Introduction:

Dysfunctional uterine bleeding (DUB) refers to abnormal uterine bleeding that occurs in the absence of any clinically detectable organic, systemic, or iatrogenic causes. It is a diagnosis of exclusion, meaning conditions such as pregnancy, pelvic infections, tumors, fibroids, endometrial hyperplasia, polyps, or bleeding disorders must be ruled out before diagnosing DUB.

Definition:

Dysfunctional uterine bleeding is defined as abnormal uterine bleeding primarily caused by anovulation due to a disruption in the hypothalamo-pituitary-ovarian (HPO) axis. It is characterized by irregular, excessive, or prolonged menstrual bleeding that is unrelated to structural abnormalities or systemic diseases.

Incidence:

DUB is a common gynecological condition seen across various age groups, with varying prevalence:

• Outpatient Department (OPD) cases: 10-20% of gynecological OPD visits are due to abnormal uterine bleeding.
• Adolescents (12-19 years): Approximately 20% experience DUB, primarily due to immature hypothalamic-pituitary-ovarian axis, leading to anovulatory cycles.
• Reproductive age (20-40 years): Incidence increases to 30%, often linked to hormonal imbalances, stress, and metabolic conditions.
• Perimenopausal women (40-50 years): The highest prevalence (up to 50%) is observed in this group due to declining ovarian function and irregular ovulatory cycles.

Types of Dysfunctional Uterine Bleeding (DUB)

DUB is categorized based on whether ovulation occurs or not:

A. Anovulatory Bleeding (Estrogen Breakthrough Bleeding)

This type of bleeding is more common and occurs due to anovulation (absence of ovulation). It is frequently seen in adolescents, perimenopausal women, and conditions like PCOS.

Pathophysiology:

• In anovulatory cycles, the corpus luteum does not form due to the absence of ovulation.
• Without corpus luteum formation, progesterone is not produced.
• Continuous unopposed estrogen secretion leads to excessive proliferation of the endometrium (endometrial hyperplasia).
• As the endometrium grows beyond its blood supply, necrosis and shedding occur irregularly, leading to prolonged and heavy bleeding.

Common Causes:

• Adolescents: Immature hypothalamo-pituitary-ovarian axis (HTOPA) causes delayed establishment of the positive feedback mechanism and LH surge required for ovulation.
• Perimenopausal Women: Declining ovarian function results in infrequent ovulation.
• Polycystic Ovary Syndrome (PCOS): Chronic anovulation due to hormonal imbalance.
• Obesity: Excess estrogen from adipose tissue contributes to unopposed estrogen stimulation.
• Thyroid Dysfunction: Can disrupt ovulation and hormone regulation.

B. Ovulatory Bleeding (Estrogen Withdrawal Bleeding)

This type of bleeding occurs despite regular ovulation but is abnormal due to luteal phase defects or endometrial dysfunction. It is more common in women of reproductive age.

Features of Ovulatory Bleeding:

• Polymenorrhea: Frequent menstrual cycles (<21 days apart).
• Oligomenorrhea: Infrequent menstrual cycles (>35 days apart).
• Functional Menorrhagia: Regular but excessive menstrual flow due to endometrial abnormalities.
• Irregular Shedding:
  • Post-menstrual spotting due to asynchronous endometrial shedding.
  • Pre-menstrual spotting due to inadequate luteal function.

Pathophysiology:

• Failure in endometrial regeneration: Normally, the endometrium starts regenerating from the 3rd day of menstruation. A defect in this process can cause prolonged bleeding.
• Inadequate Corpus Luteum Function:
  • The corpus luteum fails to form properly or produces insufficient progesterone and estrogen.
  • The endometrium does not receive enough hormonal support, leading to irregular shedding.

Key Differences Between Anovulatory and Ovulatory Bleeding

Anovulatory Bleeding

• Occurrence: Common in adolescence & perimenopause
• Ovulation: Absent
• Corpus Luteum Formation: Absent
• Hormonal Imbalance: Unopposed estrogen stimulation
• Menstrual Irregularities: Irregular, heavy, prolonged bleeding
• Endometrial Abnormalities: Excessive growth, necrosis, and shedding

Ovulatory Bleeding

• Occurrence: Common in reproductive age
• Ovulation: Present
• Corpus Luteum Formation: Present but defective
• Hormonal Imbalance: Defective progesterone secretion
• Menstrual Irregularities: Regular cycles but abnormal flow
• Endometrial Abnormalities: Irregular shedding, inadequate regeneration

Causes of Dysfunctional Uterine Bleeding (DUB)

DUB can be classified into structural and non-structural causes.

A. Structural Causes (PALM - FIGO Classification)

These causes involve physical abnormalities in the uterus or endometrium:

• Polyp:
  • Benign overgrowths of the endometrial or cervical tissue.
  • Can cause irregular bleeding, postmenstrual spotting, and intermenstrual bleeding.
• Adenomyosis:
  • Endometrial tissue grows into the myometrium (uterine muscle layer).
  • Leads to heavy menstrual bleeding, painful periods, and an enlarged uterus.
• Leiomyoma (Fibroids):
  • Benign tumors arising from the smooth muscle of the uterus.
  • Can cause heavy or prolonged menstrual bleeding (especially submucosal fibroids).
• Malignancy and Hyperplasia:
  • Endometrial hyperplasia results from prolonged unopposed estrogen stimulation, increasing the risk of endometrial cancer.
  • Postmenopausal bleeding is a red flag for malignancy.

B. Non-Structural Causes (COEIN - FIGO Classification)

These causes are related to hormonal imbalances, systemic disorders, or medication effects:

• Coagulopathy (Blood Clotting Disorders):
  • Conditions like Von Willebrand disease, thrombocytopenia, or platelet function disorders can cause excessive menstrual bleeding.
  • Patients often have a history of easy bruising, nosebleeds, or prolonged bleeding after minor injuries.
• Ovulatory Dysfunction:
  • Anovulatory cycles (PCOS, thyroid disorders, hyperprolactinemia) cause irregular and heavy bleeding.
  • Luteal phase defects result in shortened cycles or premenstrual spotting.
• Iatrogenic Causes (Medication-Induced Bleeding):
  • Hormonal contraceptives (oral pills, IUDs, implants) can cause irregular bleeding.
  • Anticoagulants (e.g., warfarin, heparin) may lead to excessive menstrual flow.
  • Glucocorticoids and chemotherapy drugs may contribute to bleeding abnormalities.

Clinical Manifestations of Dysfunctional Uterine Bleeding (DUB)

Patients with DUB may present with various symptoms, depending on the underlying cause and severity of the condition.

1. Pelvic Pain

• May be due to uterine contractions, endometrial shedding, or underlying structural abnormalities (e.g., fibroids, adenomyosis).
• Can range from mild discomfort to severe cramping.

2. Heavy Bleeding (Menorrhagia)

• Excessive or prolonged menstrual bleeding, often leading to soaking through sanitary products in a short period.
• Clots may be present due to endometrial instability.

3. Infertility

• Anovulation leads to irregular or absent ovulation, making conception difficult.
• Luteal phase defects may result in early pregnancy loss or implantation failure.

4. Secondary Anemia

• Chronic blood loss leads to iron deficiency anemia, causing:
  • Fatigue and weakness
  • Pallor (pale skin and mucous membranes)
  • Dizziness and shortness of breath

5. Uncomfortable Pressure

• Enlarged uterus (due to fibroids or adenomyosis) can cause:
  • A feeling of fullness or pressure in the lower abdomen.
  • Urinary frequency or constipation due to pressure on adjacent organs.

6. Weakness

• Due to blood loss and anemia, leading to low energy levels, difficulty concentrating, and generalized fatigue.

Investigations for Dysfunctional Uterine Bleeding (DUB)

The primary goal of investigations is to:

1. Confirm the menstrual abnormality reported by the patient.
2. Exclude systemic, iatrogenic, or organic pelvic pathology.
3. Identify the underlying cause of DUB.
4. Establish a definitive treatment plan.

1. Clinical Evaluation

🔹 History Taking

• Menstrual history: Cycle length, duration, flow pattern, presence of clots.
• Obstetric history: Pregnancy, miscarriage, or infertility.
• Medical history: Thyroid disorders, bleeding disorders, chronic illnesses.
• Drug history: Use of anticoagulants, hormonal contraceptives, steroids.
• Family history: Coagulopathy, hormonal disorders, malignancies.

🔹 Physical & Internal Examination

• General Examination:
  • Signs of anemia (pallor, fatigue, dizziness).
  • Signs of hormonal disorders (hirsutism, acne in PCOS).
• Pelvic Examination:
  • Bimanual examination to check for uterine enlargement (fibroids, adenomyosis).
  • Speculum examination for cervical pathology (polyps, infections).

2. Special Investigations

🔹 Blood Tests

• Complete Blood Count (CBC): Detects anemia, infection.
• Coagulation Profile: To rule out bleeding disorders (e.g., Von Willebrand disease).
• Thyroid Function Tests (T3, T4, TSH): To check for hypothyroidism or hyperthyroidism.
• Hormonal Assays:
  • FSH, LH: To assess ovarian function.
  • Prolactin: Elevated in hyperprolactinemia.
  • Estradiol, Progesterone: Imbalance suggests anovulatory cycles.
  • Testosterone, DHEA-S: Elevated in PCOS.

🔹 Imaging Studies

• Transvaginal Sonography (TVS):
  • Assesses endometrial thickness, polyps, fibroids, ovarian cysts.
  • Helps differentiate structural vs. functional causes.
• Saline Infusion Sonography (SIS):
  • Enhances visualization of endometrial polyps, fibroids.
• Hysteroscopy:
  • Direct visualization of the uterine cavity.
  • Detects polyps, fibroids, hyperplasia, adhesions.

🔹 Endometrial Assessment

• Endometrial Biopsy:
  • Evaluates hyperplasia, malignancy, chronic endometritis.
  • Indicated in women >45 years with abnormal bleeding.
• Laparoscopy:
  • Done if endometriosis, pelvic adhesions, or unexplained infertility is suspected.
• Endometrial Sampling:
  • Checks for histopathological abnormalities in cases of persistent abnormal bleeding.

Management of Dysfunctional Uterine Bleeding (DUB)

Since the causes of DUB vary across different age groups, management strategies are tailored based on:

• Age of the patient
• Desire for childbearing
• Severity of bleeding
• Associated pathology

Management can be categorized into three main types:

1. General Management

🔹 Rest & Reassurance

• Adequate rest during the bleeding phase is recommended.
• Reassurance and counseling, especially for adolescents, to alleviate anxiety.

🔹 Treatment of Anemia

• Iron-rich diet (green leafy vegetables, meat, nuts, fortified cereals).
• Oral iron supplements (Hematinics such as ferrous sulfate, folic acid).
• Blood transfusion in cases of severe anemia (Hb < 7g/dL).

🔹 Treatment of Underlying Conditions

• Systemic diseases (thyroid disorders, liver disease, bleeding disorders) should be investigated and managed.
• Endocrinal abnormalities (such as PCOS, hyperprolactinemia) require appropriate treatment.

2. Medical Management

🔹 Prostaglandin Synthesis Inhibitors (PSI) – Fenamates

• Mefenamic acid: Reduces pain and menstrual blood loss.
• Used in mild to moderate cases.

🔹 Antifibrinolytic Agents

• Tranexamic acid: Helps in reducing excessive bleeding by preventing clot breakdown.
• Particularly useful in cases of heavy menstrual bleeding (HMB).

🔹 Hormonal Therapy

1️⃣ Progesterone Therapy

• Medroxyprogesterone acetate (MPA): Used in anovulatory DUB to regulate cycles.
• Norethisterone acetate (NETA): Provides endometrial stability and prevents excessive bleeding.

2️⃣ Antiprogestins

• Mifepristone: Reduces endometrial thickness and bleeding episodes.

3️⃣ Combined Estrogen & Progesterone Therapy

• Oral contraceptive pills (OCPs): Used for cycle regulation in reproductive-age women.
• High-dose estrogen: Used in acute heavy bleeding to promote endometrial healing.

4️⃣ Desmopressin

• Used in cases of coagulopathy-induced bleeding (e.g., Von Willebrand disease).

3. Surgical Management

Surgical treatment is considered in severe or refractory cases where medical management fails.

🔹 Uterine Curettage

• Used for diagnostic and therapeutic purposes.
• Helps control acute bleeding episodes.

🔹 Endometrial Ablation or Resection

• Minimally invasive procedure to destroy or remove the endometrial lining.
• Used for women who do not wish to conceive.

🔹 Hysterectomy

• Definitive treatment for persistent or severe cases unresponsive to medical therapy.
• Indicated in women with recurrent heavy bleeding, fibroids, or endometrial hyperplasia.

🔹 Nd-YAG Laser

• Used for precise destruction of the endometrial lining.
• Alternative to hysterectomy in select cases.

Conclusion

Dysfunctional Uterine Bleeding (DUB) is a common gynecological disorder characterized by abnormal uterine bleeding in the absence of identifiable pelvic pathology, systemic disease, or iatrogenic causes. It primarily results from hormonal imbalances affecting the hypothalamic-pituitary-ovarian (HPO) axis, leading to anovulatory or ovulatory bleeding.

Early diagnosis and appropriate management are crucial to prevent complications such as anemia, infertility, and poor quality of life. Treatment strategies vary based on age, severity, and reproductive goals, ranging from lifestyle modifications and medical therapy (NSAIDs, hormonal treatments, antifibrinolytics) to surgical interventions (endometrial ablation, hysterectomy) in severe cases.

With timely intervention, most cases of DUB can be effectively managed, ensuring improved menstrual health and overall well-being for affected individuals.