Comparative study of Mifepristone and Ulipristal acetate as Medical management of uterine fibroids in symptomatic patients of reproductive age group

Abstract               Objective: Present study was a observational study carried out at JLNMCH, Bhagalpur Bihar to evaluate the efficacy, safety and quality of life by using ulipristal acetate 10 mg and mifepristone 25mg doses to treat uterine fibroids of two subgroups 3-5 cm and < 3cm. Method: A total number of 40 patients were recruited in the study and divided into 2 groups. Group A-receiving Mifepristone 25mg and Group B-receiving Ulipristal 10 mg orally. Both Group A and Group B further divided in 2 groups fibroid of size 3-5 cm and fibroid of size < 3cm. Results: Both Ulipristal 10mg and Mifepristone 25mg is shown to be a good and effective way Of treatment. Ulipristal acetate (10mg) is superior to mifepristone (25mg) for fibroid of size < 5cm. Conclusion: Larger Randomised controlled trial are needed to study the long term benefit of these drug.

Key Word: Mifepristone, Symptomatic fibroids, Ulipristal acetate.

INTRODUCTION

Uterine fibroids are one of the common benign uterine tumours of female reproductive age group. They may be completely asymptomatic or present with pelvic mass, obstructive uropathy, anaemia secondary to blood loss and infertility. The incidence of uterine fibroid is variable because most of them are asymptomatic hence remain undetected for years. The percentage of woman having symptomatic fibroid is reported to range from 25-30%. The risk factors for developing fibroids for developing fibroids include obesity, nulliparity, younger age at menarche and African race. The diagnosis of uterine fibroids is usually done by ultasonography examination which usually shows a well characteristic peripheral vascularity on doppler examination. The complication associated with uterine fibroids may include severe anaemia requiring intervention in the form of transfusion, red degeneration, Urinary retention, hydronephrosis secondary to obstructive uropathy and rarely sarcomatous changes. The management of uterine fibroid depends on the size, symptoms, location, age and parity of patient. Asymptomatic small fibroids can be left as such if there are no fertility issues ^10.Patient with severe symptoms affecting quality of life need surgical intervention, like Hysterscopic myomectomy for sub mucosal fibroid. Lap myomectomy for symptomatic subserosal and intramural fibroids. Total laparoscopic hysterectomy and Total abdominal hysterectomy are other options. Other less invasive procedures are uterine artery embolisation and Magnetic resonance guided focussed ultrasound surgery (MRgFUS). Various medical therapies used for fibroids are Trenexamic acid, combined oral contraceptive pills, GnRH analogs, Selective estrogen and progesterone receptor modulators. Both Mifepristone and Ulipristal are selective progesterone receptor modulator. Both of them are effective in the management of small sized fibroids. Uterine leiomyoma (fibroids) are benign tumours arising from smooth muscles and connective tissue in uterus. By reproductive age group more than 60% females are expected to have asymptomatic or symptomatic uterine fibroid. The management of uterine fibroid depends upon factors like possibility of pregnancy in future, whether preservation of uterus is desirable, severity and characteristic of symptoms. Mifepristone has been in use since 2002 but ulipristal acetate has recently been in use. This is a comparative study of Mifepristone and Ulipristal acetate for Medical management of small sized fibroids.

METHODS

A total of 50 patients with symptomatic fibroids were enrolled in this study. They were divided in two groups (Group A and Group B).each with 25 patients. Outcome of study was evaluated in terms of change in size of fibroids, reduction in pain, resolution of menorrhagia and improvement in the quality of life. Approval from ethical committee was taken and informed consent was taken from all the patients before enrolling them in the study. Menstrual blood loss was assessed using PBAC. Routine investigation like CBC. Renal and hepatic functions tests were done in all patients. TVS examination was done to know the exact number and location of fibroids. Group A received Mifepristone 25 mg and group B received Ulipristal acetate 10mg. Patient well followed up for 6 months and parameters like change in fibroid size, reduction in pain, resolution of menorrhagia and improvement of quality of life was compared between two groups.

Inclusion criteria

• Females diagnosed to be having uterine fibroids in reproductive age group.
• Patients having symptoms like menorrhagia, dysmenorrhoea, abdominal pain or any other symptoms related to fibroid.
• Single fibroid
• Patient willing to give consent.

Exclusion criteria

• Pregnant patient.
• Those who refused consent
• Condition in which mifepristone or ulipristol is contraindicated
• Patient having adenomyosis, endometrial hyperplasia or genital tract infections.

RESULTS

Table 1:

	Group –A	Group -B
Mean Age	36.5 ± 4.3 Yrs	37.2 ± 3.8 Yrs

 

Table 2: Fibroid Size In Studied Cases

Fibroid size	<3	3-5	Total
Group – A	10	10	20
Group – B	10	10	20
Total	20	20	40

 

Table 3: Reduction in symptoms in patients receiving mifepristone

	Reducing in size	Reducing in pain	Reducing in Menorrhagia
3-5 cm	35	65	75
<3 cm	25	60	70

 

Table 4: Reduction in symptoms in patients receiving ulipristol acetate ( Group –B)

	Reducing in size	Reducing in pain	Reducing menorrhagia
3-5 cm	65%	75%	80%
<3 cm	30%	70%	60%

The administration of both drugs mifepristone and ulipristal acetate in women with symptomatic fibroids was associated with decreased pain, reduced blood loss and decreased size. Both mifepristone and Ulipristal are more effective when the size of fibroid is 3-5 cm or it could be due to more severe symptoms in case of larger fibroids so greater relief. Demographic data-Out of the 40 studied cases Group A had mean age of 36.5 ±4.3 years and Group B had mean age of 37.2± 3.8 years. The analysis of presenting complaints of the patients revealed that most common presenting complaint of the patients was pain during menstruation (26/40), heavy bleeding during menses( 13/40 ), dyspareunia 11/40) and pain occurring between cycles particularly midcycles (6/40).The diagnosis of uterine fibroids was confirmed by either transabdominal or transvaginal ultrasound depending upon the size of fibroid and marital status of the patients. A total of 40 patients were selected, 20 patients had fibroid <3cm and 20 had fibroids 3-5 cm. 10 patients (group- A) with fibroids of 3-5 cm received 25 mg mifepristone and 10 patients (group –B) of 3-5 cm received ulipristal 10 mg daily. Similarly 10 patients with fibroid <3 cm received 25 mg mifeprotone (group –A), 10 patients with fibroid <3 cm received ulipristal (group- B). The analysis of groups A and B patients showed that ulipristal ( 10 mg) is more effective than mifepristone (25 mg) in reducing the size of fibroid, (65% Vs 35% and 30% Vs 25%, Reduction of pain (75% Vs 65% and 70% Vs 60%), Reduction of blood loss (80% Vs 75% and 60% 70%).So ulipristal appears to be more effective than mifepristone for fibroids of size 3-5 cm as well as <3 cm.

 

DISCUSSION

Selective progesterone receptor modulator(SPRMS) like mifepristone and ulipristal acetate have been used for the treatment 0f dysfunctional uterine bleeding and uterine myomas because of their antiproliferative effect on endometrium. Feng C in their comparative study of women with symptomatic fibroids who were treated with 5 mg or 2.5 mg of mifepristone or placebo found that mifepristone was associated with significant improvement in health related quality of life. The utility of ulipristal acetate has been tested in many randomised controlled trials. First trial of ulipristal acetate as medical management of fibroids (PEARL I) compared it with placebo in uterine fibroids. the study found that ulipristal acetate was associated with significant reduction in menorrhagia 915.92% and 19% respectively in women receiving 5 mg,10 mg and placebo. PEARL II study was another study comparing ulipristal acetate with Gn RH analogs in the medical management of uterine fibroids. the study found that menorrhagia was controlled in 90%, 98% and 89% of women receiving ulipristal acetate 5mg, ulipristal acetate 10 mg, and Gn RH analogues respectively. The result of this study is similar to the above mentioned study. Various other studies have shown the effectiveness of ulipristal acetate in decreasing menorrhagia and improving the quality of life with uterine fibroids.

 

CONCLUSION

Treatment of symptomatic fibroid by mifepristone as well as ulipristal acetate was associated with reduction in fibroid size, reduces blood loss and decreased pain. It was found that ulipristal acetate is more effective than mifepristone forall size of fibroids, <5cm.

 

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