Abstract
Menorrhagia, or heavy menstrual bleeding (HMB), is a common presenting complaint, accounting for 5% of female primary care consultations and 20% of gynaecology clinic consultations every year. The majority of these patients can be managed competently in primary care, referring patients requiring surgical intervention or those with suspected malignancy to secondary care. This article will explore the diagnosis and management of women presenting with HMB in primary care in accordance with guidelines from the National Institute for Health and Care Excellence (NICE) and the RCGP curriculum.
The GP curriculum and the ageing population
Understanding the importance of risk factors in the diagnosis and management of women’s health problems including heavy menstrual bleeding (HMB) Recognising and acting immediately in patients presenting with a gynaecological emergency, such as HMB causing haemodynamic instability Intervening urgently when malignancy is suspected Understanding the psychological impact of women’s health and providing emotional support
The menstrual cycle: The basics
To fully appreciate abnormal menstrual bleeding, it is important to have an understanding of the normal menstrual cycle. The superficial lining of the uterus is shed in response to cyclical changes in hormone levels during the menstrual cycle. This occurs on average every 24 to 35 days and includes the loss of blood and endometrial tissue for 2 to 7 days. The menstrual loss of blood and endometrial tissue is typically referred to as a period, menstrual period or menstruation. The menstrual cycle can be divided into four phases, illustrated in Fig. 1.
An illustration of the hormonal changes in oestrogen and progesterone during the normal menstrual cycle.
The follicular phase
The follicular phase begins on the first day of menstruation and ends with ovulation. Gonadotrophin-releasing hormone is secreted from the hypothalamus in response to low systemic levels of oestrogen and progesterone. This provides a signal to the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) which initiates the growth of several immature follicles within the ovary. One of these follicles becomes dominant and will secrete significant amounts of oestrogen and suppress the development of the remaining follicles.
The ovulation phase
The increased oestrogen level triggers a sharp rise in luteinising hormone (LH), known as the ‘LH surge’. This instigates the release of an egg from the dominant follicle.
The luteal phase
The remainder of the ruptured follicle forms a structure known as the corpus luteum, which continues to secrete progesterone and smaller amounts of oestrogen to thicken and maintain the lining of the endometrium for implantation of a fertilised egg. If pregnancy does not occur, the corpus luteum will degenerate and stop secreting progesterone. The decline in progesterone levels causes the endometrial lining to shed and the woman has a withdrawal bleed, known as the menstruation phase (the final stage of the menstrual cycle).
What is heavy menstrual bleeding?
The National Institute for Health and Care Excellence (NICE) defines heavy menstrual bleeding (HMB) as ‘excessive menstrual blood loss’, which is equivalent to 80 mL or more of blood loss and/or bleeding for more than 7 days during each cycle (NICE, 2017). It is believed that, on average, most women lose approximately 30-40 mL of blood per cycle. Menstrual bleeding becomes heavier with age, and is often heaviest shortly prior to the menopause. In practice, it is difficult to accurately measure the degree of blood loss, therefore, a woman’s perspective of her blood loss and the effect on quality of life is considered a more realistic, obtainable and relevant measure.
Taking a history
When consulting with a woman presenting with HMB, it is imperative to obtain a thorough history. The history can be divided into manageable segments, outlined in Fig. 2 and encompassing a gynaecological, obstetric and sexual health history.
A template for history taking for HMB.
The gynaecological history should include a thorough account of the nature of bleeding, including the date of the last menstrual period, the cycle length and the quantity of tampons or sanitary towels used within 24 hours. Ask if any clots are present or if the woman has experienced flooding of menstrual blood through the sanitary towel or clothing. This can prompt further enquiry about the impact of symptoms on quality of life, including the ability to carry out normal daily activities, the impact on work (including the number of sick days taken), social life and sex life. Any concerns about the cause of the bleeding or expectations of treatment should be explored.
In addition, consider other associated symptoms that may suggest an underlying cause, such as infection (post-coital bleeding or intermenstrual bleeding) or endometriosis (dysmenorrhoea or pelvic pain). When bleeding is unexplained, it is important to identify ‘red flag’ symptoms which may suggest underlying malignant pathology, particularly unintentional weight loss, pelvic masses or pressure-like symptoms (NICE, 2017).
The obstetric history will detail the number of previous pregnancies, including any miscarriages or ectopic pregnancies. The risk of sexually transmitted infection, predisposing to conditions such as pelvic inflammatory disease, will emerge from a sexual history. Routine checking of compliance with the cervical screening programme is recommended.
An enquiry about general health and family history can identify risk factors for gynaecological malignancy and comorbidities that may affect treatment options.
Clinical examination
NICE recommends that women presenting with HMB in the absence of related symptoms can be offered pharmacological treatment without a physical examination (NICE, 2018a). Patients with additional symptoms should have an abdominal and pelvic examination (bimanual and speculum).
Differential diagnosis
There are a number of causes for HMB. They can be classified into primary or secondary, with primary menorrhagia representing an idiopathic cause (dysfunctional uterine bleeding) and secondary causes including uterine fibroids, uterine polyps, adenomyosis, endometriosis, endometrial hyperplasia and pelvic inflammatory disease (PID).
Fibroids
Uterine fibroids (Leiomyomas) are benign tumours of smooth muscle that are oestrogen and progesterone sensitive, meaning they typically occur in women of reproductive age and regress following the menopause. They are classified by their location relative to the layers of the uterus and can be described as intramural (confined to the uterine muscle), subserosal (extending into the external uterine tissue) and submucosal (extending into the endometrial cavity). Risk factors include early puberty, obesity, family history, black ethnicity and increasing age (NICE, 2018b). The size and location of the fibroids may determine the presence and severity of symptoms, including HMB, pelvic pain, bowel (bloating, constipation) or urinary (frequency, urgency, incontinence) involvement. However, the majority of fibroids are asymptomatic and an incidental finding on pelvic ultrasound.
Adenomyosis and endometriosis
Adenomyosis is the presence of endometrial tissue within the myometrium, which is sensitive to cyclical hormone changes. It therefore most commonly occurs in premenopausal women. Symptoms include HMB and premenstrual pain, with evidence of an enlarged, tender uterus on examination (NICE, 2017). The diagnosis of adenomyosis is confirmed by a transvaginal ultrasound. Endometriosis is the presence of endometrial tissue outside of the uterine cavity and can feature deposits across the pelvis. This is also sensitive to cyclical change in hormones, leading to HMB, deep dyspareunia and chronic pelvic pain (NICE, 2014).
Dysfunctional uterine bleeding
Dysfunctional uterine bleeding (DUB) is generally considered to be a diagnosis of exclusion, when no structural or histological cause for HMB symptoms has been identified. Patients with DUB typically describe irregular and heavy bleeding in the absence of pain. It is believed to occur when the normal menstrual cycle is disturbed (usually due to anovulation) and, oestrogen is continuously secreted without the release of an egg from the dominant follicle. This means progesterone is not secreted from the corpus luteum and consequently endometrial proliferation continues. Eventually, the endometrial lining sheds as the blood supply is outgrown, leading to dysfunctional bleeding at irregular intervals. Although this condition is typically benign, the longstanding effect of unopposed oestrogen on the endometrial lining is associated with the development of endometrial hyperplasia atypia. This is the precursor to endometrial carcinoma. The overall risk for this developing in patients with DUB is estimated to be 1.33% (Pennant et al., 2016).
Other causes
Other diagnoses to consider are infections of the genital system including PID, coagulopathies such as Von Willebrand’s disease, metabolic disorders (such as hypothyroidism) and iatrogenic causes (such as chemotherapy).
Investigations
NICE guidelines recommend a full blood count to look for anaemia as part of the assessment of severity of bleeding (note that Ferritin levels are not typically indicated) in all women presenting with HMB (NICE, 2017). Testing for coagulation disorders such as Von Willebrand’s disease should be offered to women who have suffered with HMB since menarche or who have a personal or family history of a coagulation disorder (NICE, 2018a). Thyroid function tests should only be performed if the patient presents with other symptoms suggestive of thyroid disease.
Women who present with clinical features suggestive of submucosal uterine fibroids or uterine polyps (such as intermenstrual bleeding, pelvic pain or pressure-type symptoms) should undergo a hysteroscopy as an outpatient (NICE, 2018a). A hysteroscopy offers a higher sensitivity and specificity in the identification of uterine cavity abnormalities compared to pelvic ultrasound (NICE, 2017). Women with additional risk factors for endometrial cancer such as obesity, polycystic ovarian syndrome or tamoxifen treatment should have an endometrial biopsy taken at the same time. If the procedure is declined, NICE recommend pelvic ultrasound as an alternative, with explanation and patient understanding of the limitations of this imaging modality.
In women with an abdominally palpable uterus (which may suggest a large fibroid or multiple fibroids), a history or examination suggestive of a pelvic mass, or when examination is inconclusive (for example if the patient is obese), a pelvic ultrasound should be offered instead of a hysteroscopy. This imaging modality is better able to detect pathology outside the uterine cavity (NICE, 2017). In cases where there is significant dysmenorrhoea or a bulky, tender uterus (suggestive of adenomyosis), a transvaginal ultrasound is preferred to allow visualisation of the inside of the uterus. If this is declined by the patient, or considered to be unsuitable, a transabdominal ultrasound or magnetic resonance imaging scan could be offered.
Treatment of HMB
The main aim of treatment for HMB is to stabilise the patient clinically and reduce menstrual blood loss in subsequent cycles. Decisions on the most appropriate treatment option should be made collaboratively with patients, taking into account clinical status, symptoms, suspected aetiology, individual treatment preference and consideration of future fertility wishes.
For women with no identified pathology, adenomyosis, or fibroids that are less than 3 cm in diameter and not causing pressure-related symptoms, the first line treatment is a levonorgestrel intrauterine system (LNG-IUS), such as Mirena®. This is indicated when a minimum of 12 months use is expected and the woman does not wish to conceive immediately (NICE, 2017). The intrauterine device acts locally by down-regulating the number of oestrogen and progesterone receptors in the uterus. This results in endometrial atrophy and a consequent reduction in menstrual bleeding. This has been found to be more effective for HMB than oral medication (Leminen, 2012). Prior to insertion, testing for sexually-transmitted infections is recommended (but this should not delay insertion). Women should be advised that irregular bleeding in the initial months following insertion is common and it might take at least six cycles for the full benefits of the treatment to be felt. Such advice may avoid premature removal of the device.
If the LNG-IUS is unsuitable or contraindicated, non-hormonal and hormonal pharmacological agents can be offered. The non-hormonal options include haemostatic medication such as tranexamic acid and mefenamic acid to reduce menstrual flow (with studies showing tranexamic acid reducing blood flow by 26–60% and mefenamic acid by 25–50%). Mefenamic acid also acts as an analgesic and anti-inflammatory (Leminen and Hurskainen, 2012; Maybin and Critchley, 2016). Hormonal treatments include the combined oral contraception pill or cyclical oral progestogens (e.g. Norethisterone, taken from days 5–26 of the cycle) (Royal College of Obstetricians and Gynaecologists, 2013). These options are recommended for as long as they are helpful to the patient but should be stopped if there is no improvement of symptoms within three menstrual cycles.
If the above treatments are unsuccessful, symptoms are severe, or the woman declines pharmacological intervention, a referral to secondary care services should be considered for further investigation or surgical intervention.
Women with fibroids that are 3 cm or more in diameter, regardless of location, should be considered for referral to secondary care and assessment for surgical interventions including uterine artery embolization, myomectomy (either abdominal or hysteroscopic) or hysterectomy. Hormonal or non-hormonal treatments can be offered if medical management is preferred by the patient or while awaiting secondary care input.
Suspected cancer
In cases where malignancy is suspected from the history and/or examination (for example, a suspicious pelvic or abdominal mass that is unlikely to be a fibroid or evidence of ascites) then urgent referral to secondary care is indicated. If the patient has a suspected pelvic mass with other features of cancer (for example unintentional weight loss) then referral under the two-week wait pathway for suspected cancer is necessary.
KEY POINTS
The most common cause of HMB is dysfunctional uterine bleeding, however, other pathology should be considered before making this diagnosis All women presenting with HMB should have a full blood count to check for anaemia Initial symptomatic treatment with non-steroidal anti-inflammatory drugs and tranexamic acid can be offered Hormonal treatments including the combined oral contraceptive pill or cyclical progestogens can be helpful in regulating the menstrual cycle and bleeding pattern With HMB failure of treatment or the presence of fibroids larger than 3 cm in diameter requires referral to consider the possible surgical interventions Patients with symptoms or signs suggestive of underlying malignancy should be referred under the 2-week wait pathway for suspected cancer