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Heavy Menstrual Bleeding, Dysmenorrhoea and Pre-Menstrual Syndrome
Heavy Menstrual Bleeding
Heavy menstrual bleeding (HMB) is defined, for clinical purposes, as bleeding that has an adverse impact on the quality of life of a woman. It may occur alone or with other symptoms. Menstrual blood loss can be measured, but this is usually performed only for research purposes. HMB was often called ‘menorrhagia’ in the past, but this term is better avoided as it means different things to different people (e.g., the definition in the United States is different from that in the United Kingdom). HMB is the most common cause of iron-deficiency anaemia in women in high-resource settings.
Menstrual problems are becoming more prevalent, as women experience more periods in their lifetime now than their predecessors did 100 years ago (approximately 400 vs. 40 periods). This is because women have fewer children and breastfeed less (leading to lactational amenorrhoea). Only 50% of women who complain of excessive heavy bleeding, however, actually suffer from blood loss that falls outside the normal range for women not complaining of any menstrual abnormality (>80 mL/month).
The medical and surgical treatments of HMB represent an appreciable burden to health service resources. HMB is a common indication for hysterectomy, although the number of these procedures performed has fallen in the last 3 decades with the introduction of effective alternative treatments. Although a commonly performed operation, hysterectomy is a major surgical procedure. Its use needs to be balanced against the potential associated mortality and morbidity. Satisfaction rates with hysterectomy are very high, however.
Causes of HMB
A classification system for the causes of abnormal uterine bleeding (AUB) has been described by the International Federation of Gynecology and Obstetrics (FIGO), which is called the PALM-COEIN System ( Table 7.1 ). Clinicians should remember that, using this classification, a woman may have more than one entity that could contribute to AUB and that structural entities such as polyps are often asymptomatic.
Table 7.1
PALM-COEIN Classification System for Abnormal Uterine Bleeding Proposed by the International Federation of Gynecology and Obstetrics (FIGO)
| P olyp | C oagulopathy |
| A denomyosis | O vulatory dysfunction |
| L eiomyoma | E ndometrial |
| M alignancy and hyperplasia | I atrogenic |
| N ot otherwise classified |
Uterine Pathology
HMB is associated with both benign pathology (e.g., uterine fibroids, endometrial polyps, adenomyosis, pelvic infection) and, extremely rarely, malignant pathology (e.g., endometrial cancer). Over half of women with an excessively heavy blood loss of >200 mL/period will have fibroids. With the advent of high-quality ultrasound that is readily available in outpatient clinics, pathology is identified in a greater proportion of women.
Endometrial polyps are common benign localized overgrowths of the endometrium. They consist of a fibrous tissue core covered by columnar epithelium, and it is believed that they arise as a result of disordered cycles of endometrial apoptosis and regrowth. Although it is uncertain that they cause HMB, it is likely that intrauterine endometrial polyps do increase the likelihood of irregular bleeding ( Fig. 7.1 ). However, it is unlikely that small endocervical polyps detected at the time of a routine cervical smear have the same effect. Malignant transformation of such polyps is very rare.
Uterine fibroids (leiomyomas) are benign tumours of the myometrium that are present in approximately 20% of women of reproductive age. They are well-circumscribed whorls of smooth muscle cells and collagen, and may be single or multiple ( Fig. 7.2 ). Size varies from microscopic growths to tumours that weigh as much as 40 kg, and they are more common in women of Afro-Caribbean origin. Submucous fibroids project into the uterine cavity, intramural fibroids are contained within the wall of the uterus and subserosal fibroids project from the surface of the uterus. Cervical fibroids arise from the cervix.
Many are asymptomatic, but when symptoms do occur, they are often related to the site and/or size of the fibroid. Presenting symptoms include menstrual dysfunction, infertility, miscarriage, dyspareunia and pelvic discomfort. The mechanism by which fibroids adversely affect reproduction is unclear but may be related in part to distortion of the uterine cavity, affecting implantation. Fibroids that do not distort the cavity are unlikely to have an adverse impact. Women with fibroids may also present because of pressure effects on surrounding organs, such as increased frequency of micturition as a result of pressure on the bladder or even hydronephrosis due to ureteric compression. Sex steroids mediate the growth of fibroids; therefore, they grow during pregnancy and shrink after the menopause. Occasionally, necrosis of the fibroid (‘red degeneration’) leads to acute abdominal pain during pregnancy. The incidence of malignant change (leiomyosarcoma) in fibroids is considered to be extremely low (0.1%).
HMB in the Absence of Pathology
The term ‘abnormal uterine bleeding’ is commonly used in clinical practice and includes the symptoms of HMB, irregular menstruation and intermenstrual bleeding. HMB in the absence of recognisable pelvic pathology or systemic disease is a diagnosis of exclusion and is probably the most common ‘diagnosis’ reached after investigating women with HMB. Some HMB with no pathology may be ‘anovulatory’ or ‘ovulatory’, although this is not an important distinction clinically, as treatment is the same in both cases. The underlying cause is likely to reside at the level of the endometrium, although the precise nature of the vascular and endocrine abnormality remains elusive.
Medical Disorders and Clotting Defects
Very rarely, HMB is associated with medical problems, such as thyroid disease (both hypo- and hyperthyroidism), hepatic disease and renal disease (although the majority of women with end-stage renal failure are amenorrhoeic). Other symptoms of the underlying medical disorder are likely to be present.
Certain coagulation abnormalities (e.g., von Willebrand disease) and platelet defects (e.g., thrombocytopenia) are associated with an increased incidence of HMB.
Assessment of HMB
History
The number of sanitary towels used, duration of bleeding and passage of clots seem to have little correlation with the actual volume of blood lost. However, complaints of ‘flooding’ (leakage of heavy blood loss onto clothing) and having to use ‘double sanitary protection’ (pad and tampon) to prevent leakage of blood onto clothes are indicative of HMB, and are likely to have a negative impact upon the woman’s quality of life. Therefore, it is important to ask about the degree of inconvenience experienced, such as time lost from work, or becoming housebound during menses owing to fear of social embarrassment from an episode of flooding in public.
A history of irregular bleeding, dyspareunia, pelvic pain or intermenstrual or post-coital bleeding may raise the suspicion of underlying pathology, and often requires additional investigation. These can be termed ‘red flag’ symptoms.
The woman should also be questioned about symptoms suggestive of anaemia, such as fatigue and light-headedness. A history suggestive of systemic disease such as a thyroid disorder or a clotting abnormality would signal that further investigation for such causes is required. The woman should also be questioned about risk factors for endometrial cancer, such as unopposed estrogen use, tamoxifen use, polycystic ovary syndrome or family history of endometrial or colon cancer. It is also important to establish whether she has a history of thromboembolism, as many medical treatments for HMB are hormonal; thus, their use may be relatively or absolutely contraindicated.
Examination
The woman should be examined for signs of anaemia. Abdominal, bimanual and speculum examinations should be considered; however, if the history suggests HMB without structural or histological abnormality, pharmaceutical treatment can be started without carrying out a physical examination or other investigations at initial consultation in primary care. An enlarged, ‘bulky’ uterus suggests uterine fibroids; tenderness suggests endometriosis, pelvic inflammatory disease, or adenomyosis.
Investigations
Laboratory Tests
A full blood count should be carried out in all women with HMB to diagnose/exclude anaemia. Thyroid function tests and coagulation tests should be performed only if there are features in the history. No other endocrine tests are routinely indicated.
Ultrasound
Ultrasound is the first-line diagnostic tool for identifying structural abnormalities, and a pelvic ultrasound scan should be performed if either history or examination suggests structural uterine pathology. Imaging should also be undertaken in women in whom pharmaceutical treatment has failed or if it is not possible to assess the uterus clinically because of obesity. The site and size of abnormalities such as fibroids can be determined, together with assessment of the ovaries ( Fig. 7.3 ).
Endometrial Assessment
This should be performed in all women aged >45 years as well as in younger women with persistent HMB in spite of medical treatment, red flag symptoms such as irregular bleeding, or risk factors for endometrial cancer. This can take the form of an endometrial biopsy or a hysteroscopy, both of which can be carried out either as an outpatient or inpatient procedure ( Fig. 7.4 and p. 151).
Cervical Cytology
This should be performed if it is due, or if the cervix looks suspicious.
Care of women with HMB
Polyps
Benign intrauterine polyps will usually be removed by polypectomy using hysteroscopic techniques. If malignant pathology is detected, then this should be treated as appropriate.
Fibroids
Fibroids may be treated medically or surgically.
Medical
Pharmaceutical treatment should be considered when fibroids measure less than 3 cm and cause no distortion of the uterine cavity. If contraceptive and/or hormonal treatments are acceptable, the following treatments can be offered:
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Levonorgestrel-releasing intrauterine system (LNG-IUS);
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Tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs), or combined oral contraceptive (COC);
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Norethisterone (15 mg) daily from days 5 to 26 of the menstrual cycle, or;
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Injected long-acting progestogens.
Unfortunately, the symptoms caused by fibroids respond poorly to medical treatments used when there is no pathology. Therefore, in women with fibroids measuring 3 cm or more or with fibroids causing distortion of the uterine cavity, ulipristal acetate should be offered. The drug is started when menstruation has occurred, and should be taken as one 5-mg tablet daily for a treatment course of up to 3 months, up to a maximum of four intermittent courses.
Ulipristal acetate is a selective progesterone receptor modulator, a class of drugs that may have a role in the treatment of fibroid-related HMB. Treatment with this class of drugs leads to a rapid decrease in bleeding in 80% of women without leading to hypo-estrogenism or inhibiting ovarian cyclicity. Concerns have been raised regarding ulipristal acetate in the care of women with fibroids and HMB since they can cause unique changes in the endometrium that are difficult to interpret. Furthermore, cases of severe liver injury requiring transplant associated with its use have been reported. Its use in the United Kingdom is currently restricted to treating uterine fibroids in premenopausal women for whom surgical procedures are not appropriate or have not worked.
Since growth of fibroids is hormone dependent, gonadotrophin-releasing hormone (GnRH) analogues (which result in hypo-estrogenism) may be used to shrink fibroids. GnRH analogues are derivatives of natural GnRH, with modifications that confer greater potency and longer activity. Depot injection of GnRH analogues, however, leads to pituitary downregulation with hypo-estrogenism. Fibroids shrink by approximately 50% over 3 months of treatment, but regrowth occurs upon cessation of treatment. During treatment, hypo-estrogenism can result in symptoms such as hot flushes and may also cause loss of bone density. In view of concerns about osteoporosis, GnRH analogues are limited to short-term use (<6 months). ‘Add-back’ hormone replacement therapy (HRT) is required to minimize the risk of osteoporosis and other side effects.
Surgical
Hysteroscopic resection of small submucous fibroids is often possible, which can lead to improved fertility and relief of menstrual problems. Endometrial ablation in the presence of small fibroids is possible (see later discussion).
Myomectomy involves incision of the fibroid pseudocapsule, enucleation of the bulk of the tumour and closure of the resulting defect. The operation is usually performed as an open abdominal procedure, although laparoscopic techniques are sometimes employed. Myomectomy is associated with a similar degree of morbidity to hysterectomy. There is a risk of haemorrhage (due to the vascularity of fibroids) and a small possibility that an emergency hysterectomy may need to be performed during surgery to arrest uncontrollable bleeding. Furthermore, there is a risk of adhesion formation, which could compromise fertility (as a result of tubal obstruction), and the possibility that residual seedling fibroids may grow, leading to the recurrence of fibroids. GnRH analogues are often used preoperatively to shrink fibroids, with associated decreased intraoperative blood loss. Women who have undergone myomectomy are often recommended to birth by caesarean in any subsequent pregnancy because of concerns regarding uterine rupture during labour.
Uterine artery embolization (UAE), which is performed by interventional radiologists, is an effective and safe technique. It involves interruption of the blood supply to the fibroid by blocking the uterine arteries with coils or foam delivered through a catheter placed in the femoral artery. The healthy myometrium revascularizes immediately, owing to the development of collateral circulation from vaginal and ovarian vessels. Fibroids, however, do not appear to revascularize, and shrink by about 50%, a reduction which appears to be sustained. Pain following occlusion of the vessels is often severe and usually requires opiate analgesia. Potential complications include infection, fibroid expulsion and adverse effects due to exposure of the ovaries to ionizing radiation. The incidence of these is low and immediate morbidity is less than that following hysterectomy, although pain and fever from post-embolization syndrome is not uncommon and deaths (though rare) have occurred.
UAE, myomectomy, or hysterectomy should be considered in cases of HMB in which large fibroids (greater than 3 cm in diameter) are present and bleeding is having a severe impact on a woman’s quality of life. Women should be informed that UAE or myomectomy may potentially allow them to retain their fertility. Studies indicate that fertility outcomes are better in younger women, women with fewer fibroids, and when fibroids that have been distorting the endometrial cavity have been removed. There is evidence that a successful pregnancy is possible following UAE and even after failed myomectomy, although rates of miscarriage may be higher and rates of caesarean section and postpartum haemorrhage may be higher. There are also reports of transient or permanent ovarian failure after UAE in up to 5% of cases. This occurs most often in women over the age of 45 years, but there have been case reports of ovarian dysfunction in younger women.
If childbearing is complete and the woman is experiencing severe symptoms as a result of her fibroids, then hysterectomy may be considered (see later discussion).
Other Causes
In the majority of cases of HMB, no specific cause is found. Sometimes, a woman is seeking reassurance that there is no pathology and does not necessarily wish treatment. Most women, however, request treatment. The following treatments may be considered.
Medical
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