In adolescent girls shortly after menarche, the HPO axis is physiologically immature, whereby rising estrogen levels do not positively feedback to trigger an LH surge; therefore, ovulation does not occur. Ovulatory dysfunction due to HPO axis immaturity is very common in girls for the first 2 years after menarche and is often associated with irregular cycles and occasionally with AUB [3, 4, 6]. Given that Shelby has a young gynecologic age of 9 months, it is likely that her AUB is related to physiologic immaturity of the HPO axis.

The differential diagnosis of AUB is broad, and while HPO axis immaturity is the likely cause for Shelby, other diagnoses must be considered. The most common endocrinopathy in women is polycystic ovary syndrome (PCOS) , in which elevated levels of ovarian androgens are associated with ovulatory dysfunction and may present clinically as either primary or secondary amenorrhea, oligomenorrhea, or AUB. Women with PCOS may have clinical signs of androgen excess, such as acne and hirsutism, as well as obesity and insulin resistance [7]. Despite the name of the syndrome, adolescents with PCOS may or may not have polycystic ovaries, and this is not used as a criterion for diagnosis in this age group. Rarely, hyperandrogenemia may be related to late-onset adrenal hyperplasia or an androgen-secreting ovarian or adrenal tumor. While Shelby has mild facial acne, her normal body habitus, lack of hirsutism, and normal testosterone and DHEAS levels rule out PCOS or other hyperandrogenic etiologies of AUB. Other endocrinopathies which may cause AUB include thyroid dysfunction, diabetes mellitus, hyperprolactinemia, or elevated cortisol in Cushing’s syndrome. Shelby has no past medical history, exam findings, or laboratory evidence to suggest any of these endocrinopathies as cause for her excessive bleeding. Additionally, the HPO axis may be suppressed due to medical illness, emotional stress, weight loss from illness or eating disorders, or overexercising resulting in ovulatory dysfunction. HPO axis suppression typically leads to oligomenorrhea or amenorrhea, but AUB can also occur. While rare in adolescents, primary ovarian insufficiency (e.g., as a result of ovarian toxicity from chemotherapeutic agents) may result in ovulatory dysfunction leading to oligomenorrhea, amenorrhea, or AUB . Given that Shelby is a healthy adolescent of normal weight and mental health, it is unlikely that she has HPO axis suppression or ovarian insufficiency.

Aside from physiologic or endocrine causes of ovulatory dysfunction, AUB may occur in patients with a congenital or acquired bleeding disorder [8, 9]. Von Willebrand disease is a common cause of AUB and should be considered when heavy, prolonged bleeding is present from menarche, especially when it is accompanied by symptoms such as gum bleeding, epistaxis, or abnormal bruising. Other bleeding disorders include coagulation factor deficiencies, fibrinogen disorders, and platelet deficiencies or dysfunction, such as idiopathic thrombocytopenic purpura, aplastic anemia, leukemia, or Glanzmann thrombasthenia . Chronic kidney disease can lead to platelet dysfunction and decreased fibrinogen levels, and liver failure leads to platelet and vitamin K-dependent factor dysfunction, and both conditions can be associated with AUB. Shelby’s von Willebrand disease panel is negative, and she has a normal platelet count with no other signs or symptoms of abnormal bleeding; therefore, coagulation or platelet disorders are unlikely causes of her AUB .

Additional pathologic etiologies should be considered, especially in sexually active adolescents and when AUB is associated with lower abdominal pain. Sexually transmitted infections (STIs) , especially acute or chronic endometritis with or without salpingitis, caused by pathogens including N. gonorrhoeae and C. trachomatis, are potential etiologies of AUB, and testing for these STIs should always be done. A miscarriage or ectopic pregnancy could also cause pain and heavy uterine bleeding, so a pregnancy test should always be performed in patients presenting with AUB. Shelby has never had sex, and her negative pregnancy, gonorrhea, and chlamydia tests point against these diagnoses.

Finally, anatomical or structural causes of AUB, while rare in adolescents, must be considered. An external genital exam should be performed on all patients presenting with excessive vaginal bleeding to ensure that the bleeding is coming from the vagina and there are no lesions on the vulva. A full speculum and bimanual pelvic exam should be performed on all sexually active adolescents with AUB. High vaginal lacerations, usually resulting from sexual intercourse, present with profuse sudden bleeding from the vagina and often require examination under anesthesia for diagnosis and suturing. The history of sudden painless bleeding immediately after intercourse is crucial for diagnosis of this lesion, but adolescents are often so frightened and embarrassed by the bleeding that they initially deny sexual activity; a sensitive and private interview with reassurance of confidentiality is essential. Uterine fibroids or polyps are potential causes of AUB, and while they are uncommon in adolescents, a pelvic ultrasound may be useful when evaluating for the etiology of excessive bleeding in unclear cases. In addition, hemangiomas, arteriovenous malformations, and tumors of the genital tract including rhabdomyosarcomas are rare causes of AUB in adolescents.

Shelby has a gynecologic age of less than 2 years, and she had a comprehensive laboratory evaluation, which revealed no pathologic etiology so she was diagnosed with AUB due to physiologic immaturity of the HPO axis. The primary goals of treatment of AUB are to stabilize the endometrium in order to prevent further uncontrolled bleeding, as well as to correct anemia and hemodynamic instability. A combined (estrogen/progestin) oral contraceptive (COC) pill is the treatment of choice to stabilize the endometrium and prevent further bleeding for many different etiologies of AUB in adolescent girls including HPO axis immaturity. Some adolescents have contraindications to estrogen [10], in which case oral progestins alone or an antifibrinolytic medication is a safe alternative.

Combined oral contraceptive (COC) pills are typically dispensed in a pack containing 21 active hormonal pills and 7 placebo pills (Fig. 8.2). During the placebo week of each 4-week cycle, the adolescent should experience a well-controlled, typically light withdrawal bleed. We recommend that adolescent girls with anemia (Hb < 11 g/dL) take continuous active hormonal pills and discard placebo pills in order to prevent a withdrawal bleed until the anemia resolves. In addition, girls with anemia should take therapeutic doses of oral iron (e.g., ferrous gluconate 325 mg twice per day) accompanied by a stool softener to prevent iron-induced constipation. Once anemia is resolved, the adolescent may begin taking the placebo pills during the fourth week of every cycle allowing for monthly withdrawal bleeds. Therapeutic doses of iron should be discontinued once iron stores are replenished, generally 2–3 months after hemoglobin levels have returned to normal.

If an adolescent with AUB and moderate anemia (Hb 9–11 g/dL) is actively bleeding upon presentation, a COC taper, ranging from four to two pills per day, is an effective means of stopping the current bleed. Once bleeding has ceased, the COC pills should be continued at once daily dosing. Shelby has moderate anemia (Hb 9.6 g/dL) with fatigue, and she currently has light bleeding. An appropriate plan would be to administer a COC pill two times per day for 2 or 3 days to stop her current bleed, followed by once daily dosing, discarding the placebo pills to prevent further bleeding. She should also begin a therapeutic dose of oral iron with a stool softener.