycin or metronidazole to reduce PTL incidence. DATA COLLECTION AND ANALYSIS: The risk of PTL was evaluated by the odds ratio (OR) and 95% confidence interval (CI). Dichotomous data from each study were combined for meta-analysis using the Mantel-Haenszel model. MAIN RESULTS: Nine reports were included in the systematic review, with eight reports included in the meta-analysis. No reduction in the incidence of PTL was found for either metronidazole (OR 0.94, 95% CI 0.71-1.25) or clindamycin (OR 1.01, 95% CI 0.75-1.36). CONCLUSIONS: Use of oral metronidazole or vaginal clindamycin to treat BV before 28 weeks of pregnancy did not reduce the incidence of PTL. PROSPERO registration: CRD42018086173.

Double-Blind Clinical Trial of Arginine Supplementation in the Treatment of Adult Patients with Sickle Cell Anaemia.

BACKGROUND: Sickle cell anaemia (SCA) is the most prevalent monogenic disease in Brazil. In SCA, haemoglobin S (HbS) is formed, which modifies red blood cell morphology. Intravascular haemolysis occurs, in which free Hb and free radicals degrade nitric oxide (NO) and release arginase, which reduces arginine levels. Because arginine is a substrate for NO formation, this decrease leads to reduced NO (vasodilator) synthesis. SCA treatment uses hydroxyurea (HU) to maintain high foetal haemoglobin (HbF) levels and reduces HbS to avoid haemolytic episodes. OBJECTIVE: To analyse the efficacy of L-arginine as an adjuvant in the treatment of SCA patients. SETTING: The State Blood Centre of Ceará, Brazil. METHODS: This was a randomized double-blind clinical study of adults with SCA with continuous use of HU at the State Blood Centre of Ceará. The clinical study enrolled 25 patients receiving HU + L-arginine (500 mg) and 25 patients receiving HU + placebo. The treatment was carried out over four months. Laboratory tests were performed to determine the levels of the following: (1) complete blood count; (2) nitrite + nitrate; (3) HbF; and (4) reticulocytes. The clinical experiments were performed by a haematologist. The main outcome measures were nitrite and pain. RESULTS: Statistical analysis showed that the levels of NO were increased in the study group, and there was also a reduction in pain frequency using a pain frequency scale by day, week, and month. The levels of nitrite plus nitrate in the group receiving placebo plus HU did not change among the times evaluated (38.27 ± 17.27 mg/L, 39.49 ± 12.84 mg/L, 34.45 ± 11.25 mg/L, p >0.05), but in the patients who received supplementation with L-arginine plus HU, a significant increase in nitrite plus nitrate levels was observed between M0 and M4 (36.55 ± 20.23 mg/L versus 48.64 ± 20.63 mg/L, p =0.001) and M2 and M4 (35.71 ± 15.11 mg/L versus 48.64 ± 20.63 mg/L, p <0.001). It is important to note that the increase in nitrite plus nitrate levels occurred only in the fourth month of follow-up of patients in the treatment group, showing that at least 4 months of supplementation with L-arginine is necessary to show an increase in these metabolites in the serum. CONCLUSION: The use of L-arginine as a coadjuvant in the treatment of sickle cell anaemia may function as a potential tool for pain relief, consequently improving the life of patients.