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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 4  |  Page : 219-228

Homoeopathic medicine – Sepia for the management of menopausal symptoms: A multicentric, randomised, double-blind placebo-controlled clinical trial


1 Central Council for Research in Homoeopathy, New Delhi, India
2 Regional Research Institute for Homoeopathy, Mumbai, Maharashtra, India
3 Dr. D P Rastogi Central Research Institute (Homoeopathy), Noida, Uttar Pradesh, India
4 Regional Research Institute for Homoeopathy, Puri, Odisha, India
5 Clinical Research Unit for Homoeopathy, Siliguri, West Bengal, India

Date of Submission10-Feb-2018
Date of Acceptance29-Nov-2019
Date of Web Publication27-Dec-2019

Correspondence Address:
Dr. Jaya Gupta
Central Council for Research in Homoeopathy, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijrh.ijrh_8_18

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  Abstract 


Background: Based on the results of Central Council for Research in Homoeopathy's previous study, wherein Sepia was indicated and prescribed in maximum number of cases, this study was planned to further validate efficacyof Sepia in the management of menopausal symptoms. Objectives: The study was conducted with the objectives of evaluating the efficacy of homoeopathic medicine – Sepia in the management of menopausal symptoms using 'The Greene Climacteric Scale' (GCS) and the quality of life using Utian Quality of Life (UQOL) scale. Materials and Methods: A randomised double-blind placebo-controlled clinical study was conducted from April 2012 to September 2014 at four research centres of Central Council for Research in Homoeopathy. Perimenopausal cases were screened (n = 471), and those fulfilling the eligibility criteria (n = 88) were enrolled and randomised to receive either homoeopathic intervention, i.e., Sepia (n = 44) or identical placebo (n = 44) and followed up for 6 months to assess them on predefined clinical parameters. The primary outcome was the change in the menopausal complaints assessed using GCS and the secondary outcome measure was change in UQOL scale. Results: Eighty-eight patients were considered for primary outcome analysis. The primary outcome measure, i.e., total score of GCS, when compared after 6 months, was reduced from 30.23 ± 8.1 to 7.86 ± 4.6 in Sepia group (improvement of 73.9%) and from 30.05 ± 8.9 to 12.73 ± 8.3 in placebo group (improvement of 57.63%) (P = 0.001). There was a statistically significant difference between both the groups, when compared after 6 months (P = 0.001). With respect to secondary outcome, the total UQOL score was 59.09 ± 7.74 for Sepia group and 57.39 ± 7.80 for placebo group at baseline, and 62.43±7.71 for Sepia group and 63.48±7.53 for placebo group after treatment indicating slight difference in quality of life after 6 months. Conclusion: Sepia is able to allay the menopausal symptoms when prescribed on symptomatic indications as per homoeopathic principles.

Keywords: Double-blind randomised controlled trial, Greene climacteric scale, Homoeopathy, Menopause, Sepia, Utian quality of life scale


How to cite this article:
Gupta J, Kulshreshtha D, Lamba CD, Gupta P, Shinde V, Wadhwa B, Soren A, Arya J S, Koley M, Pramanik A, Parveen S, Kumar A. Homoeopathic medicine – Sepia for the management of menopausal symptoms: A multicentric, randomised, double-blind placebo-controlled clinical trial. Indian J Res Homoeopathy 2019;13:219-28

How to cite this URL:
Gupta J, Kulshreshtha D, Lamba CD, Gupta P, Shinde V, Wadhwa B, Soren A, Arya J S, Koley M, Pramanik A, Parveen S, Kumar A. Homoeopathic medicine – Sepia for the management of menopausal symptoms: A multicentric, randomised, double-blind placebo-controlled clinical trial. Indian J Res Homoeopathy [serial online] 2019 [cited 2020 Feb 19];13:219-28. Available from: http://www.ijrh.org/text.asp?2019/13/4/219/274023




  Introduction Top


Menopause is a time of many changes in the psychophysical–social functioning of women, with reduced ovarian hormonal activity and oestrogen levels.[1] Projected figures for 2026 have estimated that the population in India will be 1.4 billion, people over 60 years – 173 million and the menopausal population – 103 million. Average age of menopause is 47.5 years in Indian women with an average life expectancy of 71 years.[2] In the present day management of menopause, the age of 45–55 years is taken as the limit of normality and those menstruating after 55 years merit investigation to exclude pathology.[3]

Women around the world suffer from ailments characteristic for the menopausal period regardless of ethnic origin, skin colour or sociodemographic factors. Urogenital symptoms, fatigue and weakness, body aches and pains are the predominant symptoms in both rural and urban menopausal women.[4]

In most cases, recording a symptom score helps to make the diagnosis. Checking a follicle-stimulating hormone level or serum oestradiol and progesterone are unnecessary tests in diagnosing menopause, and androgen profiles as a routine on all peri-menopausal women are not indicated.[5] Age and time since menopause affect the balance of benefits and risks for hormone therapy (HT) use in post-menopausal women.[6] Observational studies revealed the positive role of Homoeopathy in alleviating the menopausal complaints and improving quality of life.[7],[8],[9] An audit report of National Health Service community menopause clinic through homoeopathic intervention suggested greatest response in those patients who reported headaches, vasomotor symptoms, emotional or psychological symptoms and tiredness or fatigue, respectively, as their primary symptoms.[10] Randomised-controlled trials (RCTs) on Homoeopathy for menopausal symptoms and oestrogen withdrawal symptoms in breast cancer survivors did not show statistically significant results.[11],[12] In another RCT on moderate to severe depression in peri- and post-menopausal women, individualised Homoeopathy was not only effective for depression but also improved menopause symptoms according to Greene Climacteric Scale (GCS) whereas Fluoxetine was not different from placebo in alleviating menopausal complaints.[13] In an RCT on hot flushes induced by adjuvant endocrine therapy in localised breast cancer patients, Homoeopathy alleviated the hot flushes-related disabling symptoms, providing an interesting support for better adherence to endocrine therapy, thereby reducing the risk of recurrence. There was also a positive impact on QOL.[14]

Based on the promising results of Central Council for Research in Homoeopathy's previous study,[15] wherein Sepia was indicated and prescribed in maximum number of cases (n = 53), of which 37 patients observed marked improvement, 14 had moderate improvement and 2 had mild improvement, this study was planned to further validate Sepia as drug having efficacy in the management of menopausal symptoms. This randomised double-blind placebo-controlled study was designed with an objective to compare the efficacy of Sepia against placebo in such a manner that the prescribing indications of Sepia are available in both the groups (Sepia and control).


  Materials And Methods Top


Study design

The study was a multicentric, randomised, double-blind placebo-controlled with a 6-month intervention and follow-up period.

Study setting

The study was conducted at Regional Research Institute for Homoeopathy, Puri (Odhisa); Regional Research Institute for Homoeopathy, Mumbai (Maharashtra); Clinical Research Unit in Homoeopathy, Siliguri (West Bengal) and Dr. D. P. Rastogi Central Research Institute for Homoeopathy, Noida (Uttar Pradesh).

Data collection

The study was conducted from April 2012 to September 2014. Each case was followed up for 6 months to assess the outcome of the treatment. Study data were collected at baseline, every follow-up (monthly or earlier if required) and at final/termination visit. The patients were evaluated for symptomatic and clinical assessment, laboratory parameters and adverse events, if any, as per the study protocol.

Randomisation

Same set of random numbers were generated for the four study sites. Each patient was assigned either Series 1 or Series 2 as intervention through random numbers obtained from www.randomizer.org.[16] All eligible patients were randomised to either 'Series I' or 'Series II' to receive Sepia or identical placebo. Patients and physicians both were blinded in the entire process.

Participants

The inclusion criteria for study participants were as follows: (1) perimenopausal women between 40 and 55 years of age with a history of menopausal symptoms for at least 1 month within the last one year, (2) signed the informed consent form (written consent was taken before detailed case taking to provide observational data and have their data used comparatively), (3) women presenting with indications for medicine – Sepia as per homoeopathic literature and (4) if the patient was under any treatment for the menopausal complaints or taking oral contraceptives, she was included only after the washout period of 15 days. In case, the patient was on hormone replacement therapy (HRT), she should have withdrawn HRT for at least 2 months before inclusion.

The exclusion criteria included (1) women with established menopause, either natural or artificial; (2) dysfunctional uterine bleeding/history of endometrial hyperplasia or malignancy; (3) women on long-term medication for any disease; (4) women with a history of severe psychiatric disturbance; (5) women with a history of systemic illnesses, hypertension, diabetes mellitus, cardio- or cerebro-vascular diseases, pelvic pathology requiring surgery or any malignancy and (6) women using any medicine or supplement containing oestrogen and progestin.

The patients were screened for eligibility. Routine examination and investigations including general, systemic and gynaecological examinations (per speculum, per vaginal, if required); complete haemogram; blood sugar fasting and post prandial; lipid profile, kidney function test and liver function test; urine and stool for routine and microscopical examination; ultrasonography of whole abdomen; Papanicolaou test smear if the patients agreed and mammography were done before enrollment.

All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Declaration of Helsinki [17] of 1975 and Good Clinical Practices - India.[15] Necessary clearance of the Ethical Committee was obtained. Trial was registered under Clinical Trial Registry of India under CTRI/2011/12/002269 [Registered on: 22/12/2011].

Intervention

Homoeopathic medicine – Sepia 200 C procured from Good Manufacturing Practices compliant-licensed homoeopathic pharmaceutical company. Sepia or identical placebo were prescribed in 200 C at monthly interval.

Criteria for baseline assessment and follow-up

Assessment of menopausal symptoms of all enrolled cases was taken up as per 'The GCS' (primary outcome measure) at baseline and each month for 6 months. Quality of life was also assessed using Utian Quality of Life (UQOL) scale (secondary outcome measure)[18] at baseline and at 6 months. The investigations which were out of range at baseline were repeated at the end of the treatment.

Outcomes

The outcomes were the changes in the menopausal complaints assessed using GCS and UQOL scales. The Greene Scale provides a brief measure of menopause symptoms. Severity of the problem is scored from 0 (none), 1 (mild), 2 (moderate) and 3 (severe) at baseline and on monthly follow-up till 6 months.

Statistical methods

Statistical analysis was done using IBM SPSS version 20.0 (IBP Corp, IBM SPSS statistics for windows, Armonk, NY: IBM corp.). Comparison between Sepia and placebo groups was performed at baseline to assess the randomisation effect using independent t-test. The main outcome measure of GCS changes from baseline to 6 months between groups was done using independent t-test. The UQOL changes from baseline to 6 months of follow-up were also estimated using independent t-test. The data were presented in n (no. of cases), mean ± standard deviation in all the analysis, P < 0.05 was considered statistically significant.


  Results Top


88 participants who had given written informed consent were enrolled according to the inclusion criteria. Flow diagram of the progress through the phases of a RCT of Sepia and placebo (that is, enrollment, intervention, allocation, follow-up and data analysis) is depicted in [Figure 1]. Mean age in Sepia group was 46.3 ± 3.9 and in placebo was 45.9 ± 4.2 years. At baseline, the total score of GCS was 30.23 ± 8.1 and 30.05 ± 8.89 in intervention and verum group, respectively, and UQOL score was 59.09 ± 7.74 and 57.39 ± 7.80 in intervention and verum group, respectively, at baseline. Baseline characteristics and the laboratory investigations were comparable in both the groups and statistically insignificant [Table 1].
Figure 1: Study flowchart

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Table 1: Baseline characteristics

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Symptoms of medicine – Sepia reported by patients at the time of enrollment in both the groups are mentioned cumulatively in [Table 2].
Table 2: Symptoms of Sepia reported by patients

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The primary outcome, GCS was reduced from 30.23 ± 8.1 to 7.86 ± 4.6 in Sepia group (improvement of 73.9%) and from 30.05 ± 8.9 to 12.73 ± 8.3 in placebo group (improvement of 57.63%). There was a statistically significant difference between both the groups, when compared after 6 months (P = 0.001) [Table 3] and [Table 4].
Table 3: Comparison of both the groups at 6 months

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Table 4: Independent t-test applied on Greene Climacteric Scale score (40-55 year age group) at baseline and at 6 months

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In addition to that, independent t-test has been used for change in mean of GCS from baseline to 6 months [Table 5].
Table 5: Independent t-test (changes from baseline to 6 months)

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The cases that had baseline score ≥20 (n = 82) indicating high degree of symptoms were also analysed. These 82 cases (Sepia = 42 and placebo = 40) were analysed, and there was a statistically significant difference between the two groups, when compared after 6 months (P = 0.001) [Table 5]. Improvement was observed from 2nd month onwards in Homoeopathy group [Figure 2]. Total score of GCS was reduced from 30.90 ± 7.6 to 7.81 ± 4.6 in Sepia group (improvement of 74.72%) and 31.38 ± 8.2–13.15 ± 8.3 in placebo group (improvement of 58.09%) [Table 6].
Figure 2: Greene climacteric total score

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Table 6: Comparison of both the groups at baseline (Greene Climacteric Scale score >20)

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When the cases of age group 40–50 years were analysed (Sepia= 38 and placebo = 35), there was a statistically significant difference between the two groups, when compared after 6 months (P = 0.001). Total score of GCS was reduced from 30.37 ± 7.8 to 7.92 ± 4.9 in Sepia group (improvement of 73.92%) and 31.83 ± 8.1–13.20 ± 8.1 in placebo group (improvement of 58.52%) [Table 7].
Table 7: Comparison of both groups in the age group of 40-50 years

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With respect to secondary objective, the total UQOL score was 59.09 ± 7.74 for Sepia group and 57.39 ± 7.80 for placebo group at baseline, and 62.43±7.71 for Sepia group and 63.48±7.53 for placebo group after treatment. Homoeopathy showed, however, slightly more improved quality of life in comparison with placebo after 6 months' follow-up.


  Discussion Top


Homoeopathy is a unique therapeutic system, and homoeopathic case management may involve two different types of diagnosis, namely clinical diagnosis – based on the condition and individual diagnosis – based on the symptoms of each single patient.

This study was conducted with the objectives of evaluating the efficacy of Sepia, a well-known medicine indicated in the management of menopausal symptoms. 'The GCS' and 'UQOL' were used to assess the outcome.

The most frequent symptoms on which Sepia was prescribed were irritability (52, 59%), anxiety (32, 36.4%), indifference (48, 54.5%), weeping tendency (28, 31.8%), decreased sexual desire (28, 31.8%), hot flushes (66, 75%), decreased sleep (43, 48.9%) and weakness (36, 41%).

On analysing the data of patients whose baseline score was either equal to or more than 20, there is a statistically significant difference in reduction of GCS score (P = 0.001) when compared after 6 months indicating positive response with the prescription of Sepia. There is improvement from 2nd month onwards in Sepia group.

The mean menopausal age of the sample population was 46.3 ± 3.9 years which corroborates with survey undertaken by Indian Menopause Society and found 46.2 ± 4.9 years as the average age.[18] In another observational study by Nayak et al., the mean menopausal age of the sample population was 46.66 years.[15] Therefore, it was felt pertinent to analyse data of patients between the age group (40–50 years) in this study which turned out to be statistically significant.

In another study by Andrade et al.,[19] the homoeopathic medicine of Capsicum frutescens (Malagueta) was superior to placebo in reducing the intensity of hot flashes in menopausal women after 4 weeks of treatment.

With respect to secondary objective (to assess the quality of life using UQOL), Homoeopathy showed, however, slightly better quality of life in comparison with placebo after 6 months' follow-up. This could be because the patients belonged to moderate category of symptoms at baseline; therefore, they did not report of marked improvement in quality of life.

'Single remedy' approach has been used by Shipley et al.[20] and Savage and Roe [21] on similar lines.

The limitation of this study was that after selecting Sepia as medicine for patients at baseline, the investigators were supposed to continue the same medicine during follow-up period, which contradicts the routine homoeopathic practice where there could be requirement of change in prescription. It was observed in one of the reviews that, often, in Homoeopathy, it is not possible to find the correct remedy at once and/or change the remedy as the clinical picture changes. In a case of a double-blind trial, a homoeopathic practitioner often encounters the challenges due to any three possibilities, namely, a failure to reach correct similimum, any symptom shift in patients and totality or patient being a participant of a placebo group.[22]

In the present study, double-blind, placebo-controlled methodology was adapted, which is the gold standard in conventional medicine for clinical trials using single drug intervention, but it seems that this methodology might be a constraint for achieving the sample size, as large number of patients screening is required, for recruiting/enrolling patients requiring a particular remedy. This challenge is also reported by other researchers.[19],[23]

Patients in the placebo group had undergone homoeopathic case history recording procedure that might contribute considerably to a possible treatment effect, decreasing the likelihood of identifying differences between the groups.[24]

The biggest problem faced by clinical research in Homoeopathy is that of independent reproducibility. The issue of independent reproducibility was also raised by the publication of a series of studies of homoeopathic therapy of headache. A randomised, double-blind, placebo-controlled clinical trial of the treatment of migraine with the limited range of homoeopathic medicines by Brigo and Serpelloni [25] gave strongly positive result; however, study by Whitmarsh et al.[26] and Walach et al.[27] failed to show any difference between Homoeopathy and placebo, although the two studies were of high methodology quality.[28]

Despite all these constraints for clinical trial with double-blind RCT design, this study has shown positive response of homoeopathic medicines in allaying the menopausal symptoms in comparison to placebo within the duration of 6 months.


  Conclusion Top


Sepia is able to allay the menopausal symptoms when prescribed on symptomatic indications as per homoeopathic principles. Further validation of Sepia symptoms deduced in this study can be taken up through an independent study.

Acknowledgement

The authors are especially thankful to Dr. Anil Khurana, Director General, CCRH for his valuable guidance while revising the manuscript. We are thankful to all program officers of the Institutes and units, where project was going on, for their administrative support. Last but not the least, we are thankful to all the patients for their participation in the study.

Financial support and sponsorship

Central Council for Research in Homoeopathy, New Delhi under Ministry of AYUSH, Government of India.

Conflicts of interest

None declared.



 
  References Top

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Makara-Studzińśka MT, Kryś-Noszczyk KM, Jakiel G. Epidemiology of the symptoms of menopause – An intercontinental review. Prz Menopauzalny 2014;13:203-11.  Back to cited text no. 1
    
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Sood R, Faubion SS, Kuhle CL, Thielen JM, Shuster LT. Prescribing menopausal hormone therapy: An evidence-based approach. Int J Womens Health 2014;6:47-57.  Back to cited text no. 6
    
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Nayak C, Singh V, Singh K, Singh H, Gupta J, Lamba CD, et al. Management of distress during climacteric years by homeopathic therapy. J Altern Complement Med 2011;17:1037-42.  Back to cited text no. 15
    
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Andrade DCDS, Carmona F, Angelucci MA, Martinez EZ, Pereira AMS. Efficacy of a Homeopathic Medicine of Capsicum frutescens L. (Solanaceae) in the Treatment of Hot Flashes in Menopausal Women: A Phase-2 Randomized Controlled Trial. Homeopathy 2019;108:102-7.  Back to cited text no. 19
    
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24.
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25.
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27.
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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