Metroragia la vârsta reproductivă

1. Introduction

Metrorrhagia, a type of abnormal uterine bleeding (AUB), refers to irregular, often excessive uterine bleeding that occurs between menstrual periods. In recent decades, changes in reproductive patterns – such as earlier menarche and fewer pregnancies – have led women to experience over 400 episodes of cyclical bleeding during their reproductive lifespan, a substantial increase compared to previous generations. This shift, alongside rising expectations for quality of life, has made complaints of excessive or irregular menstrual bleeding a frequent concern in clinical practice⁽¹⁾.

AUB is one of the most common reasons for gynecological consultations and referrals from general practitioners. This condition not only strains healthcare services but also significantly affects women’s physical, emotional and social well-being. Epidemiological data consistently show that reproductive-aged women are significantly more likely to experience AUB than adolescents or postmenopausal individuals, underscoring the need for targeted approaches in this population⁽²⁾.

Clinically, metrorrhagia may result from a wide range of causes, both organic and nonorganic. Organic causes include uterine fibroids, endometrial polyps, adenomyosis, malignancies, infections, and systemic disorders such as thyroid dysfunction or coagulopathies. Nonorganic causes, grouped under the term dysfunctional uterine bleeding (DUB), are often hormonal and account for a large proportion of cases in which no clear structural cause is identified. Despite advances in diagnostic tools like hysteroscopy, many women continue to be diagnosed with DUB⁽³⁾.

The high prevalence, diagnostic complexity and impact on quality of life make metrorrhagia a significant public health concern. This article aims to synthesize current literature regarding its causes, clinical presentation, evaluation and modern approaches to management in reproductive-aged women.

2. Etiology and pathophysiology

The etiology of abnormal uterine bleeding may involve structural uterine abnormalities (uterine fibroids, endometrial polyps), hormonal imbalances (in premenopausal women or adolescence), iatrogenic causes (intrauterine devices and oral contraceptive usage), endocrine disorders (such as hypothyroidism, hyperprolactinemia and polycystic ovary syndrome), coagulation defects, or early pregnancy complications.

Uterine fibroids

Fibroids (leiomyomas) are the most common tumors in women, affecting up to 70% of Caucasian and over 80% of Afro-American women by the age of 50 years old. While often asymptomatic, fibroids are frequently associated with abnormal uterine bleeding, iron-deficiency anemia, subfertility, and pregnancy complications. They may also cause pressure symptoms – commonly urinary – and, in rare cases, they compress pelvic structures, leading to renal impairment or venous thromboembolism. Despite their prevalence, the mechanisms linking fibroids and AUB remain incompletely understood.

Fibroids distorting the uterine cavity – particularly submucosal types – are most strongly associated with heavy menstrual bleeding (HMB), though debates continue regarding treatment strategies in these cases. Fibroids remain a leading cause for hysterectomy, with substantial economic and quality-of-life burdens. As more women delay childbirth, fertility-preserving, minimally invasive therapies are becoming increasingly relevant in managing fibroid-associated AUB^(4,5).

Uterine polyps

Uterine polyps are a common benign endometrial abnormality, identified in 10-15% of asymptomatic women and frequently discovered incidentally during transvaginal ultrasound or hysteroscopy. However, their clinical relevance increases significantly in women presenting with abnormal uterine bleeding – particularly metrorrhagia, or bleeding between menstrual periods – where their prevalence rises to 20-30%. Polyps are more often diagnosed in this context due to targeted imaging and hysteroscopic evaluation. Risk factors for their development include obesity, late menopause and tamoxifen use, while the influence of hormone replacement therapy remains uncertain.

Metrorrhagia is a common presentation in women with endometrial polyps, being typically caused by superficial injury to the polyp’s surface epithelium. This microtrauma, often associated with chronic inflammation and increased vascular fragility, can lead to intermittent or persistent intermenstrual spotting. Larger, pedunculated polyps can provoke heavier or prolonged bleeding episodes if ischemic necrosis occurs at the apex – usually due to thrombosis of terminal vessels or torsion of the polyp’s pedicle. These mechanisms highlight the importance of considering polyps in the differential diagnosis of metrorrhagia, particularly when structural causes are suspected^(6,7).

Nonstructural causes

Abnormal uterine bleeding (AUB) is often related to disturbances in the hormonal regulation of the menstrual cycle, which is orchestrated by the hypothalamic-pituitary-ovarian (HPO) axis. In nonstructural AUB, hormonal imbalances – particularly anovulatory cycles – cause unopposed estrogen stimulation without sufficient progesterone, resulting in irregular, prolonged, or heavy bleeding due to disorganized endometrial shedding. Alternatively, ovulatory AUB may arise from impaired endometrial hemostasis despite normal hormonal function⁽⁸⁾.

IUDs

Metrorrhagia is a frequent side effect of intrauterine device (IUD) use, particularly with copper IUDs, and may occur as irregular spotting or bleeding between periods. This bleeding results from endometrial vessel injury, increased local fibrinolysis, and impaired hemostasis caused by the device. While progestin-releasing IUDs reduce overall menstrual blood loss, they may still prolong bleeding duration. Metrorrhagia is a key reason for IUD discontinuation, with individual factors like previous menstrual patterns, parity and sensitivity influencing its occurrence⁽⁹⁾.

Combined oral contraceptives (COCs) and progestin-only contraceptives (POCs)

Combined oral contraceptives generally offer predictable, reduced menstrual bleeding, but metrorrhagia (intermenstrual bleeding) can occur, particularly in the first few months, often due to low estrogen levels, missed pills, or fragile endometrial vessels. In contrast, progestin-only contraceptives, such as injectables and implants, are more frequently associated with persistent and irregular metrorrhagia due to disrupted endometrial structure, abnormal angiogenesis, and vascular fragility. While COC-related bleeding often stabilizes with continued use, POC-related metrorrhagia is a major reason for discontinuation, highlighting the importance of anticipatory counseling and individualized contraceptive choice^(7,10).

3. Clinical presentation and diagnosis

The diagnostic goal is to determine whether the bleeding originates from a structural uterine abnormality, an endocrine disorder, a coagulation defect, or an early pregnancy complication.

The initial clinical evaluation begins with a thorough medical history and physical examination. Important history elements include: menstrual cycle characteristics (duration, volume, regularity), use of medications (especially anticoagulants, hormonal therapies), past gynecologic, obstetric, or surgical history, family or personal history of bleeding disorders⁽⁵⁾.

Physical examination often includes a speculum and bimanual pelvic exam. For nonsexually active adolescents, a transabdominal ultrasound may be performed in place of a pelvic exam. Depending on the clinical context, additional assessments may include a Pap smear, vaginal swabs for sexually transmitted infections, or endometrial sampling⁽⁵⁾.

Laboratory testing is guided by clinical suspicion. Initial work-up should include:

• Pregnancy test (urine or serum hCG) to rule out gestational causes.
• Complete blood count (CBC) to assess for anemia and thrombocytopenia.
• Serum ferritin to evaluate iron stores in cases of heavy menstrual bleeding.
• Thyroid-stimulating hormone (TSH) and prolactin levels to investigate ovulatory dysfunction.
• Coagulation studies (PT, aPTT, platelet count) if a bleeding disorder is suspected⁽¹¹⁾.

Women presenting with heavy menstrual bleeding (HMB) and any of the following should be evaluated for a bleeding disorder: menstrual duration ≥7 days with flooding or interference in daily life, history of treatment for anemia, family history of a bleeding disorder, excessive bleeding with surgeries, childbirth, or dental work⁽¹²⁾.

If these are present, further testing for von Willebrand disease (including VWF antigen, ristocetin cofactor activity, and Factor VIII levels) may be necessary. In selected cases, platelet aggregation studies should be performed⁽¹²⁾.

Imaging studies play a key role in identifying structural causes.

• Transvaginal ultrasound (TVUS) is the first-line imaging method for most patients.
• Transabdominal ultrasound is preferred in virginal or adolescent patients.
• Saline infusion sonohysterography (SIS) enhances the detection of endometrial polyps and submucosal fibroids.
• Color Doppler imaging helps identify abnormal vascular patterns suggestive of neoplasms.
• Magnetic resonance imaging (MRI) is reserved for complex cases involving distorted anatomy or suspicion of malignancy. It also helps classify fibroids and assess for leiomyosarcoma, particularly in women with risk factors such as prior radiation exposure or tamoxifen use.

Endometrial biopsy is indicated in:

• Women aged 45 or older with abnormal uterine bleeding.
• Younger women with risk factors such as obesity, chronic anovulation, or prolonged unopposed estrogen exposure.
• Patients who fail the initial medical management⁽⁵⁾.

When office biopsy is not feasible or yields inconclusive results, hysteroscopy with directed biopsy is the preferred next step. It allows the direct visualization of the uterine cavity and improves diagnostic accuracy, especially in cases of focal lesions⁽¹²⁾.

In cases of suspected uterine fibroids, imaging findings such as uterine enlargement or palpable mass guide diagnosis. Ultrasound is typically sufficient for confirmation, while MRI provides further detail on fibroid location and characteristics when surgical planning is needed. Although the risk of hidden malignancy is low, all patients undergoing surgical treatment for presumed fibroids should be counseled about this possibility.

Overall, the diagnostic approach to metrorrhagia should be systematic, integrating patient history, physical exam, laboratory investigations, and appropriate imaging. This comprehensive strategy allows clinicians to distinguish between functional and pathological bleeding causes and deliver effective, individualized care^(11-14).

4. Management and treatment options

Medical management

Management tailored to cause, age and fertility goals

Patient-centered approaches prove essential in AUB treatment, due to their various underlying etiology. The treatments require individualization based on the cause of the uterine bleeding (like structural causes or hormonal imbalances), patient’s age, reproductive plans, and comorbidities.

Structural causes treatment

• Uterine fibroid

The management of fibroids is personalized based on symptom severity, fibroid size and location, and reproductive goals. GnRH agonists reduce estrogen levels, shrinking fibroids and improving anemia from heavy bleeding; they are usually limited to six months due to side effects but can be combined with “add-back” therapy for longer use. Combined contraceptives and progestins help control bleeding but do not shrink the fibroid size. The levonorgestrel-releasing intrauterine device (LNG-IUD) effectively reduces bleeding, though its success may decrease in submucosal fibroids cases due to expulsion risk.

Surgery is always an option in significant symptoms cases, structural issues, or when medical treatments fail. The surgical approach is guided by the patient’s fertility preservation desire.

Myomectomy is preferred for women wishing to maintain fertility, with hysteroscopic removal for small submucosal fibroids and laparoscopic or open surgery for larger or intramural fibroids. Techniques like uterine artery ligation and contained morcellation help reduce bleeding and risks during surgery. Hysterectomy offers a definitive cure for those who have completed childbearing, with minimally invasive methods favored for faster recovery. Additional options like uterine artery embolization provide symptom relief for women not seeking fertility but may affect uterine function⁽¹⁵⁾.

• Endometrial polyps

Most endometrial polyps are benign, allowing expectant management in asymptomatic cases with patient counseling. Medical treatments like GnRH agonists and LNG-IUS may offer temporary symptom relief or reduce polyp formation but have limited effectiveness.

Surgical removal remains the primary treatment, with hysteroscopic polypectomy preferred for its accuracy, safety, fertility preservation, and quick recovery. Dilation and curettage (D&C) may provide temporary relief in acute bleeding, especially when clots or retained products are suspected. However, it does not offer long-term solutions and carries procedural risks and is not recommended when hysteroscopy is available⁽¹⁶⁾.

Nonstructural causes treatment

Hormonal therapy forms the foundation of treatment for nonstructural, abnormal uterine bleeding.

Combined oral contraceptives are effective in both acute and chronic settings. High-dose monophasic pills (e.g., 35 µg ethinyl estradiol with 1 mg norethindrone) are used for acute bleeding, typically three times daily for a week, followed by daily maintenance. Extended or continuous regimens can reduce bleeding frequency and volume, offering additional benefits in patients with dysmenorrhea or endometrial hyperplasia risk^(2,17).

Progestin-only therapies, such as oral norethindrone or medroxyprogesterone acetate, are suitable for patients who cannot take estrogen. These can be given cyclically or continuously, depending on ovulatory status. Depot medroxyprogesterone (DMPA) injections every three months may also induce amenorrhea over time, although side effects like weight gain and irregular bleeding are common^(2,17).

Levonorgestrel-releasing intrauterine device (LNG-IUD) is among the most effective treatments for heavy menstrual bleeding, reducing blood loss by up to 95%. It is also contraceptive, making it ideal for women not seeking pregnancy. However, insertion may be more difficult or associated with higher expulsion rates in women with large submucosal fibroids^(2,17).

GnRH agonists are occasionally used for short-term management to suppress ovarian hormone production, especially before surgery⁽⁸⁾.

Age-specific approaches consider that younger women often have bleeding due to immature HPO axis or bleeding disorders, managed mainly with COCs and progestins, while perimenopausal women may benefit more from LNG-IUS or progesterone therapy to address hormonal fluctuations and rule out premalignant changes⁽⁸⁾.

Nonhormonal therapy

Nonhormonal treatments are a valuable option for women who are trying to conceive, cannot take hormonal medications, or prefer to avoid hormonal side effects⁽²⁾.

Tranexamic acid is a first-line nonhormonal treatment, reducing menstrual blood loss by 26-54%. It is taken only during menses (1-1.3 g orally every 6-8 hours for up to five days). It is especially effective for ovulatory bleeding and may improve quality of life. However, it is contraindicated in women with a history of thromboembolism⁽²⁾.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen reduce bleeding by 10-52%, and are also useful for dysmenorrhea. They are less effective than tranexamic acid or the LNG-IUD but may be used adjunctively^(2,18).

Special considerations

Anemia is a common consequence of chronic heavy bleeding. The management includes iron supplementation, transfusion if hemoglobin is critically low, and expedited bleeding control^(2,17).

Pregnancy must be excluded before treatment; surgical options are generally avoided in pregnant patients unless life-threatening hemorrhage occurs^(2,17).

Bleeding disorders or anticoagulation use require multidisciplinary management. NSAIDs and estrogen-containing therapies may be contraindicated. Desmopressin, tranexamic acid (with caution), or LNG-IUD may be used depending on the clinical scenario and hematologist input^(2,17).

5. Prognosis and follow-up

The prognosis of metrorrhagia largely depends on its underlying cause and how promptly it is treated. Structural causes like fibroids or polyps generally respond well to targeted therapy, while hormonal or functional causes often improve with medical management. Left untreated, chronic bleeding may lead to complications such as anemia, infertility or, in rare cases, endome­trial pathology. Consistent follow-up care is essential to monitor treatment response, assess for recurrence, and modify management plans based on evolving clinical needs. Patients started on medical therapy should be reassessed within 1-3 months to evaluate bleeding control and side effects. Those undergoing surgical interventions require close postoperative monitoring and long-term surveillance, especially in cases of uterine-preserving procedures where recurrence is possible^(2,18).

Referral to a gynecologist or reproductive endocrinologist is recommended when first-line treatments fail, when significant structural abnormalities are detected, or if there’s concern for malignancy based on age, imaging or biopsy findings. Additionally, patients with persistent anemia, suspected coagulopathies or complex reproductive goals may benefit from multidisciplinary input, including hematology or fertility specialists. Timely escalation of care helps ensure optimal outcomes and prevents delays in diagnosing potentially serious conditions^(2,17).

6. Conclusions

Metrorrhagia is a common and often frustrating issue for women of reproductive age. It can have many causes, from hormonal imbalances and stress to structural is­sues like fibroids or polyps. Understanding each woman’s symptoms, medical history and future fertility plans helps guide the right treatment. For many, both hormonal and nonhormonal therapies can manage symptoms effectively. Others, encountering structural causes, may need surgical treatment. Ultimately, recognizing metrorrhagia as a condition that significantly impacts daily life, relationships and long-term health is essential. With early attention and a tailored approach, healthcare providers can help women regain control over their cycles and their well-being.  

Autor corespondent: Aida Petca, e-mail: aidapetca@gmail.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.