MENORRHAGIA: RESPONSE TO MEDICAL AND SURGICAL METHODS

Menorrhagia, more correctly now known as heavy menstrual bleeding amongst the wider picture of abnormal uterine bleeding, is one of the most common presentations to gynaecologists in the world and is estimated to occur in up to 1/3 of women of reproductive age at sometime during their lives (1). The International Federation of Gynecology and Obstetrics officially categorizes this condition using the PALM-COEIN system, which distinguishes between structural causes, including endometrium polyps, adenomyosis, fibroid/leiomyoma and malignancy; non-structural causes, such as coagulopathy and ovulatory dysfunction; and other factors including endometrium Iatrogenic factors and Unknown factors (1,2). Large proportions of affected women do not seek medical attention despite significant disruption of daily activities, as shown in population-based surveys (3); and heavy menstrual bleeding has significant psychosocial and economic consequences, too, impairing working, social and recreation, and overall quality of life (4).

 Because of current evidence-based guidelines, surgical procedures (such as endothelial ablation, myomectomy or hysterectomy) should be considered the last step of managing women who have had persistent symptoms despite the use of medications (such as tranexamic acid, NSAIDs or the levonorgestrel-releasing IUD), or who are not suitable for medications or who decline them (5-8). Although each pharmacological class has its own well-studied mechanism of action and efficacy profile, surgery provides more reliable management and decreases bleeding at a higher rate of invasiveness and, in the case of hysterectomy, lack of fertility post surgery.

 In Pakistan, menorrhagia is one of the most common causes of anaemia and seeking care at the out patient departments of the gynaecology wards of hospitals (9); however a significant percentage of women who had menorrhagia presented late, probably due to less awareness, society/cultural norms related to/avoidance of menstrual problems and also because specialist gynaecology care was not easily available outside major cities. A local study from a teaching hospital in Lahore ( Pakistan) has demonstrated that menorrhagia has a significant impact on quality of life for Pakistani women, with many suffering for several years before resorting to formal treatment (9). While hysterectomy is still most commonly performed surgery, there is an increased focus on uterus-conserving options which is becoming more prominent in the global setting and local practice for the management of heavy menstrual bleeding (10).

 Although treatment hierarchies are internationally recognized, there are few in the literature that provide comparative evidence directly between medical and surgical rates of response in the Pakistani-tertiary care context, and local clinicians have mostly extrapolated information from Caucasian populations with different demographic, micro-nutritional and healthcare-access characteristics. This gap restricts the gynaecologist's ability to provide patients with assured counselling on what might be expected from each of the treatment options. Differential comparative study of clinical outcome of medical versus surgical treatment was thus designed to assess the reduction in blood loss in menstruation, improvement in haemoglobin and satisfaction of the patient in both treatment options in women reporting menorrhagia in a tertiary-care hospital, Karachi.

140 women suffering with menorrhagia were recruited of which 70 women were assigned to medical management (Group A) and 70 women were allotted to surgical management (Group B). The age of the study population ranged from 31 to 40 years with the majority (54.3%) being in the age group. The mean age was 37.2±6.5 years. Ovulatory dysfunction was the most common underlying cause (29.3%), followed by structural causes (mainly leiomyoma (27.1%) and adenomyosis (19.3%)). Of those who had symptoms, a majority (65.7%) experienced symptoms for more than 6 months, which is similar to the pattern elsewhere described in Pakistan (9) (Table 1).

 Table 1: Baseline Demographic and Clinical Characteristics of Study Participants (n=140).

 Statistically significant differences in mean PBAC between the groups at follow-up were present ( Group A: 186 ± 42 vs. 96 ± 38; Group B: 191 ± 39 vs. 38 ± 21; p<0.001 for both groups). A satisfactory response was observed in 46 of 70 women (65.7%) in Group A compared with 64 of 70 women (91.4%) in Group B (p<0.001). There was a statistically significant increase in the mean haemoglobin in Group A (0.9 ± 0.4 g/dL) to Group B (1.8 ± 0.5 g/dL) (p<0.001) and greater number of patients in Group B had a rise in haemoglobin by>1 g/dL (84.3%) compared to Group A (41.4%) (p<0.001) (Table 2, Figure 1).

Table 2: Comparison of Treatment Outcome Between Medical and Surgical Groups at 6 Months.

Minor treatment related complications occurred in 11.4% of patients in Group A, most commonly gastrointestinal intolerance, and 18.6% of Group B which were mainly surgical site or anaesthesia related without a significant difference between groups (p=0.224). No patient in either group had a major adverse outcome, requiring intensive care or transfusion of greater than 2 units of blood.

Surgical management had a significantly higher satisfactory response rate (91.4%) compared to medical management (65.7%) and the general trend was in line with the published literature of HMB surgical vs medical management. The Cochrane review by Marjoribanks et al. directly compared the surgical and medical treatment of heavy menstruation, finding that although the medical was suitable as the initial treatment, the surgical was found to consistently provide better bleeding scores and patient satisfaction at 1 year, consistent with the findings of the present study (8). A systematic review and economic evaluation conducted by Bhattacharya et al. also indicated that both these interventions (hysterectomy or endometrial ablation) demonstrated better control of bleeding than medical management, however, the latter was more cost-efficient when fertility preservation was a goal (13).

 The high degree of satisfaction within the surgical arm is also in keeping with results from the pooled individual-patient meta-analysis conducted by Middleton et al., where hysterectomy was associated with a consistent decrease in blood loss and the highest degree of satisfaction was reported, but there were also fewer peri-operative risks during ablation (14). Alexander et al. conducted a randomised study in which patients also appeared to achieve better psychosocial change after surgery compared with nonsurgical treatment, which is also consistent with the present study Group B, where satisfaction was superior to nonsurgical cases (15). In long-term follow-up up to 10 years, the study by Hurskainen et al also reported that hysterectomy was superior in the number of symptom cases controlled, but was similar to the levonorgestrel intrauterine system LIS in improving quality of life over time (16).

 Some studies, however, have been found to produce medical response rate more similar to the surgical rate than the one found here. Both Cochrane reviews of tranexamic acid and the levonorgestrel-releasing intrauterine system demonstrated that, if both are used optimally and for sufficient durations, both treatments are associated with significant reductions in menstrual blood loss, although this reduction still appears to be greater than that with surgical methods (6,8). A levonorgestrel intrauterine system was also demonstrated to be almost as effective as transcervical endometrial resection in decreasing blood loss during menstruation over the course of a year by Kai et al. (17). There are a couple explanations for this — the lower medical response rate in the present cohort (65.7%) may be due to the inconsistent compliance among patients, and the relatively brief 6-month observation period may have underestimated the cumulative benefit of continued medical therapy noted in longer trials (18), since 46.4% of patients had leiomyoma and adenomyosis.

 The local information obtained from Yusuf in a Lahore based teaching hospital also revealed that menorrhagia significantly affected the quality of life in Pakistani women and that a significant number deferred in presentation time, which was also common in the current cohort with nearly two thirds of women having symptoms for over 6 months before enrolment (9). This late presentation may be responsible for more complicated structural disease at diagnosis in the routine local setting, in which definitive surgical therapy would perhaps be favored over medical therapy. The similar but statistically non-significant minor complication rate for the two groups in the current study (11.4% vs 18.6%, p=0.224) reflects the relatively low minor complication rates reported in recent network meta-analyses of the outcomes of endometrial ablation versus hysterectomy (10,19), where minor complications continue to be relatively uncommon when performed by an experienced surgeon.

 A number of limitations exist with this study. Treatment allocation was based on clinical indication and patient preference and not on random allocation, which could present selection bias as women undergoing surgery may have been those with more advanced or structurally evident disease. The study was conducted in a single centre and the follow-up was only 6 months, meaning that the external validity of the results and long term recurrence or late complications are not assessable. Assessment of patient satisfaction was non-validated categorical rather than standardised instrument of quality-of-life data collection which may impact the comparability of findings against other studies. For the future multicentre studies with larger follow up and randomization are recommended to confirm these results in the larger population of Pakistan.

Over 6 months, this study showed that surgical management of menorrhagia had a significantly higher satisfactory clinical response, haemoglobin recovery and patient satisfaction rate than medical therapy, while also demonstrating a comparable rate of minor complications to medical therapy. Medical therapy should however remain an initial safe and sensible approach, especially when the aetiology is non-structural, severity of the disease is low or the patient expresses a desire to preserve her fertility as a woman. These observations underwrite a tailored step wise approach to the management of menorrhagia with early counselling of realistic expectations from both treatment modalities at the local population level.

 ACKNOWLEDGMENT

The authors would like to thank the Surg Cdr Samina Naseem Khattak, Classified Gynaecologist, Department of Obstetrics & Gynaecology, PNS Shifa Hospital, Karachi for her supervision, guidance and continuous support with the design and conduct of this study.

 CONFLICT OF INTEREST

None.

 FUNDING

None.