Effect of Saleekha and Majeeth in Polycystic Ovarian Disease: An Open Observational Study

Introduction: PCOD is a common, complex reproductive endocrinopathy characterized by menstrual irregularities, hyperandrogenism, polycystic ovaries, metabolic and psychological disorders and affects up to 18% of reproductive-aged women. Objectives: To evaluate the effect of Saleekha and Majeeth in PCOD. Materials and Methods: Clinically diagnosed Patients (n=30) with PCOD in age 18-35 years with oligomenorrhea or amenorrhoea were included in the study. Patients with thyroid dysfunction, systemic diseases, endometrial tuberculosis, malignancies on hormonal treatment in the last 3 months, pregnancy, and lactation were excluded. The research drug was administered orally in a dose of 3.5 gm B.D safūf (powder) of Saleekha with Joshānda (decoction) of Majeeth 7 gm BD for 14 days/ cycle for three consecutive cycles. Outcome measures were changes in subjective parameters (nature of bleeding, duration of cycles, duration of flow, amount of flow, weight reduction) and objective parameters, pictorial blood loss assessment chart (PBAC) score, basal metabolic index (BMI), modified Ferriman Gallwey (mFG) score, acanthosis nigricans scale and pelvic ultrasonography. Data were analyzed using the paired Student t -test. Results: Marked improvement was observed in menstrual irregularity and PBAC score with p <0.001 which is highly significant after the intervention. Significant change is seen in BMI, Ovarian volume, and SF-12 with p <0.001 after treatment. Safety parameters were within the normal range. Interpretation and Conclusion: Research drugs ( Saleekha and Majeeth ) can be used as an alternate remedy in PCOD patients, as it significant effect to regularize menstruation by reduction of BMI and probably by improving insulin resistance in PCOD. No adverse effect of the research drug was noted during the trial.


INTRODUCTION
][4] The exact cause of PCOD is unknown but it has certainly been linked to a variety of aetiological factors; genetic, environmental, lifestyle etc, [1,4,] contribute to the development of PCOD.Women may present with a number of reproductive, endocrine, metabolic and psychosocial symptoms. [1,2,4,5]ng-standing PCOD can lead to long term consequences including Type 2 DM, hypertension, cardiovascular disease, [5,1,2] endometrial cancer. [1,2,5,6]Early diagnosis and treatment can help control the symptoms and prevent long-term problems. [2] Unani text book, disease has been described under the headings of Ihtibās Al-Tamth (amenorrhea) is mainly caused by dominance of khilt-i-balghm which increases the viscosity of khūn-i-hayd and from sudda as a result menstrual blood is unable to expelled out of the uterus. [7]e principle of treatment is Ilaj biz zid; the temperament of the disease being bārid ratab, the drugs having garm wa khushk mizāj; possessing the properties like muddir-i-hayd, mulattif balgham, mufattῑh are used in the management of Ihtibās Al-Tamth; Also they transform the akhlāt towards hot temperament, facilitating the metabolism of balgham to dam. [8]veral single drugs and compound formulations are enlisted in the management in PCOD patients.Drugs such as Majeeth, Saleekha is selected as research drugs to induce menstruation in PCOD patients, as they exhibit the properties of mudirr-i-bawl wa hayd, mufattih-i-sudad, munaqqi-i-jiger, munáffith-i-balgham, mu' arriq, musakhkhin, muhallil-i-awrām. [9,10]In this study Majeeth, and Saleekha has been selected based on its ingredients and as per the indications and hypothesized, which probably may regularize the menstruation by reduction in BMI and improving insulin resistance.Hence, an open observational clinical study was envisaged.

Study design
An observational clinical study.

Study duration
One and half year from December 2020-February 2022.

Selection criteria
Patient both unmarried and married between 18-35 year of age, H/o irregular periods like oligomenorrhoea or amenorrhoea with PCOD.Presence of PCO on USG pelvis, obesity was included.Patients with systemic and endocrine diseases like HTN, DM, and thyroid dysfunction pregnancy and lactating women and on contraceptives, malignancies, endometrial tuberculosis were excluded.

The procedure of study
The Inclusion criteria fulfilled patients were included in study.
Participants were asked to provide details on their demographic data.Menstruation cycle with the medical history.In each patient, history is evaluated and a complete physical examination was performed including gynecological examination, investigations, were recorded in case record form structured for the study.

Method of preparation, dosage and route of administration
The purest form of Saleekha was provided by the pharmacy of NIUM and was further authenticated by FRLHT, Bengaluru.
With an A/c no.03711450000072.The drug was finely powdered as per standard preparation and weighed 7 gm powder of Saleekha another drug Majeeth was coarse grinded and weighed 14 gm decoction of Majeeth was administered orally twice a day for 15 days and observed for commencement of menstruation for next 15 days and patient were asked to come back after 30 days for follow up and collect the drug for next cycle.

Initial screening of patients
Baseline laboratory investigations like Hb% UPT, RBS and TSH were done to rule out anemia, pregnancy, diabetes mellitus and thyroid dysfunction, and pelvic ultrasound was done to exclude pelvic pathology.Safety profile Blood Urea, Serum Creatinine, AST, ALT and Alkaline Phosphatase, was done before and after the intervention for the safety of test drug.

Subjective parameters
Nature of cycle, duration of cycle, duration of flow, amount of flow, Clinical sign of hyper-androgenism, obesity.

Outcome measures
It is assessed by change in subjective and objective parameters.

Statistical Methods
Descriptive and inferential statistical analysis has been carried out in the present study.Results on continuous measurements are presented on Mean SD (Min-Max) and results on categorical measurements are presented in number (%).5]

RESULTS
Marked improvement was observed in menstural irregularity and PBAC score with p<0.001 which is highly significant after the intervention.Significant change is seen in BMI, Ovarian volume, and SF-12 with p<0.001 after treatment.Safety parameters were with in normal range.Baseline data has been represented in (Table 1)

Age
A similar study conducted by Kouser et al. [16] reported 46.66% in the age group 20-30 years.Ghavi F et al. [17] reported 23.60 ± 2.32 and 23.14 ± 2.7 in two groups, hence, in the present study most of the patients were young adults.

Marital status
The majority of patients, 53.3% were married 46.7% were single.This is in consonance with Jzani AM et al. [19] reported 55.56%as married and 44.4% as in single.

Socioeconomic status
This finding accordance with the study of Firdose KF et al. [16] reported 53.3%, 26.7%, 20% in test group and 53.3%, 20%, 26.7% in control group belong to upper lower, lower middle, upper middle class respectively.

Family H/O PCOS
Similar study conducted by Bhat SA et al. [20] reported 82.5% and 17.5% patient had negative and positive family h/o PCOD in test group and 83.34% and 16.66% patient had negative and positive family h/o PCOD in control group respectively.

Mizāj
Saman et al. [21] reported 53.33%, 30% and 16.5% in Balghamῑ, Damvi, and safrawῑ mizāj respectively.These finding confirm the writing of ancient unani scholars quoted that this disease is more common in dominance of Khilt-i-Balgham.

Body weight
Fatemeh et al. [25] reported 41.5% weight reduction in her study.
Firdose KF et al. [16] reported 66.67% weight reduction in her study which is correlating with present study (Table 5).

Item Short Form Survey
Mean ± SD SF12 of before and after treatment were 664.20±161.69 and 820.93±148.00respectively and p value is <0.001** considered suggestive strong significant (Table 6).

Characteristics
No

Polycystic ovaries
On USG of pelvic,100% patient had PCOD at baseline which persist in 46.7% patients after treatment while, 53.3% reduction in PCO in 3 months Khatoon R. et al. [8] reported 23.34% reduction in PCO on USG in 3 months.Anjum F. et al. [23] reported 70% and 80% patients had no PCO on USG after treatment in two groups.

Hemoglobin level
Mean ± SD before and after treatment was 12.55±1.20 and 12.70±0.84respectively with p value 0.335 no significant changes was observed after treatment.
Safety profile: No significant change was observed in safety profile during the trial values are within normal limits.Moreover, the ingredients of research drugs are hepatoprotective, [31][32][33] and act as liver tonic (Table 8). [12]tcome Measures

Primary Outcome Measures
Changes in duration of cycle, duration of flow and amount of flow was achieved in 66.7%, 96.7%, 86.7% patients respectively, and weight reduction in 60% patients (Table 7).hepato-protective activity, anti-cancer, antioxidant, anti-inflammatory, insulin sensitizer and stimulating effect on uterine muscle fibres due to presence of active ingredient such as cinnamic acid, cinamaldehyde, eugenol, essential oil, tanins, rubiadin, methanol extract [34][35][36] alloxan, triterpenoids, rubimalin saponins, Anthraquinone and their glycosoids, quinone and flavonoids, [37] Finally, it can be concluded that the research drug formulation studied can be used as alternate remedy in PCOD patients, as it has significant effect in menstrual cyclicity by reduction of weight and probably by improving the insulin resistance in PCOD.

Limitation of Study
The effectiveness of the research drug formulation on menstrual cyclicity was demonstrated in small sample size, short duration of treatment, short period of 3 months only.Further investigation (hormonal profile) was not done due to funding limitation.Moreover, follow up period was relatively short.

Future Recommendations
Future research trials are recommended for a longer duration with long term follow up for better assessment, and larger sample size Moreover, the mechanism of action of each research drug needs to be studied.

CONCLUSION
Ethical clearance is obtained by Institutional Ethical Committee vide No: NIUM/IEC/2019-20/009/ANQ/01.CTRI registration done vide no.CTRI/2021/02/031070. Informed consent all the participants gave written informed consent before the study starts.Drug identification was done at FRLH Bengaluru with an a/c no.03711450000072.

Table 6 : Clinical Variables in PCOD patients studied.
This is the initial study conducted to assess the effect of Saleekha and Majeeth in Polycystic Ovarian Disease women.Even though it was a trial of short duration was observed in menstrual cyclicity, BMI, mFG, SF12, AN scale with no adverse effects.

Table 8 : Safety profile in PCOD patients studied.
30 diagnosed patients were enrolled in the study, 7 gm powder Saleekha and Majeeth 14 gm as decoction administered orally twice a day for 15 days for 3 consecutive cycles.Changes in menstrual cyclicity was achieved in duration of cycle, duration of flow and amount of flow was 66.7%, 96.7%, 86.7% respectively, weight reduction in 60%.Waist circumference, SF12, AN, mFG, ovarian volum 20%, 73.3%, 13.3%, 36.7%, 76.7% respectively.Research drug was well tolerated safety profiles within normal limits.Finally, drugs can be used as an alternative remedy in the treatment of PCOD, menstruation regulation by a reduction in weight and improving the insulin resistance in PCOD.(p =<0.001**) suggestive significant changes in mFG score (p =0.002**) and AN scale (p =0.043*)No significant changes in waist circumference >0.958(non-significant).In right ovarian volume <0.0048 and in left ovarian volume <0.0033 were observed during trial.Changes in the duration of the cycle, duration of flow, and amount of flow were achieved in 66.7%, 96.7%, 86.7% patients respectively, and weight reduction in 60% of patients.Changes in PBAC score BMI, waist circumference,12 Item Short Form Survey, acanthosis nigricans, Modified Ferriman Gallwey score, ovarian volume 100%, 60%, 20%, 73.3%, 13.3%, 36.7%, 76.7% patients respectively, after intervention.Improvement in outcome measures are attributed to mudirr-i-bawl wa hayd, mufattih-i-sudad, munnaqiye-i-jiger, munáffith-i-balgham, mu' arriq, musakhkhin,, muhallil-i-awrām hypoglycemic, hypolipidemic, hepato-protective activity, anti-cancer, antioxidant, anti-inflammatory, insulin sensitizer and stimulating effect on uterine muscle fibers due to presence of active ingredient such as cinnamic acid, cinnamaldehyde, eugenol, essential oil, tanins, alloxan, triterpenoids, rubimalin saponins, anthraquinone and their glycosides, quinone and flavonoids, etc.The research drug was safe as safety parameters were normal and no adverse effect was noted during the trial.This validates the safety of the research drug as it is proved to be hepato-protective.