In the Unani system of medicine, Tams (mensuration) implies normal menstruation with average quantity (Miqdar) and normal in quality (kaifiyat) of blood is discharged. It removes morbid matter from the body and helps in restoring health. The cycle is of 28 days including days of menstrual flow1. According to the Unani theory of humors and temperament, the human body is composed of seven principles known as Al-Umoor-e- tabiya. These factors responsible for the maintenance of health [2,3]. Buqrat, the father of humoral theory states that disturbances in any one of these can attribute to disease [2-4]. In the Unani system of medicine, the term kasrat-e-tams is used for menorrhagia. It is defined as heavy and excessive bleeding [5]. Nazf is defined as excessive and continuous bleeding from Uterus [5]. Menorrhagia is due to the weakness of quwwat-e-masika of the uterus a result of which there is excessive bleeding from the uterus [1],[6],[9],[10]. Kasrat-e-tams mainly due to altered body temperament which result in uterine affections. The etiology of kasrat-e-tams is Riqqat wa hiddat-e-dam, Ghalba-e-balgham,Ghalba-e-e-safra,Ghalba-e-sauda,Zoaf-e-reham, imtela (plethora), sue-mizaj-e-reham (change in temperament of uterus) [7-12]. The various pathological conditions in the genital tract such as polyps, ulcers or surgery alter the temperament of the uterus which weakens the muscles and vessels of the uterus [7],[10],[13]. The treatment of kasrat-e-tams in unani system of medicine is based on principle to treat the cause (izale-e-sabab), Tanqiya-e-badan with tadeel-e-mizaj and istefragh-e-madda in sue-mizaj sada and maddi respectively. Kasrat-e-tams is treated with habis and qabiz and muqawwae reham advia [14].

Menorrhagia and dysmenorrhoea form a significant part of gynaecological work. Menorrhagia is also seen in women with increased uterine vascularity such as in chronic pelvic inflammatory disease and pelvic endometriosis. The presence of an IUCD often leads to heavy and prolonged bleeding. Lastly, menorrhagia may be the result of bleeding disorders like Von Willebrand’s disease or an arteriovenous aneurysm [15,16]. A normal menstrual blood loss is 50 to 80 mL, and does not exceed 100 ml. In menorrhagia, the menstrual cycle is unaltered, but the duration and quantity of the menstrual loss are increased [16-18]. Menorrhagia, one of the most frequently encountered symptoms in gynaecology, is defined as cyclical bleeding at normal intervals which is excessive in amount and duration [19-21]. Menstrual irregularities including menorrhagia are common during reproductive age [22]. About 18 million women aged 30-55 years perceive their menstrual bleeding as exorbitant [23]. Menorrhagia is more common in the age group 35 years of age [24]. It is reported that 10 % of women's blood loss is severe enough to cause anaemia or to be clinically defined as menorrhagia [22-27]. Its prevalence is about 30% in reproductive age [28]. Menorrhagia affects the quality of life in women and imposes a financial burden [29-31]. Although menorrhagia is not life-threatening, effects on personal, social, family, and work-life of women, and thereby their quality of life [31]. Menorrhagia is largely responsible for iron deficiency and iron deficiency anaemia both of which have negative effects on women's health.31 Women’s consulting gynaecology departments, being hospitalized, and having an operation. Several studies mention the negative effects of menorrhagia on women.

As allopathic drugs have known for their side effects. Keeping in the view the present work deals with comparative study on efficacy and safety of unani drugs (Trial drug) with allopathic drug tranexamic acid (Control drug) in treatment of menorrhagia and result are presented.

Study Design

A randomized standard controlled study was carried out in the from Department of Ilmul Qabalat wa Amraz-e-Niswan, A & U Tibbia College & Hospital, Karol Bagh, New Delhi-110005, from Aug 2022- May 2023. Patients has been randomly divided into two treatment groups, test and control by following randomization method. The efficacy and safety of Unani drug and tranexamic acid were evaluated on the basis of reduction in heavy menstrual bleeding and reduction in duration of bleeding. The research protocol was approved by Institutional ethical committee prior to its commencement under IEC no. F. 5(283)/2013-Co/PF/-(UNANI)/2020-2023/9/ the trial was registered at Clinical Trial Registry of India (CTRI) CTRI no/2022/08/045012 under the registration number.

Sample size is 40 for the study. 20 in each group.

Eligibility Criteria

Women either with no pelvic pathology or with PCOD, ovarian cyst in age group of 20 to 40 years with regular cycles (21-35 days) with MBL >80 ml blood loss during their menstrual cycle with PBAC score >100 were included and those with uterine fibroid, AIDS, Syphilis, and Gonorrhoea, Diabetes (Type 1 or Type 2), systemic disease and malignancy, alcohol and other substance abuse, lactating women, thyroid dysfunction, bleeding disorders and with IUCD were excluded. CT, BT, TSH, CBC with ESR were done for exclusion.

Procedure of Study

Participants who are interested in signed a written informed consent & included in the study.   

Intervention

The trial drug was given orally in form of tablet in dose of 500 mg thrice daily from 3rd day of menses for 15 days. And controlled allopathic drug tranexamic acid 500 mg TDS was given to patient from 3rd day of menses up to bleeding stops till 10th day.

Assessment of temperament (Mizaj)

Assessment of temperament (Mizaj) has been done at baseline.

The assessment of efficacy in the test and control groups were assessed on basis of two types of parameters:

Subjective Criteria

Objective Criteria: Subjective parameters: At every visit, i.e., heavy menstrual bleeding (menorrhagia), backache and pelvic pain were assessed. These parameters were assessed through the duration of cycle, and amount of flow (no. of pads/day) used by the patient. As these parameters differ in severity from patient to patient. Each sign and symptoms had been recorded according to their grades any worsening or improvement in any of the parameters till the treatment is completed.

Objective Parameters:  At every visit PBAC score and VAS score were used to assess the amount of bleeding, duration of bleeding and pelvic pain.

Criteria of Assessment of Safety

The safety was assessed by monitoring any adverse events either volunteered by the subjects or elicited by investigator by monitoring the following investigations at baseline and also at the end of the treatment.

• Clinical assessment at every visit.
• Haematological assessment (Hb%, ESR, TLC, DLC).
• Biochemical assessment (KFT, LFT).
• Adverse drug reaction if any, these parameters indicate the renal and hepato-toxicity of the test substances with specificity toxicity in general.

Statistical Analysis

Result was evaluated and presented in tables and figures in accordance to purpose of the study. Analysed statistically by Paired T- test, Unpaired T-test and chi square test were used. P value 0.05 level was used to define statistical significance.

Total 100 patients were assessed for eligibility, 30 patients declined and 70 were willing to participate in the study, 5 withdrew the consent ,25 out of 65 patients were excluded for not meeting the inclusion criteria and remaining included in the study, 45 patients were investigated 40 patients completed the trial and 5 were lost to follow up.

Demographic Data

Age: In this study, maximum incidence is between 26-25 years and 31-35 years age group i.e., 30% in test group while maximum incidence is between 20-25 years and 26-30 years age group i.e., 30% in control group. Higher incidence of menorrhagia was observed above 26 to 35 years of age.

Socioeconomic Status

In this study, maximum patients were from middle class in both groups. In test group 4 (20%) patients were lower class, 11 (55%) patients were middle class and 5 (25%) patients were upper class. In control group 6 (30%) patients were lower class, 11 (55%) patients were middle class and 3 (15%) patients were upper class.

Marital Status 

In this study, maximum patients were married in both groups. In   test group 12 (60%) patients were married and 8 (40%) patients were Unmarried. In control group 16(80%) patients were married and 4 (20%) patients were Unmarried. This shows that menorrhagia is common in married women.

Life Style

17 (85%) patient in test group and 15 (75%) patients in control group had sedentary lifestyle, and 3 (15%) patients in test group and 5 (25%) patients in control group had hard working lifestyle.

Mizaj

In this study, 40 % patients were from safrawi mizaj in both groups then from damwi mizaj. In test group 4 (20%) patient were Damwi, 4 (20%) patients were Balghami, and 8 (40%) patients were Safrawi, 4(20%) patients were Saudavi. In control group 2 (10%) patients were Damwi, 7 (35%) patients were Balghami, and 8(40%) patients were Safrawi, 3(15%) patients were Saudavi. This shows that menorrhagia is common in patients with hot temperament. This correlates with the theory of Unani physicians  

Random Blood Sugar Findings Incidence in Test Group and Control Group: In this study maximum patients were lies in range of 50-100 mg/dl of RBS in both groups. In test group 90% patient lies in 50-100 mg/dl, 10% patients had 100-150 mg/dl and in control group 75% patients lies in 50-100mg/dl, 25% patients had 100-150mg/dl.

FSH Findings Incidence in Test Group and Control Group: In this study maximum patients were lies in range of 8-16 mIU/ml of FSH findings in both groups. In test group 35% patient lies in 4-8 mIU/ml,55% patients had 8-16 mIU/ml and 5% patients had >16 mIU/ml range and in control group 40% patients lies in 4-8 mIU/ml, 45% patients had 8-16 mIU/ml, and 15 % patient had >16 mIU/ml range.

LH Findings Incidence in Test Group and Control Group: In this study maximum patients were lies in range of 8-16 mIU/ml of LH findings in both groups. In test group 35% patient lies in range between 4-8 mIU/ml, 55% patients had 8-16 mIU/ml and 5% patients had >16 mIU/ml and in control group 40% patients lies in 4-8 mIU/ml, 45% patients had 8-16 mIU/ml, and 15 % patients had >16 mIU/ml.

T3 Findings Incidence in Test Group and Control Group: In this study maximum patients were lies in range of 110-120 ng/dl of T3 findings in both groups. In test group15% patient had lies in range between 100-110 ng/dl, 45% patients had 110-120 ng/dl 25% patient had 120-130 ng/dl and 15% patient had 130-140 ng/dl and in control group 10% patients lies in 100-110 ng/dl, 50% patients had 110-120 ng/dl, 30% patient had 120-130 ng/ml and 10 % patients had 130-140 ng/dl.

T4 Findings Incidence in Test Group and Control Group:In this study maximum patients were lies in range of 6-8 µg/dl of T4 findings in both groups. In test group 10% patient had lies in range between  4-6 µg/dl, 65% patients had 6-8 µg/dl  25% patient had 8-10 µg/dl and in control group 65% patients had 6-8 µg/dl, 35% patient had 8-10 µg/dl.

TSH Findings Incidence in Test Group and Control Group: In this study maximum patients were lies in range of 2-4 µIU/ml of TSH findings in both groups.  In test group 40% patient had lies in range between 0-2 µIU/ml, 55% patients had lies in 2-4 µIU/ml and 10% patient had lies in 4-6 µIU/ml and in control group 10% patients lies in 0-2 µIU/ml, 90% patients had 2-4 µIU/ml.

USG Findings Incidence in Test Group and Control Group: In test group 10% patient had PCOD, 10% patients had simple follicular cyst, and 80) patients had normal findings while in control group 30% patients had had PCOD, 10% patients had simple follicular cyst, and 60% patients had normal findings.

Effects of Trial Drugs on Duration of Menses

In test group, at baseline 15 % patients had duration of menses for 3-5 days which persists in 80 % patient after treatment with a percentage difference of 65%. 75% patients had duration of menses for 6-8 days which persists in 15 % patient after treatment with a percentage difference of -60%. 10% patients had duration of menses for 9-12 days which persists in 5% patient after treatment with a percentage difference of -5%, while in control group 10 % patients had duration of menses for 3-5 days which persists in 80 % patient after treatment with a percentage difference of 70%. 90% patients had duration of menses for 6-8 days which persists in 5% patient after treatment with a percentage difference of -85%. 0 % patients had duration of menses for 9-12 days which persists in 15 % patient after treatment with a percentage difference of -15%.

Mean+ SD of duration of menses before treatment ,1st,2ndand 3rd cycle(after treatment) were 7±1.123, 6.45±0.825, 5.8±0.951 and 5.2 ±0.1 in test group  and 7.5±1.5,6.75±0.91, 6.25±0.55 and6±1.6 in control group respectively . Reduction in duration of bleeding was observed during treatment from 1st cycle to post treatment follow up with p <0.001, considered as highly significant.

Effects of Trial Drugs on Amount of Flow

Before treatment none of patients in test group and control group used 1-2 pads/day. In test group 90% patients and 60% patients in control group used 1-2 pad/day after treatment. The percentage changes were +90 % in test group and +60 % in control group. 45% patients in test group and 75% in control group used 3-4 pads/day before treatment. In test group 05% patients and 40% patients in control group used 3-4 pads/day after treatment.  The percentage changes were -40% in test group and -35% in control group.55% patients in test group and 25% in control group used 5-6 pads/day before treatment. 5% patient in test group and none in control group used 5-6 pads/day after treatment. The percentage changes were -50% in test group and -25 % in control group.

Mean+ SD of duration of menses before treatment, 1st, 2^nd and 3rd cycle (after treatment) were 4.8 ±0.90, 3.35±0.745, 2.35±0.489 and 2.2±0.67 in test group and 4.2±1, 2.9±0.31, 2.7±0.47 and 2.9±1.2 in control group respectively. Reduction in duration of bleeding was observed during treatment from 1st cycle to post treatment follow up with p <0.001, considered as highly significant.

Effects of Trial Drugs on Pelvic Pain

25% patients in test group and 50% patients in control group had pelvic pain in grade 0, before treatment. 25% patients in test group and 50% patients in control group had pelvic pain in grade 0, after treatment. There was no change in percentage in test group and in control group. 30% patients in test group and 80% patients in control group had pelvic pain in grade 1, before treatment.30% patients in test group and 25% patients in control group had pelvic pain in grade 1, after treatment. There was no change in percentage in test group and -5% change in control group. 30% patients in test group and 25% patients in control group had pelvic pain in grade 2, before treatment.45% patients in test group and 20% patients in control group had pelvic pain in grade 2, after treatment. The percentage change was +15 % in test group and -5% in control group.15% patients in test group and 5% patients in control group had pelvic pain in grade 3, before treatment.0% patient in test group and 5% patient in control group had pelvic pain in grade 3, after treatment. The percentage change was -15% in test group and 0% in control group.

Mean+ SD of pelvic pain before treatment, 1st,2^nd and 3rd cycle (after treatment) were 1.35±1.039, 1.35±1.039, 1.21.30.833 and 0.8±0.833 in test group and 0.8±1, 0.85±0.988, 0.85±0.988 and 0.6±0.7 in control group respectively. Reduction in pelvic pain was observed during treatment from 1st cycle to post treatment follow up with p <0.001, considered as highly significant.

Effects of Trial Drugs on Backache

20% patients in test group and 20% patients in control group had backache in grade 0, before treatment. 20% patients in test group and 20% in control group had backache in grade 0, after treatment. There was no change in percentage in test group and in control group.25% patients in test group and 5% patients in control group had backache in grade 1, before treatment.50% patients in test group and 15% patients in control group had backache in grade 1 after treatment. There was 25% change in percentage in test group and 10% change in control group. 30% patients in test group and 45 % in control group had backache in grade 2, before treatment.30% patients in test group and 50% in control group had backache in grade 2, after treatment. There was no change in percentage in test group 5% in control group. 1% patients in test group and 30% in control group had backache in grade 3, before treatment.0% patient in test group and 15% patient in control group had backache in grade 3, after treatment. The percentage change was -5% in test group and -15% in control group.

Mean+ SD of backache before treatment, 1st, 2^nd and 3rd cycle (after treatment) were 1.6±1.095, 1.5±1, 1.35±0.875, 1.1±0.718 in test group and1.85±1.089, 1.85±1.089, 1.65±0.988, 1.6±0.994 in control group respectively . Reduction in backache was observed during treatment from 1st cycle to post treatment follow up with p <0.001, considered as highly significant.

Objective Parameters

PBAC Score:  Mean + SD of PBAC score before treatment, 1st, 2nd and 3rd cycle (after treatment). In test group the mean PBAC score values observed were 266.3±51.2, 193.1±54.7

, 127.4±61.41and 99.8±51.9. There were significant changes in PBAC score (t=16.9 p value < 0.001). The PBAC score recorded in control group were 243.7±54.1, 181.85±30.29, 157.4±26.09 and 138.3±61.4. There were significant changes in PBAC score (t=6.21 p value < 0.001).

VAS Score:  Mean+ S.D of VAS Score before treatment ,1st,2ndand 3rd cycle (after treatment).in test group the mean VAS  score values observed were 1.6±1.095, 1.5±1, 1.35±0.875, 1.1±0.718. There was significant change in VAS score (t= 3.7; p value 0.002). The VAS score recorded in control group was and1.85±1.089, 1.85±1.089, 1.65±0.988, 1.6±0.994 respectively. There was significant change in VAS score (t= 2.5; p value 0.021) VAS Score: Mean+ SD of pelvic pain before treatment, 1st, 2nd and 3rd cycle (after treatment) were 1.35±1.039, 1.35±1.039, 1.21.30.833 and 0.8±0.833 in test group. There were significant changes in VAS score (t=3.7, p value 0.002). In control group 0.8±1, 0.85±0.988, 0.85±0.988 and 0.6±0.7 respectively. There were significant changes in VAS score (t=2.9 p value 0.010).

Safety Profile

Research drugs was safe as safety parameters were within normal range.

Effect on Haemogram 

No significant changes  in  the  level  of  haemoglobin,  red blood  corpuscles  (RBC),  total  leucocytes  count  (TLC), platelets  count,  polymorphs,  lymphocyte,  eosinophils  and erythrocyte sedimentation rate (ESR) respectively had been observed  (Table-8)  in  both  trial  drug  and tranexamic acid  treated patients after 12 weeks.

Effect on LFT, KFT: No significant changes in LFT and KFT respectively had been observed (Table-7) in both trial drug and tranexamic acid treated patients after 12 weeks.

Clinical response (80-90%):  In this study, clinical response of marked reduction in duration of bleedings and number of pads used per day probably may be due to activities of research drug.

Result Showing Overall Response

In the study, in Test group out of 20, 90% patients were cured, 05% patients was relieved, 1 was 05% patients was partially relieved and 0 % patients showed no response. In the study, in Control group out of 20, 55% patients were cured, 25% patients were relieved and 20% patients partially relieved and 0% patients showed no response.

Table 1: Demographic data showing distribution of different variables of trial and control group.

Subjective Parameters

Table 2: Comparative data showing improvement od sign and symptoms of menorrhagia patients treated with trial drug and tranexamic acid.

Table 3: Comparative data showing improvement in subjective parameters of trial group and control group.

Table 4: Comparative data showing improvement in objective parameters of trial group and control group.

A total no of 100 patients completed pre baseline screening in which 40 patients met the criteria and were randomly assigned to the test (n=20) and control (n=20) group. These parameters were evaluated.

Safety Profile

Table 5: Effect of trial drug and tranexamic acid on safety profile.

Table 6: Result Showing Overall Response.

Finally, it can be inferred that research drug may be an effective therapeutic option in patients of menorrhagia, as it has been significant effect in controlling the bleeding by reduction in    MBL and DOB with improvement in quality of life by reduction in backache and pelvic pain as well. No adverse effects were encountered during the study period. Hence, research drug can be used as alternative of tranexamic acid in heavy menstrual bleeding.

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