ABSTRACT
PURPOSE: The aim of this study was to evaluate serum levels of inducible nitric oxide synthase (INOS), myeloperoxidase (MPO), total antioxidant status (TAS), and total oxidative status (TOS) in women with primary ovarian insufficiency (POI) and to compare them with healthy fertile women. We also examined the possible risk factors associated with POI.METHODS: This cross-sectional case control study was conducted in Zekai Tahir Burak Women's Health Education and Research Hospital. The study population consisted of 44 women with POI (study group) and 36 healthy fertile women (control group). In all patients, serum levels of INOS, MPO, TAS, and TOS were determined. INOS and MPO levels were measured by enzyme-linked immunosorbent assay whereas colorimetric method was used for evaluating TAS and TOS levels. Age, body mass index (BMI), obstetric history, smoking status, family history, comorbidities, sonographic findings, complete blood count values, C-reactive protein and baseline hormone levels were also analyzed. Student's t-test or Mann-Whitney U test was used to compare continuous variables between the groups; categorical data were evaluated by using Pearson χ2 or Fisher exact test, when appropriate. Binary logistic regression method was used to identify risk factors for POI.RESULTS: We found significantly elevated levels of INOS (234.1±749.5 versus133.8±143.0; p=0.005), MPO (3,438.7±1,228.6 versus 2,481.9±1,230.1; p=0.001), and TOS (4.3±1.4 versus 3.6±1.4; p=0.02) in the sera of the study group when compared to the BMI-age matched control group. However, difference in serum levels of TAS were not significant between the 2 groups (1.7±0.2 versus 1.6±0.2; p=0.15). Logistic regression method demonstrated that BMI <25 kg/m2, nulliparity, family history of POI, smoking, and elevated serum levels of INOS, MPO, and TOS were independent risk factors for POI.CONCLUSION: We found an increase in INOS, MPO, and TOS in women with POI. These serum markers may be promising in early diagnosis of POI. Further large-scale studies are required to determine whether oxidative stress markers have a role in diagnosing POI.
OBJETIVO: Avaliar os níveis séricos da sintetase nítrica induzível (INOS), da mieloperoxidase (MPO), do estado antioxidante total (EAT) e do estado oxidante total (EOT) em mulheres portadoras de insuficiência ovariana primária (IOP) e compará-las às mulheres férteis. Também examinamos os possíveis fatores de risco associados à IOP.MÉTODOS: Trata-se de estudo transversal caso-controle desenvolvido no Zekai Tahir Burak Women's Health Education and Research Hospital. A população de estudo abrangeu 44 mulheres portadoras de IOP (grupo de estudo) e 36 mulheres férteis hígidas (grupo controle). Em todas as pacientes, foram determinados os níveis séricos de INOS, MPO, EAT e EOT.Os níveis de INOS e MPO foram determinados com o uso do teste ELISA e os níveis de EAT e EOT foram determinados mediante método colorimétrico. Analisou-se também a idade, o índice de massa corporal (IMC), os antecedentes obstétricos, tabagismo, histórico familiar, comorbidades, achados sonográficos, valores completos do hemograma, proteína C-reativa e níveis hormonais basais. O teste t de Student ou o teste U de Mann-Whitney foi utilizado para comparar as variáveis contínuas entre os grupos; os dados categóricos foram avaliados pelo teste do χ2 de Pearson ou o teste exato de Fisher, conforme o caso. O método de regressão logística binária foi utilizado para identificar os fatores de risco para IOP.RESULTADOS: Encontramos níveis significativamente elevados de INOS (234,1±749,5 versus133,8±143,0; p=0,005), MPO (3.438,7±1.228,6 versus 2.481,9±1.230,1; p=0,001) e EOT (4,3±1,4 versus 3,6±1,4; p=0,02) nos soros do grupo estudo em relação ao grupo controle pareado por IMC e idade. Entretanto, as diferenças entre os níveis séricos de EAT nos dois grupos não foram significantes (1,7±0,2 versus 1,6±0,2; p=0,15). O método de regressão logística demonstrou que IMC <25 kg/m2, nuliparidade, histórico familiar de IOP, tabagismo e níveis séricos elevados de INOS, MPO e EOT foram fatores de risco independentes para IOP.CONCLUSÃO: Foram encontrados níveis aumentados de INOS, MPO e EOT em mulheres portadoras de IOP. Estes marcadores séricos podem ser promissores para o diagnóstico precoce de IOP. Novos estudos em larga escala são necessários para determinar se os marcadores de estresse oxidativo desempenham um papel no diagnóstico da IOP.
Subject(s)
Humans , Female , Adult , Oxidative Stress , Primary Ovarian Insufficiency/metabolism , Biomarkers , Case-Control Studies , Cross-Sectional Studies , Nitric Oxide Synthase Type II/blood , Peroxidase/blood , Primary Ovarian Insufficiency/blood , Risk Assessment , Risk FactorsABSTRACT
OBJECTIVE: To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment. METHODS: Twenty-one adult female Sprague-Dawley rats were used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 microg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4degrees C for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30degrees C for hormone assays. RESULTS: All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Mullerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group. CONCLUSION: G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.
Subject(s)
Animals , Female , Anti-Mullerian Hormone/blood , Antineoplastic Agents/toxicity , Biomarkers/blood , Cisplatin/toxicity , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Fertility Preservation/methods , Granulocyte Colony-Stimulating Factor/therapeutic use , Ovarian Follicle/drug effects , Primary Ovarian Insufficiency/blood , Rats, Sprague-DawleyABSTRACT
BACKGROUND. Premature ovarian failure is a rare syndrome characterized by cessation of menstruation before 35 years of age associated with an elevated gonadotropin level (serum follicle stimulating hormone > 40 IU/L) and oestrogen deficiency. Premature ovarian failure is often the result of an autoimmune process and involvement of other endocrine glands has been reported but available studies are hampered by a lack of uniformity in diagnostic criteria. METHODS. The endocrine profile of 37 north Indian women with premature ovarian failure was studied. The investigations included measurement of serum follicle stimulating hormone, luteinizing hormone, oestradiol, prolactin, total thyroxine, total triiodothyronine and thyroid stimulating hormone. To assess adrenocortical reserve, adrenocorticotropic hormone stimulated plasma cortisol levels were estimated. RESULTS. Eighteen (49%) patients had extraovarian endocrine abnormalities. Eight (22%) had abnormal thyroid function tests and 12 of 29 (41%) patients tested for adrenocortical reserve showed impaired response of plasma cortisol to adrenocorticotropic hormone stimulation. CONCLUSION. Extraovarian endocrine (especially adrenocortical) involvement is frequent in patients with premature ovarian failure. Because none of the patients had overt clinical evidence of thyroid or adrenocortical disease, we suggest that tests for thyroid and adrenal function be performed routinely in females presenting with premature ovarian failure.