HOW TO IDENTIFY NORMAL AND ABNORMAL UTERINE BLEEDING: EXPERT INSIGHTS

Abnormal uterine bleeding (AUB) is a prevalent gynecological concern affecting women of reproductive age, characterized by deviations from the normal menstrual cycle. A thorough understanding of the normal reproductive endocrinology and physiology is crucial for diagnosing and managing these abnormalities.

The Endocrinology and Physiology of the Normal Menstrual Cycle

The regular, cyclical shedding of the uterine lining, known as menstruation, is orchestrated by a complex interplay of hormones regulated by the hypothalamic-pituitary-ovarian (HPO) axis. The cycle, typically lasting 21-35 days with bleeding for 3-7 days, begins with the follicular phase. Here, the hypothalamus releases gonadotropin-releasing hormone (GnRH), stimulating the anterior pituitary to secrete follicle-stimulating hormone (FSH). FSH acts on the ovaries, promoting the development of several ovarian follicles. As these follicles grow, they produce estrogen, which initially exerts negative feedback on GnRH and FSH. However, as a dominant follicle emerges and continues to produce increasing amounts of estrogen, it triggers positive feedback, leading to a surge in luteinizing hormone (LH) from the pituitary. This LH surge is the pivotal event that induces ovulation, the release of a mature egg from the dominant follicle, approximately 24-36 hours later.

Following ovulation, the remnants of the ruptured follicle transform into the corpus luteum, which primarily produces progesterone and some estrogen. This marks the luteal phase. Progesterone prepares the endometrium (uterine lining) for potential implantation of a fertilized egg by increasing its vascularity and glandular secretions. If fertilization and implantation do not occur, the corpus luteum degenerates after about 10-14 days, leading to a sharp decline in estrogen and progesterone levels. This hormonal withdrawal causes the breakdown and shedding of the endometrium, resulting in menstruation. If pregnancy occurs, the developing embryo produces human chorionic gonadotropin (hCG), which signals the corpus luteum to continue producing progesterone, thus maintaining the uterine lining and preventing menstruation.

Premenstrual Syndrome (PMS)

While not directly a cause of abnormal uterine bleeding, Premenstrual Syndrome (PMS) is a common condition characterized by a cluster of recurrent physical, emotional, and behavioral symptoms that occur during the luteal phase of the menstrual cycle and resolve with the onset of menstruation. The exact pathophysiology of PMS is not fully understood but is believed to involve cyclical hormonal fluctuations, particularly in estrogen and progesterone, interacting with neurotransmitter systems, especially serotonin. Symptoms can vary widely among individuals and may include mood swings, irritability, anxiety, depression, fatigue, bloating, breast tenderness, headaches, and food cravings. While PMS itself doesn’t cause AUB, the emotional and physical distress associated with it can impact a woman’s perception and reporting of menstrual symptoms.

Defining Abnormal Uterine Bleeding (AUB)

Abnormal uterine bleeding (AUB) is a broad term encompassing any menstrual bleeding that deviates from the normal pattern in terms of frequency, regularity, volume, duration, and timing. The International Federation of Gynecology and Obstetrics (FIGO) has developed a standardized classification system (PALM-COEIN) to categorize the causes of AUB, aiming to improve diagnosis, treatment, and research.

• PALM refers to structural causes:
  • Polyp: Benign growths of endometrial tissue.
  • Adenomyosis: Endometrial tissue found within the muscular wall of the uterus (myometrium).
  • Leiomyoma (fibroids): Benign tumors of smooth muscle in the uterine wall.
  • Malignancy and hyperplasia: Cancer of the uterus or precancerous overgrowth of the endometrium.
• COEIN refers to non-structural causes:
  • Coagulopathy: Bleeding disorders such as von Willebrand disease.
  • Ovulatory dysfunction: Irregular or absent ovulation, often seen in conditions like polycystic ovary syndrome (PCOS), thyroid dysfunction, or hypothalamic amenorrhea.
  • Endometrial: Primary endometrial disorders related to local hemostatic mechanisms or inflammation.
  • Iatrogenic: Bleeding caused by medical interventions such as hormonal contraception, intrauterine devices (IUDs), or anticoagulation.
  • Not yet classified: Rare or unusual causes as well as conditions not fitting into other categories.

AUB can manifest in various ways: intermenstrual bleeding (bleeding between periods), heavy menstrual bleeding (HMB) which is excessively heavy or prolonged menstrual bleeding, irregular bleeding, amenorrhea (absence of menstruation), and postcoital bleeding.

Pathophysiology and Etiologies of Abnormal Uterine Bleeding

The pathophysiology of AUB is diverse and directly linked to its underlying cause.

• Structural causes (PALM):
  • Polyps and Leiomyomas: These benign growths can distort the uterine cavity, disrupt endometrial integrity, and cause increased vascularity, leading to heavy or intermenstrual bleeding.
  • Adenomyosis: The presence of endometrial tissue within the myometrium triggers chronic inflammation and hypertrophy of the uterine muscle, resulting in painful and heavy menstrual bleeding.
  • Malignancy and Hyperplasia: Both cervical and endometrial cancers, as well as endometrial hyperplasia (including atypical hyperplasia), can cause abnormal bleeding due to breaches in the normal vascular and endometrial architecture or hormonal imbalances promoting uncontrolled endometrial proliferation.
• Non-structural causes (COEIN):
  • Coagulopathy: Systemic bleeding disorders impair the body’s ability to form blood clots, leading to prolonged or heavy menstrual bleeding, and sometimes easy bruising or bleeding from other sites.
  • Ovulatory Dysfunction: In anovulatory cycles, the endometrium proliferates under sustained estrogen stimulation without adequate progesterone to stabilize or induce shedding. This can lead to irregular shedding, resulting in unpredictable, often heavy, or prolonged bleeding episodes. Conditions like PCOS, extreme weight fluctuations, excessive exercise, stress, and thyroid disorders disrupt ovulation.
  • Endometrial Dysfunction: This category includes primary issues with the endometrial lining’s ability to regulate local hemostasis, such as impaired vasoconstriction or fibrinolysis. Infections or inflammation within the endometrium (endometritis) can also disrupt normal shedding.
  • Iatrogenic Causes: Hormonal contraceptives, particularly during initiation or if misused, can cause irregular spotting or breakthrough bleeding. IUDs can sometimes lead to heavier or irregular bleeding. Anticoagulant medications inherently impair hemostasis, increasing the risk of AUB.

Evaluation and Initial Management of Abnormal Uterine Bleeding

A systematic approach is essential for evaluating AUB. The initial evaluation involves a comprehensive medical history, including menstrual history (cycle length, regularity, flow, duration, associated symptoms), sexual history, obstetric history, medical history (including bleeding disorders, thyroid disease, liver/kidney disease), family history, and medication use. A physical examination, including a pelvic exam, is crucial.

Diagnostic testing typically begins with a pregnancy test to rule out pregnancy-related bleeding. Complete blood count (CBC) assesses for anemia due to blood loss. Thyroid-stimulating hormone (TSH) levels are checked to rule out thyroid dysfunction. Depending on the patient’s age and risk factors, further investigations may include:

• Transvaginal Ultrasound (TVUS): This is the primary imaging modality to assess the uterus and ovaries, identifying structural abnormalities like fibroids, polyps, adenomyosis, and ovarian cysts.
• Endometrial Biopsy: Recommended for women over 45, or younger women with risk factors for endometrial hyperplasia or cancer (e.g., obesity, PCOS, history of unopposed estrogen exposure), to evaluate the endometrial lining.
• Cervical Cytology (Pap smear) and HPV testing: To rule out cervical causes of bleeding.
• Hormonal assays: FSH, LH, prolactin, and androgens may be considered in cases of suspected ovulatory dysfunction, particularly in younger women.
• Coagulation studies: If a bleeding disorder is suspected.

Initial Management of AUB focuses on stabilizing the patient, controlling bleeding, and addressing the underlying cause. For acute, heavy bleeding, initial management might involve:

• High-dose estrogen or oral contraceptive pills (OCPs): To rapidly stabilize the endometrium and stop bleeding.
• Progestins: To stabilize the proliferative endometrium.
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Can reduce menstrual blood loss by inhibiting prostaglandins.
• Tranexamic acid: An antifibrinolytic agent that can significantly reduce menstrual blood loss.

Once the acute bleeding is controlled, management shifts to addressing the specific diagnosis and preventing recurrence.

Ethnic and Racial Disparities: Significant disparities exist in the diagnosis, treatment, and outcomes of AUB among different ethnic and racial groups. For example, Black women are more likely to experience fibroids, which disproportionately contribute to AUB, and often present with more severe symptoms and larger fibroids. These disparities can be attributed to a complex interplay of factors including genetic predispositions, socioeconomic status, access to healthcare, implicit bias in healthcare providers, and cultural beliefs surrounding health and menstruation. Patients from marginalized communities may face greater barriers to seeking timely medical care, experience longer diagnostic delays, and receive less aggressive or less effective management strategies. Addressing these disparities requires culturally competent care, increased awareness among healthcare providers, and efforts to improve equitable access to resources and treatments.

Medical and Surgical Management Options for AUB

The management of AUB is tailored to the underlying cause, severity of bleeding, patient’s age, desire for fertility, and overall health status.

Medical Management:

• Hormonal Therapies:
  • Combined Oral Contraceptives (COCs): Regular use can regulate cycles, reduce flow, and alleviate pain.
  • Progestins (oral or injectable): Can be used cyclically to stabilize the endometrium or continuously to suppress menstruation.
  • Levonorgestrel-releasing intrauterine system (LNG-IUS): Highly effective in reducing menstrual blood loss, often to the point of amenorrhea, and also provides contraception.
  • Gonadotropin-releasing hormone (GnRH) agonists: Used for short-term management to induce a temporary menopausal state, significantly reducing bleeding and shrinking fibroids, often prior to surgery.
• Non-Hormonal Therapies:
  • NSAIDs: (e.g., ibuprofen, naproxen) Reduce pain and menstrual blood loss.
  • Tranexamic Acid: A powerful option for episodic heavy bleeding.
• Management of underlying conditions: Treating thyroid disorders, bleeding disorders, or PCOS is crucial.

Surgical Management is considered when medical management fails, bleeding is severe or life-threatening, or in cases of significant structural abnormalities.

• Hysteroscopy: Allows direct visualization of the uterine cavity and targeted removal of polyps or fibroids (myomectomy).
• Endometrial Ablation: A procedure to destroy the uterine lining, effectively stopping or significantly reducing menstruation. It is generally for women who have completed childbearing.
• Uterine Artery Embolization (UAE): For fibroid-related bleeding, this procedure blocks the blood supply to fibroids, causing them to shrink.
• Myomectomy: Surgical removal of fibroids, preserving the uterus and therefore fertility.
• Hysterectomy: The surgical removal of the uterus. This is a definitive treatment for AUB and is typically reserved for severe cases, women who have completed childbearing, or when other treatments have failed.

Value-Based Care and Patient Safety: In the context of AUB, value-based care emphasizes delivering the best patient outcomes at the lowest cost. This involves selecting treatments that are effective, evidence-based, and minimize unnecessary interventions. For instance, using LNG-IUS or medical management for heavy bleeding may be more cost-effective and carry fewer risks than immediate surgical intervention for many patients. Patient safety is paramount and involves careful consideration of the risks and benefits of each treatment option, proper patient selection, skilled execution of procedures, and thorough post-treatment monitoring. Minimally invasive surgical techniques and judicious use of hormonal therapies contribute to improved patient safety and faster recovery. Open communication with patients about treatment goals, expectations, and potential side effects is essential for shared decision-making and prioritizing their well-being.

In conclusion, understanding the intricate hormonal regulation of the normal menstrual cycle is the cornerstone for identifying and managing abnormal uterine bleeding. By systematically evaluating patients, considering the diverse etiologies, and employing a personalized approach to medical and surgical management, healthcare providers can significantly improve the quality of life for women experiencing AUB, while actively working to mitigate existing health disparities and promote value-based, safe, and effective care.

References

• ACOG Practice Bulletin No. 128: Management of Abnormal Uterine Bleeding. Obstet Gynecol. 2012;120(6):1459-1472.
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• Fraser, I. S., et al. (2011). The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. International Journal of Gynecology & Obstetrics, 115(2), 151-157.
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• Munro, M. G., et al. (2018). FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in the reproductive years: extension of the classification system to the management of abnormal uterine bleeding (AUB-Management). International Journal of Gynecology & Obstetrics, 142(3), 399-407.
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