Dr. Kiran Guleria provides expert insights on the approach of diagnosis and treatment for heavy menstrual bleeding in adolescent girls in India.

Abnormal uterine bleeding (AUB) is defined as vaginal bleeding (mostly of uterine origin) that is abnormal in duration, volume, frequency and/or regularity. It accounts for almost half of the gynaecologic issues among adolescents and often ignored as normal menstrual irregularity during adolescence.

AUB and/or its underlying factors have potential long term health consequences, poor life quality and school attendance. Thus, evaluation of the menstrual cycle should always be done in any adolescent female during all routine medical visits.

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What is a normal period (cycle) in an adolescent?

Menarche usually occurs between the ages of 11 to 13 years. The normal cycle in an adolescent occurs every 21 to 45 days with bleeding lasting between 2 to 7 days. Later, the cycles become more frequent at 21 to 34 days interval, similar to adults, in 60 to 80% of adolescents by the third year of menarche.

The International Federation of Gynecology and Obstetrics (FIGO) recommends the use of the term AUB to describe any aberration of menstrual volume, regulation, duration and/or frequency in a woman who is not pregnant (Table 1).

Table 1. Abnormal uterine bleeding- FIGO recommendations for menstrual terminology
Category	Definition
Disorders in regularity
Irregular menstrual bleeding	Variation >20 days over a period of one year
Absent menstrual bleeding (amenorrhoea)	No bleeding in a 90-day period
Disorders in frequency
Infrequent menstrual bleeding (oligomenorrhoea)	One or two episodes in a 90-day period
Frequent menstrual bleeding	More than four episodes in a 90-day period
Disorders in amount of flow
*Heavy Menstrual Bleeding (HMB)	Excessive blood loss (usually >80 ml) which interferes with the woman's physical, emotional, social, and material quality of life and which can occur alone or with other symptoms
*Heavy & prolonged menstrual bleeding	Excessive blood loss exceeding 8 days
Light menstrual bleeding	Bleeding less than 5 ml in a period
Disorders of duration of flow
*Prolonged menstrual bleeding	Menstual periods that exceed eight days on a regular basis
Shortened menstrual bleeding	Menstrual bleeding lasting less than two days
Heavy Menstrual Bleeding (HMB) is denoted by * and in bold

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Causes of HMB in adolescents

FIGO defines the aetiology of AUB by PALM-COEIN [Polyp, Adenomyosis, Leiomyoma, Malignancy, Hyperplasia (structural causes); Coagulopathy, Ovulatory dysfunction, Endometrial, Latrogenic and not yet classified (non-structural causes)] classification system.

In adolescents, HMB typically occurs at irregular intervals, indicating that it is anovulatory. If it occurs at regular intervals or at the onset of menses, it is often due to a bleeding disorder. Less commonly, HMB may be caused by systemic illness or structural lesions. It is rarely due to structural causes (1.3 to 1.7%).

Anovulatory cycles owing to immature hypothalamic-pituitary-ovarian axis is the most common cause of HMB among adolescents. Coagulopathy is seen among 5 to 28% of hospitalised adolescents with HMB with von Willebrand disease (vWD) contributing to almost 13%. Rest can be due to other coagulation factor deficiencies, immune thrombocytopenia, platelet dysfunction, thrombocytopenia secondary to malignancy or its treatments.

Infections like genital tuberculosis should also be kept in mind in a country like ours. The differential diagnosis of HMB in adolescents is summarised below.

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Differential diagnosis of heavy menstrual bleeding in adolescents

1. Endocrine causes
   • Anovulatory bleeding
   • PCOS
   • Thyroid disease
   • Other causes
2. Bleeding disorders
   • von Willebrand disease
   • Platelet dysfunction
   • Thrombocytopenia
   • Clotting factor deficiency
3. Pregnancy
   • Abortion
   • Ectopic pregnancy
   • Gestational trophoblastic disease
4. Infections
   • Tuberculosis
   • Cervicitis
5. Disorders of the uterus
   • Myoma
   • Adenomyosis
   • Polyps
   • Cancer
6. Intrauterine device
7. Medications
   • Depot medroxyprogesterone
   • Anticoagulants
8. Trauma
9. Foreign body
10. Endometriosis

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HMB evaluation- Examination & investigations

The focus of initial evaluation is to determine whether the bleeding is acute and causing haemodynamic instability through careful history taking, physical examination, laboratory testing and imaging.

History should be taken both with and without the parents to respect the girl’s privacy. It should include; menstrual history (age of menarche, regularity, duration, number of pads/tampons per day), sexual history, past medical history (systemic illness, current/recent medication), systemic (such as obesity, PCOS, hypothyroidism, hyperprolactinemia, hypothalamic or adrenal disorder) and family history (coagulopathy, hormone sensitive cancers). A history of heavy menses since menarche, surgery related bleeding, bleeding associated with dental work, bruising or epistaxis with a frequency of at least once per month, frequent gum bleeding and bleeding symptoms in the family point to an underlying bleeding disorder.

Examination should focus on vital signs, haemodynamic instability, presence of goitre, pallor, bruising, petechiae and/or signs of androgen excess for underlying diagnosis. Pelvic examination with a speculum or transvaginal ultrasonography can be done in sexually active adolescents. In others, transabdominal gyne scan provides non-invasive information about genital tract structural lesions, PCOS, endometriosis etc. especially in adolescents in whom the physical examination is limited.

Laboratory evaluation: The minimum should include; urine/serum hCG, complete blood count, peripheral blood smear, ferritin level, thyroid function tests, prothrombin time, activated partial thromboplastin time and fibrinogen. Adolescents at risk of bleeding disorders should undergo testing for vWD; plasma von Willebrand factor (vWF) antigen and functional tests for vWF and factor VIII. Additional tests include exclusion of infection in sexually active adolescents and genital tuberculosis. A haematologist referral may be sought in some.

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Treatment

Providing haemodynamic stability, correction of anaemia and maintenance of normal cycles constitute the main goals in management of HMB. Depending upon severity (Table 3), treatment options include blood and component transfusion, iron supplementation, non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics, combined oral contraceptives (COCs), progesterone, desmopressin and GnRH analogues.

Table 3. Severity classification
Mild	Longer menses (>7 days) or frequent cycles (<3 weeks) for two months in succession, with slightly or moderately increased bleeding, a normal (≥12 g/dL) to mildly decreased (10 to 12 g/dL) haemoglobin.
Moderate	Heavy or frequent (every 1 to 3 weeks) menses, with Hb of ≥10 g/dL.
Severe	Heavy bleeding with a haemoglobin level of <10 g/dL.

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Mild anovulatory uterine bleeding

Treament options range from observation alone, NSAIDs, such as ibuprofen and naproxen sodium, to hormonal therapy for anovulatory uterine bleeding, along with iron supplementation 60 mg elemental iron per day. Re-evaluation should be done at three months or sooner if the bleeding persists or becomes more severe.

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Moderate anovulatory uterine bleeding

These patients can also be managed on an outpatient basis. In addition to iron supplementation, hormonal therapy (COCs or progestins) is necessary to stabilise endometrial proliferation and shedding. In adolescents who are actively bleeding, COCs containing at least 30 mcg of ethinyl E2 are a better choice, one pill every 8 to 12 hours until the bleeding stops, and then one pill per day for at least 21 days. Treatment is continued for 3 to 6 months until the haemoglobin level reaches ≥12 g/dL.

Progestin therapy can be an alternative to COCs for adolescents who are not currently bleeding or if oestrogen therapy is contraindicated, such as arterial/venous thromboembolic disease, hepatic dysfunction, migraine with aura and/or oestrogen dependent tumours. The options are:

• Micronised oral progesterone (200 mg/day)
• Medroxy progesterone acetate (10 mg/day)
• Norethindrone acetate (2.5 to 5 mg/day)
• Depot-medroxyprogesterone acetate (DMPA)
• Levonorgestrel-releasing intrauterine device

The last two are options for those who need contraception or cannot take pills. Oral progestin is given from the 5th to 25th day or atleast for 12 days every month. Bleeding occurs 2 to 7 days after cessation. If bleeding does not start within one week of cessation of tablets the patient should be re-evaluated.

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Severe anovulatory uterine bleeding

Patients with Hb <7 g/dL and those with Hb <10 g/dL but are actively bleeding and haemodynamically unstable (tachycardia, hypotension, orthostatic vital signs) must be hospitalised and promptly evaluated and transfused blood and blood products. Oral iron supplementation must be started as soon as the patient is stable enough to take oral pills.

Hormone therapy for hemostasis consists of monophasic COCs containing 30 to 50 mcg ethinyl estradiol, one tablet every six hours for 2 to 4 days, every eight hours for next three days and then every 12 hours for the next 14 days. Additional anti-emetic treatment may be necessary. For maintenance, COCs are used in a cyclic pattern for three to six months until Hb of ≥12 g/dL is attained.

Progestin therapies may be an option for patients who have a contraindication for COCs. For acute management, oral progestogen-MPA 30 mg/day in divided dose for 3 to 4 days followed by 20 mg/day for the next 21 days are given and are better than either DMPA or a levonorgestrel-intra uterine device. For maintenance MPA 10 mg/day can be given cyclically for next 3 to 6 months.

In addition, haemostatic agents such as tranexamic acid, aminocaproic acid and desmopressin may also be needed. Tranexamic acid 3 to 4 g/day in three doses for 4 to 5 days is an effective treatment for HMB and is more effective than placebo. Although there is no evidence for increased incidence of thrombotic events associated with tranexamic acid, having a history of or active thromboembolic disease or an intrinsic risk for thrombosis are contraindications for tranexamic acid use.

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Follow-up

If irregular menses or HMB persists under hormone therapy for three months or recurs after cessation of therapy, the patient should be assessed and treated for possible problems of hypothalamic-pituitary-ovarian axis, PCOS, haematological and structural causes. Adolescents with structural causes- myoma, fibroid polyps, malignancy etc. will need specific fertility sparing surgical management.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author Dr. Kiran Guleria is the Director-Professor at Department of Obstetrics & Gynecology, University College of Medical Sciences & GTB Hospital, Delhi.