Introduction

Fibroids although benign, are commonly associated with abnormal uterine bleeding Murji A et al1 In some women it is asymptomatic but it is the leading cause of hysterectomy. Conversely women do experience symptoms. The most common are increase in menstrual bleeding, known as menorrhagia, sometimes with blood clots, sometimes causes pelvic pain, painful menstruation, infertility, pressure on the bladder, which may cause frequent urination and a sense of urgency to urinate and, rarely, the inability to urinate; pressure on the rectum, resulting in constipation, pelvic pressure, "feeling full" in the lower abdomen, lower abdominal pain. Fibroid can increase up to umbilicus, and/ pelvic mass discovered during a physical examination. Previously it is most preferred therapy was surgery. Now Medical therapy is preferred in symptomatic fibroid, to relieve symptoms in infertility, and in pre and peri menopause women, in preoperative conditions to reduce size. This oral medication can be used before surgery to reduce size so that blood loss during surgery will be less and transfusion of blood during surgery will be less and fibroid can be easily removed through laparoscopy. Ulipristal reduces bleeding and achieves amenorrhea. J. Simon W.H. Catherino et al2 Oral medical management for fibroid is selective progesterone receptor modulator - Ulipristal acetate (UPA). Simon James et al3 menstrual bleeding was controlled in 92% of the women who received 10 mg of Ulipristal acetate. Jacques Donnez et al.4 Stated that other medical therapies like GnRH agonist for fibroids have limitations. GnRH agonists cause side effects such as hot flashes and atrophic vaginitis, osteoporosis that may reduce adherence to therapy and require add back therapy but Ulipristal is well tolerated Simon JA et al.5 Ulipristal acetate can effectively control bleeding, pain and reduce fibroid volume, and restore QoL in patients with symptomatic fibroids Jacques Donnez et al.6 It eliminates the need for surgery or postpones surgery and has efficacy equivalent to surgery and cheaper alternative

Aim

To determine effectiveness of Ulipristal in symptomatic fibroid by assessing reduction in heavy menstrual bleeding, pain and improvement in activity score.

To determine effectiveness of Ulipristal in symptomatic fibroid by assessing fibroid size number and volume or its disappearance and to determine its efficacy

Materials and Methods

P rospective study conducted at Saveetha Medical College and hospital Gynaec outpatient Department. Study was conducted from September 2018 to Dec 2018 first week. Women between 20- 45 years both unmarried and married attending gynaec OPD with fibroid with symptoms of heavy menstrual bleeding (HMB), pain abdomen during period, with Infertility were recruited after ethical Clarence and informed consent. Monthly blood loss was assessed with pic torial blood loss chart (PBAC) and pain was assessed with short form Mc Gill pain questionnaire pain score. After routine investigation including LFT, USG abdomen and Pelvis were done for all subject and mapping of fibroid(size, volume, number, situation) and endometrial thickness and ovaries were assessed by 2D USG and Sonologist was blinded about the study. Women were selected by convenient sampling and Ulipristal was given 10mgs per day for 13 weeks. Women were evaluated at the end of every month for symptoms and USG was repeated to assess the reduction in size of fibroid. At the end of 13^th week along with routine investigations, fibroid mapping and endometrial thickness and ovaries were assessed by 2D USG by the Sonologist. Improvement in anaemia was assessed by Hb and PCV and improvement in menstrual loss by PBAC and improvement in pain was assessed by short form Mc Gill pain questionnaire pain score. Quality of life was assessed by Activity score which was assessed by Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, social functioning. To assess side effects, spontaneously reported or elicited by non-leading questions and were recorded. For safety LFT, triglycerides & glucose, endometrial thickness were assessed at the end of the study. Women were followed up for drug-free up to 12 weeks

Results

Statistical Analysis was done by mean, percentage analysis and pair T test for Pre and Post treatment analysis with p value of < 0.05 statistic carried out at an confidence interval of 95 % shows the standard deviation.

In the study maximum 36.6% age group were between 36 -40years followed b y 26.6% between 31-35 years, 23.30% between 26 -30years, minimum between 20-25 were 6. 66% and 41-45 years were 6.66% (Figure 1) Nulliparous women in the study were 6.66% and 93.6% were multiparous. Predominant symptoms among the women were heavy menstrual blood loss and was assessed by Pictorial blood loss score and 66.66% had PBAC of 130 and above 20% had PBAC between 121 - 130, PBAC of 120-111 in 6.6% of women,110-100 PABC in 6.6%.None of the women had PBAC <100. After treatment perimenopausal women who had h eavy menstrual loss, bleeding was reduced within 15 - 20 days and 13.33% women went in for Amenorrhea. After 13 weeks treatment women 20% women had PBAC score <100 , PBAC score 100-110 in 6 3.33% of women, PBAC between 111 -1 20 score in 3.33% PABC score 120 and above were Nil. There is appreciable improvement in reduction in menstrual blood loss (Figure 2) Hb level was increased to 12 gm in 53.3% women and in 40% above 9gm (Figure 3). In the study pain during periods was the next complaint. Pain was assessed by short form Mc Gill pain questionnaire pain score was based on pain nature like excruciating, horrible, distressing and discomfort and mild. There is considerable improvement in pain during periods af ter treatment with a p value of 0.001 (Table 1) In the study fibroid volume reduction > 25% in 23.33% of women, between >25 to < 50% in 53.33% of women >50% in 13.33% women and in 10% of women fibroid disappeared when fibroid size was 3cm which was sustained during follow-up.(Figure 3). In the study no evidence of significant changes in endometrial thickness seen in USG or laboratory results during the course of treatment. Activity score was assessed by Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well- being, social functioning. Study results showed activity score for the various quality factor had improved considerably after treatment as evidenced by the P value 0.0001. (false) There was no adverse reaction during the study period and during the follow-up. Side effects like headache and breast tenderness was reported by in 6.66% of women

Figure 1

Age Distribution

Figure 2

Menstrual blood loss before and after treatment

Figure 3

Hb level increased after treatment

Figure 4

Percentage of Fibroid size and volume reduction after treatment

Discussion

In the study major complaint among women were heavy menstrual blood loss which was scored by PBAC. Study conducted by Jacques Donnez and Olivier Donnez6 control of bleeding seen >80% and PBAC score from >200 reduced to < 100 at the end of second course but in the study reduction in PBAC score was seen in 86.6%. Study by Jacques Donnez et al6 median reduction in size of fibroid volume after 5gs and at the end of 10mgs Ulipristal was 54% and 58% but in the study 53.33% reduction between >25% to 50% sizeand volume and in 10% fibroid disappeared. In the study head ache and breast tenderness were reported. In the study no changes in endometrial thickness similar to Jacques Donnez M.D, Olivier Donnez, M.D. Dace Matule, M.D et al.7 I n the study there was sufficient improvement in quality of life due to reduction in size and marked improvement in with a p value of 0.0 001. Jacques Donnez, Guillaume E Courtoy, Olivier Donne et al8 in his review article and his key message stated that Ulipristal acetate significantly reduces fibroid size and controls bleeding and improves quality of life, which is similar to the study. Jacques Donnez Marie-Madeleine et al9 stated that Fibroids are highly prevalent and leads to high health burden and has an impact on their quality of life and has economic impact. As current treatment mostly surgical there is need for new options. In the study fibroid was treated effectively with 10 mgs Ulipristal for 13 weeks which is similar to the statement by Donnez J, Dolmans M et al10 that SPRMs such as Ulipristal are proven to treat fibroid effectively. In the study perimenopausal women Ulipristal arrest ed bleeding and in few women lead to amenorrhea, hence most perimenopausal women prefer Ulipristal than surgery. Singh SS11 concluded that Ulipristal may decrease the incidence of surgical and other modality of treatment

Conclusions

Ulipristal was efficient in controlling heavy menstrual bleeding and amenorrhea was developed in perimenopausal women. There was reduction in fibroid volume and disappearance of fibroid in few women which was sustained during follow-up. Pain during periods and quality of life was considerably improved. During treatment there was no adverse reaction and very few side effects were noticed. Ulipristal can be an alternative to surgery Hence results of the study concluded that Ulipristal is both effective and safe for fibroid treatment. It is a novel therapy for fibroid management

Study funded

Meyer Vitabiotics