Adolescence is when a girl becomes a woman with mature reproductive function. It is associated with gradual changes in the production of sex hormones. Therefore, menstrual cycle abnormalities, including menorrhagia, are common until the final stage of ovarian development and achievement of adult levels and patterns of sex hormone secretion. In addition, menstruation may be the first hemostatic challenge for these girls. Thus, heavy menstruation may be the presenting symptom of a coagulation abnormality. There are other causes of menorrhagia in adolescents that should not be overlooked.
Menorrhagia or heavy menstruation in adolescents has major health implications. Acute severe hemorrhage is not uncommon and can require hospitalization and blood transfusion. Less severe but untreated forms lead to anemia. Menorrhagia also affects school attendance and other aspects of quality of life. It can be a source of major concern for girls and their parents. Therefore, health care providers should be aware of and skilled in the evaluation and management of this common adolescent problem. This article discusses the causes, clinical evaluation, and management of menorrhagia in adolescent girls.
MENSTRUATION IN ADOLESCENT GIRLS
Menstruation occurs as a result of maturation of the hypothalamic-pituitary-gonadal axis. However, menarche is not the endpoint of this process. Its development continues for up to 5 additional years before cyclic ovarian function is established. Therefore, menstrual cycles during adolescence are usually anovulatory or associated with shortened or insufficient function of the corpus luteum. This leads to irregular, heavy, and prolonged menstrual periods, which is usually referred to as dysfunctional uterine bleeding.
A 2-year longitudinal study of menstrual patterns in adolescent girls by the World Health Organization1 found that the mean cycle length decreased steadily from 50.7 days in the first cycle to 30 days by 24 months. Only 19% of the girls had regular cycles during the first three cycles. However, 67% had achieved regular menstrual cycles 2 years later. The duration of bleeding episodes immediately after menarche was also more variable than that of later episodes. Twenty-one percent were outside the usual range of 3 to 7 days at menarche, whereas only 9% were outside of this range by the sixth cycle.1
The hormonal pattern of adolescent menstrual cycles was studied by Apter et al.2 They found that most cycles were anovulatory during the first 2 years of gynecologic age (years since menarche), as determined by peak serum progesterone levels of less than 1.0 ng/mL. The frequency of ovulation increased to more than 80% at 5 years of gynecologic age, when peak serum progesterone levels were 5 to 15 ng/mL.1 Using the salivary progesterone assay, Read et al.3 also found a high frequency of anovulation among adolescent girls. Ovulation occurred in only 14% to 20% of the cycles in the first 2 years after menarche, but increased to 56% by the fourth year.
In a more recent study by Vuorento and Huhtaniemi,4 measurement of salivary progesterone levels demonstrated that approximately one-third of adolescents had anovulatory cycles, and the proportion remained high for up to 20 years. However, they reported much higher rates of ovulation (67%, 72%, and 75% at the gynecologic ages of 1, 2, and 4 years, respectively). Frequent irregular menstrual cycles with long follicular phases occurred during adolescence. However, in contrast to previous findings that secretion of progesterone during the luteal phase improves gradually, they found that the corpus luteum could function normally from the beginning of ovulatory cycles, although transient disturbances occurred 3 to 4 years after menarche.
In anovulatory cycles, follicle-stimulating hormone stimulates ovarian follicular maturation and estrogen production. The latter induces the endometrium into a proliferative phase. However, there is no mid-cycle surge of luteinizing hormone to cause ovulation. Therefore, no corpus luteum is formed and no progesterone is produced. The unopposed estrogen thus continues to stimulate the endometrium in its proliferative phase. Eventually the follicle involutes and the estrogen production decreases. This leads to endometrial shedding and withdrawal bleeding. The endometrium in its thick proliferative state (unlike secretory endometrium in ovulatory cycles) is shed in an irregular and incomplete fashion, often resulting in excessive or prolonged bleeding.
CAUSES OF MENORRHAGIA
Menorrhagia is defined as menstrual blood loss in excess of 80 mL per cycle. This definition is based on a significant increase in the risk of iron deficiency from that amount of blood loss.5 The prevalence of menorrhagia in a population of 476 randomly selected Swedish women (including 95 adolescent girls) was 11%.6 Similarly, a 12% prevalence has been reported in a study of 307 adolescent Nigerian girls.7
The causes of menorrhagia are generally divided into four groups: (1) dysfunctional uterine bleeding; (2) local causes; (3) systemic causes; and (4) iatrogenic causes.
Dysfunctional Uterine Bleeding
In adolescents, menorrhagia is usually dysfunctional.8 For example, dysfunctional uterine bleeding has been reported to account for 73% to 74% of cases of severe adolescent menorrhagia leading to anemia or requiring admission to the hospital.910 Dysfunctional uterine bleeding has been postulated to cause 95% of the cases of less severe menorrhagia. However, this incidence may be lower now because physicians have become more aware of some relatively common underlying local (eg, polycystic ovarian disease) and systemic (mainly bleeding disorders) conditions and because the evaluation and diagnosis of menorrhagia may have improved.
The most common local cause of menorrhagia is polycystic ovarian disease, which causes anovulatory menorrhagia. This condition is underdiagnosed in adolescent girls and some of the so-called dysfunctional uterine bleeding may be due to this disease. Polycystic ovarian disease should be considered in girls with menorrhagia and signs of chronic anovulation and hyperandrogenism. Uterine vascular malformations are rare in this category, but have been reported in adolescents and should be considered in severe intractable menorrhagia not responding to medical management. Unlike in adults, uterine fibroids, adenomyosis, endometriosis, endometrial polyps, and malignancies are extremely rare causes of menorrhagia in adolescents.
A large proportion of adolescents with menorrhagia requiring admission to the hospital have a significant systemic illness. The most frequent is hematologic disease, reported in 16%u to 19%9 of such cases. The most common hematologic disorders are von Willebrand disease (VWD), Glanzmann thrombasthenia, idiopathic thrombocytopenia, and the carrier state of hemophilia. Others include Fanconi anemia, aplastic anemia, or leukemia. Less common hemostatic disorders may be encountered more frequently in certain populations. Examples are factor XI deficiency in Ashkenazi Jews and combined factor V and factor VII deficiency in Iranians.
The frequency of bleeding disorders in milder forms of adolescent menorrhagia has not been studied. However, evidence is increasing that implicates bleeding disorders, especially VWD, in women with menorrhagia.1213 The reported prevalence ranges from 11% to 17%. Menorrhagia, particularly when it begins at menarche, can be used to predict the risk for a bleeding disorder. It may be the only presenting symptom of these disorders, especially in their mild forms. Therefore, testing for these disorders is recommended in adolescents with menorrhagia, especially those not responding to medical treatment or those with a family history suggesting VWD. Other systemic causes of menorrhagia include endocrine disorders (particularly hypothyroidism) and chronic illnesses (mainly chronic liver or renal failure).
The most common iatrogenic causes of menorrhagia in adolescents are inappropriate use of oral contraceptives and chemotherapy that results in a hematologic disorder. Smith et al. found that chemotherapy was responsible for 11% of admissions for acute adolescent menorrhagia.11
CLINICAL EVALUATION AND DIAGNOSIS
Attending a gynecology clinic or being admitted to a gynecologic ward for heavy menstruation can cause fear and anxiety in a young adolescent girl. Therefore, time should be spent putting her at ease and gaining her confidence before taking any menstrual or gynecologic history. She, not her mother, should be asked for information. She should also be given the opportunity to talk about any confidential matters without her mother present. Special adolescent gynecology programs with staff experienced in adolescent development, psychology, and problems are becoming increasingly popular for the treatment of these girls.
Obtaining a complete and accurate menstrual history is important. This should include assessment of gynecologic age, the pattern of the menstrual cycle, the severity of blood loss, menstrual pain, and other associated symptoms. However, it is well documented that a woman's description of her menstrual blood loss often correlates poorly with actual blood loss.14 Therefore, we recommend using a menstrual calendar (Fig. 1) to assess the pattern of the menstrual cycles and a pictorial blood assessment chart (Fig. 2) to assess the menstrual loss. A good bleeding history that concentrates on bleeding after any surgical intervention or dental extraction and includes any family history of bleeding disorders is also essential. In addition, a review of the history of sexual behavior, current use of contraceptives, history of chronic illnesses, and systems, focusing on the endocrine system, should be conducted.
A thorough physical examination should then be performed. In examining an adolescent girl, the physician should assess her stage of pubertal development, plus look for signs of anemia, thyroid disorders, bruising and petechial hemorrhages, and other chronic disorders. The decision of whether to perform a pelvic examination should be individualized to each patient according to her age, gynecologic age, sexual history, and menstrual history. A young virginal girl with irregular heavy periods who has mild or no pain and is not anemic does not usually require a pelvic examination. On the other hand, the older adolescent girl who is sexually active should have a complete pelvic examination and be tested for infection (eg, Chlamydia trachomatis). The possibility of pregnancy should not be overlooked, and a pregnancy test is recommended.
Diagnostic testing should also be individualized according to the history. A full blood cell count should be performed for all girls with menorrhagia, and iron studies are recommended for those with low hematocrit values. Coagulation studies should always be considered, especially for girls with menorrhagia beginning at menarche and persisting longer than 2 to 3 years, a positive bleeding history or family history, and severe menorrhagia that results in anemia requiring hospital admission or blood transfusion.
Figure 1 . An example of a menstrual calendar.
Figure 2. An example of a pictorial blood assessment chart and the scoring system used to assess menstrual blood loss.
As noted earlier, VWD is the most common bleeding disorder found in patients with menorrhagia. This disease is described in more detail in the article by Montgomery and Kroner in this issue. When testing for this disorder, physicians must remember that although bleeding time and activated partial thromboplastin time are usually prolonged in patients with VWD, results of these tests may be normal in patients with mild disease. Therefore, they are not sufficiently sensitive to use for screening and diagnosis.
Other recommended investigations include thyroid function tests, serum follicle-stimulating hormone, luteinizing hormone, prolactin, and testosterone, free androgen index, and sex hormone serum binding globulin. Specific investigations to exclude adrenal problems (which can result in irregular heavy bleeding) may occasionally be necessary. These problems include lateonset congenital adrenal hyperplasia and Cushing syndrome. A pelvic ultrasound scan is helpful when pelvic examination is difficult or local abnormalities are suspected.
Hysteroscopy, dilatation and curettage, or both are usually unnecessary in adolescent menorrhagia. However, these should be considered in the hemodynamically compromised patient with acute severe menorrhagia or severe menorrhagia not responding to high doses of hormonal therapy. They may be beneficial because removal of blood clots and thickened endometrium usually results in temporary cessation of uterine bleeding. At the same time, the possibility of uterine pathology can be excluded. These procedures should also be considered for patients with polycystic ovarian disease and untreated chronic anovulation because endometrial cancer has been diagnosed in girls as young as 16 years.15
Adolescent dysfunctional uterine bleeding is a self-limited condition that usually resolves with the maturation of the hypothalamic-pituitary-gonadal axis. In mild cases with normal hemoglobin and hematocrit values, management consists of reassurance and regular followup until regular menstrual cycles are established, to ensure adequate iron intake and prevent anemia.
In patients with moderate dysfunctional uterine bleeding resulting in a significant anemia (hemoglobin of 9 to 11 g/dL and hematocrit of 30% to 35%) who are hemodynamically stable, hormonal therapy is recommended to regulate the cycle, prevent the development of hypertrophic endometrium due to unopposed estrogen of anovulatory cycles, and reduce the loss of blood. Estrogen and progesterone in the form of oral contraceptives are the most commonly used therapy for adolescent menorrhagia and are generally effective. If hormonal therapy is still required to stop heavy and prolonged bleeding, higher doses of estrogen and progesterone are necessary. This can be achieved by starting with four pills per day and tapering to one pill per day during 21 days. When high doses of estrogen and progesterone are used, nausea and vomiting are common. Antiemetics should be given as required. A withdrawal bleed is then allowed and oral contraceptives are continued in the usual manner for 4 to 6 months.
To enhance patient compliance and reduce parental anxiety, detailed information about the hormonal therapy and possible side effects such as nausea, breast tenderness, spotting, and breakthrough bleeding should be discussed. Patients and parents should be reassured that there is no evidence that this treatment has any harmful effect on growth or the future reproductive ability of adolescent girls. Adequate iron therapy to correct anemia and replenish iron stores should commence.
When estrogen is contraindicated, cyclic oral progestagens are an alternative hormonal therapy. This results in regular and more predictable bleeding, but there is little evidence to support significant reduction in total blood loss. Nonsteroidal anti-inflammatory drugs such as mefenamic acid and antifibrinolytics such as tranexamic acid can also be helpful in reducing blood loss during menstruation. However, these treatments do not regulate the menstrual cycle. Mefenamic acid also has a beneficial effect of reducing dysmenorrhea.
Adolescents with severe active menorrhagia and signs of acute blood loss or severe anemia (hemoglobin > 8 g/dL) should be hospitalized and receive blood transfusions as necessary. Intravenous conjugated estrogen (25 mg every 6 hours), in addition to high doses of oral contraceptives has been used to stop the bleeding. However, Falcone et al.8 found no difference in outcome when comparing combined treatment with oral therapy alone. In addition, this intensive treatment may be associated with an increased risk of thromboembolism. Therefore, we do not recommend its use. Hysteroscopy and dilatation and curettage may be necessary.
Gonadotrophin-releasing hormone analogues are effective for cessation of bleeding, and amenorrhea can be achieved by 6 weeks. Due to hypoestrogenic side effects (mainly bone demineralization), this is not effective long-term treatment for menorrhagia. The combination of this therapy with some form of estrogen appears promising, but its long-term effectiveness and safety in adolescents needs to be determined.
The hormonal therapy discussed above is also effective in the management of menorrhagia due to various underlying disorders, including polycystic ovarian disease, coagulopathies, and chronic illnesses. Occasionally, specific treatments are required to control bleeding. These include desmopressin nasal spray, clotting factor concentrates, or platelet transfusion, depending on the coagulation defect. Menorrhagia due to thyroid disorders is controlled once euthyroid status is obtained. Unlike dysfunctional uterine bleeding, menstrual problems in these patients are long-standing and recurrent. This expectation should be addressed with the patient, as should the long-term implications of the underlying disease on her health. Regular follow-up and close collaboration among all health care professionals are essential to rninimize morbidity and improve quality of life.
Menorrhagia is a common problem for adolescents, with major influences on health and quality of Ufe. Adolescent menorrhagia is usually dysfunctional due to immaturity of the hypothalamic-pituitary-gonadal axis. However, in a significant proportion of cases, an underlying disorder may be identified, such as polycystic ovarian disease or a coagulation disorder (eg, vWD). Most adolescents will have normal, regular menstrual cycles, but some may require gynecologic evaluation and hormonal therapy for persistent or severe bleeding. The diagnosis and treatment of these is a particular challenge. Appropriate clinical evaluation and an individualized approach to treatment are essential for optimal patient care.
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