Abnormal Uterine Bleeding

Epidemiology and Definitions

Epidemiology

Abnormal uterine bleeding (AUB):

• Lifetime incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: affects 10%–35% of women of reproductive age
• Accounts for ⅓ of gynecological outpatient visits
• 21%–67% of cases develop iron-deficiency anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types.

Normal menstrual bleeding

• Normal frequency (cycle length): ≥ 24 days to ≤ 38 days
• Normal duration: ≤ 8 days
• Normal flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure volume: no physical, social, or emotional distress caused by flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Determined by patient
  • Average flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure is approximately 30 mL
• Normal regularity: variation between shortest and longest cycles is ≤ 7–9 days (or average cycle length ± 4 days)
  • 18–25 and 42–45 years of age: ≤ 9 days
  • 26–41 years of age: ≤ 7 days

Abnormal uterine bleeding

• Symptomatic abnormalities in the regularity, duration, frequency, and volume of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
• Also includes intermenstrual bleeding (IMB) (bleeding between normal menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle)
• Variation may be:
  • Acute AUB: bleeding in sufficient quantity that warrants immediate intervention to prevent further blood loss
  • Chronic AUB: abnormalities in uterine bleeding present for most of the last 6 months

Updated nomenclature

Owing to the previous lack of consistency Consistency Dermatologic Examination in terminologies surrounding AUB, a new system was developed in 2011 to describe and classify AUB.

• Abnormalities in frequency:
  • Infrequent uterine bleeding: 
    • Menstrual interval > 38 days
    • Previously called oligomenorrhea Oligomenorrhea Polycystic Ovarian Syndrome
  • Frequent uterine bleeding:
    • Menstrual interval < 24 days
    • Previously called polymenorrhea
• Abnormalities in volume:
  • AUB/heavy menstrual bleeding (HMB):
    • Excessive menstrual blood loss (objectively defined as > 80 mL blood loss/cycle)
    • Can be based on heavy flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure, as determined by the patient
    • Interferes with physical, social, emotional, and/or material quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life
    • Independent of cycle duration, frequency, or regularity (although abnormalities may coexist)
    • Previously called menorrhagia
  • Light menstrual bleeding:
    • < 5 mL blood loss/cycle
    • Infrequent
    • While rare, may result from cervical stenosis Cervical Stenosis Secondary Amenorrhea or intrauterine synechiae Synechiae Scar tissue from prior surgery. Infertility
• Abnormalities in regularity:
  • Irregular uterine bleeding: variation between shortest and longest cycles is ≥ 8‒10 days 
  • In some young women, long cycles evolve and eventually fit the usual variation.
• Abnormalities in duration:
  • Prolonged uterine bleeding: menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle lasting > 8 days
  • No consensus on lower limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation: ↓ duration is not specifically related to a clinical condition, except for amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System.
• IMB: 
  • Bleeding between the cyclic, regular Regular Insulin onset of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle that can be:
    • Random
    • Cyclic (early, mid, or late cycle)
  • Previously called metrorrhagia
  • Includes breakthrough bleeding (from hormone administration) and postcoital bleeding
• Absence of menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle:
  • Primary amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System: 
    • No menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle by 13 years of age in the absence of secondary sex characteristics Secondary sex characteristics Gonadal Hormones 
    • No menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle by 15 years of age regardless of secondary sex characteristics Secondary sex characteristics Gonadal Hormones
    • Secondary sex characteristics Secondary sex characteristics Gonadal Hormones include the development of breasts Breasts The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. Breasts: Anatomy, axillary hair, and pubic hair.
  • Secondary amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System:
    • Absence of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle for 3 months after previously regular Regular Insulin menstrual cycles
    • Absence of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle for 6 months after previously irregular menstrual cycles
    • Absence of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle for 3 cycle lengths (in women with infrequent menstrual bleeding)

Etiologies

The causes of AUB are classified according to the PALM-COEIN system, which is an acronym.

PALM (structural causes)

• Polyp (AUB-P):
  • Overgrowth of epithelial cells arising from the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development
  • Risk factors: obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, tamoxifen Tamoxifen One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. Antiestrogens use, ↑ age
• Adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis (AUB-A):
  • Presence of endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development (stroma and glandular tissue) within the uterine myometrium
  • Often associated with endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis
• Leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility (AUB-L):
  • Leiomyoma-submucosal (AUB/HMB-L_SM)
  • Leiomyoma-other (AUB/HMB-L_O)
• Malignancy Malignancy Hemothorax and hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation (AUB-M):
  • Endometrial 
  • Uterine sarcomas

COEIN (non-structural causes)

• Coagulopathy (AUB-C):
  • Seen in 20% of adolescents with AUB
  • Common AUB-Cs: platelet-function disorders, von Willebrand’s disease
  • Deficient coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis (V, VII, VIII, IX, XI, XII) 
• Ovulatory dysfunction (AUB-O):
  • Polycystic ovarian syndrome Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome ( PCOS PCOS Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome): most common cause of ovarian dysfunction
  • Functional hypothalamic amenorrhea Functional Hypothalamic Amenorrhea Secondary Amenorrhea (stress, overexercising, eating disorders)
  • Primary ovarian insufficiency Primary ovarian insufficiency Cessation of ovarian function after menarche but before the age of 40, without or with ovarian follicle depletion. It is characterized by the presence of oligomenorrhea or amenorrhea, elevated gonadotropins, and low estradiol levels. It is a state of female hypergonadotropic hypogonadism. Etiologies include genetic defects, autoimmune processes, chemotherapy, radiation, and infections. The most commonly known genetic cause is the expansion of a cgg repeat to 55 to 199 copies in the 5′ untranslated region in the X-linked fmr1 gene. Primary Ovarian Insufficiency (POI)
  • Other endocrine disorders
  • Age-related anovulation Anovulation Suspension or cessation of ovulation in animals or humans with follicle-containing ovaries (ovarian follicle). Depending on the etiology, ovulation may be induced with appropriate therapy. Polycystic Ovarian Syndrome near menarche Menarche The first menstrual cycle marked by the initiation of menstruation. Menstrual Cycle or menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause
• Endometrial (AUB-E):
  • Endometritis Endometritis Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. Postpartum Endometritis or pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease ( PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease): commonly chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia
  • Endometrial atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation (thin, fragile endometrial tissue Endometrial tissue The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Endometriosis) in post-menopausal women
• Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome (AUB-I):
  • Contraceptives (including intrauterine devices Intrauterine devices Contraceptive devices placed high in the uterine fundus. Hormonal Contraceptives (IUDs))
  • Anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
  • Chemotherapy Chemotherapy Osteosarcoma
  • Selective estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors modulators
  • Drugs related to dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS metabolism: antidepressants, antipsychotics
• Not yet classified (AUB-N)

Clinical Presentation

Presentation of PALM (structural causes)

Presentation of COEIN (non-structural causes)

Diagnosis

History and exam

• Menstrual history Menstrual History Child and Adolescent Care to classify AUB
• Screen for AUB-C based on history (any 1 of the following requires lab evaluation):
  • HMB since menarche Menarche The first menstrual cycle marked by the initiation of menstruation. Menstrual Cycle
  • 1 of the following:
    • Postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage
    • Surgery-related bleeding
    • Severe bleeding with dental work
  • 2 or more of the following:
    • Bruising 1–2 times every month
    • Epistaxis Epistaxis Bleeding from the nose. Granulomatosis with Polyangiitis ( nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal) bleeds) 1–2 times every month
    • Frequent gum bleeds
    • Family history Family History Adult Health Maintenance of bleeding symptoms
• Uterine abnormalities on exam:
  • Symmetrical Symmetrical Dermatologic Examination enlargement → suspect:
    • AUB-A
    • AUB-M
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Asymmetrical enlargement → suspect AUB-L
  • Severe tenderness → consider PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease (AUB-E)

Laboratory tests

• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test: if positive → obstetric complications (e.g., ectopic)
• CBC:
  • ↓ Hemoglobin or hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia → anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types related to AUB/HMB
  • ↓ Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology → further workup for AUB-C
  • ↑ WBCs → present in PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease → consider AUB-E (especially with pelvic tenderness)
• Coagulation tests (if patient screens positive during history taking):
  • PT, PTT, INR
  • Screening Screening Preoperative Care for von Willebrand’s disease:
    • von Willebrand factor von Willebrand factor A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in von Willebrand diseases is due to the deficiency of this factor. Hemostasis antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination test
    • von Willebrand functional assay
    • Factor VIII Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor viii/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Hemostasis activity
• Endocrine tests for AUB-O:
  • Order for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with infrequent bleeding or amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System:
    • Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH)
    • Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy
    • Follicle-stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle)
    • Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins
    • Androgen levels
  • Interpretation:
    • ↑/↓ TSH: thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy disease 
    • ↑ Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy: hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia
    • ↑ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle with ↓ estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins: POI
    • ↓ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle with ↓ estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins: functional hypothalamic amenorrhea Functional Hypothalamic Amenorrhea Secondary Amenorrhea
    • ↑ Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens: PCOS PCOS Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome
• Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia screen:
  • Endometritis Endometritis Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. Postpartum Endometritis/ PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease → AUB-E
  • Cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea → vaginal bleeding without AUB

Cytology and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

• Endometrial biopsy Endometrial Biopsy Diagnostic Procedures in Gynecology:
  • To rule out AUB-M
  • 45 years of age to menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause with any AUB
  • < 45 years of age with AUB and other risk factors:
    • Unopposed estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy exposure ( obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, ≥ 6 months of ovarian dysfunction)
    • Tamoxifen Tamoxifen One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. Antiestrogens use
    • Lynch or Cowden syndromes 
• Pap smear Pap smear Cytological preparation of cells collected from a mucosal surface and stained with Papanicolaou stain. Cervical Cancer Screening:
  • Ensure that cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer screening Screening Preoperative Care is updated.
  • Consistent post-coital bleeding suggests cervical pathology.

Imaging

• Transvaginal ultrasound Transvaginal Ultrasound Obstetric Imaging (TVUS):
  • 1st-line imaging modality for AUB
  • AUB-P: thickened endometrial lining
  • AUB-L: hypoechoic Hypoechoic A structure that produces a low-amplitude echo (darker grays) Ultrasound (Sonography), well-circumscribed, round mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast 
  • AUB-A: enlarged uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy with heterogenous echotexture
  • AUB-M: thickened endometrial lining in postmenopausal women
• Saline infusion sonogram Saline Infusion Sonogram Infertility ( SIS SIS Infertility):
  • Injection of saline into the uterine cavity for distension during sonography Sonography The visualization of deep structures of the body by recording the reflections or echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1. 6 to 10 megahertz. Diagnostic Procedures in Gynecology 
  • Ideal test for the diagnosis of:
    • AUB-P
    • Submucosal AUB-L
    • Other uterine pathologies that contribute to infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility: septa, synechiae Synechiae Scar tissue from prior surgery. Infertility
• Pelvic MRI:
  • 2nd-line modality if TVUS is unable to provide sufficient information
  • Rarely required
• Hysteroscopy Hysteroscopy Endoscopic examination, therapy or surgery of the interior of the uterus. Diagnostic Procedures in Gynecology:
  • Surgical alternative to SIS SIS Infertility
  • Allows for simultaneous diagnosis (visualization with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma) and treatment of AUB-P and submucosal AUB-L

Management

Management approach

• Dependent on hemodynamic stability:
  • General supportive measures in bleeding:
    • Stabilization (fluid resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome)
    • Transfusion, if needed
  • Acute heavy uterine bleeding:
    • IV estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy
    • Dilation and curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors
• Dependent on the underlying etiology:
  • Structural causes (PALM) → surgical resection (often, but not always)
  • AUB-O → medical management
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease → antibiotics
  • AUB-C → medical management

Medical management

• Minimize HMB with progestin therapy:
  • Oral contraceptive Oral contraceptive Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors pills (OCPs)
  • Levonorgestrel-containing IUDs
  • High-dose oral progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives: norethindrone Norethindrone A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. Noncontraceptive Estrogen and Progestins, medroxyprogesterone acetate Medroxyprogesterone acetate A synthetic progestin that is derived from 17-hydroxyprogesterone. It is a long-acting contraceptive that is effective both orally or by intramuscular injection and has also been used to treat breast and endometrial neoplasms. Hormonal Contraceptives
• Minimize HMB with anti-fibrinolytics: tranexamic acid Tranexamic acid Antifibrinolytic hemostatic used in severe hemorrhage. Hemophilia (alternative to hormone therapy)
• Treat underlying endocrine disorders:
  • Bromocriptine Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. Parkinson’s Disease Drugs or cabergoline ( hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia)
  • Levothyroxine Levothyroxine Thyroid Replacement Therapy ( hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism)
  • Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics ( hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics seen in PCOS PCOS Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome)
• Iron supplementation Iron Supplementation Iron Deficiency Anemia in anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
• Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways management for dysmenorrhea or pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways ( NSAIDs NSAIDS Primary vs Secondary Headaches)

Surgical management

• Women desiring future fertility:
  • Surgical resection of polyps (polypectomy)
  • Surgical resection of leiomyomas (myomectomy)
• After childbirth:
  • Endometrial ablation
  • Uterine-artery embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding (for large leiomyomas only)
  • Hysterectomy (definitive treatment of AUB)

Differential Diagnosis

• Non-uterine lower genital-tract bleeding: vaginal bleeding that may arise from the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy due to either cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea or vaginitis, which irritates the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy. Cervical, vaginal, or vulvar bleeding due to lacerations secondary to trauma may also occur. Diagnosis is made based on a pelvic exam, screening Screening Preoperative Care for gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea and chlamydia infections Chlamydia Infections Chlamydial infections are a group of infectious diseases caused by bacteria belonging to the Chlamydiaceae family. The 3 species that can infect humans are Chlamydia trachomatis, C. pneumoniae, and C. psittaci. The most common infection is an STI caused by C. trachomatis, which affects the genitourinary tract. Chlamydial Infections, and using a wet mount and potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia hydroxide smear of vaginal fluid to confirm vaginitis. The patient should also have an up-to-date Pap smear Pap smear Cytological preparation of cells collected from a mucosal surface and stained with Papanicolaou stain. Cervical Cancer Screening and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of any suspicious vulvovaginal lesions.
• Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection ( UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (UTIs)): a condition that may present with hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma and can sometimes be mistaken for uterine bleeding. If the patient only notes AUB while urinating, and/or has any bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess symptoms, urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children and culture should be ordered. Treatment is with antibiotics.