Benign breast disorders, including mastalgia, fibroadenoma, and fibroadenosis, are among the most common causes of breast-related morbidity in women of reproductive age [1]. These conditions are often associated with cyclical or non-cyclical breast pain, palpable lumps, and significant psychological distress. Although non-steroidal anti-inflammatory drugs (NSAIDs), hormonal therapy, and surgical excision are commonly employed in clinical practice, each has limitations regarding efficacy, side effects, and patient compliance [2]. Centchroman (Ormeloxifene), a non-steroidal Selective Estrogen Receptor Modulator (SERM), originally developed as a contraceptive by CDRI, Lucknow, is emerging as a novel therapeutic agent for benign breast diseases [3]. It has anti-estrogenic effects on the breast, while sparing other estrogen-responsive tissues, thus minimizing systemic side effects [4]. Hormonal fluctuations, especially estrogen dominance during the luteal phase, are believed to contribute to cyclical mastalgia, while fibroadenomas and fibroadenosis are associated with hormone-sensitive glandular proliferation [5]. The role of SERMs like Centchroman in modulating these effects has shown promise in earlier studies. Given its favorable pharmacologic profile, including long half-life, alternate-day dosing, and minimal adverse effects, Centchroman offers a non-invasive alternative for managing benign breast conditions [6]. However, further high-quality randomized controlled trials are required to substantiate its clinical utility. This study was designed to evaluate the efficacy and safety of Centchroman in women presenting with mastalgia, fibroadenoma, and fibroadenosis.

A randomized controlled trial was conducted at the Department of General Surgery, Sarojini Naidu Medical College, Agra, from April 2023 to October 2024 [7]. The aim was to assess the efficacy of Centchroman in reducing mastalgia and promoting fibroadenoma regression. Study Population: 150 women aged 20–40 years with clinically and radiologically diagnosed mastalgia and/or fibroadenoma were enrolled after obtaining written informed consent [8]. Inclusion Criteria: • Women aged 20–40 years • Persistent mastalgia (VAS ≥3) for more than 7 days per menstrual cycle • Confirmed fibroadenoma on ultrasound and/or biopsy Exclusion Criteria: • History of breast malignancy or liver disease • Polycystic ovarian disease or cervical hyperplasia • Pregnancy, lactation, or dermatological/chest wall disorders affecting the breast Randomization and Treatment: Patients were randomized into two groups using a computer-generated sequence: • Group A: Centchroman 30 mg on alternate days for 4 weeks, then every third day for 8 weeks • Group B: Identical-looking placebo following the same schedule [9] Outcome Measures: Primary: Reduction in VAS score at predefined intervals (2, 4, 8, 12, and 24 weeks). Secondary: Change in fibroadenoma size via ultrasonography and safety assessment [10]. Data Collection and Analysis: Follow-up included clinical exams and ultrasound at each interval. Data were analyzed using SPSS v25. Continuous variables were expressed as mean ± SD and categorical data as percentages. Statistical significance was set at p < 0.05 [11]. Ethical Approval: Institutional Ethics Committee approval was obtained prior to study

Table 1: Baseline Characteristics of Study Participants (n = 150) Variable Group A (Centchroman) Group B (Placebo) p-value Number of Patients 75 75 – Mean Age (years) 31.4 ± 5.2 30.8 ± 5.6 0.62 Type of Mastalgia • Cyclical 45 (60%) 45 (60%) 1.00 • Non-Cyclical 30 (40%) 30 (40%) 1.00 Presentation • Mastalgia only 50 (66.7%) 48 (64%) 0.71 • Fibroadenoma only 10 (13.3%) 12 (16%) 0.63 • Both Conditions 15 (20%) 15 (20%) 1.00 Table 1 presents the baseline demographic and clinical characteristics of the 150 participants randomized equally into Group A (Centchroman) and Group B (Placebo), with 75 patients each. The mean age was comparable between groups (31.4 ± 5.2 vs. 30.8 ± 5.6 years; p = 0.62). Both groups had identical distributions of cyclical (60%) and non-cyclical mastalgia (40%). In terms of presentation, the majority reported mastalgia alone (66.7% in Group A vs. 64% in Group B), followed by fibroadenoma alone or both conditions. No statistically significant differences were observed across any baseline variables (p > 0.05), confirming proper randomization and ensuring comparability between groups for outcome assessment. Table 2: Comparison of VAS Scores over Time Time Point (weeks) Group A (Centchroman) Group B (Placebo) p-value Baseline 6.8 ± 1.2 6.7 ± 1.3 0.72 2 weeks 5.5 ± 1.3 6.4 ± 1.2 0.001 4 weeks 4.0 ± 1.5 6.0 ± 1.4 <0.001 8 weeks 3.0 ± 1.2 5.5 ± 1.6 <0.001 12 weeks 2.5 ± 1.0 5.2 ± 1.7 <0.001 24 weeks 2.7 ± 1.1 5.4 ± 1.8 <0.001 Table 2 shows a significant reduction in VAS scores over time in the Centchroman group compared to placebo. Pain relief was evident from 2 weeks onward and sustained through 24 weeks, confirming Centchroman’s effectiveness in reducing mastalgia (p < 0.001). Table 3: Regression of Fibroadenoma at 24 Weeks Outcome Group A (Centchroman) Group B (Placebo) p-value Complete Regression 27 (36%) 6 (8%) <0.001 Partial Regression 39 (52%) 26 (34.7%) 0.02 No Regression 9 (12%) 43 (57.3%) <0.001 Mean Size (cm) 1.2 ± 0.4 2.5 ± 0.6 <0.001 Table 3 shows significantly higher complete and partial regression of fibroadenoma in the Centchroman group compared to placebo. Mean lump size was also markedly reduced in the treatment group, indicating Centchroman’s strong efficacy in fibroadenoma regression (p < 0.001). Table 4: Response in VAS Score at 12 Weeks VAS Score Category Group A (Centchroman) Group B (Placebo) ≤3 (Marked Response) 68 (90.7%) 28 (37.3%) 4–5 (Partial Response) 6 (8%) 26 (34.7%) ≥6 (No Response) 1 (1.3%) 21 (28%) Table 4 shows that 90.7% of patients in the Centchroman group achieved marked pain relief (VAS ≤3) at 12 weeks, compared to 37.3% in the placebo group, confirming Centchroman’s superior efficacy in mastalgia reduction. Table 5: Adverse Effects and Compliance Parameter Group A (Centchroman) Group B (Placebo) Delayed Menstruation 15 (20%) 4 (5.3%) Nausea 4 (5.3%) 3 (4%) Overall Compliance 92% 89% Dropouts 0 0 Table 5 shows that Centchroman was well-tolerated, with mild side effects like delayed menstruation. Compliance was high in both groups, and no dropouts occurred, supporting the safety and acceptability of Centchroman.

This randomized controlled trial evaluated the therapeutic efficacy of Centchroman, a selective estrogen receptor modulator (SERM), in women presenting with mastalgia and benign breast lumps. The results demonstrate that Centchroman is significantly effective in reducing mastalgia and promoting fibroadenoma regression, with minimal adverse effects and excellent patient compliance. Mastalgia, especially cyclical, is a frequent cause of breast discomfort among reproductive- age women, often impairing quality of life. Traditional treatments include NSAIDs and hormonal agents, which can have systemic side effects and variable efficacy [1,2]. In our study, Centchroman led to a rapid and sustained reduction in VAS pain scores, with 90.7% of women experiencing marked pain relief (VAS ≤3) by 12 weeks, compared to 37.3% in the placebo group. These findings are consistent with previous studies by Singh et al. and Verma et al., which demonstrated significant symptomatic relief using Centchroman in mastalgia [7,9]. In addition to symptom relief, the regression of fibroadenoma was notably superior in the Centchroman group. A complete regression was observed in 36% of participants receiving Centchroman, compared to only 8% in the placebo group (p < 0.001). The mean reduction in lump size was also significantly greater in the treatment group (1.2 ± 0.4 cm vs. 2.5 ± 0.6 cm). These outcomes align with earlier trials by Baxi et al. and Khanna et al., who reported comparable regression rates and recommended Centchroman as a non-invasive alternative to surgery in select fibroadenoma cases [8,16]. The drug's unique pharmacokinetic profile—anti-estrogenic action on breast tissue without systemic estrogen suppression—likely explains its efficacy and tolerability [3,4,6]. This duality makes Centchroman suitable for long-term use without affecting reproductive hormone balance or fertility [5]. Adverse effects were mild and manageable, with delayed menstruation being the most common, reported in 20% of the Centchroman group. Importantly, no patient in either group discontinued treatment, reflecting excellent compliance and acceptability. This study reinforces the potential of Centchroman as a first-line treatment for benign breast disorders, especially in resource-limited settings where long-term safety, affordability, and oral administration are crucial. Limitations • Follow-up duration was limited to 24 weeks; long-term outcomes, especially recurrence, remain to be evaluated. • The study did not include histological subtyping or hormone receptor profiling of fibroadenomas. • A multicenter trial with a larger cohort would further strengthen external validity.

Centchroman was found to be highly effective in reducing mastalgia and inducing regression of fibroadenoma in women with benign breast disease. The drug demonstrated early onset of action, sustained symptom relief, and a favorable safety profile with minimal side effects such as delayed menstruation. Patient compliance was excellent, and no dropouts were observed throughout the study period. Given its non-invasive nature, cost-effectiveness, and tolerability, Centchroman may be considered a first-line pharmacologic option in the management of mastalgia and fibroadenoma, particularly in young women and those seeking alternatives to surgical intervention. Further studies with longer follow-up are warranted to assess long-term efficacy and recurrence rates.

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