|Year : 2016 | Volume
| Issue : 1 | Page : 24-35
A multicentric randomized clinical trial of homoeopathic medicines in fifty millesimal potencies vis-à -vis centesimal potencies on symptomatic uterine fibroids
Praveen Oberai1, B Indira2, Roja Varanasi3, Padmalaya Rath4, Bindu Sharma1, Arti Soren5, K. S. V Bharatha Laxmi6, Anita Sharma2, Pratima Devi7, Maya Padmanabhan1, Vikram Singh1, Chaturbhuja Nayak1
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Central Research Institute (H), Kottayam, Kerala, India
3 Central Council for Research in Homoeopathy, Kottayam, Kerala, India
4 Dr. D.P. Rastogi Central Research Institute (H), Noida, Uttar Pradesh, India
5 Regional Research Institute (H), Puri, Odisha, India
6 Clinical Research Unit (H), Chennai, Tamil Nadu, India
7 Regional Research Institute (H), Guwahati, Assam, India
|Date of Submission||07-May-2015|
|Date of Acceptance||11-Feb-2016|
|Date of Web Publication||21-Mar-2016|
Central Council for Research in Homoeopathy, 61-65 Institutional Area, Janakpuri, New Delhi - 110 058
Source of Support: None, Conflict of Interest: None
Objective: The primary objective was to evaluate the effects of homoeopathic medicines in fifty millesimal (LM) potencies vis-à -vis centesimal (CH) potencies on symptomatic uterine fibroids.
Materials and Methods: A multicentric randomized clinical trial was conducted at six centers under the Central Council for Research in Homoeopathy. Patients were screened for symptomatic uterine fibroids with the preset inclusion and exclusion criteria. A consultant specialized in obstetrics and gynecology was engaged at each center to screen and follow-up the enrolled patients. Homoeopathic physicians engaged in the study were responsible for prescription and follow up for 12 months. The primary outcome was changes in symptoms of uterine fibroid on a visual analog scale (VAS) of 0–10 and findings through ultrasonography (USG) between LM and CH potencies. The secondary outcome was to assess the changes in uterine fibroid symptom quality of life questionnaire (UFSQOL). Data analysis was done as per intention to treat (ITT) analysis.
Results: Of 216 patients enrolled in the study (LM: 108 and CH: 108), 209 patients were analyzed under modified ITT (LM: 106, CH: 103). Both LM and CH potencies were equally effective in reducing the symptoms (percentage change) due to uterine fibroid on VAS scale after 1 year of treatment (P > 0.05). The health-related quality of life (HRQOL) and subdomains of UFSQOL also showed equal effectiveness in both the groups (P = 0.05). However, no difference was observed in all the USG findings except for uterine volume (P = 0.03). There was overall difference before and after homoeopathic treatment irrespective of assigned groups, i.e., LM or CH (P < 0.05) in all the above parameters. The medicines frequently prescribed were: Pulsatilla, Sulphur, Lycopodium, Sepia, Phosphorus, Calcarea carbonica, and Natrum muriaticum.
Conclusion: LM and CH potencies are equally effective in giving symptomatic relief to patients suffering from symptomatic uterine fibroids.
Keywords: CH potencies, Homoeopathy, Leiomyomata, LM potencies, Randomized clinical trial, Uterine fibroids
|How to cite this article:|
Oberai P, Indira B, Varanasi R, Rath P, Sharma B, Soren A, Laxmi KB, Sharma A, Devi P, Padmanabhan M, Singh V, Nayak C. A multicentric randomized clinical trial of homoeopathic medicines in fifty millesimal potencies vis-à -vis centesimal potencies on symptomatic uterine fibroids. Indian J Res Homoeopathy 2016;10:24-35
|How to cite this URL:|
Oberai P, Indira B, Varanasi R, Rath P, Sharma B, Soren A, Laxmi KB, Sharma A, Devi P, Padmanabhan M, Singh V, Nayak C. A multicentric randomized clinical trial of homoeopathic medicines in fifty millesimal potencies vis-à -vis centesimal potencies on symptomatic uterine fibroids. Indian J Res Homoeopathy [serial online] 2016 [cited 2021 Feb 25];10:24-35. Available from: https://www.ijrh.org/text.asp?2016/10/1/24/179148
| Introduction|| |
Uterine fibroids (leiomyomas) are common benign smooth muscle tumors of the uterus. They are found approximately in 25–35% women of reproductive age (30–40 years) and in nulliparous or women of low parity., Estimating the overall prevalence of fibroids in the population is difficult as it depends on various factors however the Agency for Healthcare Research and Quality, US, documented the cumulative incidence of 70–80% by age 50. In Mysore, India, Maitri  documented 55% of women with fibroids in the third decade of age. Fibroids can lead to a variety of symptoms including heavy periods, pain, difficulty to conceive, or problems with pregnancy such as miscarriage and premature labor. The distribution of fibroid in the body of the uterus is broadly as: Intramural or interstitial (75%), submucous (15%), and subserous (10%). These symptoms and consequences have been shown to diminish the quality of life.,,
Both surgical and radiological therapies are frequently used for the management of this tumor; medical therapies are considered the first-line treatment and the ultimate is surgery. Long-term use of these conventional therapeutics has adverse effects.,, For women who wish to retain the uterus for future pregnancies, myomectomy is known but whether this improves fertility outcomes is still questionable. Uterine artery embolism though has an advantage over myomectomy and hysterectomy for symptomatic uterine fibroids but is associated with a higher rate of minor complications and soon requires surgical intervention within 2–5 years of the initial procedure  with much costs. Although the presence of myomas is almost never associated with mortality, it may cause morbidity and affect the quality of life.,
Homoeopathy is a system of medical science wherein prescription is personalized to individuals. Physicians use different scales of potencies such as centesimal (CH), fifty millesimal (LM), and decimal (X) in their practice. These scales differ in their method of preparation, i.e., potentization and succussion. Hahnemann  in his 6th edition of Organon of medicine mentions the benefits of new method of preparation of medicines, i.e., renewed dynamization or fifty millesimal (LM) potencies in comparison to potencies in CH scale, i.e., in the later scale the medicine can be repeated with increase in dynamic power of each dose. Further cure of chronic disease can be achieved more rapidly, using gradually increased doses of series of LM medicines. Homoeopathic medicines have shown positive results in treating patients suffering from fibroids. Popov's study  shows that homoeopathic medicines can not only control pain and abnormal endometrial bleeding but also reducing the size and stop the growth of the tumor. Iqbal et al. in their cohort study showed positive results in terms of reduction and resolution of fibroids. Case reports , demonstrate both symptomatic relief and reduction of fibroid size with homoeopathic medicines using both (CH) and LM potencies. Adler  review of Hahnemann's Paris case records shows the superiority of the LM potencies in comparison with the CH dynamization and it was based on a significant number of experiments with the two potencies. Basing on above results with different scales of potencies in Homoeopathy, a randomized clinical trial was undertaken to evaluate the homoeopathic potencies LM versus CH in the management of symptomatic uterine fibroids.
| Materials and Methods|| |
A multicentric randomized clinical trial was conducted on women suffering from symptomatic uterine fibroids to evaluate the effectiveness of individualized homoeopathic medicines in LM potencies vis-a-vis CH potencies. The Council's Ethical Committee approved the study protocol. Investigators experienced in dealing with this disorder were trained on the protocol. Written informed consent was received from all the patients enrolled. The study had also been registered retrospectively in clinical trial registry India, CTRI/2011/12/002211. Gynecologists and ultrasonologists were consulted during the study period for diagnosis, screening, enrollment, and follow-up assessment of the enrolled patients.
The study was conducted for a period of 2 years and 6 months (from June 2009 to November 2011) which includes follow-up period of 1-year, at six centers under the Central Council for Research in Homoeopathy: Central Research Institute (H), Kottayam, Kerala; Central Research Institute (H), Noida, Uttar Pradesh; Regional Research Institute (H), Shimla, Himachal Pradesh; Regional Research Institute (H), Puri, Orissa; and Regional Research Institute (H), Guwahati, Assam and Clinical Research Unit (H), Chennai, Tamil Nadu. Patients meeting all of the following criteria were eligible for study participation.
The inclusion criteria were as follows: Premenopausal women (18–45 years of age), presence of any of the symptoms such as abnormal uterine bleeding (profuse menstruation or intercyclic menstruation), pelvic heaviness, pain during menstruation, pain during intercourse, and pressure symptoms such as urinary frequency, constipation, uterine fibroids confirmed by pelvic and/or transvaginal ultrasonography, if patient is taking oral contraceptive pills (OCPs) then the patient was advised to stop pills till it exhaust for the ongoing cycle, followed by re-assessment of symptoms in the next cycle enrollment, patients under hormonal replacement therapy were included in the study after a washout period of 3 months and diabetic patients with haemoglobin A1C ≤8%.
Patients with calcified fibroid, coagulation disorders, extrauterine fibroid, polyp, cervical fibroid, any fibroid causing hydronephrosis, fibroid with solid ovarian mass, haemoglobin (Hb) <7 g/dl (severe anemia), inability to comply with the study protocol, including psychiatric diseases, pregnancy, malignant condition of genitourinary tract, H/O any other malignancy, desiring immediate surgical management for uterine fibroid, desiring for childbearing in the next year, insisting to use OCPs were excluded.
The homoeopathic medicines in LM or CH potencies were procured from a good manufacturing practices certified company. Investigators were instructed to make an in-depth interview with the patient, as per the guidelines laid down by Hahnemann in the 6th edition of Organon of medicine. The women enrolled in the study were not on any other nonpharmacological intervention. Before selection of a remedy homoeopathic procedure such as analysis, evaluation, and constructing totality of symptoms with repertorization was carried out. However, the final decision of selection of medicine was done after consultation with Materia Medica.
Patients randomized to the LM group received individualized homoeopathic medicine for 1 year customized to each patient which started with 0/1 potency, followed by next higher potency, serially, as per the need of the case. The investigator had trained the pharmacist and instructed the patients for the preparation and dispensing of LM potencies with precision as follows: One globule (poppy-seed size) of the desired potency was dissolved in 120 ml of distilled water, containing 2.4 ml (2% v/v) of dispensing alcohol, premixed in it, followed by ten uniformly-forceful downward strokes given against the bottom of the phial. The medicine was given once daily in the morning, on an empty stomach as long as improvement continued. Any change triggered after administration (status quo/improvement/deterioration/) led to frequent repetition/change of remedy following homoeopathic principles.
The dosage and repetition were decided a priori by a group of homoeopathic physicians experienced in their clinical practice. Each and every indicated medicine started with 30C potency, three times a day for 3 days. Each dose consisted of four medicated globules of sugar (size no. 20). If the patient reported during menstrual cycle, the indicated medicine was administered from the 5th day of menstrual cycle. In the case of need of a higher potency in the second prescription the repetition schedule for 200 CH potency was one dose daily for three consecutive days; for 1M potency, one dose daily for two consecutive days and in the case of 10M potency only a single dose. If the choice of remedy was a nosode, then the prescription began with 200 CH potency instead of the 30C potency.
The women were assessed for menstrual bleeding, dysmenorrhea, dyspareunia, and pressure symptoms (constipation, urinary frequency, and pelvic heaviness) at every menstrual cycle by the investigator which was scored on a visual analog scale 0–10, where 0 indicates no severity and 10 indicates maximum severity as described by previous researchers., Ultrasonography (abdominal and/or transvaginal) was done at baseline, 6th and 12th month to measure the size of uterine fibroids and uterine volume. The size of fibroids was measured taking the three main diameters (D1/D2/D3) and applying the formula of the ellipsoid (D1 × D2 × D3 × 0.52).,, An arithmetic mean of the sizes was used in the presence of two or more fibroids.
The UFS-QOL as devised by Spies et al. was used at the baseline, 6th month, and at 12 months to see the effect of homoeopathic medicines on the quality of life of patients suffering from symptomatic uterine fibroids.
Hemogram which includes Hb, packed cell volume, mean cell volume, mean cell Hb (MCH), and MCH concentration, respectively, were measured at baseline and at every 3 months to assess hemogram.
From the previous study, it has been seen that the percentage of change in the size of uterine fibroid after homoeopathic treatment is 26.8%. Considering it to be the lowest change in percentage assuming 25% change in symptoms for patients taking CH potency and a change of 20% more, i.e., 45% in patients taking LM potency with α-0.05 and power of 85%. As per the sample size table by Fleiss, the sample estimated to be 120 participants in each group.
Patients were randomized into two groups as per the random numbers were generated with the help of computer-based software available at www.randomizer.org. Block randomization with a block size of two was considered for randomization to divide the patients equally in both the groups. Due to individualized nature of homoeopathic prescription blinding of the investigator was avoided. After final selection of medicine, all patients were randomized to either CH or LM group.
Reporting adhered to the consolidated standards of reporting trials and RedHOT. Statistical Package for the Social sciences (SPSS) version 20 for Windows was used for all the data analysis using modified intention to treat (mITT) principle. As the data were skewed, all test were carried out using nonparametric statistical tools. A percentage change in all symptoms due to uterine fibroid, i.e., bleeding, dysmenorrhea, dyspareunia, and pressure symptoms (constipation, urinary frequency, and pelvic heaviness) was calculated at the 6th month and 12th month and were compared. The formula used for calculation of percentage is as follows: Comparisons were also made for size of fibroid and UFS-QOL which were the secondary outcome of the study. P < 0.05 was considered as significant.
| Results|| |
Participant including screening, enrollment, and dropouts is shown in [Figure 1]. Of 878 women screened, a total of 216 women diagnosed with uterine fibroid were enrolled. Data of seven women (two women from LM group and five women from CH group) did not complete their baseline information, so data of these women were not considered for analysis. Of 108 patients in each group, 106 women from Homoeopathic LM potency and 103 women from CH group were analyzed under mITT. The two groups were well matched for baseline characteristics [Table 1] and were comparable (P ≥ 0.05). Thirty-six women from CH group and 35 from LM group dropped at various levels of follow-up. Their values were carried forward for analysis following last observation carry forward method. The mean age of the patients (participants) was 38.5 ± 5.2 years. The mean duration of the illness/symptoms was 2.7 ± 2.9 years and 2.3 ± 2.4 years in LM and CH potencies, respectively.
|Table 1: Baseline characteristics of women studied under modified intention-to-treat (n=209)|
Click here to view
Analysis of Symptoms
The primary outcome [Table 2] was to assess the changes in symptoms due to a uterine fibroid. At the end of 6th and 12th menstrual cycle, both the scales of potencies showed equally effective in improving the symptoms (median percentage) of the patients (P > 0.05). Thus, there was overall treatment differences for homoeopathic therapy in all the symptoms, i.e., menstrual disturbances, dysmenorrhea, dyspareunia, pelvic heaviness, urinary frequency (P < 0.005) except for constipation (P = 0.18).
|Table 2: Changes in primary and secondary outcomes at 6th and 12th month|
Click here to view
Analysis of the Uterine Fibroid Symptom Quality of Life Questionnaire
The secondary outcome was related to the assessment of uterine fibroid symptom quality of life (UFSQOL). Both the potencies were equally effective in bringing changes in eight subscale scores of UFSQOL [Table 2] i.e., at 6th month; symptom severity (P = 0.21), concern (P = 0.36), activities (P = 0.33), energy (P = 0.34), control (P = 0.46), self-consciousness (0.67), sexual function (P = 0.80), and HRQOL total (P = 0.26). At the 12th month, symptom severity (P = 0.43), concern (P = 0.59), activities (P = 0.30), energy (P = 0.75), control (P = 0.19), self-consciousness (0.88), sexual function (P = 0.70), and HRQOL total (P = 0.64), respectively. Further, over a period 12 months the symptom severity score of the UFS-QOL decreased significantly (median at 6th month 15.6%, 12th month: 21.9%, P < 0.001) in all the patients irrespective of the intervention group. The HRQOL scores also showed a significant increase (median at 6th month 13.8%, 12th month: 21.7%, P < 0.001). All other parameters such as concern, activities, energy, control, self-consciousness, and sexual function also improved.
There were no significant changes from baseline to 6th month and from baseline to 12th month [Table 2] in the size of fibroids, laboratory parameters (P > 0.05) between the groups. However, significant improvement was found in uterine volume (P = 0.01) Hb (0.5 ± 1.8 g/dL, P = 0.01) at 12th month. After 1 year of treatment, 12 fibroids diminished completely, 175 fibroids remained status quo, seven fibroids decreased in size, and 13 increase in size [Table 3]. Only five patients were referred on request due to large fibroid size.
The commonly indicated medicines were Pulsatilla (n = 33), Sulphur (n = 23), Lycopodium (n = 22), Sepia (n = 18), Phosphorus (n = 18), Calcarea carbonica (n = 16), and Natrum muriaticum (n = 16). The details of medicines prescribed in each group are given in [Table 4]. The single prescription was given to 163 women while 46 women required a change of medicine [Table 5]. During the study period, no adverse events were noted.
|Table 4: Response of homoeopathic medicines in LM and CH potencies in patients with symptomatic uterine fibroid who were prescribed only one medicine throughout the treatment|
Click here to view
| Discussion|| |
Few case reports and observational studies ,,, carried out with homoeopathic intervention on uterine fibroid showed beneficial effects. None of the studies has systematically evaluated the effects individualized homoeopathic treatment. This trial evaluated the effect of individualized homoeopathic intervention in uterine fibroid comparing LM and CH potencies which are commonly used in homoeopathic practice were discovered by Hahnemann. The former scale of potency is the latest which was published posthumously. There is always a dilemma which potency acts better and can be administered easily. Thus, the trial was conducted to assess between the two potencies. Further due to nature of the disease and ethical reasons, placebo group as comparator arm was not kept. Hormonal replacement therapy of modern medicine was also not kept as comparator due to the nature of action of medicine which is organ specific whereas in Homoeopathy it is holistic.
The results show no significant difference between the different potencies (LM and CH) in improving the symptoms and quality of life of women suffering from symptomatic uterine fibroids; however, the overall percentage reduction in uterine fibroid symptoms due to homoeopathic treatment was highly significant. The quality of life in both the groups improved significantly. Popov study  reflects 26.8% improvement in patients taking Homoeopathy in CH potency whereas in our study it is 29% thus the findings are substantiated. Further, neither the investigators nor the patients found it difficulty in preparing the medicine in LM potency. However, few patients showed their unwillingness and found difficulty to take the medicine while travelling as it was of liquid. The compliance of the patients for intake of LM medicines was good if the investigator made the patients understand it. There was no statistically significant reduction in the size of fibroid; however, homoeopathic medicines significantly reduced uterine volume (P = 0.03). The reduction may not be due to a decrease in myoma size but rather appeared to affect only myometrium.
The medicines indicated and prescribed, i.e., Pulsatilla., Sulphur, Lycopodium, Sepia, Phosphorus, Calcarea carbonica, and Natrum muriaticum are notably in consensus with the study done by Iqbal et al. and Popov. Hence, this study reflects the possibility that individualized homoeopathic medication could control the symptoms and slow down the growth of fibroid. However, longer treatment period is required for observing more treatment benefits.
The main strength of this study is that there were no side effects observed during the study period. The intervention is cost effective in comparison modern or conventional medicine ,,,,,,, wherein the treatment is very costly and ultimate is hysterectomy which has to be done at the cost of fertility. Another strength was involvement of gynecologists, who along with the homoeopathic physicians observed treatment effects, adding credibility to the study.
This study has few limitations. First is a lack of investigator blinding which was not possible due to the individualized nature of the intervention and patients were informed in a manner suggesting that two different types of treatment would be compared. The results of this study can be useful to patients where there is no urgency for surgical intervention and reduce out of pocket costs.
| Conclusion|| |
Homoeopathic medicines may offer an effective treatment option for women with symptomatic uterine fibroid and can improve the patients' quality of life.
The authors acknowledge the contribution of gynecologists and ultrasonologist for extending their consultation and help in enrollment and assessment of outcome in follow-up of the patients. Dr. Alok Kumar, Former Director General, Dr. Raj. K. Manchanda, Director General, Dr. Anil Khurana, Deputy Director(H), officer in charges of respective centers for their administrative support. Dr. Debadatta Nayak, Research Officer (H)/S-2 for his technical support during the preparation of protocol. Dr. Shilpa Sharma, Senior Research Fellow (H), DDPRCRI (H), Noida for assisting in data verification. The acknowledgements are also extended to patients for their support and participation.
Financial Support and Sponsorship
Central Council for Research in Homoeopathy
Conflicts of Interest
There are no conflicts of interest.
| References|| |
Padubidri VG, Daftary NS. In Howkins and Bourne Shaw's Text Book of Gynecology. 14th
ed. India. Elsevier; 2008. p. 316.
Buttram VC Jr., Reiter RC. Uterine leiomyomata: Etiology, symptomatology, and management. Fertil Steril 1981;36:433-45.
Ouyang DW, Economy KE, Norwitz ER. Obstetric complications of fibroids. Obstet Gynecol Clin North Am 2006;33:153-69.
Spies JB, Coyne K, Guaou Guaou N, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002;99:290-300.
Tristan M, Orozco LJ, Steed A, Ramírez-Morera A, Stone P. Mifepristone for uterine fibroids. Cochrane Database Syst Rev 2012;8:CD007687.
Ke LQ, Yang K, Li J, Li CM. Danazol for uterine fibroids. Cochrane Database Syst Rev 2009; 2009 Jul 8;(3):CD007692.
Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001;2 (1):CD000547.
Metwally M, Cheong YC, Horne AW. Surgical treatment of fibroids for subfertility. Cochrane Database Syst Rev 2012;11:CD003857.
Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev 2012;5:CD005073.
Myers ER, Barber MW, Couchman GM, Datta S, Gray RB, Ashby TG et al
. Management of Uterine Fibroids (Evidence Report/Technology Assessment No. 34, Contract 290-97-0014 to the Duke Evidence-based Practice Center). AHRQ Publication No. 01-E052. Rockville, MD: Agency for Healthcare Research and Quality; July, 2001. [cited 15 March 2015], Available from: http://www.ncbi.nlm.nih.gov/books/NBK33644
Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al.
A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study. Health Technol Assess 2008;12:1-248, iii.
Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril 2007;87:725-36.
Banerjee DD. Text Book of Pharmacy. New Delhi: B Jain Publishers (P). Ltd.; 2007.
Hahnemann S. Organon of Medicine. Reprint 6th
Edition. New Delhi: B Jain Publishers; 1982, p. 290.
Hahnemann S; Organon of the Medicine Art. Edited and annotated by Reilly WB, the sixth edition of Dr. Samuel Hahnemann's work of genius based on translation by Steven Decker; first Indian edition; B Jain Publishers; New Delhi: 2010
Popov AV. Homoeopathy in treatment of patients with fibromyoma of the uterus. Br Homeopath J 1992;81:164-7.
Iqbal JQ, Ali S, Vatsalya B, Ponnan HB, Nikhat PS. Role of homoeopathic medicines in treating uterine fibroid: A prospective observational study. Indian J Res Homoeopathy 2012;6:3-14.
Iqbal JQ, Ali S, Nikhat PS, Vatsalya B. A case of uterine fibroid. Indian J Res Homoeopathy 2008;2:50-8.
Sevar R. Aurum muriaticum natronatum – Four case reports. Homoeopathy 2007;96:258-69.
Adler UC, Adler MS. Hahnemann's experiments with 50 millesimal potencies: A further review of his casebooks. Homoeopathy 2006;95:171-81.
Kent JT. Lectures in Homeopathic Philosophy. New Delhi: B Jain Publishers; 2006
Hahnemann S. The Chronic Diseases, Their Peculiar Nature and Their Homoeopathic Cure. New Delhi; B Jain Publishers Pvt. Ltd.; 1999.
Varelas FK, Papanicolaou AN, Vavatsi-Christaki N, Makedos GA, Vlassis GD. The effect of anastrazole on symptomatic uterine leiomyomata. Obstet Gynecol 2007;110:643-9.
Palomba S, Orio F
Jr., Morelli M, Russo T, Pellicano M, Zupi E, et al.
Raloxifene administration in premenopausal women with uterine leiomyomas: A pilot study. J Clin Endocrinol Metab 2002;87:3603-8.
Yang CH, Lee JN, Hsu SC, Kuo CH, Tsai EM. Effect of hormone replacement therapy on uterine fibroids in postmenopausal women – A 3-year study. Maturitas 2002;43:35-9.
Joseph LF. Statistical Methods for Rates and Proportions. 1st
ed. Hoboken, New Jersey: John Wiley and Sons, Inc.; 1973.
Magalhães J, Aldrighi JM, de Lima GR. Uterine volume and menstrual patterns in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas. Contraception 2007;75:193-8.
Evans P, Brunsell S. Uterine fibroid tumors: Diagnosis and treatment. Am Fam Physician 2007;75:1503-8.
Sankaran S, Manyonda IT. Medical management of fibroids. Best Pract Res Clin Obstet Gynaecol 2008;22:655-76.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]