Experiencia en el tratamiento de la hemorragia uterina anormal en adolescentes con enfermedad renal crónica / Experience in the treatment of uterine hemorrhage in adolescents with chronic renal disease

Resumen: Introducción: La enfermedad renal crónica (ERC) se asocia con alteraciones menstruales, y el manejo del sangrado uterino suele ser complejo por las condiciones de este grupo de pacientes. El objetivo de este trabajo fue describir la respuesta clínica al tratamiento hormonal de las alteraciones menstruales de adolescentes con ERC. Métodos: Se presentan los datos de una serie de casos de pacientes adolescentes con ERC que cursaron con alteraciones menstruales y que recibieron tratamiento desde el año 2008 al 2012. Se identificaron las características del trastorno menstrual, del tratamiento hormonal recibido y de la respuesta al mismo. El análisis estadístico fue descriptivo. Resultados: Se estudiaron 11 pacientes de sexo femenino con edad promedio de 14.5 años, que se encontraban en prediálisis (n = 1), diálisis peritoneal (n = 7) y hemodiálisis (n = 3). Las pacientes presentaron hiperpolimenorrea asociada a la opsomenorrea (n = 3), en su mayoría clasificadas como hemorragia uterina anormal secundaria. El tratamiento, en general, fue con progestágenos de manera inicial (clormadinona con o sin medroxiprogesterona) o bien con anticonceptivos combinados. En la mayoría de las pacientes se obtuvo una respuesta favorable; sin embargo, hubo casos en los que fue necesario modificar la dosis y el tiempo de tratamiento. Conclusiones: La mayor parte de las adolescentes con ERC que han sido tratadas por hemorragia uterina anormal en nuestro estudio tuvieron una respuesta favorable al tratamiento hormonal.

Abstract: Background: Chronic kidney disease (CKD) is associated with menstrual abnormalities and management of uterine bleeding is often complex because of the conditions in this group of patients. The aim of this study was to describe the clinical response to hormonal treatment of menstrual alterations in adolescents with CKD. Methods: We present data of cases of adolescent patients with CKD who had undergone menstrual changes and received treatment during the period 2008 to 2012. The characteristics of the menstrual disorder, hormone treatment received, and response to treatment were evaluated. The statistical analysis aplicated to analyze the results was descriptive. Results: We studied 11 patients with a mean age of 14.5 years, who were in predialysis (n = 1), peritoneal dialysis (n = 7), hemodialysis (n = 3). Patients had hyperpolymenorrhea associated with opsomenorrhea (n = 3), mostly classified as secondary abnormal uterine bleeding. Treatment, in general, was with progestins initially (chlormadinone with or without medroxyprogesterone) or combined contraceptives. In the majority of the patients, a favorable response was obtained; however, there were cases where it was necessary to modify the dose and time of treatment. Conclusions: The majority of adolescents with CKD who have been treated for abnormal uterine bleeding in our study had a favorable response to hormonal treatment.

Beneficios no anticonceptivos de 0, 02 mg de etinilestradiol/2 mg de acetato de clormadinona administrados en un régimen de 24+4 días / Non-contraceptive benefits of 0.02 mg ethinylestradiol /2 mg chlormadinone acetate in a 24 +4 days intake regimen

Objetivo: Demostrar la influencia sobre las molestias emocionales y físicas (beneficios no anticonceptivos) experimentadas durante el primer año de uso de un anticonceptivo oral combinado (AOC) que contiene 0,02 mg de etinilestradiol (EE) y 2 mg de acetato de clormadinona (ACM) administrado en un régimen de 24 + 4 días de placebo. Diseño del estudio: Análisis adicional de las sensaciones subjetivas registradas en los diarios de 1665 participantes de un estudio de Fase III multicéntrico, no controlado, de administración múltiple, después de 13 ciclos de EE/ACM en un régimen de administración de 24 + 4 días, publicado previamente. Resultados: Se informó de menor frecuencia de molestias emocionales y físicas en el ciclo de medicación 13 en comparación con los datos en la admisión y en el ciclo 1. La incidencia de ánimo depresivo se redujo en 84,5 por ciento y 72,2 por ciento respectivamente, y la irritabilidad en 87,3 por ciento y 66,0 por ciento. Las cefaleas se redujeron en 75,5 por ciento y 74,7 por ciento, las molestias mamarias en 77,1 por ciento y 66,1 por ciento, y la dismenorrea preexistente en 77,9 por ciento y 67,6 por ciento respectivamente. El abandono prematuro del estudio a causa de las molestias fue marginal, y el perfil del sangrado fue aceptable. Conclusiones: Un AOC de baja dosis que contiene 0,02 mg de EE + 2 mg de ACM, administrado en un régimen de 24 + 4 días, reduce significativamente la mayor parte de las molestias emocionales y físicas que se presentan durante los ciclos espontáneos de las mujeres, y se combina con un adecuado perfil de sangrado.

Objective: To demonstrate the influence on physical and psychological complaints during the first year of intake of the combined oral contraceptive (COC) 0.02 mg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA), administered in a regimen of 24 days of CMA/EE intake followed by 4 days of placebo intake. Study design: The subjective feelings of non-contraceptive benefits registered in women's diaries of 1,665 subjects participating in a multicentre, uncontrolled, multiadministration, Phase III trial, published elsewhere, were analyzed post-hoc after 13 cycles intake of EE/CMA in a 24 +4 days intake regimen. Results: Emotional complaints were reported less frequently at medication cycle 13 compared with admission and cycle 1. Depressive mood was reduced by 84.5 percent and 72.2 percent, irritability by 87.3 percent and 66.0 percent; physical complaints were also reduced: headaches by 75.5 percent and 74.7 percent, breast discomfort by 77.1 percent and 66.1 percent; pre-existing dysmenorrhea by 77.9 percent and 67.6 percent. Premature termination due to complaints was only marginal, the bleeding profile was accepted. Conclusions: The low-dose COC, 0.02 mg EE/2 mg CMA, administered in a 24 +4 day regimen, reduces significantly most of the emotional and physical complaints occurring during spontaneous cycles of women, combined with an adequate bleeding profile.

Possible modulating action of plant infusion of Ocimum sanctum L. on chromosomal aberrations and sister chromatid exchanges induced by chlormadinone acetate in human lymphocytes in vitro.

Chlormadinone acetate (CMA) is a synthetic progesterone analogue. It has its usage in oral contraceptives formulations and also for estrous synchronization of animals. The aim of the present study is to study the anti- genotoxic activity of the plant infusion against the CMA induced genotoxic damage on cultured human lymphocytes, using chromosomal aberrations and sister chromatid exchanges (SCFs) as parameters. For chromosomal aberration analysis, the treatment of 40 microM of CMA was associated with 4.33% abnormal metaphases. The treatment of 40 microM of CMA, separately with 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) gm l(-1) of plant infusion results in the reduction of the number of abnormal metaphases i.e. 2.67%, 2.00% and 1.67% respectively. For sister chromatid exchange analysis, the frequency of sister chromatid exchange per cell (SCE(S)/Cell) for the treatment of 40 microM of CMA was 6.43. The treatment of 40 microM of CMA, separately with 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) gm l(-1) of plant infusion results in the significant reduction of the frequency of SCE(S)/Cell i.e. 3.76, 3.01 and 2.94, respectively, as compared to the CMA (40 microM) treatment alone (6.43). The used dosages of plant infusion did not increase chromosomal aberrations and sister chromatid exchanges at significant level as compared to the untreated. The results of the present study suggest that the plant infusion per se does not have genotoxic potential, but can modulate the genotoxicity of chlormadinone acetate in human lymphocytes in vitro.

Experiencia chilena con el uso de un anticonceptivo oral combinado de acetato de clormadinona/etinilestradiol: estudio no intervencional / Efficacy, tolerability and safety of an oral contraceptive containing ethinylestradiol/chlormadinone acetate: the Chilean experience

Objetivos: Evaluar en mujeres chilenas, la eficacia, tolerabilidad y seguridad del anticonceptivo Belara® (Acetato de Clormadinona 2 mg y Etinilestradiol 0,03 mg) (ACM/EE). Métodos: Estudio no intervencional, multicéntrico, prospectivo, de 6 ciclos de seguimiento, evaluando efectividad anticonceptiva, estabilidad de ciclo, tolerabilidad, seguridad y acción sobre peso, piel y cabello. Resultados: ACM/EE fue tomado por 593 mujeres durante 3426 ciclos. Hubo 2 embarazos durante el seguimiento, uno voluntario y otro involuntario; en ninguno de los casos se consideró como falla del método. Durante el tratamiento se observó mejoría progresiva en la estabilidad del ciclo menstrual, sangrado intermenstrual, amenorrea y dismenorrea, con frecuencia de 4,5%, 1,4%, 2,5% y 11,6% al sexto ciclo, respectivamente. El porcentaje de mujeres con piel normal incrementó de 25,5% antes del tratamiento a 63,6% después de seis meses de administración continua de ACM/EE. El peso promedio se mantuvo estable durante el tratamiento. Los eventos adversos mas frecuentes fueron: cefalea (10,4%), aumento de peso (8,3%), mastalgia (6,1%) y trastornos del ánimo (2%). El 11% de las usuarias (n=63) suspendió ACM/EE antes de terminar los 6 meses de observación. El 97,2% de los médicos y 96,1% de las usuarias calificaron los resultados con ACM/EE como “buenos o muy buenos”. Conclusiones: Similar a los resultados reportados en la literatura europea, este estudio realizado en población chilena, confirma la eficacia, seguridad y tolerabilidad de ACM/EE así como los beneficios antiandrogénicos adicionales sobre piel y cabello, y su efecto neutral sobre el peso corporal.

Objectives: To evaluate the efficacy, tolerability and safety of the contraceptive Belara® (chlormadinone 2 mg/ethinylestradiol 0.03 mg; ACM/EE) in chilean women. Methods: Non interventional, multicentric, prospective, 6 cycles follow up trial, evaluating contraceptive efficacy, cycle stability, tolerability, safety, and effect on hair and skin. Results: AMC/EE was taken by 593 women for a total of 3426 cycles. Two pregnancies were reported during follow-up, one voluntary and the other involuntary; they were not considered failure of the method. Progressive improvement in cycle stability, intermenstrual bleeding, amenorrhea and dysmenorrhea occurred during the treatment period reaching 4.5%, 1.4%, 2.5% y 11.6% at the 6th cycle respectively. The percentage of women with normal skin increased from 25.5% prior to treatment, to 63.6%, after taking ACM/EE during six months. The average body weight was maintained throughout treatment. The most frequent adverse events were: headache (10.4%), weight increase (8.3%), breast tenderness (6.1%) and mood changes (2%). An 11% of users (n=63) discontinued the use of ACM/EE before completing the observational period of six months. A 97.2% of physicians and 96.1% of users qualified the results with ACM/EE as “good or very good”. Conclusions: Similar to the results reported in the European literature, this study in the Chilean population confirmed the efficacy, safety and tolerability of ACM/EE, together with its antiandrogenic benefits on skin and hair, and its neutral effect on body weight.

The Influence of Chlormadinone Acetate on the Total and Free Serum Prostate Specific Antigen Levels in Men with Benign Prostatic Hyperplasia / 대한비뇨기과학회지

PURPOSE: Chlormadinone acetate (CMA) therapy for benign prostatic hyperplasia (BPH) may lower the serum prostate specific antigen (PSA) level. However, little is known about the effect of CMA on the total or free serum PSA levels of PSA. Such information would be important since PSA testing is useful for prostate cancer screening. Thus, we prospectively studied the effect of CMA therapy on the total and free serum PSA levels. MATERIALS AND METHODS: The patients with lower urinary tract symptoms (LUTS) and BPH who were aged over 50 years were treated with 50mg CMA for 6 months. Men with a PSA level greater than 10ng/ml were excluded to reduce the likelihood of including cases of occult prostate cancer. Those with suspicious findings on the digital rectal examination and serum PSA testing were biopsied to rule out prostate cancer. alpha- blocking agents were permitted to treat the men with LUTS. Serum levels of the total and free PSA were measured at the study baseline and after approximately 3 and 6 months. The prostate volume (PV) was assessed by transrectal ultrasonography. RESULTS: The analysis included 170 patients with a mean age of 67.9 years, a baseline PV of 47.3ml and a baseline total PSA of 4.1ng/ml. The total PSA levels declined from 4.1ng/ml at baseline to 2.0ng/ml after 6 months of treatment (50.7% decrease, p<0.01). The mean percent free PSA (21% to 22% at baseline) was not significantly altered by CMA treatment. The PSA levels and PV at baseline did not affect the rate of decline of PSA. CONCLUSIONS: The total PSA serum levels decreased by an average of 50% during CMA therapy, but the percent free PSA did not change significantly. This information is potentially useful in the interpretation of the PSA data that's used for early detection of prostate cancer in the men receiving CMA.

Protective role of allicin and L-ascorbic acid against the genotoxic damage induced by chlormadinone acetate in cultured human lymphocytes.

In our present study, different doses of allicin and L-ascorbic acid were tested against the genotoxic damage induced by chlormadinone acetate (CMA; 40 microM) using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as the parameters. Treatment with allicin and L-ascorbic acid resulted in reduction of CAs and SCEs. The results suggested a protective role of allicin and L-ascorbic acid against CMA induced genotoxic damage.

Induction of chromosomal aberrations and sister chromatid exchanges by chlormadinone acetate in human lymphocytes: a possible role of reactive oxygen species.

Genotoxicity study of a synthetic progestin chlormadinone acetate (CMA) was carried out in human lymphocytes using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameter. Effect of CMA was studied at 10, 20, 30 and 40 microM. CMA was genotoxic at 30 and 40 microM. With a view to study the possible mechanism of genotoxicity of CMA, superoxide dismutase (SOD) and catalase (CAT) were used separately and in combination along with the CMA (40 microM) at different doses. SOD treatment increased CAs and SCEs at both the doses. CAT treatment decreased the frequencies of CAs and SCEs in both, separately and in combination with SOD, suggesting a possible role of reactive oxygen species for the genotoxic damage.

Cambios ultrasonográficos y en lípidos en el síndrome de ovario poliquÝstico de acuerdo al tipo de tratamiento / Ultrasonographic and lipid changes in polycystic ovary syndrome according to the type of treatment

OBJECTIVE: To determine the ultrasonographic and lipid changes in women with polycystic ovary syndrome (PCOS) according to the type of hormonal treatment. STUDY DESIGN: Thirty-two women with clinical and ultrasonographic diagnosis of PCOS were studied and randomly distributed in one or another treatment group. Group I: chlormadinone (2 mg/day for 5 days every month) (n = 16) and Group II: ethinylestradiol 35 micrograms plus desogestrel 150 mg (21 days every month) (n = 16). At baseline and at third month a pelvic ultrasound was done to assess the number and size of follicles, also total cholesterol and triglycerides were measured. RESULTS: In both groups a significant decrease was found in the number of follicles in both ovaries, but only in group II there was a significant decrease in follicular size in both ovaries. No differences were found between the groups in the number of follicles or in the final follicular size. In both groups, a significant decrease was found in total cholesterol levels, without changes in triglycerides levels. CONCLUSION: Only combined therapy decreased follicular size. So the type of treatment should be based on patient expectations such as sexual activity, or for control of androgen excess.

Development of selective androgen receptor modulators and their therapeutic applications / 中华男科学杂志

Androgens control a broad range of physiological functions. The androgen receptor (AR), a steroid receptor that mediates the diverse biological actions of androgens, is a ligand inducible transcription factor. Abnormalities in the androgen signaling system result in many disturbances ranging from changes in gender determination and sexual development to psychiatric and emotional disorders. Androgen replacement therapy can improve many clinical conditions including hypogonadism and osteoporosis, but is limited by the lack of efficacious and safe therapeutic agents with easy delivery options. Recent progress in the area of gene regulation by steroid receptors and by selective receptor modulators provides an opportunity to examine if selective androgen receptor modulators (SARMs) could address some of the problems associated with current androgen therapy. Since the composition of the transcriptional initiation complex recruited by liganded AR determines the specificity of gene regulation, synthetic ligands aimed at initiating transcription of tissue and promoter specific genes offers hope for developing better androgen therapy. Establishment of assays that predict synthetic ligand activity is critical for SARM development. Advancement in high throughput compound screening and gene fingerprinting technologies, such as microarrays and proteomics, will facilitate and accelerate identification of effective SARMs.

La proporción de formas moleculares de gonadotropinas se altera en pacientes con síndrome de ovarios poliquísticos / The proportion of gonatropins molecular forms is altered in patients with polycystic ovaries syndrome

En general las hormonas protéicas circulan como varias formas moleculares con actividad biológica diferentes y su proporción sufre modificaciones de acuerdo al ambiente hormonal en que se encuentra, tanto en condiciones fisiológicas como patológicas. Las gonadotropinas, tanto LH como FSH, en condiciones naturales de hipoestrogenismo como es durante la menopausia, presentan las formas moleculares grandes como las predominantes y este perfil cromatográfico en suero muestra un cambio a las formas moleculares intermedias cuando de administran estrógenos. Durante un ciclo ovulatorio se puede demostrar la predominancia, alrededor de la ovulación, de las isoformas de peso intermedio que son las más activas biológicamente. En el presente trabajo se tomó como modelo de estudio a mujeres con ciclos anovulatorios con el diagnóstico de síndrome Leventhal y se encontró que después de un sangrado menstrual inducido con un progestágeno, el perfil cromatográfico era polimorfo e irregular, lo cual fue comparado con el perfil cromatográfico obtenido en el suero de mujeres durante un ciclo ovulatorio. En este último se observó la predominancia de las formas intermedias de LH y FSH en el día 14 del ciclo por lo cual se puede concluir que las isoformas biológicamente más activas de las gonadotropinas constituyen la mayor proporción durante una etapa crucial como es la periovulatoria

Effect of Chlormadinone acetate(Prostal / 대한비뇨기과학회지

Based on the theory that benign prostatic hypertrophy may be induced by androgenic effect of testosterone derivatives, especially 5-alpha - dihydrotestosterone, on prostatic tissue, Chlormadinone acetate(CMA), potent oral synthetic antiandrogen was investigated in the treatment of benign prostatic hypertrophy. Twenty-two patients of prostatic hypertrophy were studied over six months period with a special reference to uroflowmetry and following results were obtained : 1) Chlormadinone acetate induced improvement of obstructive urinary symptoms in terms of uroflowmetric measurement. 2) It is very worthwhile to initiate medical treatment before undergoing any surgical intervention or when surgery is contraindicated.

A Clinical Investigation for Effect of Chlormadinone acetate(Prostal / 대한비뇨기과학회지

The hypertrophied prostate is the most common cause of infravesical obstrcutions, in the male patients with 50 years old or above. Though the cause of benign prostatic. hypertrophy has not clearly identified yet, recently it has been clarified that androgen, especially dihydrotestosterone, may play a great role in the benign prostatic hypertrophy. The author carried out to investigate the effect of Chlormadinone acetate-potent oral synthetic anti-androgen agent on prostatic volume and obstructive urinary symptoms induced by hypertrophied pro. static gland. The following results were obtained; 1. 23 patients were studied :19 patients with benign prostatic hypertrophy and 4 patients with benign prostatic hypertrophy and 4 patients with prostatic cancer. The mean age of patients was 72 years old. 2. The mean prostatic volume was markedly decreased from 58.7+/-2.94cc before treatment to 23.6+/-1.06cc 16 weeks after treatment. 3. Obstructive urinary symptoms, residual urine and nocturnal frequency were improved after treatment. 4. Judging from the fracts mentioned above, it may be believed that Chlormadinone acetate increase the effect of transurethral resection and prevent the rehypertrophied prostate after transurethral resection of prostate.