Added: Anderson Garey - Date: 19.07.2021 12:09 - Views: 17763 - Clicks: 5915
Try out PMC Labs and tell us what you think. Learn More. To evaluate the efficacy and safety of 2. Included in the study were women with symptomatic uterine fibroids. Group I: half a tablet of 5 mg 2. Two endometrial biopsies were performed. Increase in average hemoglobin, changes in fibroid and uterine volume, and symptomatic improvement. The average hemoglobin at the end of treatment was 0. In both groups there were similar reductions in fibroid volumes. Clinical improvement was more ificant in the 5 mg group. Approximately half of women aged 35—49 years have uterine fibroids and almost half of them have heavy bleeding often causing severe anemia.
At one time it was thought that only estrogens played a part in the development of uterine myomas, now we know that progesterone also plays its part in their growth and that mifepristone, by inhibiting the latter, influences this development. There is enough existing scientific evidence to show that low doses of only 5 mg mifepristone are as efficient and safe as those of 10 mg. Eisinger et al, 21 in a pilot study with only 17 cases and using doses of 2.
The aim of this study was to facilitate surgery by improving hematological conditions and reducing the volume of any such surgery. This is a multicenter randomized clinical trial to evaluate the efficacy and safety of daily doses of 2. The study protocol was approved by the respective research committees at each hospital. All subjects gave their informed consent to participate in the study. The clinical trial was performed in accordance with the revised version of the Declaration of Helsinki and adhered to good clinical practice standards. The trial began in November and the last subject included was evaluated in May The use of a placebo group was discarded so as not to deprive the subjects of any therapeutic opportunity as there is published evidence that mifepristone in low doses reduces fibroid size, produces relief of associated symptomatology, and improves the general condition of the subject prior to surgery.
Subjects were recruited from the hospital gynecological classification consultancies. Women of childbearing age with symptomatic uterine fibroids requiring treatment to improve their general condition before undergoing hysterectomy or myomectomy were eligible for the trial. The inclusion criteria was: a symptomatic uterine leiomyomas, b indication for surgery hysterectomy or myomectomyand c agreement to record on a monthly basis all vaginal bleeding episodes, mifepristone side effects, and to have ultrasound examinations at What is half of 5 mg evaluation session.
The exclusion criteria was: a pregnancy or the desire to get pregnant, b breastfeeding, c hormonal contraception or any hormonal therapy in the last 3 months, d s or symptoms of pelvic inflammation, e adnexal tumors, f suspicion or diagnosis of cervical—uterine or ovarian cancer, g s or symptoms of mental illness, h unexplained genital bleeding, i anemia due to sickle-cell disease, j suffering from a serious illness, and k antiprogesterone contraindications.
After evaluation of inclusion and exclusion criteria and gathering and submitting all the information needed to participate in the trial, the subjects ed the informed consent. Oral administration of half a 5 mg tablet 2. Oral administration of one tablet of 5 mg mifepristone every 24 hours for 3 months.
The mifepristone was supplied by Litaphar Laboratories Azpeitia, Spainin individual 5 mg tablets. Treatment began in both groups between the second and fourth days of menstruation. At every evaluation session the subjects were given a phial containing the medication they required up until the next visit and this continued until the end of treatment.
The subjects satisfying all requirements were included in the trial in the order they ed it What is half of 5 mg were ased to one or other of the treatment groups by means of a random computer-generated list. Complete gynecological examination with pregnancy test, Pap test, and abdominal or vaginal ultrasound examination of the uterus prior to commencement and every 30 days until termination of treatment.
Fibroid volume was calculated using the formula: 0. The total volume of the uterus was calibrated using the ly mentioned formula. Endometrial thickness in millimeters was also measured by ultrasound. All ultrasound calibrations were performed using ultrasound diagnostic equipment SSD; Aloka Co, Ltd, Mitaka-shi, Tokyo, Japan and carried out by two ultrasound medical specialists. Measurements taken in the various follow-up periods were carried out without the specialists knowing the of calibrations, they only knew the location of the myoma they had to measure if the subject had more than one fibroid.
Blood samples were taken for hematological studies and liver function at the first visit and every 30 days until termination of treatment. It was decided beforehand that any subject presenting transaminase alterations of values over three times their normal maximum limit, in line with US Food and Drug Administration FDA recommendations, would be eliminated from the trial. Given the climate of estrogenic predominance stimulated by mifepristone due to the elimination of gestagen action, the risk of endometrial hyperplasias appearing was considered to be greater.
An endometrial biopsy was taken during surgery from subjects undergoing myomectomy. Once treatment was terminated the subjects underwent surgery between 3 and 10 days later. At each visit the subjects were given a form where they were to record bleeding episodes, side effects of mifepristone, and any other relevant information; these forms were handed in at the following visit.
It was measured at the beginning and every 30 days until termination of treatment. As secondary variables of efficacy, measurement of the changes registered in the fibroid and uterus dimensions was performed using ultrasound at each evaluative consultancy. We consider metrorrhagia to be the bleeding that occurs between menstrual periods; we consider hypermenorrhea to be menstruation lasting a few days with the subject suffering a greater than normal blood loss.
The variables to evaluate safety were a changes in endometrial thickness measured by ultrasound mmb side effects of mifepristone: amenorrhea, hot flushes, nausea, dizziness, vomiting, and fatigue, c changes in liver transaminase levels: aspartate aminotransferase AST and alanine aminotransferase ALT ; these three parameters were evaluated every month until termination of treatment, and d frequency of histological endometrial anomalies at the end of treatment. In administering 5 mg mifepristone over 3 months the average hemoglobin was expected to be 1.
It was assumed the variances were similar and these were considered equal to 1. Analysis of hemoglobin changes was performed using the t -test for independent samples comparison between the treatment groups and the t -test for paired samples comparisons within each mifepristone group. Differences between the treatment groups regarding fibroid and uterine volumes and endometrial thickness in each evaluative period were analyzed by t -test.
The t -test was used to analyze pelvic pain and hypermenorrhea in only those subjects who had symptoms prior to treatment. Side effects of mifepristone are presented in descriptive statistical graphs and normal approximation for proportions was used in comparing treatments.
The data was processed using SPSS software v. In all, subjects in both centers were referred to the trial, 22 of them failed to satisfy the inclusion criteria. One hundred forty-six of In Havana, of the 47 subjects included in the 2.
Of the 48 included in the 5 mg group there were two dropouts: one due to surgery for fibroid necrobiosis before completing the first month and the other abandoned the trial in the second month of treatment. In Managua, of the 24 subjects included in the 2. Of the 27 included in the 5 mg group there were two dropouts: one due to fibroid expulsion in the first month and one due to elevated transaminases after 1 month of treatment 60 and 72 IU of AST and ALTrespectively.
In total, in the two centers there were twelve of 71 Table 1 shows the general characteristics of all the subjects included in the clinical trial. There were no ificant differences between the treatment groups for any of them. No subject was diagnosed with fibroid-associated sterility. There were 15 of 71 In total, the fibroids studied were made up as follows: 30 of Once treatment was over, surgery was refused by four of 63 6. The average hemoglobin levels at the end of treatment were In the 2.
Thirty days after beginning treatment there were 20 of 59 Three months into treatment fibroid volume was not reduced, compared to its initial value, in six of 48 At the end of treatment, compared to pretreatment values, uterine volume was not reduced in 14 of 48 Table 4 shows the changes in fibroid symptom prevalence before treatment and at each evaluative period. There was amenorrhea in 28 of 60 Hot flushes were reported at least once during treatment by 14 of 24 Hot flushes were reported at least once during treatment by nine of 38 Hot flushes were reported in the three evaluative consultations by one subject in the 2.
In total, in both centers hot flushes were reported at least once during treatment by 23 of 62 At some point during treatment the following side effects of mifepristone were reported: a nausea by four of 50 8.
During the treatment period there were four of 71 5. In the 5 mg group there were six of 75 8. Table 7 shows changes in endometrial thickness during treatment.
Between the beginning and end of treatment, irregular vaginal bleeding at some time was reported by 19 of 63 Over the 3 months of treatment some spotting was reported by 29 of 63 In the endometrial biopsies before and after treatment there was no diagnosis of simple hyperplasia, atypical or not, nor was any other pathology found and there were no ificant differences between the two mifepristone groups.
In the posttreatment endometrial biopsies eleven of 8. The remaining diagnoses in both groups were compatible with secretory or proliferating endometria.
In all, hysterectomies were performed with or without double adnexectomy on 51 of 57 In six of 57 The average postoperative stay in hospital for subjects in Cuba was 3. In those in Nicaragua, the average postoperative stay in hospital was 2.
In Table 8 we have presented some surgery data according to mifepristone groups. This multicenter trial presents some differences in the subjects included: 1 the size of the fibroids is 2. In the latter study the subject age is on average 3 years older than in our studies. Despite the difference in the final hemoglobin levels between both groups being ificant, it is only 0.
Our percentages of amenorrhea are superior to those obtained by Eisenger et al in the only study carried out to date with 2.
Table 4 shows that the 5 mg group as a whole experiences a ificantly greater clinical improvement at the end of treatment, this greater clinical efficacy can be seen particularly in pelvic pressure, rectal pain, and hypermenorrhea; that is to say, the subjects in the 5 mg group improve faster even when this clinical improvement levels out in both treatment groups in only one part of their symptoms. These differences are probably behind the greater of dropouts in the 2.
A greater efficacy in the 5 mg mifepristone group may also be indicated by the submucous fibroid being expelled at the end of the first month of treatment as well as by the greater of cases that refused to undergo surgery. The 9. With regard to safety, the elevated transaminases are low percentage-wise and of minimum clinical ificance since the levels never rise above IU at most. These percentages are similar to other studies.
The side effects produced by mifepristone are similar in both groups, including the hot flushes which are the only substantial mifepristone side effect. We believe that there is some bias in collecting data on this symptom in the Nicaraguan center. Although the intensity of hot flushes has never been studied, the impression the researchers have is that they are of an intensity, duration, and frequency much greater than those of the physiological menopause or those brought on by gonadotropin-releasing hormone analogs.
Moreover, in none of our four clinical trials published, 16 — 19 which included around subjects, has there been a single case of dropout from treatment due to hot flushes nor has treatment for such been requested.
With regard to surgical variables logically, there were no differences between the various surgical parameters studied since these could only have been evident had they been compared to a group that did not receive mifepristone, ie, a placebo group. In this case ificant differences would certainly have been observed between the sizes of the removed fibroid or uterus, ease of surgery, or blood loss.
The of the posttreatment endometrial biopsies do not include any simple hyperplasia, atypical or not, being within the classical diagnostic or those recently established by Mutter and Horne, or PAECs 2425 for endometria under the effect of progesterone receptor modulators like mifepristone.
There are no ificant differences between the two treatment groups. The percentages of histological changes of the PAEC type are similar to those obtained by Fiscella et al. The histological changes found in the present trial are similar to those observed with other progesterone receptor modulators like CDB When compared with other progesterone receptor modulators like ulipristal that have proved their efficacy in this field, our are similar to those obtained with this medicine.
So, therefore, this new therapeutic technique for uterine fibroids offers us an ongoing medical as opposed to surgical treatment. The data obtained in other studies indicate that this therapeutic technique could be viable. One of the weak points of this trial is not evaluating the impact on quality of life which is shown to have increased in the study by Eisinger with a dosage of 2.
By way of conclusion we could say that: 1 the difference in efficacy between the two doses is not huge, since both achieve reductions in fibroid and uterine volumes, symptomatic improvement, and have minimal side effects, and 2 the 5 mg dose presents the following advantages: a slightly greater symptomatic improvement, b greater speed in the onset of this improvement, c ificant difference in the normalization of hemoglobin levels, d ificantly less irregular bleeding, and e ificantly lower of dropouts from treatment.
Part c is particularly important when the subject finally comes to surgery as it enables her to undergo an operation in better hematological shape thus decreasing the chances of blood transfusions. Therefore, for these reasons, in our opinion, the dose to be used in future should be 5 mg.
National Center for Biotechnology InformationU. Int J Womens Health. Published online Mar Author information Copyright and information Disclaimer.What is half of 5 mg
email: [email protected] - phone:(497) 716-6900 x 7700
Is mg equal to mg?