Heavy menstrual bleeding in adolescents

Menstruation is a normal part of adolescence, but for girls with excessive uterine bleeding, it can be associated with significant morbidity. Perhaps because their mothers or other family members struggled with troublesome menstrual periods, adolescents may not realize that their experiences are atypical or that help is available. The American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) strongly encourage medical providers to routinely assess patterns of menstrual bleeding in all adolescent girls in order to identify possible pathology and to improve their quality of life.¹ 

Defining the symptoms

Abnormal uterine bleeding (AUB) is defined as a significant alteration in the pattern or volume of menstrual blood flow. Heavy menstrual bleeding (HMB) and heavy and prolonged menstrual bleeding are now the preferred terms for excessive menstrual blood loss; intermenstrual bleeding is the preferred term for bleeding between periods. These terms are better understood by patients and may be used in place of the more ambiguous menorrhagia and menometrorrhagia, respectively.² For ease of discussion, HMB will be used to refer to both heavy and prolonged menstrual bleeding.

Contrary to the once popularly held belief that “anything goes” during the first 1 to 2 years after menarche, most adolescents in fact have fairly regular menstrual bleeding patterns, even at young gynecologic ages. Large prospective studies documenting patterns of menstrual bleeding in young adolescents demonstrate that during the first gynecologic (ie, post-menarchal) year, 88% to 94% of menstrual bleeds last 3 to 7 days, with less than 0.5% of bleeding episodes lasting more than 10 days.^3,4 A joint AAP-ACOG committee, after reviewing the epidemiologic studies of menses in adolescents, has defined the normal parameters of menstrual cycles in young females
(Table 1).¹

Review of menstrual physiology

The normal menstrual cycle starts with the first day of menstrual flow (Figure 1). Under the influence of follicle-stimulating hormone (FSH) secreted by the anterior pituitary gland, the ovaries produce estrogen, which, in turn, stimulates proliferation of the endometrium. FSH also stimulates follicular development in the ovary, and a dominant follicle ultimately emerges.

The midcycle surge of luteinizing hormone (LH) triggers ovulation; the remnant follicle becomes the corpus luteum. Progesterone, secreted by the corpus luteum, has critical immunologic, anatomic, and hemostatic effects on the endometrium. When the corpus luteum degenerates, progesterone levels fall, and this progesterone withdrawal triggers the next menstrual bleed, typically 14 days after ovulation.

Within the hypothalamic-pituitary-ovarian (HPO) axis, complex feedback mechanisms influence and control these processes. Maturation of the HPO axis is not complete until several years after menarche; consequently, anovulatory cycles are common, if not the norm, among young adolescents.⁵ When ovulation does not occur, the corpus luteum does not form, and the endometrium is not exposed to progesterone. Unopposed estrogen stimulation of the endometrium causes ongoing proliferation, reduced hemostasis, and relatively unrestrained angiogenesis. Eventually the endometrial vasculature becomes unstable, and bleeding occurs. This bleed may be indistinguishable from an ovulatory bleed, or it may be prolonged and excessive. In fact, anovulation, caused by immaturity of the HPO axis, is the most common cause of AUB in adolescents.

Causes of abnormal uterine bleeding

As noted, most AUB in adolescents is related to immaturity of the HPO axis and subsequent anovulatory bleeding in the absence of any anatomical pathology or persistent hormonal aberration (Table 2). This condition, termed dysfunctional uterine bleeding, however, is a diagnosis of exclusion.

Pregnancy complications and pelvic inflammatory disease or other sexually transmitted infection (STI) should be considered in any sexually active adolescent, particularly when pain is a presenting feature, because simple anovulatory bleeding should be painless. Polycystic ovary syndrome (PCOS), a common cause of anovulatory bleeding, may be suggested by the presence of obesity, hirsutism, acne, and acanthosis nigricans. Common medications, including hormonal contraceptives and selective serotonin reuptake inhibitors,⁶ may cause alterations in menstrual bleeding patterns. Significant systemic illnesses such as eating disorders or inflammatory bowel disease may affect the HPO axis as well, causing anovulation. Anatomic causes of HMB such as polyps or vascular malformations occur rarely in adolescents, but may be considered in those who do not respond to treatment as anticipated.

Although severe bleeding disorders manifest in early childhood, it is not unusual for HMB to be the presenting symptom leading to the diagnosis of a mild bleeding disorder. Von Willebrand disease, platelet storage pool deficiencies and other platelet function disorders, connective tissue disorders such as Ehlers-Danlos syndrome (EDS), thrombocytopenia, hemophilia carriage, and clotting factor deficiencies each may lead to HMB. Among adolescents with HMB, the prevalence of von Willebrand disease may be as high as 36%, and the prevalence of platelet dysfunction as high as 44%.⁷ A positive response to screening questions (Table 3) is highly indicative of the presence of a bleeding disorder in adult women with HMB.⁸

Evaluation: History and physical examination

When taking a menstrual history and assessing cycle length, it is necessary to ask explicitly the time from the first day of a given period to the first day of the next to avoid confusion or reporting of the number of days between 2 menstrual bleeds (time from the end of a given menstrual bleed to the beginning of the next; Table 4). A menstrual calendar can be useful for documenting the bleeding pattern and response to treatment. Alternatively, numerous smart phone applications are available, often at no cost, to help a woman track her periods. A search for “period tracker” will lead to several of these apps.

Quantifying blood loss is challenging because adolescents have a limited frame of reference for “normal” menstrual flow, and menstrual product use reflects both amount of flow and personal preference for frequency of pad or tampon changes.

In girls reporting heavy periods, one should assess for other evidence of abnormal mucocutaneous bleeding, such as easy bruising, prolonged bleeding after minor injuries (such as shaving “nicks”), epistaxis that is frequent or difficult to control, or excessive bleeding after surgical procedures, including the common procedures of tonsillectomy or a tooth extraction.⁷

A careful family history of both gynecologic bleeding (including postpartum bleeding) and nongynecologic bleeding is important when assessing for a heritable bleeding disorder. A history of joint dislocation or subluxation may suggest EDS.

Further history should include an assessment of medication use, including recent history of hormonal contraceptives. A history of genital trauma or surgery, including pregnancy termination, should be obtained. A sexual history is critical, with an assessment of current pregnancy risk and STI risk.

A comprehensive physical examination should be performed, which in most cases will be normal. Tachycardia and hypotension may signal acute hemodynamic instability and the need for rapid intervention. The presence of tachycardia, pallor, or a heart murmur suggests anemia. Petechiae or excessive bruising may suggest a platelet defect or another bleeding disorder. As noted, obesity, acne, hirsutism, and acanthosis nigricans may be present in a patient with PCOS.

A musculoskeletal examination should be performed, with attention paid to joint hypermobility, suggesting EDS. A Beighton score of 5/9 or more meets the criterion for joint hypermobility associated with EDS (Table 5).⁹ External inspection of the genitalia is sufficient for diagnosis in most patients. A sexually active patient may warrant a complete pelvic examination (speculum and bimanual exams), particularly if pain is present, if her heavy bleeding represents an acute change from her previous pattern, or if she fails to respond as anticipated to treatment.

Laboratory evaluation

If the patient reports heavy periods but her history does not in fact suggest that her bleeding pattern is outside the range of normal, a screening hemoglobin (Hg) may be sufficient to rule out anemia, and no more labs may be required. A complete blood count with white blood cell differential and platelet count should be obtained in patients whose history and physical findings suggest HMB and anemia. A measure of iron stores, such as a ferritin level, can help guide iron replacement recommendations.

If a bleeding disorder is suspected, prothrombin time and activated partial thromboplastin time should be measured. Because these studies will not always be abnormal in patients with mild bleeding disorders, it is reasonable also to obtain von Willebrand studies, including factor VIII, von Willebrand factor antigen (VWF:Ag), and ristocetin cofactor (VWF:RCo) activities. According to guidelines published by the National Heart, Lung, and Blood Institute, VWF:Ag and VWF:RCo levels under 30 IU/dL provide a definitive diagnosis of von Willebrand disease. Levels of 30 IU/dL to 50 IU/dL are considered low and may be seen in patients with partial quantitative VWF deficiency (type 1 disease).¹⁰

Exogenous estrogen has been shown to increase VWF levels.¹¹ Patients with a partial VWF deficiency who are already on estrogen-containing therapies (such as a combination oral contraceptive pill [OCP]) may therefore have normal VWF activity measurements. It may be reasonable, if clinical suspicion is high, to discontinue estrogen therapy for several weeks and repeat VWF levels. If estrogen is needed to control symptoms, however, this may not be in the best interest of the patient.

Platelet function analysis, known in some laboratories as closure time, is appropriate to screen for a platelet function disorder and has replaced the measurement of a bleeding time in most settings. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) may cause prolongation of these studies; patients should be off NSAIDs if at all possible for 24 to 48 hours before obtaining these studies.

In the setting of acute HMB, blood type and cross-match and a fibrinogen level should be obtained as well. In patients for whom transfusion is being considered, it is ideal to obtain all laboratory studies before administration of exogenous blood products.

The specific clinical features of the individual patient should guide additional laboratory evaluation. Sexually active adolescents should be tested for pregnancy and STIs, including gonorrhea and chlamydia, which can cause endometritis, cervical friability, and bleeding. A total and free testosterone level can aid in the diagnosis of PCOS if evidence of virilization is present. A thyroid-stimulating hormone test is appropriate as a test for a thyroid disturbance. A pelvic ultrasound may be indicated if there is a suspicion of structural pathology or if the patient does not respond to treatment as expected.

Treatment

Several treatment options are available to manage HMB (Table 6). Combination OCPs are appropriate and effective treatment for most adolescents with HMB, including those with mild bleeding disorders.¹¹ Norgestrel 0.3 mg/ethinyl estradiol 30 µg is commonly prescribed for this indication, although any monophasic pill containing 30 µg to 35 µg of estrogen may be used as first-line therapy. Estrogen contraindications, such as migraine with aura, inherited thrombophilia, and history of thrombosis (or high risk of developing thrombosis), must be excluded.

If the patient is not actively bleeding at the time of the office visit, the OCP may be prescribed and started at any time in the menstrual cycle; it is not necessary to wait until the start of her next menses. The OCP may be used in the standard fashion, taking 1 pill a day and completing all pills in the 28-day pack, including the placebo pills at the end of the pack.

Alternatively, extended cycling may be prescribed, such as levonorgestrel 0.15 mg/ethinyl estradiol 30 µg 84/7ee, in which 84 days of combination hormone pills are followed by
7 days of low-dose estrogen. Although extended cycling may lead to fewer scheduled bleeds and faster recovery from anemia, breakthrough bleeding is a common adverse event during the first several months of use and one that often is not tolerated by adolescents, particularly those who are using the medication exclusively for cycle control as opposed to contraception.

Girls who are experiencing ongoing bleeding at the time of their evaluation may require more aggressive hormonal therapy. Those who are bleeding briskly (changing pads or tampons every few hours) may require a combination OCP 4 times a day until bleeding is stopped (typically within 2-3 days). This may then be tapered to
3 times a day for the next 2 days, followed by 2 times a day for the next 1 to 2 weeks, then once daily.¹²

Tapering too quickly may result in a resumption of bleeding. Girls whose bleeding is prolonged but not heavy may respond to a twice-daily pill for several days, tapering to once daily after their bleeding stops. If bleeding resumes, titrate back up to the number of tablets required to suppress it, then resume a slow taper. Patients must be explicitly instructed to discard placebo pills when using these higher-dose OCP regimens.

For patients in whom estrogen is contraindicated or poorly tolerated, progesterone may be used by itself.¹² Oral medroxyprogesterone 10 mg may be used daily in a continuous fashion or in a cyclic pattern of 10 to 12 days monthly. Norethindrone acetate 5 mg to 10 mg daily is an alternative oral progesterone regimen. Both may be used up to every 4 hours until bleeding stops, then tapered to once daily over the next 2 to 3 weeks. Neither provides reliable contraception.

Depot medroxyprogesterone acetate (DMPA) 150 mg, given as an intramuscular injection every 12 weeks, may be more appropriate for patients needing pregnancy prevention. Although amenorrhea is a common adverse effect of DMPA, in some adolescents it causes prolonged or erratic bleeding, limiting its use in this population.

The levonorgestrel intrauterine system (LNG-IUS), however, is generally associated with a significant reduction in menstrual blood flow for most users (many of whom become completely amenorrheic), including women with bleeding disorders.¹³ In fact, the LNG-IUS has US Food and Drug Administration approval for the treatment of HMB in women choosing it as a contraceptive. Its use in nulliparous adolescents who do not need contraception is off label, but it can be effective in the mature adolescent who can tolerate the insertion procedure.¹⁴

Patients should be seen frequently while their medication regimens are being optimized until it is clear that they have stopped bleeding, and symptoms and anemia, if present, are improving. Hormonal therapies should be continued for
6 to 12 months, at which time the patient’s need should be reassessed. At that time, it may be reasonable for patients who are eager to discontinue hormones to undergo a trial off them, with close follow-up. If the medication is working well, however, many adolescents will prefer to stay on them, and the medication may be continued indefinitely.

Tranexamic acid, an antifibrinolytic agent, is a relatively new option for the treatment of HMB in the United States, although it has been used for years in other countries. It is available as a 650-mg pill that is administered at a dose of 1300 mg 3 times daily for up to 5 days during menses. It may reduce menstrual blood loss by 34% to 54%.¹⁵ Tranexamic acid may be considered as first-line treatment in patients who wish to avoid hormonal medications or those who prefer to take a medication only during menses, rather than all month long. Unlike combination OCPs, it will not provide monthly cycle regulation and may be best used in patients whose periods are cyclic but heavy.

There is a theoretical concern of increased risk of thrombosis in patients taking hormonal contraception and tranexamic acid at the same time, although the actual clinical significance of this has not been determined. Tranexamic acid is approved for women of reproductive age, but there is limited published evidence describing its use in young adolescents.

These treatments are typically used first line in patients with bleeding disorders as well. Many patients with von Willebrand disease, platelet function disorders, and EDS respond nicely to desmopressin nasal spray (oral desmopressin is ineffective), with improvement of their clotting measurements.¹⁶ If the managing hematologist has determined that a patient is responsive, desmopressin may be used on days 1 and 2 or days 1 and 3 of heavy bleeding. Use beyond 2 doses is unlikely to provide further benefit. Further management of HMB in patients with bleeding disorders should be done in conjunction with their hematologists.

Iron supplementation is appropriate for virtually all patients with HMB. The patient’s degree of anemia, iron deficiency, and gastrointestinal tolerance of iron products will determine her specific regimen. An adolescent may be hesitant to volunteer a constipation history, so the clinician should inquire about this as a possible reason for nonadherence to iron therapy.

Hospitalization

Hospitalization is indicated for patients who are hemodynamically unstable, are severely anemic (Hb <7-8 g/dL), or whose Hb is declining significantly with repeated measurements. It may also be appropriate for patients who are briskly bleeding and symptomatic with syncope or lightheadedness. Of course, fluid resuscitation and stabilization of the vital signs are the top priorities.

Conjugated estrogens intravenous 25 mg every 4 to 6 hours may be given until bleeding stops (typically in fewer than 48 hours).¹² Alternately, a combination OCP such as norgestrel
0.3 mg/ethinyl estradiol 30 µg every 4 to 6 hours may be used. If estrogen is contraindicated, the patient may be treated with norethindrone acetate 5 mg to 10 mg orally every 4 hours or medroxyprogesterone 10 mg orally every 4 hours. Antiemetics should be available to patients receiving high doses of estrogen. When bleeding is stopped, an oral hormone taper should begin, using either progesterone or a combination OCP.

Patients with bleeding disorders should be managed in conjunction with a hematologist. Desmopressin, factor concentrates, tranexamic acid, and platelet transfusions may be appropriate for some patients, depending on their particular disorder. Blood transfusion may be appropriate for severely anemic or symptomatic patients. Gynecologic
procedures such as dilatation and curettage and balloon tamponade may be considered in cases of refractory bleeding but rarely are necessary
in adolescents.

Cases in which adolescents fail to respond to hormonal or antifibrinolytic treatment within 48 hours are rare. Strong consideration should be given to the possibility of an underlying bleeding disorder or other gynecologic pathology in these patients, and consultation with hematology may be warranted.

Summary

Heavy menstrual bleeding is common but may significantly impair an adolescent’s quality of life. Although it is often simply a reflection of HPO axis immaturity, a careful history and high index of suspicion may reveal an underlying bleeding disorder. In either case, many effective treatments are available.

Take-home messages

Heavy menstrual bleeding is common but may significantly impair an adolescent’s quality of life. Several treatment options are available to manage heavy menstrual bleeding.

References

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4. Flug D, Largo RH, Prader A. Menstrual patterns in adolescent Swiss girls: a longitudinal study. Ann Hum Biol. 1984;11(6):495-508.

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9. Levy HP. Ehlers-Danlos syndrome, hypermobility type. In: Pagon RA, Bird TD, Dolan CR, et al, eds. GeneReviews. Seattle, WA: University of Washington; 1993. www.ncbi.nlm.nih.gov/books/NBK1279/. Last update September 13, 2012. Accessed October 11, 2012.

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11. Blombäck M, Konkle BA, Manco-Johnson MJ, Bremme K, Hellgren M, Kaaja R; ISTH SSC Subcommittee on Women’s Health Issues. Preanalytical conditions that affect coagulation testing, including hormonal status and therapy. J Thromb Haemost. 2007;5(4):855-858.

12. James AH, Kouides PA, Abdul-Kadir R, et al. Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):124-134.

13. Chi C, Huq FY, Kadir RA. Levonorgestrel-releasing intrauterine system for the management of heavy menstrual bleeding in women with inherited bleeding disorders: long-term follow-up. Contraception. 2011;83(3):242-247.

14. Aslam N, Blunt S, Latthe P. Effectiveness and tolerability of levonorgestrel intrauterine system in adolescents. J Obstet Gynaecol. 2010;30(5):489-491.

15. Naoulou B, Tsai MC. Efficacy of tranexamic acid in the treatment of idiopathic and non-functional heavy menstrual bleeding: a systematic review. Acta Obstet Gynecol Scand. 2012;91(5):529-537.

16. Rose SS, Faiz A, Miller CH, Saidi P, Philipp CS. Laboratory response to intranasal desmopressin in women with menorrhagia and platelet dysfunction. Haemophilia. 2008;14(3):571-578.