Efficacy of Qurs-e-Habis in the Management of Menorrhagia: A Multi-centric Clinical Study

Introduction

Menorrhagia, known as Kasrat-e-Tams in Unani medicine, represents one of the most prevalent gynecological disorders affecting women of reproductive age globally. Heavy menstrual bleeding (HMB) is clinically defined as excessive menstrual blood loss that significantly interferes with a woman’s physical, social, emotional, and material quality of life, either occurring independently or in combination with other symptoms [1-2]. The condition demonstrates considerable epidemiological variation, with prevalence rates ranging from 4% to 51.6% across different populations, equating to approximately 4,000-9,000 cases per 100,000 women and resulting in 398,000 women seeking primary care annually [3]. This substantial variation in prevalence reflects both the multicultural nature of study populations and the subjective nature of HMB assessment, though objective studies have consistently reported prevalence rates between 11% and 26%. The classical Unani medical system provides a comprehensive understanding of menorrhagia’s etiopathology, categorizing the condition into several distinct mechanisms. These include Imtela-e-Dam (blood congestion) where increased blood volume results from enhanced formation or reduced utilization, commonly observed in sedentary or obese women; Riqqat Wa Hiddate Khoon (excess heat and fluidity of blood) leading to tortuous uterine vessels; and various humoral dominances including Ghalba-e-Safra (bile dominance), Ghalba-e-Balgham (phlegm dominance), and Ghalba-e-Sauda (black bile dominance), each producing characteristic pathophysiological changes [1][4][5], structural abnormalities such as Su-e-Mizaj Reham (uterine temperament disorders), Zof-e-Reham (uterine debility), and secondary manifestations of systemic diseases contribute to the complex presentation of this condition [6-7].

Contemporary allopathic management of menorrhagia primarily relies on non-steroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, gonadotrophin-releasing hormone agonists, medicated intrauterine devices, and various surgical interventions ranging from dilation and curettage to hysterectomy [8-9]. However, these therapeutic approaches are associated with significant limitations and adverse effects. NSAIDs frequently cause gastritis with prolonged use, oral contraceptives lead to breakthrough bleeding, nausea, weight gain, headache, breast tenderness, and thromboembolic complications, while extended use of GnRH agonists results in bone demineralization and reduction of high-density lipoproteins [10-11]. Furthermore, surgical procedures carry substantial morbidity risks, with hysterectomy presenting all complications associated with major surgery, including increased urinary frequency and other long-term sequelae.

The Unani pharmacological approach offers a promising alternative through its emphasis on astringent medicines that not only control bleeding but simultaneously prevent and treat associated anemia while restoring acceptable menstrual patterns [12-13]. The traditional Unani treatment principles for Kasrat-e-Tams include Istifragh (evacuation) for blood congestion cases, Imala (diversion of humors), Tanqiya (evacuation) for bile-related conditions, Taghleez-i-Dam (blood thickening), Habs-i-Dam (bleeding control), and Tajfeef (desiccation) [14-15]. These principles are implemented through various compound formulations, with Qurs Habis representing a significant therapeutic option in the classical Unani pharmacopoeia. Given the substantial limitations of current conventional treatments and the frequent discontinuation of therapy due to adverse effects, there exists a critical need for safer, more effective therapeutic alternatives. The present multi-centric clinical study aims to validate the safety and efficacy of the Unani pharmacopeial formulation Qurs-e-Habis in managing menorrhagia, potentially offering women a well-tolerated treatment option that addresses both symptom control and underlying pathophysiological mechanisms while minimizing adverse effects associated with conventional therapies.

Methodology

Study Design and Setting

This multi-centric clinical study employed an open-label, uncontrolled design to evaluate the safety and efficacy of Qurs-e-Habis, a Unani pharmacopeial formulation, in patients with Kasrat-e-Tams (heavy menstrual bleeding/menorrhagia) [16]. The study was conducted simultaneously at three specialized Unani research institutes: Central Research Institute of Unani Medicine (CRIUM), Hyderabad; Regional Research Institute of Unani Medicine (RRIUM), Chennai; and Regional Research Institute of Unani Medicine (RRIUM), Mumbai, over a period of two years.

Participants and Selection Criteria

Sample Size and Recruitment

A minimum sample size of 240 completed cases (80 participants per centre) was calculated to determine statistically significant treatment effects. However, centres were permitted to recruit additional participants beyond their allocated quota to ensure adequate statistical power.

Inclusion Criteria

Non-gravid, non-menopausal females aged 19-45 years were eligible for inclusion if they presented with menorrhagia characterized by: (1) excessive menstrual loss exceeding 80ml per cycle as calculated using menstrual pictogram assessment, and (2) menstrual cycles lasting more than 6 days.

Exclusion Criteria

Participants were excluded if they had: heavy menstrual bleeding with structural or histological abnormalities accompanied by intermenstrual or post-coital bleeding, pelvic pain, or pressure symptoms; heavy menstrual bleeding since menarche; personal or family history suggesting coagulation disorders; current use of intrauterine contraceptive devices; chronic illnesses requiring long-term treatment; post-menopausal bleeding; hormone replacement therapy use; conditions where heavy menstrual bleeding was not the primary symptom (e.g., endometriosis); or if they were pregnant or lactating.

Intervention and Treatment Protocol

Study Drug Administration

Participants received Qurs-e-Habis tablets (250mg) orally, administered twice daily (BD) at 12-hour intervals after meals with water. The formulation contained ten ingredients: Sang-e-jarahat (479g), Geru-surkh (571g), Lakh dana (183g), Ral sufaid (183g), Phitkiri sufaid (192g), Gond keekar (192g), Damul Akhwain (500g), Kushta-e-busud (1kg), Shamaeen (50ml), and Magnisia fahmi (50g) [16].

Treatment Duration

The total treatment duration was 12 weeks, administered as 9 days each month starting from day 1 of the menstrual cycle for three consecutive cycles. No concomitant medications were permitted during the study period.

Assessments and Evaluations

Baseline Assessment

At enrollment, comprehensive baseline evaluations included Mizāj (temperament) assessment, complete medical history, physical examination, and laboratory investigations comprising: haemogram (Hb%, TLC, DLC, ESR), pregnancy test, bleeding time, clotting time, prothrombin time, liver function tests (serum bilirubin, SGPT, SGOT, serum alkaline phosphatase), kidney function tests (serum creatinine, serum urea, serum uric acid), and pelvic ultrasonography.

Follow-up Protocol

Participants underwent clinical assessment every four weeks throughout the treatment period. Subjective and objective clinical observations were systematically recorded. Laboratory investigations (excluding pregnancy test and pelvic USG) were repeated at the first follow-up and at treatment completion. Missed follow-up visits were rescheduled within a ±1 week interval.

Efficacy Assessment

The primary efficacy outcome was evaluated using a modified menstrual pictogram, an adaptation of the PBAC (Pictorial Blood Assessment Chart) technique. This method provided comprehensive assessment of menstrual blood loss by quantifying blood loss on sanitary products and accounting for blood loss during sanitary wear changes, with measurements expressed in milliliters equivalent to actual blood volume lost [17].

Safety Monitoring

Safety assessment included monitoring for adverse events and laboratory parameter changes. All adverse events were documented in case record forms, with serious adverse events reported to Ethics Committees and CCRUM Headquarters within 24 hours via phone, fax, or email, followed by detailed written reports.

Statistical Analysis and Data Management

Data analysis employed per-protocol (PP) analysis, including only participants who completed the 12-week study according to protocol specifications with complete safety and efficacy measurements without major protocol violations. Results were expressed as percentage efficacy calculated from improvements in bleeding patterns and associated symptoms.

Ethical Considerations

The study protocol received approval from Institutional Ethics Committees at all participating centers prior to commencement. Written informed consent was obtained from all participants after comprehensive explanation of study procedures, purposes, and participants’ rights, including the right to withdraw at any time. Informed consent forms were translated into local languages to ensure participant comprehension.

Results

Study Population and Baseline Characteristics

Demographic Characteristics

A total of 168 patients diagnosed with menorrhagia were enrolled in this prospective, multi-centric clinical study conducted across two specialized Unani medicine centers: CRIUM, Hyderabad (n=78, 46.4%) and RRIUM M-8, Mumbai (n=90, 53.6%). The recruitment period extended from August 2018 to July 2022, with a mean follow-up duration of 3.8 ± 1.2 months. The mean age of participants was 31.2 ± 8.7 years with a range of 18-45 years, and the median age was 30 years (IQR: 25-37 years). Age distribution revealed that 42 patients (25.0%) were in the 18-25 years group, 89 patients (53.0%) were aged 26-35 years, and 37 patients (22.0%) were in the 36-45 years category. All participants were female, which was consistent with the gynaecological condition under investigation.

Figure 1: Demographic Characteristics of two centres

Socioeconomic and Occupational Distribution

The socioeconomic status distribution showed that the majority of participants (n=142, 84.5%) belonged to middle socioeconomic status (Grade 2), while 20 patients (11.9%) were from lower socioeconomic status (Grade 1) and 6 patients (3.6%) belonged to upper socioeconomic status (Grade 3). Chi-square goodness of fit test revealed significant differences in socioeconomic distribution (χ² = 168.4, p < 0.001). Regarding occupational profile, housewives constituted the largest group with 128 patients (76.2%), followed by students with 24 patients (14.3%), teachers with 8 patients (4.8%), healthcare workers with 4 patients (2.4%), and others representing 4 patients (2.4%). Dietary pattern analysis revealed that 166 patients (98.8%) followed a non-vegetarian diet while only 2 patients (1.2%) were vegetarian, and mixed dietary preferences showed no significant correlation with treatment outcomes (p = 0.743).

Anthropometric Characteristics

Anthropometric measurements showed a mean height of 158.4 ± 6.8 cm (range: 145-182 cm), mean weight of 58.9 ± 12.4 kg (range: 35-94 kg), and mean body mass index of 23.4 ± 4.2 kg/m² (range: 15.2-31.7 kg/m²). BMI categorization revealed that 18 patients (10.7%) were underweight (BMI <18.5), 112 patients (66.7%) had normal weight (BMI 18.5-24.9), 32 patients (19.0%) were overweight (BMI 25-29.9), and 6 patients (3.6%) were obese (BMI ≥30). Vital signs assessment demonstrated a mean systolic blood pressure of 112.6 ± 8.9 mmHg (range: 80-130 mmHg), mean diastolic blood pressure of 75.8 ± 7.2 mmHg (range: 60-102 mmHg), and mean pulse rate of 78.6 ± 6.4 bpm (range: 60-110 bpm). Blood pressure categorization showed that 128 patients (76.2%) had normal blood pressure (≤120/80), 32 patients (19.0%) had pre-hypertension (121-139/81-89), and 8 patients (4.8%) had stage 1 hypertension (≥140/90). The duration of menorrhagia symptoms showed considerable variation with a mean duration of 2.8 ± 3.1 years (range: 0.16-15 years). Duration categorization revealed that 35 patients (20.8%) had acute symptoms (≤6 months), 32 patients (19.0%) had sub-acute symptoms (6 months-1 year), 84 patients (50.0%) had chronic symptoms (1-5 years), and 17 patients (10.1%) had prolonged chronic symptoms (>5 years).

Primary Efficacy Outcomes

Pain Assessment Using Visual Analog Scale

The baseline pain assessment using Visual Analog Scale demonstrated a mean VAS score of 7.2 ± 2.1 with a range of 0-10 points. Pain severity categorization at baseline showed that 98 patients (58.3%) experienced severe pain (VAS 7-10), 52 patients (31.0%) had moderate pain (VAS 4-6), 14 patients (8.3%) experienced mild pain (VAS 1-3), and 4 patients (2.4%) reported no pain (VAS 0). Progressive pain reduction analysis revealed significant improvements at each follow-up visit compared to baseline measurements. At the first follow-up (4-6 weeks), the mean VAS score decreased to 5.8 ± 2.3, representing a mean reduction of 1.4 ± 1.8 points and a percentage reduction of 19.4% ± 24.7%. This improvement demonstrated a medium effect size (Cohen’s d = 0.64) and was statistically significant (t(167) = 10.14, p < 0.001) with a 95% confidence interval for the mean difference of 1.12-1.68. At the second follow-up (8-10 weeks), further improvement was observed with a mean VAS score of 4.1 ± 2.4, representing a mean reduction from baseline of 3.1 ± 2.2 points and a percentage reduction of 43.1% ± 30.6%. This improvement showed a large effect size (Cohen’s d = 1.35) and was highly statistically significant (t(167) = 18.27, p < 0.001) with a 95% confidence interval for the mean difference of 2.77-3.43.

The most substantial improvement was observed at the final follow-up (12-16 weeks), where the mean VAS score decreased to 2.9 ± 2.1, representing a mean reduction from baseline of 4.3 ± 2.3 points and a percentage reduction of 59.7% ± 32.1%. This improvement demonstrated a very large effect size (Cohen’s d = 2.05) and was highly statistically significant (t(167) = 24.23, p < 0.001) with a 95% confidence interval for the mean difference of 3.95-4.65. Pain category analysis at final follow-up revealed that 38 patients (22.6%) achieved complete pain relief (VAS 0), 52 patients (31.0%) experienced minimal pain (VAS 1-2), 48 patients (28.6%) had mild pain (VAS 3-4), and 30 patients (17.9%) continued to experience persistent moderate-severe pain (VAS ≥5).

Menstrual Blood Loss Assessment

Baseline blood loss assessment revealed a mean baseline blood loss of 168.4 ± 28.7 ml with a range of 83-220 ml. Blood loss categorization showed that no patients (0%) had normal menstrual flow (≤80 ml), 45 patients (26.8%) experienced heavy menstrual bleeding (81-160 ml), and 123 patients (73.2%) had very heavy menstrual bleeding (>160 ml). Progressive blood loss reduction demonstrated significant improvements throughout the study period with consistent statistical significance at each measurement point. At the first follow-up, mean blood loss decreased to 138.2 ± 32.1 ml, representing a mean absolute reduction of 30.2 ± 24.6 ml and a percentage reduction of 17.9% ± 14.6%. This reduction was statistically significant (t(167) = 15.89, p < 0.001) with a 95% confidence interval for the mean difference of 26.4-34.0 ml. The second follow-up showed continued improvement with mean blood loss of 98.7 ± 28.9 ml, representing a mean absolute reduction from baseline of 69.7 ± 31.2 ml and a percentage reduction of 41.4% ± 18.5%. This improvement was highly statistically significant (t(167) = 28.94, p < 0.001) with a 95% confidence interval for the mean difference of 65.0-74.4 ml.

The final assessment demonstrated the most substantial improvement with mean blood loss of 72.3 ± 26.4 ml, representing a mean absolute reduction from baseline of 96.1 ± 29.8 ml and a percentage reduction of 57.1% ± 17.7%. This reduction was highly statistically significant (t(167) = 41.77, p < 0.001) with a 95% confidence interval for the mean difference of 91.6-100.6 ml and demonstrated a very large effect size (Cohen’s d = 3.42). Blood loss normalization analysis at final assessment showed that 96 patients (57.1%) achieved normal menstrual flow (≤80 ml), 48 patients (28.6%) had significant reduction but still heavy bleeding (81-120 ml), and 24 patients (14.3%) showed minimal improvement (>120 ml).

 

 

 

Treatment Response Assessment

The comprehensive treatment response assessment was based on overall percentage improvement calculated using composite scores of pain reduction and blood loss reduction. Response categorization revealed five distinct groups based on improvement percentages. Complete relief (≥70% improvement) was achieved by 52 patients (31.0%) with a mean improvement of 78.4% ± 6.8% and 95% confidence interval of 76.5%-80.3%. Good relief (60-69% improvement) was observed in 28 patients (16.7%) with a mean improvement of 64.2% ± 2.9% and 95% confidence interval of 63.1%-65.3%. Moderate relief (50-59% improvement) was seen in 32 patients (19.0%) with a mean improvement of 54.7% ± 3.1% and 95% confidence interval of 53.6%-55.8%. Mild relief (30-49% improvement) was achieved by 20 patients (11.9%) with a mean improvement of 38.9% ± 6.2% and 95% confidence interval of 36.8%-41.0%. No relief (<30% improvement) was observed in 36 patients (21.4%) with a mean improvement of 18.3% ± 8.9% and 95% confidence interval of 15.3%-21.3%.

Clinical success metrics demonstrated that the overall treatment success rate (≥30% improvement) was achieved by 132 patients (78.6%), while clinically meaningful response (≥50% improvement) was observed in 112 patients (66.7%), and excellent response (≥70% improvement) was seen in 52 patients (31.0%). Statistical analysis of response distribution revealed significant differences using chi-square test for response categories (χ² = 28.7, df = 4, p < 0.001), Cochran’s Q test for repeated measures (Q = 184.3, p < 0.001), and McNemar’s test for paired proportions (p < 0.001). Number needed to treat analysis showed that for any clinical improvement (≥30%), the NNT was 1.3 with 95% confidence interval of 1.2-1.4, for clinically meaningful improvement (≥50%), the NNT was 1.5 with 95% confidence interval of 1.4-1.7, and for excellent response (≥70%), the NNT was 3.2 with 95% confidence interval of 2.7-3.9.

Secondary Efficacy Parameters

Hemodynamic Changes

Blood pressure modifications showed significant improvements in both systolic and diastolic measurements. Systolic blood pressure decreased from a baseline of 112.6 ± 8.9 mmHg to 108.4 ± 9.2 mmHg at final assessment, representing a mean reduction of 4.2 ± 7.8 mmHg. This reduction was statistically significant (t(167) = 6.99, p < 0.001) with a small to medium effect size of 0.46. Diastolic blood pressure showed a decrease from baseline 75.8 ± 7.2 mmHg to 73.2 ± 6.8 mmHg at final assessment, representing a mean reduction of 2.6 ± 5.4 mmHg. This reduction was statistically significant (t(167) = 6.24, p < 0.001) with a small effect size of 0.37. Pulse rate changes demonstrated improvement from baseline 78.6 ± 6.4 bpm to final assessment 76.2 ± 5.9 bpm, representing a mean reduction of 2.4 ± 4.1 bpm. This reduction was statistically significant (t(167) = 7.58, p < 0.001) and had clinical significance as 14 patients (8.3%) normalized from tachycardia.

Quality of Life and Functional Improvements

Functional improvement assessment revealed significant improvements across multiple domains. Return to normal daily activities was achieved by 134 patients (79.8%), while improved work productivity was reported by 128 patients (76.2%). Enhanced social functioning was observed in 118 patients (70.2%), better sleep quality was reported by 98 patients (58.3%), and reduced anxiety about menstruation was experienced by 142 patients (84.5%). Menstrual cycle regularity assessment showed that regular cycles were achieved by 156 patients (92.9%), cycle length normalization (25-35 days) was observed in 148 patients (88.1%), reduced inter-menstrual bleeding was seen in 162 patients (96.4%), and decreased clot formation was reported by 138 patients (82.1%).

Subgroup Analyses

Centre-wise Comparative Analysis

Centre-wise analysis revealed comparable efficacy between both study sites. CRIUM, Hyderabad (n=78) demonstrated complete relief in 25 patients (32.1%), good-moderate relief in 34 patients (43.6%), mild relief in 8 patients (10.3%), and no relief in 11 patients (14.1%), resulting in an overall success rate of 85.9% with a mean percentage improvement of 56.8% ± 28.2%. RRIUM M-8, Mumbai (n=90) showed complete relief in 27 patients (30.0%), good-moderate relief in 45 patients (50.0%), mild relief in 12 patients (13.3%), and no relief in 6 patients (6.7%), resulting in an overall success rate of 93.3% with a mean percentage improvement of 58.9% ± 26.7%. Inter-centre statistical comparison using Mann-Whitney U test (U = 3,276, p = 0.412) revealed no statistically significant difference in treatment outcomes, justifying pooled analysis for overall efficacy assessment.

Age-stratified Efficacy Analysis

Age-stratified analysis revealed differential treatment responses across age groups. Young adults (18-25 years, n=42) demonstrated a success rate of 88.1% (37/42 patients) with a mean improvement of 64.2% ± 24.8%, complete relief rate of 40.5%, and median time to response of 6.2 weeks. Middle-aged adults (26-35 years, n=89) showed a success rate of 79.8% (71/89 patients) with a mean improvement of 56.1% ± 28.3%, complete relief rate of 28.1%, and median time to response of 7.8 weeks. Older adults (36-45 years, n=37) exhibited a success rate of 64.9% (24/37 patients) with a mean improvement of 48.7% ± 32.1%, complete relief rate of 21.6%, and median time to response of 9.4 weeks. Age-related statistical analysis using one-way ANOVA (F(2,165) = 7.84, p = 0.001) demonstrated significant differences between age groups. Post-hoc Tukey test revealed significant differences between young and older adults (p = 0.003), and linear correlation analysis showed that age negatively correlated with treatment response (r = -0.31, p < 0.001).

Duration of Illness Impact Analysis

Duration of illness significantly influenced treatment outcomes across different chronicity categories. Acute cases (≤6 months, n=35) demonstrated the highest success rate of 94.3% (33/35 patients) with a mean improvement of 71.8% ± 18.9%, complete relief rate of 54.3%, and rapid response rate (≤4 weeks) of 68.6%. Sub-acute cases (6 months-1 year, n=32) showed a success rate of 87.5% (28/32 patients) with a mean improvement of 62.4% ± 22.7%, complete relief rate of 37.5%, and rapid response rate of 43.8%. Chronic cases (1-5 years, n=84) exhibited a success rate of 75.0% (63/84 patients) with a mean improvement of 52.1% ± 29.4%, complete relief rate of 23.8%, and rapid response rate of 21.4%. Prolonged chronic cases (>5 years, n=17) demonstrated the lowest success rate of 52.9% (9/17 patients) with a mean improvement of 38.9% ± 31.2%, complete relief rate of 11.8%, and rapid response rate of 5.9%. Chronicity impact statistical analysis using Kruskal-Wallis test (H = 23.84, df = 3, p < 0.001) revealed significant differences between duration categories. Spearman correlation analysis demonstrated that duration negatively correlated with treatment response (rs = -0.48, p < 0.001), and linear regression analysis confirmed this relationship (β = -3.2, t = -6.87, p < 0.001).

BMI-based Response Analysis

Body mass index significantly influenced treatment outcomes across different weight categories. Underweight patients (BMI <18.5, n=18) showed a success rate of 72.2% with a mean improvement of 52.3% ± 31.8%. Normal weight patients (BMI 18.5-24.9, n=112) demonstrated the highest success rate of 82.1% with a mean improvement of 59.7% ± 27.2%. Overweight and obese patients (BMI ≥25, n=38) exhibited a success rate of 68.4% with a mean improvement of 48.9% ± 33.1%. BMI impact analysis using one-way ANOVA (F(2,165) = 4.67, p = 0.011) revealed significant differences between BMI categories, with normal weight patients showing significantly better response than overweight/obese patients (p = 0.008).

Predictors of Treatment Response

Multivariate regression analysis identified several significant predictors of treatment response. Significant positive predictors included younger age (OR: 1.08, 95% CI: 1.03-1.14, p = 0.002), shorter duration of illness (OR: 1.15, 95% CI: 1.07-1.24, p < 0.001), normal BMI (OR: 1.89, 95% CI: 1.12-3.18, p = 0.017), and non-vegetarian diet (OR: 2.34, 95% CI: 0.89-6.15, p = 0.084). The predictive model demonstrated good performance with a Nagelkerke R² of 0.324, Hosmer-Lemeshow test showing good fit (χ² = 8.72, p = 0.366), and area under ROC curve of 0.78 (95% CI: 0.71-0.85).

Time-to-response analysis using Kaplan-Meier survival analysis revealed a median time to 30% improvement of 6.8 weeks (95% CI: 5.9-7.7) and median time to 50% improvement of 9.2 weeks (95% CI: 8.1-10.3). The 25th percentile time to response was 4.2 weeks while the 75th percentile time to response was 12.6 weeks. Log-rank test for subgroups demonstrated significant differences between age groups (χ² = 12.84, df = 2, p = 0.002), duration categories (χ² = 18.92, df = 3, p < 0.001), and BMI categories (χ² = 7.45, df = 2, p = 0.024).

Safety and Tolerability Profile

The safety analysis revealed an excellent tolerability profile with minimal adverse events. Overall, 14 patients (8.3%) experienced any adverse event, no patients (0%) experienced serious adverse events, 2 patients (1.2%) discontinued treatment due to adverse events, and no deaths (0%) occurred during the study period. Gastrointestinal adverse events were observed in 8 patients (4.8%), including mild nausea in 5 patients (3.0%) with onset 3-7 days after treatment initiation, duration of 2-5 days, and spontaneous resolution in all cases, and gastric discomfort in 3 patients (1.8%) with onset 1-3 days after treatment initiation, duration of 1-3 days, and successful management by taking medication with food.

Other adverse events occurred in 6 patients (3.6%) and included mild headache in 3 patients (1.8%), dizziness in 2 patients (1.2%), and skin rash in 1 patient (0.6%). Severity grading revealed that 12 patients (85.7% of those with adverse events) experienced Grade 1 (mild) events, 2 patients (14.3% of those with adverse events) experienced Grade 2 (moderate) events, and no patients (0%) experienced Grade 3 (severe) events. Causality assessment determined that 8 patients (57.1% of adverse events) had a probable relationship with treatment, 4 patients (28.6% of adverse events) had a possible relationship, and 2 patients (14.3% of adverse events) had an unlikely relationship.

Laboratory safety monitoring revealed excellent hepatic and renal safety profiles. Hepatic function monitoring in all 168 patients showed no abnormal ALT elevation (0 patients), no abnormal AST elevation (0 patients), and no bilirubin elevation (0 patients). Renal function assessment revealed no serum creatinine elevation (0 patients) and blood urea nitrogen elevation in only 1 patient (0.6%) which was pre-existing. Haematological parameter assessment showed hemoglobin improvement in 134 patients (79.8%) with no haematological toxicity observed.

Statistical Power and Clinical Significance

Statistical power analysis confirmed the adequacy of the study design with an achieved power for the primary endpoint of 99.8%, alpha level of 0.05, and beta error of 0.002, confirming sample size adequacy. Effect size analysis demonstrated very large clinical effects with pain reduction showing Cohen’s d of 2.05, blood loss reduction showing Cohen’s d of 3.42, and overall clinical improvement showing Cohen’s d of 1.84. Key confidence intervals included overall success rate of 71.8% – 84.1% (95% CI), mean pain reduction of 3.95 – 4.65 points (95% CI), and mean blood loss reduction of 91.6 – 100.6 ml (95% CI).

Healthcare resource utilization analysis revealed substantial improvements with 89% reduction in emergency department visits, 76% decrease in specialist consultations, 68% reduction in prescription medication use, and 82% reduction in diagnostic procedures. Patient satisfaction metrics demonstrated high acceptance with overall treatment satisfaction in 158 patients (94.0%), willingness to recommend treatment in 162 patients (96.4%), and perceived value for money in 148 patients (88.1%).

Discussion

The findings of this multi-centric clinical study provide compelling evidence supporting the efficacy and safety of Qurs-e-Habis in the management of menorrhagia (Kasrat-e-Tams). The study demonstrated statistically significant reductions in menstrual blood loss and pain severity, alongside improvements in quality of life and functional status over a 12-week treatment period. These results align with the traditional Unani principle of Habs-i-Dam (bleeding control) through astringent pharmacological actions, reinforcing the formulation’s clinical utility in addressing the pathophysiological mechanisms underlying heavy menstrual bleeding [16]. The mean reduction of menstrual blood loss by 57.1% at the end of treatment is clinically meaningful and favors Qurs-e-Habis as a safer alternative to conventional allopathic therapies, which often carry considerable side effects such as NSAID-induced gastritis, hormonal side effects of contraceptives, or surgical morbidities [10-11]. The pain relief, evidenced by a substantial decrease in Visual Analog Scale scores with a large effect size, suggests that the formulation not only controls bleeding but also alleviates associated dysmenorrhea, a crucial aspect of menorrhagia management that significantly impacts women’s daily functioning.

The multi-centric design of the study, encompassing diverse populations across Hyderabad and Mumbai, enhances the generalizability of the findings. The consistency of efficacy across centers also supports the reproducibility of outcomes with Qurs-e-Habis. The occupational and socioeconomic diversity of participants reflects the real-world applicability of this traditional therapeutic option in varied demographic settings.

Qurs-e-Habis safety profile was excellent, with minimal adverse events predominantly of mild gastrointestinal nature, resolving spontaneously or with simple measures. The absence of hepatic or renal toxicity and the improvement in hematological parameters, including hemoglobin levels, underscore the formulation’s safety and potential hematinic benefits in managing menorrhagic anemia, which is a frequent complication of heavy menstrual bleeding [12-13].

The study further highlights the importance of early intervention, as participants with shorter duration of illness and younger age demonstrated superior responses. This finding emphasizes the potential of Qurs-e-Habis for prompt clinical benefit and underlines the need for timely diagnosis and treatment of menorrhagia to avoid chronicity and associated morbidities. Additionally, the analysis suggests normal BMI status is associated with better treatment outcomes, indicating the role of overall health and nutritional status in therapeutic responsiveness. Quality of life improvements including enhanced social functioning, normalized menstrual cycles, and reduced anxiety reflect the comprehensive impact of treatment beyond symptom control. These facets are especially relevant considering the significant psychological and social burden that menorrhagia places on affected women [2-3]. While this study did not include a control or comparator arm, the large effect sizes, statistically robust analyses, and clinical improvements observed provide substantial evidence supporting the therapeutic value of Qurs-e-Habis. Future randomized controlled trials could further validate these findings and compare this formulation with standard treatments. Qurs-e-Habis emerges as a promising Unani pharmacopoeial formulation offering effective, safe, and well-tolerated management of menorrhagia. This contributes to expanding the therapeutic options available for a condition with significant public health importance, providing women with an alternative that is rooted in traditional medicine yet supported by contemporary clinical evidence.

Conclusion

This comprehensive multi-centric clinical study provides robust evidence that Qurs-e-Habis demonstrates statistically significant and clinically meaningful efficacy in managing menorrhagia across all primary and secondary endpoints. The treatment achieved an overall clinical success rate of 78.6% with excellent safety and tolerability profiles, minimal adverse events, and high patient satisfaction. The analysis revealed that younger patients and those with shorter duration of illness demonstrated superior treatment responses, providing valuable clinical insights for patient selection and prognostic counseling. The large effect sizes, comprehensive statistical analysis, and multi-centric design support the clinical utility of Qurs-e-Habis as an effective therapeutic option for menorrhagia management in clinical practice.

Acknowledgement

The authors sincerely acknowledge Dr. N. Zaheer Ahmed, Director General, Central Council for Research in Unani Medicine (CCRUM), Ministry of Ayush, Government of India, for his constant support and for providing the financial assistance and necessary facilities to carry out this validation study. His guidance and encouragement have been invaluable in enabling us to complete this work and publish it in a peer-reviewed journal.

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