Abnormal uterine bleeding is one of the most common gynaecological symptoms seen in women of reproductive and perimenopausal age. It is bleeding from the body of the uterus that is irregular in regularity, frequency, duration, and/or quantity, when compared to menstruation. The disorder can manifest itself in either heavy periods, prolonged periods, irregular periods, intermenstrual bleeding, or as a combination of these. While there are many functional and structural abnormalities that can cause abnormal uterine bleeding, continued bleeding may have significant systemic consequences, such as depletion of body iron stores and the development of iron-deficiency anaemia (1-3).

Iron-deficiency anaemia occurs when iron deficiency occurs because it is being lost faster than it is being absorbed or released from reserves. Increased risk to women with heavy/long periods, as iron stores are depleted gradually and a measurable decrease in haemoglobin levels is not observed until there is a significant loss of blood. As iron deficiency worsens, one may experience microcytic and hypochromic changes of the erythrocytes and symptoms of fatigue, weakness, dizziness, pallor, decreased exercise tolerance, and dyspnea. Iron-deficiency anaemia can have adverse effects on physical functioning, cognition, occupational productivity and quality of life besides haematological effects. Therefore, the early diagnosis and management of iron deficiency anemia in women with abnormal uterine bleeding is a crucial part of women's health management (4, 5).

Abnormal uterine bleeding is caused in part by abnormalities of the structure of the uterus and endometrium. Uterine leiomyomas may contribute to the increased menstrual blood loss due to distoring the endometrial cavity, enlarging endometrial surface, abnormal uterine contractility and alteration of local vascularity. Heavy or painful periods can also be caused by adenomyosis, and endometrial polyps or abnormalities of endometrial thickness can cause irregular or intermenstrual bleeding. Because it's non-invasive, widely available, relatively inexpensive, and can detect many clinically relevant uterine and adnexal abnormalities, pelvic ultrasonography is often used as a first line imaging modality for evaluation of women with abnormal uterine bleeding (6, 7).

Iron supplementation is an important initial therapy for iron deficiency anaemia, and oral iron is the treatment of choice in haemodynamically stable women. Ferrous sulfate is the most commonly prescribed product since it is readily available, effective and relatively inexpensive. There is a need for adequate treatment to raise the haemoglobin level and to slowly restore the depleted iron stores. But, the response can depend greatly on the patient. Even with adequate oral iron intake, iron levels may not improve if the period is too heavy, iron is not well absorbed, a structural defect in the pelvis fails to pass, or a gastrointestinal intolerance occurs, or if there is a significant baseline iron deficiency or a malabsorption problem. Hence, treatment response should be evaluated in conjunction with an investigation into the underlying cause of uterine blood loss and not in isolation as an anaemia (8-10).

Although the relationship between abnormal uterine bleeding and iron deficiency is well recognized, fewer studies have simultaneously evaluated the severity of anaemia in relation to specific pelvic ultrasound findings and subsequent response to oral ferrous sulfate therapy. Understanding these associations may help identify women at greater risk of severe iron deficiency or inadequate response to oral treatment. Therefore, the present study was conducted to determine the association of iron-deficiency anaemia with pelvic ultrasound findings in women with abnormal uterine bleeding and to assess their response to oral ferrous sulfate therapy.

This prospective observational study with a pre–post therapeutic assessment was conducted at Pak International Medical College, Peshawar from February 2025 to August 2025. A total of 89 women presenting with abnormal uterine bleeding (AUB) and laboratory-confirmed iron-deficiency anaemia were enrolled. Participants were recruited through a consecutive non-probability sampling technique after assessment in the outpatient or gynaecology department. Women of reproductive and perimenopausal age who presented with heavy, prolonged, irregular, or intermenstrual uterine bleeding and who fulfilled the laboratory criteria for iron-deficiency anaemia were considered eligible. Before enrolment, the purpose and procedures of the study were explained to each participant, and written informed consent was obtained. Women with abnormal uterine bleeding and haemoglobin levels below the laboratory reference range together with biochemical evidence of iron deficiency were included. Iron deficiency was identified on the basis of reduced serum ferritin and supportive red-cell indices, including low mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), where applicable. Patients with known bleeding disorders, chronic kidney disease, chronic liver disease, haemoglobinopathies, active gastrointestinal bleeding, malignancy, pregnancy, severe systemic illness, or anaemia attributable primarily to causes other than iron deficiency were excluded. Pre-enrolment women who were on parenteral iron treatment, blood transfusion, or long term (more than three months) therapeutic iron supplementation were also excluded to reduce the possibility of their baseline haematological parameters being affected by these treatments.Data collection was done by using a structured data collection form, which recorded detailed demographic, reproductive, menstrual and clinical information. Variables recorded were age, body mass index, parity, duration and pattern of abnormal uterine bleeding, menstrual duration, number of sanitary pads used on the heaviest days of the period, passage of clots, intermenstrual bleeding, pelvic pain, tiredness, generalized weakness, dizziness, exertional dyspnoea and pallor. Complete blood count with haemoglobin, haematocrit, MCV, MCH and MCHC were performed along with serum ferritin, serum iron, total iron-binding capacity, and transferrin saturation if available, in the laboratory. Haemoglobin concentration was defined as mild, moderate or severe anaemia based on the predefined study criteria. All participants received a standardized imaging protocol performed by a pelvic ultrasonography (US) performed by a highly experienced radiologist/sonologist. The clinical suitability of the patients was used to determine transabdominal and/or transvaginal ultrasonography. Ultrasonographic parameters were uterine size, endometrial thickness, uterine leiomyoma, number and maximum diameter of uterine fibroids, location of fibroids, presence of adenomyosis, presence of endometrial polyp, presence of ovarian cysts, and other relevant pelvic abnormalities. When fibroids were present they were also classified as submucosal, intramural or subserosal. Normal pelvic ultrasound was defined as the absence of a detectable structural abnormality and used to compare the results of participants who did not have a structural abnormality. A standardized imaging protocol was performed by a pelvic ultrasonography (US) technique by a highly experienced sonologist/radiologist. The clinical suitability of the patients was used to determine transabdominal and/or transvaginal ultrasonography. Uterine size, endometrial thickness, uterine leiomyoma, number of uterine fibroids, maximum diameter of uterine fibroids, location of uterine fibroids, presence of adenomyosis, presence of endometrial polyp, presence of ovarian cysts and other relevant pelvic abnormalities were considered to be the ultrasonographic parameters. If fibroids occurred they were also grouped as submucosal, intramural and subserosal. “Normal” pelvic ultrasound was the absence of a detected structural abnormality and was used for comparison of the results of the participants without the presence of a structural abnormality. After the baseline assessment, all subjects were given oral ferrous sulfate therapy in accordance with the standard therapeutic protocol used by the treating physician, and with the aim of furnishing a therapeutic dose of elemental iron. Patients were educated on use of medication, dietary recommendations to help with iron absorption, and common GI side effects. In follow-up assessment compliance was evaluated through patient history and the review of medication use. Patients were re-evaluated at the end of the treatment period, and the following main haematological parameters were measured again. Changes in the haemoglobin concentration were used to define treatment response as the primary measure and changes in haematocrit, MCV, serum ferritin, serum iron, and transferrin saturation were used as secondary measures. The haematological response was considered adequate if there was a clinically significant rise in haemoglobin following oral iron therapy as outlined in the study protocol. The main results of the study were the relationship between the iron-deficiency anaemia and the pelvic ultrasound results and the haematological changes following oral ferrous sulfate treatment. Secondary outcomes consisted of variations in the haemoglobin and iron indices for different ultrasound abnormalities, especially uterine fibroids and adenomyosis, and the effect of non-haemorrhagic and non-anaemic menstrual periodization and baseline anaemia severity and therapy compliance on therapeutic response. All the data were entered and analyzed on IBM SPSS Statistics version 25.0. Data for continuous variables were presented as mean ± SD for normally distributed variables or as median and interquartile range (IQR) for other variables. Categorical variables were summarised using frequencies and percentages. The Shapiro–Wilk test was used to test the normality of continuous variables. Paired-samples t-test was used for normally distributed data, and Wilcoxon signed-rank test for data that were not normally distributed when they were compared with pre- and post-treatment lab parameters. Comparisons between two independent groups were made using an independent-samples t-test or Mann–Whitney U test and comparisons between more than two groups were made using analysis of variance or Kruskal–Wallis test. The Chi-square test or Fisher's exact test was used to test associations between categorical variables (including ultrasound findings, severity of anaemia, and treatment response). A p-value < 0.05 was seen as statistically significant.

The total number of women included in the study was 89 with high level of iron-deficiency anaemia and abnormal uterine bleeding. Participants' mean age was 36.8 ± 8.1 years, with majority of the female participants being in age group 31–40. The mean body mass index was 26.4 ± 4.2 kg/m². Most of the participants were multiparous, and a fewer number were nulliparous. The most common clinical manifestations were fatigue, generalized weakness, dizziness, and pallor.

Table 1. Baseline demographic and clinical characteristics of study participants (n=89)

For a median of about six months, there had been abnormal uterine bleeding. More than half of the participants had heavy menstrual bleeding and this was the most common bleeding pattern. There was also a high prevalence of prolonged menstruation and passage of blood clots.

Table 2. Characteristics of abnormal uterine bleeding among participants

A mean haemoglobin concentration of 9.3 ± 1.3 g/dL was found in the baseline laboratory evaluation. The median serum ferritin level was 10.8 (5.7) ng/mL and the mean MCV was 72.9 (6.8) fL, which are typical of iron-deficiency anaemia. The most common type of anaemia was moderate.

Table 3. Baseline haematological and iron-profile findings

Pelvic ultrasonography revealed a structural abnormality in at least one of the women in 62 of 89 women (69.7%). The most common were uterine fibroids, followed by adenomyosis and endometrial abnormalities. Twenty-seven participants had a normal structure on pelvic ultrasonography.

Table 4. Pelvic ultrasound findings among women with abnormal uterine bleeding

Some participants had more than one ultrasound abnormality; therefore, percentages may exceed 100%.

The most common type of fibroid was intramural fibroids among women with fibroids. Woman with fibroids and adenomyosis had lower mean haemoglobin than women with normal pelvic ultrasound.

Table 5. Association of pelvic ultrasound findings with baseline haemoglobin and anaemia severity

There was a significant difference in mean haemoglobin levels between the women who were diagnosed with uterine fibroids and women who were diagnosed as normal on their ultrasound. Women with fibroids and adenomyosis were also more likely to have moderate-to-severe anaemia. The overall correlation between anaemia severity with the pelvic ultrasound was statistically significant (p=0.003).

Everyone was started on oral ferrous-sulfate treatment and then reevaluated following the prescribed treatment duration. Therapy resulted in significant increases in haemoglobin, haematocrit, MCV, serum ferritin, serum iron and transferrin saturation. The mean haemoglobin level was 9.3 ± 1.3 g/dL before treatment and 11.4 ± 1.2 g/dL after treatment, which is a mean increase of around 2.1 g/dL.

Table 6. Haematological response to oral ferrous sulfate therapy

An adequate haematological response (clinical improvement in haemoglobin level after oral iron therapy) was seen in 68 participants (76.4%) and inadequate response in 21 participants (23.6%). The treatment response was less among women who had fibroids, who had persistent heavy menstrual bleeding (HMB), who had severe baseline anaemia, and women who were not adherent to treatment.

Table 7. Factors associated with response to oral ferrous sulfate therapy

Women with normal pelvic ultrasonography had a greater likelihood of achieving an adequate response to oral ferrous sulfate compared with those with structural pelvic abnormalities (88.9% vs. 71.0%, p=0.041). Similarly, the presence of uterine fibroids was associated with a comparatively lower treatment response (p=0.048). Persistent heavy menstrual bleeding was strongly associated with inadequate haematological recovery (p=0.004).

Overall, oral ferrous sulfate therapy produced a statistically significant improvement in haematological and iron-profile parameters. However, women with structural causes of abnormal uterine bleeding, particularly uterine fibroids, tended to have more severe anaemia at baseline and a less pronounced treatment response. These findings suggest that correction of iron deficiency is more successful when the underlying cause of persistent uterine blood loss is simultaneously identified and appropriately managed.

The present study evaluated the relationship between iron-deficiency anaemia, pelvic ultrasonographic abnormalities, and response to oral ferrous sulfate therapy among women presenting with abnormal uterine bleeding. A substantial proportion of participants demonstrated structural abnormalities on pelvic ultrasonography, with uterine fibroids being the most frequent finding, followed by adenomyosis, increased endometrial thickness, and endometrial polyps. Women with structural pelvic abnormalities had lower haemoglobin concentrations and a greater frequency of moderate-to-severe anaemia compared with those who had a normal pelvic ultrasound. These findings support the clinical concept that persistent or excessive uterine blood loss caused by underlying pelvic pathology can substantially contribute to depletion of iron stores and subsequent development of iron-deficiency anaemia (11-13). In this study, heavy bleeding was the most common form of irregular bleeding, and was often associated with longer periods of bleeding and with the presence of clots. The amount of iron lost during the periods can gradually decrease iron levels in the body, especially when it is not being replaced from the diet. This relationship was evidenced in the low baseline haemoglobin, serum ferritin, serum iron level, MCV and transferrin saturation values of the study participants. Many women may be moderately anaemic for a long time without being adequately evaluated, further indicating the prevalence of moderate anaemia. Other symptoms like pallor, generalized weakness, fatigue, exertional dyspnoea and dizziness were also prevalent and confirmed the general clinical effect of iron deficiency on daily activities and quality of life (14-16). The most significant relationship of uterine fibroids was observed with the severity of anaemia. The mean haemoglobin values of women with fibroids were lower and a higher proportion of women with moderate-to-severe anaemia compared to women with normal ultrasonographic findings. This may be attributed to an increase in endometrial surface area, a change in uterine contractility, vascular changes, and prolonged or heavy menstrual bleeding that occurs with leiomyomas, particularly those that are distorted and/or near the endometrial cavity. Relatively lower haemoglobin levels were also seen in adenomyosis which could be due to increased menstrual bleeding and extended duration of bleeding. The observations support the value of pelvic ultrasonography in women with AUB as correcting anaemia alone may result in only temporary improvement if the structural cause of blood loss is not treated (17, 18). The oral ferrous sulfate therapy led to significant improvement in haematological and iron-related parameters. The mean haemoglobin level rose from 9.3 g/dL to 11.4 g/dL after therapy, and the levels of serum ferritin, serum iron, MCV, haematocrit and transferrin saturation also significantly improved. The oral iron was shown to be an effective first line treatment for more than 3/4 of the participants who had an adequate haematological response. However, around 1/4 responded poorly to the question. Incomplete restoration of haemoglobin and iron stores may be due to continued blood loss, poor adherence, gastrointestinal intolerance, severity of baseline iron depletion and structural uterine abnormalities (19, 20). Women with uterine fibroids, with a persistent heavy menstrual bleeding, with the highest baseline anaemia and with the lowest adherence to oral iron had a comparatively lower treatment response. The implications for practical use of the findings are clear, as these findings point to a need not to limit treatment to iron replacement. In women with chronic abnormal uterine bleeding, evaluation and treatment of the underlying cause of the bleeding should proceed simultaneously. Effective iron supplementation, appropriate treatment of uterine fibroids or adenomyosis and regular monitoring of compliance can enhance the effectiveness of iron supplementation and minimise the risk of reincurring anaemia. The small number of patients and the one-centre design, as well as the short duration of follow-up, were limitations of the study. The estimation of menstrual blood loss was mainly subjective rather than objective, with a greater duration of follow-up allowing to ascertain whether the correction of anaemia was maintained after the end of the treatment. What is needed is more research into long-term haematological recovery and the comparison of oral iron with other iron-replacement therapies based on type and severity of the underlying uterine pathology in future multicentre studies with larger sample sizes.

Iron-deficiency anaemia was closely associated with pelvic ultrasonographic abnormalities among women presenting with abnormal uterine bleeding. Uterine fibroids were the most frequent structural finding and were associated with lower haemoglobin levels and greater severity of anaemia. Oral ferrous sulfate therapy significantly improved haemoglobin and other iron-related indices in the majority of participants; however, therapeutic response was less favorable among women with persistent heavy menstrual bleeding, fibroids, severe baseline anaemia, and poor treatment adherence. These findings highlight the importance of combining iron replacement with appropriate investigation and management of the underlying cause of abnormal uterine bleeding. Pelvic ultrasonography can therefore play an important role in identifying structural pathology and guiding more comprehensive treatment aimed at achieving sustained correction of iron deficiency.

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