|Year : 2018 | Volume
| Issue : 1 | Page : 35-45
Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study
Chetna Deep Lamba1, Praveen Oberai1, Raj K Manchanda1, Padmalaya Rath2, P Hima Bindu3, Maya Padmanabhan1
1 Central Council for Research in Homeopathy, New Delhi, India
2 Dr. D. P. Rastogi Central Research Institute (H), Noida, Uttar Pradesh, India
3 Extension Centre of Drug Standardization Unit, Princess Durru Shehvar Children's and General Hospital, Hyderabad, Telangana, India
|Date of Web Publication||3-Apr-2018|
Dr. Praveen Oberai
Central Council for Research in Homoeopathy, New Delhi
Source of Support: None, Conflict of Interest: None
Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ). Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling the eligibility criteria were enrolled (n = 60) and randomised to either the homoeopathic intervention (HI) (n = 30) or identical placebo (P) (n = 30) with uniform lifestyle modification (LSM) for 6 months. Results: The menstrual regularity with improvement in other signs/symptoms was observed in 60% of the cases (n = 18) in HI + LSM group and none (n = 0) in control group (P = 0.001). Statistically significant difference (P = 0.016) was observed in reduction of intermenstrual duration (from 76.1 ± 37.7 to 46.6 ± 38.7 days) in HI + LSM in comparison to placebo + LSM group (from 93.0 ± 65.2 to 93.9 ± 96.2 days). In PCOSQ, also, significant improvement was observed in HI group in domains of weight, fertility, emotions and menstrual problems (P < 0.05) with no difference in body hair (P = 0.708). No change was observed in respect of improvement in the ultrasound findings. Pulsatilla was the most frequently indicated medicine (n = 12, 40%). Conclusion: HI along with LSM has shown promising outcome; further comparative study with standard conventional treatment on adequate sample size is desirable.
Keywords: Homoeopathy, Hyperandrogenism, Lifestyle modification, Menstrual regularity, Polycystic ovary syndrome, Polycystic Ovary Syndrome Questionnaire
|How to cite this article:|
Lamba CD, Oberai P, Manchanda RK, Rath P, Bindu P H, Padmanabhan M. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study. Indian J Res Homoeopathy 2018;12:35-45
|How to cite this URL:|
Lamba CD, Oberai P, Manchanda RK, Rath P, Bindu P H, Padmanabhan M. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study. Indian J Res Homoeopathy [serial online] 2018 [cited 2019 Jan 21];12:35-45. Available from: http://www.ijrh.org/text.asp?2018/12/1/35/229067
| Introduction|| |
Polycystic ovary syndrome (PCOS) is a complex metabolic, endocrine and reproductive disorder. Overall, the disorder appears to be an ancient complex genetic trait, perhaps dating at least 50,000 years ago. Various guidelines ,,, have been issued regarding diagnosis of PCOS. While there are certain consistencies between the criteria offered by the different groups, important differences exist. Each issuing group considers PCOS a diagnosis of exclusion. Because 20%–30% of otherwise normal women have evidence of multiple cysts on their ovaries, the presence of polycystic ovaries (PCOs) alone was not considered sufficient by any group. The prevalence estimates also vary according to the criteria from 4%–8% as per the NIH/NICHD criteria to as high as 15%–20% when the ESHRE/ASRM criteria are used. A cross-sectional study among adolescent and young girls in Mumbai, India, indicated the prevalence of 22.5% by Rotterdam and 10.7% by Androgen Excess Society criteria. Its clinical characteristics include hyperandrogenism, chronic anovulation, insulin resistance and infertility. Whilst reproductive features are prominent, it has potential for major metabolic consequences including obesity, type 2 diabetes mellitus (DM2) and cardiovascular disease. It remains a syndrome, and as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for diagnosis. Known disorders such as late-onset congenital adrenal hyperplasia that mimic the PCOS phenotype should be excluded. A meta-analysis suggested that PCOS is significantly associated with increased coronary heart disease risk. Endometrial cancer also seems to be more frequent in women with PCOS. Therefore, PCOS has numerous long-term health risks.
In conventional medical system, metformin, oral contraceptives, antiandrogens, clomiphene citrate and thiazolidinediones are used for symptomatic management. Metformin is commonly used either alone or in combination with other medicines. It reportedly reduced hyperinsulinaemia and hyperandrogenaemia, independently of changes in body weight. In a large number of cases, these changes were associated with striking, sustained improvements in menstrual abnormalities and resumption of ovulation, but it causes gastrointestinal intolerance in 30% (nausea, abdominal pain and/or diarrhoea) of patients. It is contraindicated in liver disease and certain other clinical conditions. Other medicines recommended too have side effects for long use; hence, there is a need to explore the possibility of its management with Homoeopathy. Sanchez-Resendiz and Guzman-Gomez  and Gupta  have evaluated homoeopathic intervention (HI) in PCOS and have shown positive outcomes, but were lacking in choosing appropriate diagnostic criteria. Therefore, this study was conducted with the primary objective to evaluate the efficacy of HI in establishing the menstrual regularity with either ultrasonological improvement or improvement in hirsutism/acne.
Lifestyle modification (LSM) is also essential, and it is reported that even 5%–10% weight loss has led to significant clinical benefits improving psychological outcomes, reproductive and metabolic features.
Studies suggest that women suffering from PCOS are most exposed to several psychological problems. It exerts a negative impact on female identity and contributes to the deterioration of quality of life. The mental consequences can be depression and mood disorder., The depression and anxiety are more common as compared with healthy women. Depression is often associated with obesity and metabolic abnormalities., The depression and anxiety did not show a significant change after treatment with oral contraceptive pills (OCPs). Biological, social and psychological consequences of PCOS among women of reproductive age are opening a new perspective on management of women's health in these patients. Therefore, as secondary objective, PCOS questionnaire (PCOSQ), which evaluates emotional aspects along with body hair, weight, infertility and menstrual problems, was used for the assessment of quality of life.
| Materials and Methods|| |
A randomised, placebo-controlled study with 6-month intervention and follow-up was conducted at two centres.
The inclusion criteria were as follows: (1) females aged between 18 and 36 years; (2) participants with oligomenorrhoea (intermenstrual period of more than 35 days for 3 consecutive cycles)/amenorrhoea for more than 3 months (2 years after menarche); (3) participants with ultrasound findings of PCOs (the PCO had at least one of the following: either 12 or more follicles measuring 2 ± 9 mm in diameter or increased ovarian volume [>10 cm3]. If there was evidence of a dominant follicle [>10 mm] or a corpus luteum, the scan was repeated during the next cycle. Only one ovary fitting this definition or a single occurrence of one of the above criteria is sufficient to define the PCO ); (4) participants with clinical evidence of hirsutism (Ferriman score 8 and above) and/or acne (acne global severity scale score 1 and above); (5) participants with body mass index (BMI) of 23 and above; (6) participants willing to adopt healthy diet and to regular exercise (at least 30 min of exercise at least 5 days a week) regimen and (7) participants willing to provide written informed consent.
The exclusion criteria were as follows: (1) cases with a history of DM, Cushing's disease and hyperprolactinaemia; (2) untreated hypo- or hyperthyroidism; (3) history of adrenal hyperplasia and adrenal tumour; (4) ovarian tumour; (5) hyperthecosis; (6) significant renal impairment; (7) history of intake of drugs aldactone/metformin or history of OCP use or intake of drugs known to interfere with carbohydrate metabolism prior 4 weeks before enrolment; (8) pregnancy and breast feeding and (9) any other systemic diseases.
The study was conducted at Dr. D. P. Rastogi Central Research Institute (H), Noida, and Extension Clinical Research Unit of Drug Standardization Unit at Princess Durru Shehvar Children's and General Hospital, Hyderabad. Two trained homoeopaths, 1 at each centre with experience of more than 5 years, were the investigators. They were given training before initiation of the study to minimise the bias. The patients were screened for eligibility and underwent pelvic ultrasound, complete blood count with erythrocyte sedimentation rate, fasting glucose, thyroid function test, serum prolactin, basal morning 17α-hydroxyprogesterone, complete urine examination and urine pregnancy test in case of married women with amenorrhoea before enrolment.
Patients fulfilling the eligibility criteria were enrolled and randomised as per computer-generated randomisation chart  to receive either the HI or the identical placebo (P) as illustrated in [Figure 1]. Medicines were given in Q, 6c, 30c, 200c or 1M potency as per the prescribing totality. Mother tinctures were only prescribed in persistent amenorrhoea. The medicines were repeated as per need in accordance with the principles of Homoeopathy. All the study participants were asked to follow healthy diet and to take up regular exercise (at least 30 min of exercise at least 5 days a week).
Criteria for baseline assessment and follow-up
All the enrolled participants underwent complete case taking along with clinical examination, baseline investigations for sex hormone-binding globin, luteinising hormone/follicle-stimulating hormone (LH/FSH) ratio, total testosterone, dehydroepiandrosterone sulphate, fasting serum insulin, glucose insulin ratio, tryglycerides and high-density lipoprotein-cholesterol at baseline and filled PCOSQ.
Patients were assessed at monthly interval (or earlier as per the need) for 6 months. Symptomatic assessment, clinical examination and PCOSQ evaluation were done at every month. Patients reported the menstrual cycle data (duration of bleeding, length of cycle, i.e. number of days from beginning of menstrual period to the beginning of next one, characteristic of discharge, etc.) and filled up PCOSQ. The presence of male-pattern terminal hair growth on the face or body, indicating androgen excess, was assessed with the modified Ferriman–Gallwey visual scoring method. The nine body areas were rated from 0 (absence of terminal hairs) to 4 (extensive terminal hair growth), and the numbers in each area were added to obtain the total score. A score ≥8 was taken to define hirsutism and maximum possible score was 36. Acne was evaluated by investigator as per acne global severity scale score from 0 to 1 wherein 0 represented normal skin and 5 reflected most inflammatory acne. Any intercurrent complaint was managed as per the presenting signs and symptoms in both the groups. During follow-up, assessment was made in both the groups equally by the investigators; however, in the placebo group, different nomenclature was used for prescribing placebo. At completion of the study, in addition to these assessments, pelvic ultrasound was done to evaluate any change in PCO. The investigations which were out of range at baseline were repeated at end of the treatment.
Primary outcome was the establishment of menstrual regularity which was defined as having at least 5 menstrual cycles within 6 months along with either ultrasonological improvement of PCO (normal scan or reduction in ovarian follicles/volume at 6 months) or improvement in hirsutism/acne (reduction of Ferriman acne score at 6 months). Secondary outcomes were to compare the changes in domains of PCOSQ. Five domains consisting of emotions, body hair, weight, infertility and menstrual problems were quantified, so that the patient's subjective feelings could be compared initially and at the end of the study. Each domain has a range of questions wherein each question is associated with a 7-point scale in which 7 represents optimal function and 1 represents the poorest function.
Being a pilot study, 60 cases of PCOS were enrolled, 30 in verum and 30 in placebo group.
Separate sets of random numbers were generated for the two study sites using stratified (centre as the strata) randomisation method.
The patients fulfilling the eligibility criteria were enrolled and randomised as per computer-generated randomisation chart and received either the HI or the identical placebo. Allocation concealment was not done.
Only the patients were blinded to the identity of the treatment group. Homoeopathic and placebo medicines were identical. The taste of the medicines was kept identical so as to blind the patients' gustatory sense.
The study was conducted from February 2014 to May 2015.
Each case in both the groups was followed up for 6 months to assess the outcome results of the treatment. The study data were collected at baseline, every follow-up (monthly or early if required) and at final/termination visit. The patients were evaluated for symptomatic, clinical assessment, laboratory parameters and adverse events, if any.
Data obtained during the study were verified and analysed using Statistical Package for the Social Sciences version 20. Data were managed in a pre-designed pro forma and managed in an excel sheet. Before statistical analysis, normality assessment was done using Kolmogorov–Smirnov test. Accordingly, the demographic details and baseline characteristics of both the groups were compared using Chi-square test. BMI, waist–hip ratio, Ferriman scale, laboratory investigations, etc., were compared using Independent Student's t-test.
In lost to follow-up cases, the changes in menstrual cycle were considered as per the last LMP reported; however, the last observation carry forward method was applied for the assessment of Ferriman and acne score. Data are expressed in n (%), mean ± standard deviation. Statistical significance was considered at P < 0.05.
Regulatory and ethical approval
The study protocol was in accordance with the latest revision of the Declaration of Helsinki  on human experimentation and the good clinical practices, India. Necessary clearance of the institutional ethics committee was obtained. All the patients were enrolled in the study after getting their consent. The trial is registered with Clinical trial registration India (CTRI).
| Results|| |
Of 120 cases of PCOS screened from the outpatient department of both the study sites, 60 were enrolled according to the inclusion criteria. Flow diagram of the progress through the phases of a parallel randomised trial of Homoeopathy + LSM and placebo + LSM (i.e. enrolment, intervention allocation, follow-up and data analysis) is depicted in [Figure 1]. Baseline characteristics were comparable in both the groups and were not statistically significant in spite of some variation. History of abortion was in four cases in Homoeopathy and five cases in placebo arm. All the laboratory investigations were within normal range except LH/FSH ratio which was above 2 in both the groups [Table 1].
The primary objective was achieved in 60% of cases in Homoeopathy + LSM and none in the placebo + LSM groups which was statistically significant (P = 0.001). In secondary outcomes also, statistically significant difference was observed in PCOSQ scores in the domains of weight, fertility, emotions and menstrual problems. Significant changes were not observed in ultrasonography (USG) findings [Table 2].
Mean reduction of intermenstrual duration (from first menstrual period after enrolment and from baseline) was significant in Homoeopathy group. The BMI and acne showed significant reduction from baseline to end of the study. Hirsutism did not show any change in both the groups as per Ferriman scale and PCOSQ. Three pregnancies were reported in the Homoeopathy and two in placebo group during the study period [Table 2]. However, five more pregnancies were reported within 2 months after the study period in the Homoeopathy group without any additional treatment. At baseline, LH/FSH was out of range in 15 patients (3.4 ± 1.7) in Homoeopathy and in 18 patients in placebo group (2.6 ± 0.5). After 6 months of treatment, it reduced in 9 cases in both the groups (1.5 ± 1.0), which was not statistically significant.
Dietary advice was followed by all the patients in both the groups. Exercise schedule was followed by 26 and 27 patients in Homoeopathy and placebo groups, respectively.
Acute illnesses (diarrhoea, vomiting and upper respiratory infections) were reported in four cases (two in Homoeopathy and two in placebo group). These cases were given homoeopathic medicines in frequent doses and resolved without any other treatments.
The commonly indicated medicines were Pulsatilla (n = 12), Natrum muriaticum (n = 4), Sepia (n = 3), Calcarea carbonica (n = 3), Lycopodium (n = 3), Phosphorus (n = 2), China (n = 1), Nux vomica (n = 1) and Sulphur (n = 1). The single medicine was given to 23 cases and 7 cases required the change of medicine [Table 3].
| Discussion|| |
The study was undertaken keeping in view the growing incidence of PCOS causing reproductive, endocrine and metabolic dysfunction. Primary objective, i.e. the establishment of regular menstrual cycle along with improvement in either ultrasonology or hirsutism/acne, was achieved in 60% of cases in Homoeopathy + LSM and in none in the placebo + LSM groups. The same trend was seen in PCOSQ showing statistically significant difference in the domains of weight, fertility, emotions and menstrual problems, except hirsutism. Significant changes were not observed in USG findings of PCO. Although USG indicated that five cases were worse (increase in ovarian volume and/or number of follicles) but only two reported increase in intermenstrual duration as compared to baseline in Homoeopathy group, whereas in placebo group, USG of 12 cases was worse but 19 reported increase in intermenstrual cycle. Therefore, composite factor assessment is essential rather than one factor assessment.Pulsatilla was the most frequently indicated medicine (n = 10, 33.3%) in this study population., Single medicine was indicated in 23 cases which did not require subsequent change in prescription.
A 6-month study of metformin and pioglitazone improved menstrual cyclicity in more than 90% of cases of PCOS; the other features of PCOS, i.e., weight gain and cosmetic problems although mentioned, were not evaluated. Thus, existing treatments including the conventional, so far, have mostly been directed at the symptoms but not at the syndrome itself. Therefore, Homoeopathy has an edge as it holistically treats the patient.
LSM has a positive role in the management of PCOS. The study outcome in this arm, i.e. achievement of two pregnancies, reduction in intermenstrual duration with improvement in either ultrasonology or hirsutism/acne in nine cases, USG findings suggestive of normal ovaries in 4 cases and improvement in 9 and slight reduction in BMI and FSH/LH although not significant, indicates that LSM influences the management of PCOS. However, it improves the outcome as an adjunct to the therapy. A systematic review and meta-analysis also suggested that LSM improved blood glucose or insulin levels but had no significant effect on pregnancy rate, and the effect on hirsutism was unclear.
To eliminate the recall bias (a systematic error caused by differences in the accuracy of the LMP reported), intermenstrual duration was calculated from two time points. First, from the LMP reported by the patient at baseline and second, the intermenstrual duration was calculated from the menstrual period that occurred just after enrolment in the study. The overall risk of bias  was minimal as only one domain (allocation concealment) out of six had high risk of bias. The outcome measures were not likely to be influenced by lack of blinding as the regularisation of menstrual cycle is patient reported.
Trial limitations include the short duration of follow-up for the assessment of continuity of menstrual regularity and regarding the changes in ultrasonological appearance of PCO. Furthermore, the pregnancy was not defined as an outcome parameter considering 6-month follow-up period; however, eight pregnancies (including five pregnancies reported within 2 months after the study period in the Homoeopathy group without any additional treatment) were reported in Homoeopathy and two in placebo group. LH: FSH, fasting serum insulin, etc. were done at 6 months only for the cases in which these were out of range at baseline. Although Vitamin D deficiency can be an effective factor in the development of PCOS and Vitamin D supplementation can play a role in prevention of this condition, it was not evaluated. The effect of only LSM was insignificant with respect to primary objective, although it had some influence in management of PCOS. Therefore, it is felt that it was not appropriate to have only LSM arm as this age group has major concerns for menstrual irregularity and infertility. Further, the study could not avoid the selection bias and ascertainment bias due to nonblinding and lack of allocation concealment.
| Conclusion|| |
HI along with LSM has shown promising outcome in managing PCOS and improvement in QOL; thus, HI alleviates not only the disease per se but also the patient as a whole. Further comparative study with standard treatment on adequate sample size is desirable.
Dr. Anil Khurana, Deputy Director General; Dr. Vikram Singh, Former Deputy Director (H); and Dr. Jaya Gupta, Scientist-4, are acknowledged for providing technical co-operation and administrative support from time to time. The authors are thankful to Dr. Madhu Aggarwal, Head, Department of Obstetrics and Gynaecology, Dr. B. R. Sur Homoeopathic Medical College and Hospital, New Delhi; Dr. Neelam Aggarwal, Professor and Senior Consultant, Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research, Chandigarh and Dr. Ajay Ajmani Senior Consultant, Department of Endocrinology, BLK Super Specialty Hospital, New Delhi for the expert review of the protocol. Authors are grateful to Dr. Ravindra Mohan Pandey, Professor and Head, Department of Biostatistics, All India Institute of Medical Sciences, New Delhi for the review of the protocol, manuscript and valuable inputs in statistical analysis.
Contributions of Dr. Y. Suryanarayana, Former SRF(H) and Dr. Shilpa Former SRF (H), for assisting in the study and Dr. Sampoornam S-4,(Biochemistry) for conducting the hormonal assessment at CRI (H), Noida, are acknowledged.
Authors acknowledge Dr. Abdul Wajid, Superintendent, Princess Durru Shehvar Children's and General Hospital, Hyderabad, and Officer-In charge, CRI (H), Noida for the constant support and encouragement during the project. The co-operation of the patients enrolled in the study is appreciated that provided an opportunity to probe the scope of homoeopathic medicines.
Use of the PCOSQ, authored by Dr. Gordon Guyatt, et al. was made under license from McMaster University, Hamilton, Canada, with the permission of the copyright owner, The Endocrine Society, Maryland, USA.
Financial support and sponsorship
The study was funded by the Central Council for Research in Homoeopathy, under Ministry of AYUSH, Government of India.
Conflicts of interest
| References|| |
Azziz R. Introduction: Determinants of polycystic ovary syndrome. Fertil Steril 2016;106:4-5.
Shriver EK. Polycystic Ovary Syndrome (PCOS). National Institute of Child Health and Human Development. US Department of Health and Human Services National Institutes of Health; 2017. Available from: https://www.nichd.nih.gov/health/topics/pcos
. [Last accessed on 2017 Jan 31].
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al.
The Androgen Excess and PCOS Society Criteria for the Polycystic Ovary Syndrome: the Complete Task Force Report. Androgen Excess and PCOS Society. Strengthening Care for Women with Androgen Excess Disorders. Available from: http://www.ae-society.org/pdf/guidelines/AEPCOS.pdf
. [Last accessed on 2013 Sep 24].
Boyle J, Teede HJ. Polycystic ovary syndrome – An update. Aust Fam Physician 2012;41:752-6.
Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013;6:1-3.
Joshi B, Mukherjee S, Patil A, Purandare A, Chauhan S, Vaidya R, et al.
Across-sectional study of polycystic ovarian syndrome among adolescent and young girls in Mumbai, India. Indian J Endocrinol Metab 2014;18:317-24.
Reproductive Endocrinology: The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7.
Zhao L, Zhu Z, Lou H, Zhu G, Huang W, Zhang S, et al.
Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): A meta-analysis. Oncotarget 2016;7:33715-21.
Peigné M, Dewailly D. Long term complications of polycystic ovary syndrome (PCOS). Ann Endocrinol (Paris) 2014;75:194-9.
Sheehan MT. Polycystic ovarian syndrome: Diagnosis and management. Clin Med Res 2004;2:13-27.
Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, et al.
Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: A randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 2000;85:139-46.
Gupta G. Polycystic Ovarian Disease (PCOD). The Homoeopathic Heritage; May, 2009.
Sanchez-Resendiz J, Guzman-Gomez F. Polycystic ovary syndrome. Boletin Mex Homeopatica 1997;30:11-5.
Ganie MA, Kalra S. Polycystic ovary syndrome – A metabolic malady, the mother of all lifestyle disorders in women – Can Indian health budget tackle it in future? Indian J Endocrinol Metab 2011;15:239-41.
Kohlné Papp I. Psychosocial approach in polycystic ovary syndrome. Orv Hetil 2014;155:1867-71.
Podfigurna-Stopa A, Luisi S, Regini C, Katulski K, Centini G, Meczekalski B, et al.
Mood disorders and quality of life in polycystic ovary syndrome. Gynecol Endocrinol 2015;31:431-4.
McCook JG, Reame NE, Thatcher SS. Health-related quality of life issues in women with polycystic ovary syndrome. J Obstet Gynecol Neonatal Nurs 2005;34:12-20.
Cinar N, Kizilarslanoglu MC, Harmanci A, Aksoy DY, Bozdag G, Demir B, et al.
Depression, anxiety and cardiometabolic risk in polycystic ovary syndrome. Hum Reprod 2011;26:3339-45.
Cinar N, Harmanci A, Demir B, Yildiz BO. Effect of an oral contraceptive on emotional distress, anxiety and depression of women with polycystic ovary syndrome: A prospective study. Hum Reprod 2012;27:1840-5.
Cronin L, Guyatt G, Griffith L, Wong E, Azziz R, Futterweit W, et al.
Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS). J Clin Endocrinol Metab 1998;83:1976-87.
Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: International consensus definitions. Hum Reprod Update 2003;9:505-14.
Randomization Chart. IBM SPSS ver 20.0.
Hahnemann S. Organon of Medicine. Reprint 5th
ed. New Delhi: B Jain Publishers; 1982.
Yildiz BO. Assessment, diagnosis and treatment of a patient with Hirsutism. Nat Clin Pract Endocrinol Metab 2008;4:294-300.
Tanwar S, Khilnani GD. Effects on menstruation pattern of polycystic ovarian syndrome (Pcos) cases in a comparative study of metformin and pioglitazone. IOSR J Dent Med Sci 2016;15:29-35. Available from: http://www.iosrjournals.org
. [Last accessed on 2013 Sep 24].
Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. Int J Womens Health 2011;3:25-35.
Domecq JP, Prutsky G, Mullan RJ, Hazem A, Sundaresh V, Elamin MB, et al.
Lifestyle modification programs in polycystic ovary syndrome: Systematic review and meta-analysis. J Clin Endocrinol Metab 2013;98:4655-63.
Gaikwad VA, Deshpande H, Menon D. Association of hypovitaminosis D and insulin resistance in polycystic ovary syndrome. J Evol Med Dent Sci 2017;6:1015-8.
[Table 1], [Table 2], [Table 3]