¿La progesterona natural micronizada previene el trabajo de parto pretérmino?: Revisión sistemática de literatura / Does Natural Micronized Progesterone Prevent Preterm Labor?: Systematic Literature Review / A progesterona natural micronizada previne o trabalho de parto prematuro?: Revisão sistemática da literatura

Introducción. La progesterona es una hormona que favorece el mantenimiento del embarazo, es la protagonista de la fisiopatología del trabajo de parto pretérmino. De esta manera, se propone realizar una revisión sistemática que permita demostrar la utilidad de la progesterona natural micronizada en la mitigación de los efectos deletéreos del trabajo de parto pretérmino. Metodología. Revisión sistemática en la que se utilizaron los términos "MeSH" y "No ­ MeSH". Se empleó el programa "Publish or Perish" y bases de datos como: Medline, PubMed, Embase, Clinical Key, Cochrane Library, Scopus y Google Scholar. Se incluyeron artículos de revisión, meta-análisis, artículos originales (publicaciones preliminares o completas), resúmenes de congresos, seminarios publicados, libros de texto, protocolos hospitalarios regionales y consensos nacionales, en donde cada autor evaluó individualmente cada artículo y aplicó la herramienta CASPE. Resultados. En la literatura no es posible encontrar pautas concisas internacionales sobre el uso de la progesterona micronizada frente a la amenaza de trabajo de parto pretérmino (TPP). En general, para la mitigación del trabajo de parto, según lo analizado por los autores, se recomienda usar progesterona natural micronizada en cápsulas de 100 a 400 mg/día vía oral o 100 a 200 mg cada 12 a 24 horas vía vaginal. Desde la semana 16 hasta la semana 36 de gestación por vía oral y desde la semana 24 a 34 de gestación por vía vaginal. Discusión. El uso de la progesterona micronizada ha demostrado mitigar complicaciones posteriores al trabajo de parto pretérmino, sin embargo, no hay consenso sobre la dosificación y las vías de administración. Sumado a lo anterior, los estudios analizados pueden contener sesgos, por lo que se deja a elección del clínico el uso este medicamento. Conclusiones. La progesterona natural micronizada podría ser empleada para mitigar el trabajo de parto pretérmino según los artículos analizados por los autores a lo largo de la revisión. Sin embargo, se necesitan más estudios para legitimar dicha hipótesis.

Introduction. Progesterone is a hormone that favors maintaining pregnancy. It is the protagonist of the physiopathology of preterm labor. In this sense, a systematic review is proposed to demonstrate the usefulness of natural micronized progesterone in mitigating the harmful effects of preterm labor. Methodology. A systematic review in which the terms "MeSH" and "No ­ MeSH" were used. The "Publish or Perish" program was used, as well as databases, such as: Medline, PubMed, Embase, Clinical Key, Cochrane Library, Scopus, and Google Scholar. Review and meta-analysis articles, original articles (preliminary or complete publications), congress summaries, published seminars, textbooks, regional hospital protocols and national consensuses were included, in which each author individually assessed each article and applied the CASPE tool. Results. It was not possible to find concise international guidelines on using micronized progesterone for the threat of preterm labor (PTL) in literature. According to what the authors analyzed, for the mitigation of labor it is generally recommended the use of natural micronized progesterone in 100 to 400 mg/day capsules orally or 100 to 200 mg every 12 to 24 hours through the vagina. From week 16 to week 36 of pregnancy orally and from week 24 to 34 through the vagina. Discussion. Using micronized progesterone has demonstrated mitigating complications subsequent to preterm labor. However, there is no consensus on dosage and routes of administration. Added to the above, the analyzed studies may contain biases, reason why using this medication is left to the physician's discretion. Conclusions. Natural micronized progesterone can be used to mitigate preterm labor according to the articles the authors analyzed throughout the review. However, more studies are needed to validate this hypothesis.

Introdução. A progesterona é um hormônio que favorece a manutenção da gravidez, é a protagonista da fisiopatologia do parto prematuro. Dessa forma, propõe-se a realização de uma revisão sistemática que permita demonstrar a utilidade da progesterona natural micronizada na mitigação dos efeitos deletérios do trabalho de parto prematuro. Metodologia. Revisão sistemática em que foram utilizados os termos "MeSH" e "Não­MeSH". Foram utilizados o programa "Publish or Perish" e bases de dados como: Medline, PubMed, Embase, Clinical Key, Cochrane Library, Scopus e Google Scholar. Foram incluídos artigos de revisão, meta-análises, artigos originais (publicações preliminares ou completas), resumos de congressos, seminários publicados, livros didáticos, protocolos hospitalares regionais e consensos nacionais, onde cada autor avaliou individualmente cada artigo e aplicou a ferramenta CASPE. Resultados. Não é possível encontrar na literatura diretrizes internacionais concisas sobre o uso de progesterona micronizada diante da ameaça de trabalho de parto prematuro (TPP). Em geral, para a mitigação do trabalho de parto, conforme analisado pelos autores, recomenda-se o uso de progesterona natural micronizada em cápsulas de 100 a 400mg/dia por via oral ou 100 a 200mg a cada 12 a 24 horas por via vaginal. Da 16ª à 36ª semana de gestação por via oral e da 24ª à 34ª semana de gestação por via vaginal. Discussão. O uso de progesterona micronizada demonstrou mitigar as complicações após o trabalho de parto prematuro, no entanto, não há consenso sobre a dosagem e as vias de administração. Além do exposto, os estudos analisados podem conter vieses, pelo que cabe ao médico escolher o uso deste medicamento. Conclusões. A progesterona natural micronizada poderia ser utilizada para mitigar o trabalho de parto prematuro de acordo com os artigos analisados pelos autores ao longo da revisão. No entanto, mais estudos são necessários para legitimar essa hipótese.

Analytical performance of a candidate reference measurement procedure for serum 17α-hydroxyprogesterone based on liquid chromatography tandem mass spectrometry / 中华检验医学杂志

Objective:To determine the analytical performance of a candidate reference measurement procedure for 17α-hydroxyprogesterone in human serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Methods:The serum spiked with a deuterium-labeled internal standard was extracted from serum from individual undergoing physical examination by liquid-liquid extraction with n-hexane/ethyl acetate (3∶2, v/v), separated by C18 reversed-phase chromatography and detected by positive electrospray ionization mass spectrometry. According to the Clinical and Laboratory Standards Institute (CLSI) C62-A documents, the analytical performance including linearity, limit of detection,limit of quantitation,relative matrix effect,precision and trueness,carry-over and specificity was evaluated.Results:The linear range of 17α-hydroxyprogesterone by LC-MS/MS was 0.21-119.67 μg/L. The limit of detection and limit of quantitation were 5.218 ng/L and 0.116 μg/L. The relative matrix effects were -0.02%, -0.40% and -0.90% for sera and solution mixtures in 3 different ratios (50∶50, 80:20 and 20∶80). The coefficients of variation ( CVs) of intra-assay were 1.73%-2.11%, 0.98%-1.71%, 0.47%-0.87% at 0.164 μg/L, 14.81 μg/L, 81.63 μg/L and the CVs of inter-assay were 1.82%, 1.03%, 0.80% at above three concentrations. The average recovery rates of 3 levels (0.5, 20 and 100 μg/L) were 100.4%, 101.7%, 102.8%, respectively. The measured values of GBW09829 of National Institute of Metrology were within the specified uncertainty range. Conclusion:The candidate reference measurement procedure for 17α-hydroxyprogesterone in human by LC-MS/MS is established with good accuracy and precision, which can be clinically used for measurement traceability.

Precocious puberty due to congenital adrenal hyperplasia. Case report / Pubertad precoz por hiperplasia adrenal congénita. Reporte de caso

Abstract Introduction: Premature pubarche occurs in girls before the age of 8 or boys before the age of 9 and is a sign of precocious puberty associated with increased growth acceleration. Precocious puberty can be caused, among others, by nonclassic congenital adrenal hyperplasia (CAH). Case presentation: This is a case of a 4 1/2-year-old who developed premature pubarche six months before consultation, and whose parents were first-degree cousins. She had advanced bone age, her external genitalia were normal and her height was inconsistent with her mid-parental height. After performing an adrenocorticotropic hormone test (ACTH test) and other hormone tests, it was found that she had high levels of 17-hydroxyprogesterone (17-OHP), which allowed diagnosing her with nonclassic CAH. Based on this diagnosis, glucorticoid therapy was ordered, and after one year of starting the treatment she had a favorable clinical outcome and did not show any secondary sex characteristics or bone age progression. Conclusion: Nonclassic CAH is the most frequent cause of precocious puberty. Considering that this type of hyperplasia may be asymptomatic during the early days or years of life, its diagnosis must be suspected in children with precocious puberty, increased growth acceleration and advanced bone age.

Resumen Introducción. La pubarca antes de los 8 años en niñas y de los 9 años en niños, es una manifestación de la pubertad precoz asociada al aumento en la velocidad de crecimiento. La hiperplasia adrenal congénita (HAC) no clásica es una de las causas de pubertad precoz. Presentación de caso. Paciente femenina de 4 años y medio y con padres consanguíneos (primos hermanos) quien inició pubarca 6 meses antes de ser llevada a consulta. La niña presentaba edad ósea avanzada, talla discordante con la talla media parental y sus genitales externos eran normales. Luego de realizar el test de estimulación con hormona adrenocorticotropa y otros exámenes hormonales, se encontró que sus niveles de 17-hidroxiprogesterona eran elevados, lo que permitió diagnosticarla con HAC no clásica. Con base en este diagnóstico, se inició tratamiento con glucocorticoides y luego de un año de tratamiento la paciente tuvo una buena evolución clínica, ya que no se observó progresión de los caracteres sexuales secundarios ni de la edad ósea. Conclusión. La HAC no clásica es la causa más frecuente de la PPP. Ya que este tipo de hiperplasia puede ser asintomática durante los primeros días o años de vida, se debe sospechar su diagnóstico en la infancia cuando haya pubarca precoz, mayor velocidad de crecimiento y edad ósea avanzada.

Analysis of the Influencing Factors of 17-Hydroxyprogesterone Level and the Correlation between 17-Hydroxyprogesterone Level and the Clinical Parameters Related to Adrenal Cortical Function in Very-Low-Birth-Weight Infants

PURPOSE: 17-Hydroxyprogesterone (17-OHP) screening results are difficult to interpret owing to the many influencing factors, and confirming the test results takes time. In this study, we examined the factors that affected the 17-OHP level in premature infants. We also evaluated the correlation between 17-OHP level and the clinical parameters related to adrenal cortical function. METHODS: From January 2012 to April 2017, 358 very-low-birth-weight infants (VLBWI) born with birth weights of < 1,500 g were included in the study. Their 17-OHP levels were measured in the neonatal screening test after birth and analyzed by considering various factors that may have influenced the values. RESULTS: The 17-OHP levels negatively correlated with gestational age and birth weight. The values of the parameters that affected the 17-OHP levels were significantly higher in the infants with respiratory distress syndrome (RDS). In relation to the clinical parameters, blood pressure measured within 24 hours, 72 hours, and 1 week after birth negatively correlated with the 17-OHP level. Serum sodium and 17-OHP levels 24 hours after birth were found to be positively correlated. Urine outputs in 1 and 3 days after birth showed significant positive correlations with the 17-OHP level. CONCLUSION: The 17-OHP levels of the VLBWIs were higher when gestational age and birth weight were lower, and were influenced by RDS in the VLBWI. In addition, hypotension and urine output values may be useful in the neonatal intensive care unit as a predictor of early adrenal insufficiency.

Relationships of Basal Level of Serum 17-Hydroxyprogesterone with that of Serum Androstenedione and Their Stimulated Responses to a Low Dose of ACTH in Young Adult Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

A single measurement of serum 17alpha-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R2 = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.

Establishment of the Separate Cutoff Values of 17-alpha-hydroxyprogesterone in Neonatal Screening Program for Congenital Adrenal Hyperplasia according to Birth Weight / 임상검사와정도관리

BACKGROUND: In Korea, 17-alpha-hydroxyprogesterone (17-OHP) neonatal screening for congenital adrenal hyperplasia (CAH) has a high false positive rate. Preterm infants have higher levels of 17-OHP than term infants. We established the separate cutoff values of 17-OHP under the guideline of the Clinical and Laboratory Standard Institute C28-A3 to reduce a false positive rate. METHODS: The 17-OHP enzyme-immunoassay was used in blood spots of 22,601 newborns. To decide whether to partition cutoff values based on sex, sampling date and birth weight was assessed by Z-test and standard deviation (SD) ratio. If the result was significant, we estimated the cutoff value with 90% confidence intervals (CIs) using the nonparametric method. RESULTS: In the subclasses based on sex and sampling date, the results were not significant. However, the birth weight-adjusted subclasses (SD ratio > 1.5) showed that it was necessary to distinguish low-birth-weight infants from the others. We selected the subclass categories to reflect the concept of low- or very-low-birth-weight infant. The maximum percentile to define a 90% CI was chosen in each subclass. After applied the re-estimated cutoff value, the recall rate was decreased from 0.6% to less than 0.2%. CONCLUSIONS: The birth weight-adjusted cutoff value of 17-OHP in neonatal screening for CAH can be reduced the false positive rate of low-birth-weight infants. This approach would decrease unnecessary blood draws, medical evaluation, parental anxiety and burden on health care resources.

Changes in High Levels of 17 alpha-Hydroxyprogesterone at Neonatal Screening / 대한소아내분비학회지

PURPOSE:There are some cases of false positive in neonatal screening for congenital adrenal hyperplasia. To understand its significance of the increased 17 alpha-hydroxyprogesterone(17 alpha-OHP) levels in the cases of positive result, we followed its levels during infancy. METHODS:From July 1997 to June 1998, totally 1,730 babies were screened for congenital adrenal hyperplasia(CAH) measuring 17 alpha-hydroxyprogesterone(17 alpha- OHP) using an enzyme immunoassay(EIA) on dried blood spots. In infants of positive result, the radioimmunoassay(RIA) was used measuring 17 alpha-OHP in serum. And we followed up the levels of 17 alpha-OHP during infancy. Cortisol and ACTH were also measured and followed up in the morning simultaneously. RESULTS:No CAH was detected during the study period. With the 13 ng/mL cutoff limit for 17 alpha-OHP before March 1998, the recall rate was 3.09%. With the 20 ng/mL cutoff limit after March 1998, the recall rate was decreased to 1.58%. Follow-up of the high levels of 17 alpha-OHP in positive cases showed a sharply decreased curve according to age. CONCLUSION: In clinically normal neonates, the high levels of 17 alpha-OHP at screening decreased continuously during infancy.

Changes in High Levels of 17 alpha-Hydroxyprogesterone at Neonatal Screening / 대한소아내분비학회지

PURPOSE:There are some cases of false positive in neonatal screening for congenital adrenal hyperplasia. To understand its significance of the increased 17 alpha-hydroxyprogesterone(17 alpha-OHP) levels in the cases of positive result, we followed its levels during infancy. METHODS:From July 1997 to June 1998, totally 1,730 babies were screened for congenital adrenal hyperplasia(CAH) measuring 17 alpha-hydroxyprogesterone(17 alpha- OHP) using an enzyme immunoassay(EIA) on dried blood spots. In infants of positive result, the radioimmunoassay(RIA) was used measuring 17 alpha-OHP in serum. And we followed up the levels of 17 alpha-OHP during infancy. Cortisol and ACTH were also measured and followed up in the morning simultaneously. RESULTS:No CAH was detected during the study period. With the 13 ng/mL cutoff limit for 17 alpha-OHP before March 1998, the recall rate was 3.09%. With the 20 ng/mL cutoff limit after March 1998, the recall rate was decreased to 1.58%. Follow-up of the high levels of 17 alpha-OHP in positive cases showed a sharply decreased curve according to age. CONCLUSION: In clinically normal neonates, the high levels of 17 alpha-OHP at screening decreased continuously during infancy.

Correlation of Corpus Luteum Size, beta-hCG, Progesterone, and 17alpha-hydroxyprogesterone in Early Pregnancy / 대한산부인과학회잡지

Pregnancy maintenance is dependent on the presence of a functional corpusluteum (CL) for a few weeks after implantation. However, the factors responsible for the rescue of the CL during earlypregnancy have not been fully clarified. This study was designed to evaluate whether the change in size of the CL ofearly pregnancy, serum concentration of progesterone, 17alpha-hydroxyprogesterone,or beta-hCG correlated with the gestational age or were predictive of pregnancyoutcome. We retrospectively analysed thirty-six women between 4~9 weeks' gestation. All women underwent transvaginal ultrasound measurement of the CL size andgestational sac(or crown-rump length). Blood was drawn from each patient on the day of the ultrasound examinationto measure hormone concentration. Fifteen women experienced vaginal bleeding and abdominal pain.Among them, four women were aborted. There was no significant positive correlation between CL size and serumprogesterone, 17alpha-hydroxyprogesterone or beta-hCG both in normal and abnormal pregnancy. A positive correlation was observed between the gestational age and progesterone orbeta-hCG in normal pregnancy, but not in abnormal pregnancy(threatened or spontanousabortion). In conclusion, close correlation between the gestational age and serum concentrationof progesterone or beta-hCG may reflect the normal function of CL. Therefore, abnormal response of CL or abnormal production of beta-hCG cause a disturbancein progesterone secretion leading to the abnormal pregnancy.

Correlation of Corpus Luteum Size, beta-hCG, Progesterone, and 17alpha-hydroxyprogesterone in Early Pregnancy / 대한산부인과학회잡지

Pregnancy maintenance is dependent on the presence of a functional corpusluteum (CL) for a few weeks after implantation. However, the factors responsible for the rescue of the CL during earlypregnancy have not been fully clarified. This study was designed to evaluate whether the change in size of the CL ofearly pregnancy, serum concentration of progesterone, 17alpha-hydroxyprogesterone,or beta-hCG correlated with the gestational age or were predictive of pregnancyoutcome. We retrospectively analysed thirty-six women between 4~9 weeks' gestation. All women underwent transvaginal ultrasound measurement of the CL size andgestational sac(or crown-rump length). Blood was drawn from each patient on the day of the ultrasound examinationto measure hormone concentration. Fifteen women experienced vaginal bleeding and abdominal pain.Among them, four women were aborted. There was no significant positive correlation between CL size and serumprogesterone, 17alpha-hydroxyprogesterone or beta-hCG both in normal and abnormal pregnancy. A positive correlation was observed between the gestational age and progesterone orbeta-hCG in normal pregnancy, but not in abnormal pregnancy(threatened or spontanousabortion). In conclusion, close correlation between the gestational age and serum concentrationof progesterone or beta-hCG may reflect the normal function of CL. Therefore, abnormal response of CL or abnormal production of beta-hCG cause a disturbancein progesterone secretion leading to the abnormal pregnancy.