This is a prospective study of 24 weeks duration on 50 women with dysfunctional uterine bleeding, who attended to out-patient department of Obstetrics & Gynaecology at King George Hospital, Visakhapatnam, Andhra Pradesh, India. After getting approval from the Institutional Ethics Committee, newly diagnosed dysfunctional uterine bleeding patients of >18years were randomly included in this study. The patients with pelvic pathology like endometriosis, fibroids, pelvic inflammatory disease, known case or suspected or with a history genital tract malignancy, lactating mothers, those with heavy bleeding necessitating emergency treatment, and those who were on estrogen, progesterone, testosterone or danazol, prostaglandin synthetase inhibitors, antifibrinolytic therapy were excluded. Patients with history of hypersensitivity or allergy to Ormeloxifene were also excluded. The patients meeting the inclusion criteria were explained in detail about the nature of the study, its purpose, regimen, procedure and follow-up. Informed consent was taken from all the patients included in the study. At the screening visit, patients were examined and detailed menstrual history was obtained to determine patient’s eligibility for enrollment in the study. After initial screening, the demographic data, past medical history, findings of physical and clinical examination were recorded in the case report form. Routine haematological investigations like CBC, CT, BT, thyroid profile, ultrasound abdomen, endometrial histopathology and liver functions tests were done. Patients meeting the inclusion criteria were treated with Ormeloxifene tablet 60 mg, twice a week. The total duration of the study was of 24 weeks for each patient. All the patients were advised to take study medication regularly, every Sunday and Wednesday for the first 12 weeks and then once a week for another 12 weeks. Treatment schedule was continued irrespective of menstrual periods. The patients were advised to come for follow-up at 4^th, 8^th ,12^th and 25^th week of treatment initiation or earlier if needed. The main outcome measures- menstrual blood loss, endometrial thickness, Hemoglobin levels were assessed at baseline and at the 25^th week of study. Pictorial blood loss assessment chart (PABC) [7] was used to measure the menstrual blood loss, a method that correlates well with the alkaline haematin test [8]. The women were asked to use certain sanitary products which have been shown to have similar absorbent capacities [9], and record the number of sanitary products used each day and the degree of soiling of each pad used. Number and size of clots passed were also noted. Scores were assigned to different degree of soiling of sanitary products and number and size of clots passed [Table/Fig-1]. A PABC score of greater than or equal to 100 indicated a menstrual blood loss greater than or equal to 80 ml and was considered diagnostic for menorrhagia [7]. We also recorded the adverse events of the drug during the study and by questionnaire recorded the subjective assessment of passage of clots and dysmenorrhoea. Dysmenorrhoea was categorized as absent, mild, moderate and severe. The endometrial thickness was measured initially and 25^th week of the study at premenstrual phase by transabdominal ultrasound scan which was done by radiologist. The data obtained was analyzed using the paired t-test and the difference between the two proportions of the nominal data was analyzed by Z-test.

Out of 63 patients enrolled, 50 completed the study and 13 lost the follow-up. Age of the treated patients ranged between 18 to 51 years and maximum number of patients were in the age group between 21 to 30 years (42%). [Table/Fig-2] depicts the demographic data of the patients in the study. Bleeding was more common in multipara, this may be due to altered pituitary ovarian function following delivery. [Table/Fig-3] represents that there was significant decrease of median PABC score from baseline to 25^th week of treatment follow-up and the reduction was found to be statistically significant (p<0.001). Twenty four out of fifty patients (48%) recorded mean PABC score of less than 100 at the end of study period. There was a significant reduction of endometrial thickness at the end of 25^th week. The mean difference was found to be statistically significant (p<0.001). Majority of patients had anaemia when enlisted into the study as defined by WHO (haemoglobin <12 gm/dl). There was a significant increase in post-treatment haemoglobin level when compared to baseline haemoglobin level. The mean increase of 1.3 gm / dl of haemoglobin level was statistically significant (p<0.001). 84% of patients had significant relief from dysmenorrhoea (p<0.001). Presence of clots in menstrual flow is a clear cut evidence of abnormality associated with DUB. 59% of patients had significant relief from passage of clots (p<0.002). [Table/Fig-4] indicates that out of fifty cases Cyclical bleeding was most common and was observed between 21 to 30 years of age group. Acyclical bleeding was commonly seen in peri-menopausal women and below 20 years of age. During the study period there were no major side effects, the observed effects were amenorrhoea (10%), giddiness (4%), abdominal pain (4%), headache (2%), which did not require termination of treatment.

Dysfunctional uterine bleeding occurs more commonly in the first five years after a women starts menstruating and as she approaches menopause, but it can occur at any time period. For women with DUB who wish to retain fertility, pharmacological approaches are the only currently available options. Among the other pharmacological agents, some are effective only for anovulatory DUB, some are useful only for ovulatory DUB, and still others may be effective for both. Pharmacological agents such as NSAIDS, oral contraceptive pills, progestins, danazol, GnRH agonists and antifibrinolytic drugs all reduce menstrual blood loss, however, the assets are limited to the duration of treatment. In our study we have analyzed the efficacy of Ormeloxifene in patients with dysfunctional uterine bleeding and our results suggested that there was a significant reduction of menstrual blood loss, these results are similar to other studies [10,11]. The results of the present study showed that there was a significant rise of haemoglobin level which was also similar to other studies [10–13]. when endometrial thickness was compared between baseline and post treatment period, there was a significant reduction of endometrial thickness with this drug. These results are similar to other studies [10–14].

Dysmenorrhoea is a frequent complaint more reported by most of the patients. In the present study a total of 36 patients reported dysmenorrhoea during initial week and by the end of the study only 6 patients reported improvement which was similar to other studies [10,11,13,15]. Although our sample size was small, we got significant reduction in menstrual blood loss. The ultimate aim of pharmacological management of dysfunctional uterine bleeding is to restore the natural cycle of orderly endometrial growth and shedding. The choice of treatment must be opted in relation to several factors like presence of anovulatory or ovulatory cycles and the need for contraception. Patients preference (particularly desire to avoid hormonal therapy), contraindications to treatment also play a major role. Inspite of treatment advances, DUB is still a significant cause of morbidity and mortality. Current therapies frequently fall short of providing full remission, due to unwanted effects. At the end , the treatment opted should be started only after the benefits of the treatment are weighed against the risks. In this scenario Ormeloxifene being a non-steroidal, non- hormonal agent it targets the disease with favourable profile.

Ormeloxifene was found effective in reducing menstrual blood loss in patients with DUB. It was found to be an excellent drug in controlling the systems of dysfunctional uterine bleeding without effecting normal endocrinal and physiological parameters. Pharmacological agents such as NSAIDs, oral contraceptive pills, progestins, danazol, GnRH agonists and antifibrinolytic drugs, they reduce menstrual flow, however, the benefits are limited due to the duration of therapy and as single agent is not suitable to all age groups. We conclude that Ormeloxifene is suitable for the treatment of DUB, in all age groups with effective therapeutic efficacy and with least side effects, study also shows that the compliance of the patient is good because of convenient dosage schedule and no need for medicine intake every day. Further studies with large sample size is needed to throw light regarding the efficacy and safety of the agent.