Approach to Abnormal Uterine Bleeding in Adolescents

Adolescents have frequent menstrual problems such as irregular menses, painful cycles and prolonged or heavy menstrual bleeding (HMB). Abnormal uterine bleeding (AUB) is defined as bleeding from uterine corpus that is abnormal in duration, volume, frequency and/or regularity. Due to immaturity of the hypothalamic-pituitary-ovarian (HPO) axis, AUB is common in adolescents ( 1 , 2 ). Furthermore, inherited or acquired bleeding diathesis may further intensify the existing hormonal imbalance and increase morbidity of the underlying condition. In addition to these problems, hyperprolactinemia, thyroid disorders and polycystic ovary syndrome (PCOS) are the common underlying endocrine disorders. AUB decreases quality of life, affects school attendance and limits sports and social activity participation ( 3 ). Although the management of this problem has evolved over time, the most important goal remains to alleviate the anxiety of both affected girls and their families and to identify the underlying medical conditions that may have chronic health effects for these girls. In this paper, the most common causes of AUB will be discussed and current management will be reviewed.

Although the age of onset of puberty has tended to decrease over the past few decades, the age of menarche has remained constant at 12-13 years ( 4 ). At present, more than 90% of girls are menstruating before age of 14 years. Menarche is generally considered as anovulatory bleeding. The time required for HPO axis maturation following menarche, which is thought to result in ovulatory cycles and subsequent regular bleeding, varies between six months and three years. Due to ovulatory dysfunction, in the following months after menarche, irregular and unpredictable, heavy and prolonged, and, rarely, skipped menses for less than three months may occur ( 5 ). Thus perception of “normal” menstrual cycle may vary in these girls and their families. As in adults, menstrual cycles are between 21 and 34 days, last for seven days or fewer, with an average blood loss of 30-40 mL leading to 3-6 pads or tampon usage per day ( 6 ). HMB is the most common form of AUB and is defined as excessive menstrual blood loss that interferes with a woman’s physical, social, emotional or material quality of life ( 7 ). Some additional signs of HMB include changing pad or tampon more often than every one to two hours, use of double hygiene protection, frequent soiling of clothes or bed sheets and blood clots more than one inch (2.54 cm) in diameter ( 8 ). The causes of HMB may be classified using the Polyp, Adenomyosis, Leiomyoma, Malignancy-Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic and Not yet classified (PALM-COEIN) classification which is divided into structural causes including PALM and hyperplasia and non-structural causes which include COEIN ( 9 ). The structural causes of HMB are rarely seen in the adolescent age group. AUB might also be classified as acute or chronic. Acute AUB refers to an episode of heavy bleeding which is sufficient in quantity to require immediate intervention to prevent further blood loss. Abnormalities in quantity, regularity and/or timing in the last six months may all be defined as chronic AUB ( 10 ). Usually, chronic menstrual bleeding that exceeds 80 mL will result in anemia.

AUB in adolescents is a challenging and often neglected problem. Cycle to cycle variability, differences in menstrual hygiene, the wide variety of menstrual hygiene pads or tampons available, inconsistency in giving information about menstrual regularity and bleeding amounts make initial assessment of AUB even more difficult in these girls ( 11 ). Patients and their families may not know what is “normal” and patients may not inform their families about menstrual irregularities. In addition, most bleeding disorders may not be as obvious until menarche. Although during this period, AUB may occur more frequently due to anovulation, bleeding disorders may also accompany this condition.

When adolescents present with acute AUB, physical examination should focus on signs of acute blood loss and the etiology of bleeding. While tachycardia and orthostatic hypotension may be the only signs of severe anemia, it should be kept in mind that young patients will not present with clinical signs, despite severe anemia. While the presence of bruises and petechiae on the skin may indicate an underlying coagulation disorders, pallor may be seen due to anemia. In adolescents who are sexually active, trauma, foreign body, structural causes and pelvic inflammatory diseases can be investigated by pelvic and bimanual examination.

After acute menstrual bleeding ceases, these girls require treatment for long-term bleeding control. In addition to diet optimization and iron supplementation, hormonal treatments are used. Hormonal treatments include OCP, oral, injectable and implantable progesterone and the LNG-releasing intrauterine device (LNG-IUD). For OCP, continuous or extended-cycle regimes are recommended for stabilization of the endometrium. Combinations of 30-50 mcg of ethinyl estradiol and levonorgestrel or norgestrel are more effective in reducing bleeding than in low-dose and new generation progesterone-containing preparations. Depot medroxyprogesterone acetate is also used for long-term bleeding control. Since there is a risk of hematoma with intramuscular administration, subcutaneous injection is recommended. To reduce the likelihood of initial breakthrough bleeding, therapy is applied more frequently than the usual 12-week cycle ( 32 ). Since daily, monthly and quarterly use of some formulas can be difficult for adolescents the LNG-IUD may be preferred. The LNG-IUD is active for up to five years after being placed in the uterine cavity. Additional benefits of the LNG-IUD are highly effective contraception, higher continuation rates and higher satisfaction rates when used for bleeding control compared with OCP in an adolescent population ( 33 ). In adolescents with bleeding disorders, the LNG-IUD has been demonstrated to be effective in controlling menstrual bleeding ( 34 , 35 ). Since breakthrough bleeding caused by etonorgestrel implants is a common side effect, it is not usually used for the treatment of AUB.

Initial evaluation of adolescents presenting with acute AUB should include screening for pregnancy, anemia, bleeding disorders, iron deficiency and thyroid disease ( 15 ). Complete blood count, blood type, cross match and pregnancy test should be first line tests. In addition, partial thromboplastin time, prothrombin time, activated partial thromboplastin time and fibrinogen level are the initial evaluation for disorders of hemostasis. All adolescents with abnormal initial test or positive screening results for disorders of hemostasis should be evaluated by assessment of von Willebrand-ristocetin cofactor activity, von Willebrand antigen and factor VIII for diagnosis of von Willebrand disease and other coagulopathies ( 16 ). Since exogenous estrogen use may increase von Willebrand Factor concentrations into the normal range, it is necessary to perform the test either before starting hormone treatment or seven days after the end of treatment to prevent false negative results ( 17 ). If patient’s history or physical examination findings are suggestive of PCOS, testosterone (free/total), DHEAS and prolactin should be evaluated. Sexually active adolescents should be screened for Neisseria gonorhhea and Chylamidia trachomatis infections with nucleic acid amplification tests. Routine pelvic imaging is considered unnecessary since structural etiologies are rarely seen in this group. However, in the girls who do not respond to initial treatment, transabdominal ultrasonography may be more appropriate than transvaginal ultrasonography.

Girls with light or mild bleeding, indicated by normal Hb concentrations, should be reassured that observation is sufficient, unless there is an impairment of quality of life. NSAIDs can be used to reduce the amount of bleeding. If bleeding persists or becomes more severe, re-evaluation of the patient is required. If the Hb concentrations of these girls are found to be in the 10-12 gr/dL range, observation or OCP are valuable therapeutic options and 60 mg daily iron treatment should be commenced. If hormonal therapy is chosen, monophasic OCP, with 30-50 mcg ethinyl estradiol content, can be used every 8-12 hours until bleeding slows, then the therapy should be tapered to one pill daily over the course of a few days and therapy should be continued for at lesat 21 days. In the presence of moderate bleeding or Hb concentration in the range 8-10 gr/dL, oral contraceptive treatment should be initiated as described above and continued until the Hb concentration is above 12 gr/dL with at least six months of iron supplementation. In the presence of a contraindication to estrogen therapy or alternative treatment in adolescents with anemia, progesterone therapy can be an option. Available progesterone therapies are oral medroxyprogesterone acetate (10 mg/day), micronized oral progesterone (200 mg/day) or norethindrone acetate (2.5-5 mg/day), which should be given for 12 days in every cycle ( 31 ).

AUB in adolescents may be acceptable at the beginning of the reproductive age when menstrual cycle regularity is not established, or may be the first sign of a severe underlying bleeding disorder. Girls with AUB should be evaluated with care and a wide differential diagnosis should be borne in mind. Medical therapy is usually an effective and sufficient treatment. Generally, adolescents respond well to therapy. Hematology consultation, imaging methods and clinical intervention should be considered in patients who do not respond to treatment.

In these girls, clinicians should evaluate the features of the menstrual cycle like a vital sign ( 12 ). An accurate history of patient’s cycles is the main issue for diagnosis, to determine if her experiences are normal or abnormal. The onset of menarche, cycle length, variability over time and the amount of menstrual bleeding should be evaluated. After providing a suitable conversation environment, sexual activity should be questioned. Pregnancy and its related complications should also be part of the initial investigation in girls presenting with AUB. Although AUB is often caused by anovulatory cycles, severe bleeding may be the first sign of an underlying condition and this may be a diagnosis of exclusion. PCOS, another cause of anovulatory cycles, should be kept in mind as a common underlying etiology of AUB, since it can easily be missed in this age group ( 13 ). Excessive bleeding during menarche can usually indicate an underlying bleeding disorder, while regular but excessive bleeding may also be indicative of bleeding disorders. Von Willebrand disease, platelet function defects, thrombocytopenia and clotting factor deficiencies are the most common bleeding disorders in adolescent girls that present with HMB. Up to 36% of adolescents with AUB may have an underlying coagulopathy ( 14 ). Using a screening tool for underlying bleeding diathesis in adolescents with AUB can assist the physician. Initial screening for an underlying disorder of hemostasis in patients with excessive menstrual bleeding should be structured by the medical history. A positive screening result comprises the following circumstances: - Heavy menstrual bleeding since menarche - One of the following conditions: - Postpartum hemorrhage, - Surgery-related bleeding, - Bleeding associated with dental work. - Two or more of the following conditions: - Bruising, one to two times per month, - Epistaxis, one to two times per month, - Frequent gum bleeding, - Family history of bleeding symptoms. Patients with a positive screening test should be considered for further evaluation, including consultation with a hematologist and testing for von Willebrand factor and ristocetin cofactor. In intermenstrual bleeding, cervicitis and hormonal contraception may be implicated. In adolescents who do not respond to standard medical therapy, structural causes of bleeding should be excluded. Table 1 for common causes for AUB in adolescents.