COMPARATIVE STUDY ON SAFETY AND EFFICACY OF THE DECOCTIONS OF SESAMUM INDICUM, NIGELLA SATIVA AND ITS COMBINATION ON POLYCYSTIC OVARY SYNDROME

COMPARATIVE STUDY ON SAFETY AND EFFICACY OF THE DECOCTIONS OF SESAMUM INDICUM, NIGELLA SATIVA AND ITS COMBINATION ON POLYCYSTIC OVARY SYNDROME

S. H. K. Deepthika, K. P. K. R. Karunagoda * and Pathirage Kamal Perera *

Department of Ayurveda Pharmacology and Community Medicine, Faculty of Indigenous Medicine, University of Colombo, Sri Lanka.

ABSTRACT: This study investigated the efficacy and safety of three herbal decoctions for managing Polycystic Ovary Syndrome (PCOS), a condition affecting 2–26% of women globally and considered incurable within allopathic medicine and offers symptomatic treatments. This randomized, single-blind clinical trial, conducted between February 2022 and June 2024, enrolled 90 PCOS patients diagnosed by the Rotterdam (2003) criteria. Participants were randomly allocated into three intervention groups: Nigella sativa (Arm I), Sesamum indicum (Arm II), and a combination of both (Arm III). Each group received 30 ml of the assigned decoction twice daily over three months. Clinical parameters were assessed using established grading scales, including androgenic alopecia, hirsutism, acne, and acanthosis nigricans. Additionally, ultrasound scans (USS) were performed pre- and post-treatment to evaluate changes in ovarian morphology. Results indicated a significant reduction in ovarian volume for Arms I (P=0.029) and II (P=0.008) and an increase in follicle size across all three arms. The number of participants with polycystic ovarian morphology significantly decreased in Arm I (P=0.016) and II (P=0.004). However, one-way ANOVA revealed no statistically significant differences between the three groups regarding subjective clinical symptoms or objective ultrasound parameters. The study concludes that all three interventions effectively regulate menstruation and enhance follicular maturity. Among the three, the combined therapy of Nigella sativa and Sesamum indicum (Arm III) demonstrated the most pronounced benefits. These findings suggest that Nigella sativa and Sesamum indicum, individually or in combination, hold potential as therapeutic options for PCOS management without any side effects.

Keywords: Polycystic ovary syndrome, Nigella sativa, Sesamum indicum, Hirsutism, Acanthosis nigricans

INTRODUCTION: Polycystic Ovary Syndrome (PCOS) ranks as one of the most common endocrine diseases in women of reproductive age ¹. The prevalence of PCOS varies by ethnicity, yet most clinical evidence suggests it is about 6-7%.

PCOS affects women of South Asian descent at an earlier age, with more severe symptoms and a more considerable prevalence ².

Polycystic Ovary Syndrome is characterized by the appearance of multiple small cysts in the ovaries, menstrual irregularities, and signs of excess androgen production such as hirsutism (excess facial or body hair), male or female pattern balding (hair loss), acanthosis nigricans (skin discolorations), and acne. Regarding menstrual irregularity, menses may be irregular, oligo-menorrheic (reduced frequency of menstruation), or amenorrheic (periods of six months or more without menstruation). In addition, PCOS is linked to obesity, insulin resistance, hypertension, elevated levels of lipids, and metabolic syndrome. A PCOS women with these high-risk features is more likely to get type II diabetes and cardiovascular diseases ³.

According to Ayurveda, PCOS can be mostly related to “Pushpaghni Jataharini,” a disease mentioned in Kashyapa Samhita ⁴ and considered a disorder involving Vata, Pitta, Kapha, Medas, Artavavahasrotas, and shukra/arthavadhatu, and its cysts are similar to Kaphaja Granthi (Granthi refers to knotty elevation). According to Ashtangahridaya and Susruta Samhita, it refers to nodular or glandular swelling with a hard, knotty, and rough appearance ⁵.

According to allopathic medicine, PCOS is an incurable condition and suggested symptom-focused treatments, such as hormone therapy, in-vitro fertilization, embryo transfer, and gamete intra-fallopian transfer. However, these have not been 100% effective, have adverse effects, and are not readily accessible to everyone. Hence, finding new treatment options for PCOS is essential. This research study aimed to evaluate the effectiveness of three herbal decoctions for PCOS: Nigella sativa (Arm I), Sesamum indicum (Arm II), and a combination of the two (Arm III).

MATERIAL AND METHODS:

Study Area: This study was conducted in the Gynecology clinic of the National Ayurveda Teaching Hospital, Borella, from February 2022 to June 2024. Patients were selected from those seeking treatments for PCOS and subfertility.

Participants: Participation in this research is voluntary. Patient recruitment was done by screening for eligibility criteria (inclusion, exclusion and diagnostic criteria).

Inclusion Criteria: PCOS women diagnosed by Rotterdam (2003) diagnostic criteria ⁶ for women between 20 and 40 years are included.

Exclusion Criteria: To ensure correct clinical assessment, conditions other than PCOS, suffering from other diseases that cause the same similar signs and symptoms of PCOS. (Thyroid disorders, severe insulin resistance, androgen-secreting neoplasm, etc., were excluded.) Patients having disorders of the reproductive tract, such as tuberculosis, carcinoma, and congenital deformities of the reproductive tract and other chronic illnesses, such as cardiac disease and hypertension, etc. and patients who are already on other treatment regimens were excluded.

Ethical Approval: The Ethics Review Committee, Institute of Indigenous Medicine (ERCIIM), University of Colombo, Sri Lanka (ERC no: 19/85) granted ethics approval, and the specialty board – Prasutitantra Streeroga of the Postgraduate Institute of Indigenous Medicine, Colombo University, Sri Lanka - approved the study protocol.

Sample Size: In PCOS cases, 3 months of conventional treatment response is about 30%, according to clinical experience in the conventional group.  In this clinical trial, I wished to test if a new therapeutic regimen can increase the response in PCOS patients to 60% with a power (1- b) of 80%. The type 1 error risk (2a) should be 5%. With 10% dropouts into account, 43 patients per group were included, resulting in a total of 129 patients being allocated.

Randomization: Participants were recruited randomly from the three arms. A randomization sequence was generated using an online randomization website. Each group was enrolled with an allocation ratio of 1:1:1.

Treatment Protocol:

TABLE 1: DRUG DOSAGE AND METHOD OF DRUG ADMINISTRATION

Participants in Arms I, II, and III received oral medication for twelve weeks. Drug dose and administration were carried out as in Table 1.

Follow-Up: Study participants were followed for three months.

Preparation of the Drugs: Decoctions were prepared according to one of the basic formulations of Kwatha mentioned in Ayurveda Pharmacopeia Part I ⁷.

Outcome Measurements:

Changes in PCOS-related Clinical Findings: Findings of day 12 Trans Abdominal Sonography (TAS) or Trans-Vaginal Sonography (TVS) (ovarian volume, Largest Follicle size and endometrial thickness). Assessment of clinical features by Rotterdam (2003) Diagnostic criteria were carried out before and after the treatment. Standard grading systems like the Global Acne grading System ⁸, Ferri-man-Gall -wey Scale ⁹, Sinclair Scale ¹⁰, and the Burke’s quantitative scale ¹¹ were used to assess those clinical features.

Safety Assessment: Each patient underwent hematological and biochemical investigations for safety assessment. FBS, AST/ALT, serum creatinine and GFR were taken before and after treatments.

RESULTS AND DISCUSSION: This randomized, single-blind comparative clinical trial was conducted from Feb 2022 to June 2024. There were several random clinical trials conducted using Ayurveda drugs for PCOS. However, this is the first trial to assess the main clinical signs of PCOS using standard scientifically evaluated questionnaires. According to scientifically calculated data, 129 samples were divided into three arms using a computerized random chart. Due to the COVID-19 pandemic, fuel shortage, and economic crisis periods, it could not allocate 43 patients per group. Thirty patients were allocated to Arm I; 33 patients were allocated to Arm II, and 30 patients were allocated to Arm III.  Due to heavy bleeding, two patients from Arm II were deducted, and one patient from Arm I was not continued due to raised gastritis symptoms after consuming the drug. Ultimately, 29 patients for Arm I, 31 for Arm II and 30 for Arm III continued till the end of the intervention.

TABLE 2: DISTRIBUTION OF PATIENTS’ DEMOGRAPHIC AND SOCIO-ECONOMIC CHARACTERISTICS BY TREATMENT GROUP

The age of the patients in the three treatments was within the ranges of early twenties and late thirties. Significant deviations between the three treatments cannot be seen in the patient’s age. Most of the patients in Arm II and Arm III were unmarried, whereas most in Arm I were married. Very few of the patients had up to primary education for all treatments. The majority of patients in Arm I group have got tertiary education while majority of patients in Arm II group have had secondary education. Most patients in all three groups have been doing mental-oriented jobs. The next highest number of patients in Arm I and II Treatments were housewives, while those in Arm II group were students. The number of patients who are doing physically oriented jobs is very low in all Arms. The mean age of menarches of the patients was almost the same for all treatment groups.

Clinical Presentation of the Sample:

TABLE 3: DISTRIBUTION OF THE SYMPTOMS OF THE PATIENTS

The most common symptom shown by patients was hirsutism. It has been shown by 75 patients out of 90 (83.3 %). The next highly reported symptom was oligomenorrhea, which was mentioned by 74 patients out of 90 (82.2 %). The symptom recorded from the least number of patients was amenorrhea (17.8 %).

Assessment of USS Findings:

TABLE 4: DESCRIPTIVE STATISTICS AND TESTING THE TREATMENT EFFICACY FROM USS DATA

* Significant at 5% level SD: Standard Deviation.

Considering the paired t-test, in Arm I, there was a significant drop in the volume of the left ovary, while Arm II showed a significant drop in the right ovary. For all the groups there were significant increases of the largest follicle size after giving the respective treatment.

TABLE 5: TESTING THE TREATMENT EFFICACY FROM POLYCYSTIC OVARIES

* Significant at 5% level

After the treatment, it shows a significant reduction in the number of patients with PCO by the ultrasound scan findings in Arm I (P = 0.016) and Arm III groups (P = 0.004).

TABLE 6: TESTING THE TREATMENT EFFICACY OF REGULAR MENSTRUATION FOR EACH TREATMENT GROUP

* Significant at 5% level

Looking at the p-values of the table, it can be concluded that a significantly greater number of patients’ menstruation has been regular after giving for all the arms.

Comparison of the Treatments:

TABLE 7: ANOVA TEST FOR USS DATA

Since, all the p-values are greater than 0.05, there is no sufficient statistical evidence to conclude that at least one average value on differences (before – after treatment) of treatment was not different from other treatments for every measurement. Hence, it is evident that there are no differences between the three arms concerning the volume of ovaries, endometrial thickness, and the largest follicle size.

TABLE 8: ANOVA – SUBTRACTED DATASET ON SIGNS AND SYMPTOMS

Since, all the p-values are greater than 0.05, there is no sufficient statistical evidence to conclude that at least one average score difference (before treatment – after treatment) of a treatment was not different from other treatments for all signs and symptoms. Hence, it is concluded that there are no differences between the three Arms with respect to hirsutism, acanthosis nigricans, acne and androgenic alopecia. As the p-value of the sign acne is less than 0.05, it can be concluded that there is a treatment effect on the treatment Arm II & III on reducing acne. However, it has not shown positive effectiveness in reducing hirsutism, acanthosis nigricans, and androgenic. Although Allopathic treatments can relieve PCOS symptoms, the recurrence rate is substantial following drug withdrawal, resulting in an extensive financial burden for both patients and society. As a result, comprehensive research into PCOS is critical ¹². According to a prevalence study conducted in 2005-2006, Sri Lanka reported the highest symptom of oligo/amenorrhea (95%) and 11 women with hirsutism (5%) ¹³. However, considering the present study, the most common symptom shown by patients Table 3 was hirsutism. Seventy-five patients have shown it out of 90 (83.3 %). The following highly reported symptom was oligomenorrhea, which 74 patients mentioned out of 90 (82.2 %). As the tested sample, one-fourth of the PCOS patients were with the constitution of Pitta Kapha (25.6%). The following highest number of patients’ constitution was Pitta (22.2%). High Pitta Kapha and Pitta constitution could be attributed to the selected age range. Pitta and Kapha were the most prominent in this age range ¹⁴. Some research has investigated the mechanisms by which weight gain and obesity contribute to the pathogenesis of PCOS via the lens of its three cardinal hallmarks of metabolic dysfunction, hyperandrogenism, and reproductive dysfunction, including the essential involvement of the insulin pathway ¹⁵.

Hence, Obesity/High BMI is a risk factor for PCOS. 42 patients in this study out of 90 were overweight and above in terms of their BMI values. The study focused on the primary outcome which was the return of regular periods in individuals with oligo/amenorrhea. Secondary outcome measures for PCOS were clinical presentations such as hirsutism, acanthosis nigricans, Acne, boldness, and ultrasound scan parameters. A significantly greater number of patients’ menstruation has been regular after giving treatment in Arm I, Arm II and Arm III Table 6.

As ultrasound scan parameters, Arms I and II showed significant deduction of ovarian volume and all three Arms showed significant increases in the follicle size after giving the respective treatment Table 4. There was a significant drop in the number of patients with polycystic ovaries in the USS after the treatment in the Arm I and Arm II Table 5.

Since, the p-value of sign acne is less than 0.05, it can be concluded that there is a treatment effect in Arms II and III on reducing acne. But it has not been significantly effective in reducing hirsutism, acanthosis nigricans, and androgenic. All the p-values related to clinical signs of Arm I are more significant than 0.05. Hence it has to be concluded that there is no treatment effect of the treatment Arm I on reducing clinical signs of hirsutism, acanthosis nigricans, acne and androgenic alopecia. When comparing three Arms by one-way analysis of variance (ANOVA) tests, it was proved that there are no differences between the three Arms concerning the objective parameters (obtained from Ultrasound Scan) and the subjective parameters (Hirsutism, Acanthosis nigricans, Acne, Boldness). The Chi-Square test was also carried out to test the association between the three Arms, and insignificant results were obtained. The pregnancy rate in subfertility patients was not statistically measured in this study.

However, the highest pregnancy rate, 11.7%, was recorded from Arm I (Nigella sativa group), while Arm III recorded an 11.11% pregnancy rate. Serum creatinine, GFR, SGOT, SGPT and FBS were tested as safety routine investigations before and after the treatment. According to the p-values of the results, Arm II and Arm III have been positively effective in reducing FBS.

However, there were no significant changes for other assessments after giving the treatments. Due to insignificant changes, the safety of three decoctions was proven. Insulin resistance, the most common metabolic feature, is found in almost 35%-80% of PCOS women ¹⁶. Insulin resistance is a major contributor to many obesity-related diseases ¹⁷.

Hence, PCOS is aggravated by obesity, primarily through worsening insulin resistance. A medicine that reduces weight and insulin resistance could benefit PCOS.  Arm II and Arm III both show positive effects in reducing BMI and reducing FBS. Hence Arm II or Arm III could be taken as the best treatment options. There is scientifically provided evidence regarding the beneficial effects of sesame on body adiposity indices ¹⁸ and the significant positive effects on fasting blood glucose ¹⁹.

TABLE 9: SIGNS AND SYMPTOM EVALUATION ACCORDING TO ROTTERDAM CRITERIA

Arm I consist of Nigella sativa decoction, Arm II consists of Sesamum indicum decoction and Arm III consists of Nigella sativa and Sesamum indicum combined decoction. Considering all positive effects of all parameters, Arm III (Nigella sativa + Sesamum indicum decoction) shows more positive effects. Hence, Nigella sativa and Sesamum indicum both can be used as single drugs and as combinations for PCOS conditions. Sesamum indicum identified as the better, most cost-effective herb for Sri Lankan PCOS patients among the three decoctions.

CONCLUSION: This study proves that all three arms improve follicular maturity and regulate menstruation significantly in PCOS cases. The USS reported the Nigella sativa treated arms significantly reduced PCO appearance, while the Sesamum indicum arm showed a significant clinical acne reduction. Considering the positive effects of all parameters, Arm III (Nigella sativa + Sesamum indicum decoction) significantly reduces PCOS appearance in USS, regularizing the menstruation and reducing some features related to hyperandrogenism. Hence, the study found that the combined preparation of Nigella sativa and Sesamum indicum showed a more significant effect on PCOS-related symptoms.

Recommendations: Some signs and symptoms, such as Acanthosis nigricans, Obesity, and Skin tags, appear due to long-term hormonal imbalances, and reducing these symptoms will take more time.

Considering the patient, the present clinical study period was three months, and it is not enough period to change the above symptoms. Therefore, long-term multi-center clinical trials are needed to observe such changes.

ACKNOWLEDGMENTS: Our honored thanks to the Director of the National Ayurveda Teaching Hospital and all the staff of Stree Roga Clinic of NATH. Wehumbly thank all the participants in this study for their cooperation. Further, we thank Dr. Priyadarshana Dharmawardhane for his valuable help, cooperation, and guidance in data processing.

CONFLICTS OF INTEREST: There is no conflict of interest.

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    How to cite this article:

    Deepthika SHK, Karunagoda KPKR and Perera PK: Comparative study on safety and efficacy of the decoctions of Sesamum indicum, Nigella sativa and its combination on polycystic ovary syndrome. Int J Pharm Sci & Res 2025; 16(5): 1300-07. doi: 10.13040/IJPSR.0975-8232.16(5).1300-07.

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