Gynaecological disorders

Learning Outcomes

After studying this chapter you should be able to:

Knowledge criteria

Describe the causes, significance and management of disorders of menstruation, including intermenstrual, postcoital and postmenopausal bleeding, menstrual irregularity, heavy menstrual bleeding, dysmenorrhoea and secondary amenorrhoea.
Describe the PALM COEIN concept of assessment and classification of causes of abnormal uterine bleeding.
Describe the problems of puberty, including precocious puberty and delayed puberty. Recognize that endometriosis is a condition that often starts in adolescence.
Describe problems of the perimenopause, including abnormal bleeding, vasomotor and other symptoms, osteoporosis and hormone-replacement therapy.
Describe benign conditions of the lower genital tract, including vulval pruritus, vaginal discharge and pelvic pain.
Describe the causes, significance and management of Bartholin’s abscess/cyst, abdominal pain of uncertain origin and acute unscheduled vaginal bleeding.

Clinical competencies

Assess and plan the initial investigation of a patient presenting with abnormal uterine bleeding, pelvic pain, vaginal discharge and amenorrhoea.
Interpret the results of the common investigations in benign gynaecological disorders.
Counsel a patient about indications, contraindications, principles and complications of the common surgical procedures in gynaecology.

Introduction

Benign gynaecological conditions affect women’s lives in ways that often remain hidden from society and from health systems. Many aspects of benign conditions such as heavy menstrual bleeding (HMB) and debilitating pelvic pain are often tolerated by women and sometimes dismissed as normal by health care professionals. Many of these conditions do have significant implications for women’s health and wellbeing, family and social relationships, the working lives of women and their ability to conceive. The recognition of benign gynaecological conditions requires education of women about what symptoms can be considered part of normal reproductive life and what symptoms may require investigation and treatment. Full appreciation of benign gynaecological conditions also requires that health care professionals develop a deeper understanding of managing reproductive health issues and of identifying potential pathological conditions.

Benign conditions of the upper genital tract

The uterus

The formation of the uterus results from the fusion of the two Müllerian ducts; this fusion gives rise to the upper two-thirds of the vagina, the cervix and the body of the uterus. Congenital anomalies arise from the failure of fusion, or the absence or partial development of one or both ducts. Thus, the anomalies may range from a minor indentation of the uterine fundus to a full separation of each uterine horn and cervix ( Fig. 16.1 ). These conditions are also commonly associated with vaginal septa.

Symptoms and signs

The majority of uterine anomalies are asymptomatic and are usually diagnosed in relation to complications of pregnancy. However, the presence of a vaginal septum may result in dyspareunia and postcoital bleeding (PCB).

The presence of a double uterus may also be established at routine vaginal examination, when a double cervix may be seen. The separation of the uterine horns is sometimes palpable on bimanual vaginal examination, but in most cases the uterus feels normal and there is a single cervix. When only one horn is present, the uterus may be palpable as lying obliquely in the pelvis. The abnormality of two uterine horns and one cervix is known as uterus bicornis unicollis ( Fig. 16.2 ).

Partial atresia of one horn of the uterus or a septate vagina resulting in obstruction to menstrual outflow from one horn of the uterus may result in a unilateral haematocolpos and haematometra with retrograde spill of menstrual fluid. In this case, the patient may present with symptoms of dysmenorrhoea and will have a palpable mass arising from the pelvis.

The complications of pregnancy in women with these uterine anomalies include:

Recurrent miscarriage: the role of congenital abnormalities in early pregnancy loss is unclear. For example, the incidence of uterine septa is the same in women with normal reproductive histories. However, there is an association with cervical incompetence, which may lead to mid-trimester miscarriage. This problem is usually associated with the subseptate uterus and is not common in unicornuate uterus or uterus bicornis bicollis.
Pre-mature labour.
Malpresentation of the fetus ( Fig. 16.3 ).
Retained placenta.

Diagnosis and management

As many cases are asymptomatic, the diagnosis may arise only as a coincidental finding and requires no treatment or intervention. Where the diagnosis is suggested by the history, further investigation should include hysterography and hysteroscopy.

Surgical treatment

The role of surgical reconstruction of a double uterus in women with infertility is difficult to assess, as there are no controlled studies demonstrating the benefits in pregnancy outcome. Consideration should be confined to women who have a history of recurrent miscarriage and where the abnormality is one of uterus bicornis unicollis or there is a uterine septum.

The operation of plastic reconstruction of the uterus with unification of two uterine horns or excision of the uterine septum is known as metroplasty ( Fig. 16.4 ). An incision is made across the fundus of the uterus between the uterotubal junctions, taking care not to involve the intramural portion of the tube. The cavities are then reunited by suturing the surfaces together in the anteroposterior plane. If there is a septum, it is simply divided by diathermy, and the cavity is then closed by suturing the transverse incision in the anteroposterior plane. Surgery of this type is associated with postoperative infertility in some cases and with a risk of uterine rupture in subsequent pregnancy.

Fig. 16.4, Metroplasty (right) for the reunification of a bicornate uterus or the division of a uterine septum (left).

An alternative surgical management is to divide the septum by diathermy through a hysteroscope inserted through the cervix.

Endometrial polyps

Endometrial polyps (EPs) are localized outgrowths from the surface of the endometrium. They appear at any age from the early reproductive years through to the postmenopausal period. EPs are usually benign lesions but have been implicated in subfertility, as removal of these lesions may improve rates of pregnancy and/or reduce pregnancy loss. There are differences in morphology, function and symptoms between different polyps, and attempts are now being made to develop a detailed subclassification system, as a component of the FIGO PALM-COEIN system (see later), which will allow clarification and improved understanding of the different types of polyps.

Symptoms

EPs are usually asymptomatic lesions, but they may contribute to abnormal uterine bleeding (AUB) manifesting as either intermenstrual bleeding (IMB), HMB or postmenopausal bleeding. Occasionally, protrusion of the polyp through the cervix may result in PCB. Attempts by the uterus to expel the polyp may cause colicky, dysmenorrhoeic pain.

Signs

EPs are usually detected during the investigation for AUB and infertility. If the polyp protrudes through the cervix, it may be difficult to distinguish from an endocervical polyp ( Fig. 16.5 ). EPs can be visualized on transvaginal ultrasound. They are most easily detected in the secretory phase of the menstrual cycle when the non-progestational type of glands in the polyp stand out in contrast to the normal surrounding secretory endometrium. If their presence is suspected either clinically or on transvaginal ultrasound, further clarification can be undertaken by performing a transvaginal sonohysterography ( Fig. 16.6 ) and/or office or inpatient hysteroscopy, with or without directed excisional biopsy.

Fig. 16.5, Endometrial polyp protruding through the cervical os.

Fig. 16.6, Sonohysterogram demonstrating the endometrial polyp (outlined by the markers) extending into the fluid-filled cavity.

Pathology

EPs are localized overgrowths of the surface endometrium. Grossly, they are smooth, cylindrical structures, tan to yellow in colour after removal. Microscopically, they consist of a fine fibrous tissue core covered by columnar epithelium glands. The endometrium encasing the polyps varies from normal endometrium to endometrium that is unresponsive to cyclical hormonal influences. Occasionally the endometrial surface develops simple or complex hyperplasia and, rarely, malignant change occurs.

Treatment

Small (1 cm or less) asymptomatic polyps may resolve spontaneously, and in these cases watchful waiting can be the treatment of choice. However, in women suffering from bleeding symptoms or infertility, surgical excision with removal of the polyp base is required. Traditionally, EPs were removed by dilatation and curettage (D&C) under general anaesthesia, but because blind curettage may miss EPs in 50–85% of cases, removal is best performed under hysteroscopic guidance or by performing curettage followed by reintroducing the hysteroscope to ensure that all the lesions have been removed. Using modern equipment, this can often be done without anaesthesia or with injection of local anaesthetic into the cervix.

Benign tumours of the myometrium

Uterine leiomyomas (‘fibroids’)

Uterine fibroids (or, more accurately, leiomyomas) are the most common benign tumour of the female genital tract and are clinically apparent in around 25% of women. They are smooth muscle tumours that vary enormously in size from microscopic growths to large masses that may weigh as much as 30–40kg. Fibroids may be single or multiple and may occur in the cervix or in the body of the uterus. There are three main types of fibroids according to their anatomical location. The most common of these lie within the myometrium (intramural fibroids). Those located on the serosal or outer surface that extend outwards and deform the normal contour of the uterus are subserosal fibroids. These may also be pedunculated and only connected by a small stalk to the serosal surface ( Fig. 16.7 ). Fibroids that develop near the inner surface of the endometrium distend the endometrium and extend into the endometrial cavity, either causing a distortion of the cavity or filling the cavity if they are pedunculated are submucous fibroids. Cervical fibroids are similar to other sites in the uterus. They are commonly pedunculated but may be sessile and grow to a size that will fill the vagina and distort the pelvic organs.

Fig. 16.7, Uterine fibroids produce symptoms that are determined by their site.

The size and site of the tumour have a considerable effect on the symptoms. Subserosal fibroids can put pressure on adjacent organs and cause bowel and bladder symptoms. Submucosal fibroids can lead to HMB and infertility. This HMB can be exceedingly heavy with submucous lesions. Cervical fibroids have symptoms similar to other cervical polyps, and in addition, during attempted extrusion, acute local pain can occur, as well as when there is degeneration of a fibroid or torsion of a pedunculated fibroid. Nowadays there is a strong recommendation to use the FIGO PALM-COEIN classification system (see later) to describe the location of individual fibroids and link these characteristics with symptoms.

The aetiology of fibroids is not well understood, although there is a significant genetic contribution. They are more common in women who are of Afro-Caribbean ethnicity, are overweight, are nulliparous, have polycystic ovary syndrome (PCOS), have diabetes, have hypertension and have a family history of fibroids. Pregnancy causes enlargement, and menopause is associated with some shrinkage.

Histopathology

Myomas consist of whorled masses of unstriated muscle cells, varying amounts of fibrous tissue and accompanying connective tissue. The main blood supply of a fibroid is localized within the pseudo-capsule around the outside of the main muscle mass, and it is these thin-walled venules which contribute to HMB.

Pathological changes

Fibroids can undergo a range of pathological changes, including hyaline degeneration, cystic degeneration, calcification, infection and abscess formation and necrobiosis. The latter, known as red degeneration , can occur in pregnancy or after treatment with embolization. Rarely, with an incidence of between 0.13% and 1%, sarcomatous change can occur.

Symptoms and signs

Some 50% of women with fibroids are asymptomatic, and the condition may only be discovered during routine pelvic examination: either at the time of cervical cytology or in the management of a pregnancy. Where symptoms do occur, they are often related to the site of the fibroids. The common presenting symptoms are as follows:

Abnormal uterine bleeding: Submucous and intramural fibroids commonly cause HMB. Submucous fibroids may cause irregular vaginal bleeding, particularly if associated with overlying endometritis or if the surface of the fibroid becomes necrotic or ulcerated. Although a rare occurrence, submucous fibroids may prolapse through the cervix, resulting in profuse bleeding.
Pain: Pelvic pain is a fairly common symptom that may occur in association with HMB. Acute pain is usually associated with torsion of the pedicle of a pedunculated fibroid, prolapse of a submucous fibroid through the cervix or the ‘red degeneration’ associated with pregnancy where haemorrhage occurs within the leiomyoma, causing an acute onset of pain.
Pressure symptoms: A large mass of fibroids may become apparent because of palpable enlargement of the abdomen or because of pressure on the bladder or rectum. Women may describe reduced bladder capacity with urinary frequency and nocturia. A posterior-wall fibroid exerting pressure on the rectosigmoid can cause constipation or tenesmus.
Complications of pregnancy: Recurrent miscarriage is more common in women with submucous fibroids. Fibroids tend to enlarge in pregnancy and are more likely to undergo red degeneration. A large fibroid in the pelvis may obstruct labour or make caesarean section more difficult. There is an increased chance of postpartum haemorrhage, and the presence of fibroids increases the risk of threatened pre-term labour and perinatal morbidity.
Infertility: Obvious fibroids are found in 3% of women with infertility, but ultrasound scanning demonstrates a substantially higher number. The proportion increases greatly with age (up to 50% by the age of menopause). Up to 30% of women with uterine fibroids will have difficulty conceiving. Submucous and intramural fibroids are more likely to impair infertility than subserous ones. The mechanism may be mediated by mechanical, hormonal and local molecular regulatory factor effects.

The diagnosis can usually be confirmed by transvaginal ultrasound scans of the pelvis. However, a solid ovarian tumour may occasionally be mistaken for a subserous fibroid, and a fibroid undergoing cystic degeneration may mimic an ovarian cyst.

Management

Most fibroids are asymptomatic and do not require treatment. In symptomatic women the choice of approach may be dictated by factors such as the patient’s desire for future fertility, the importance of uterine preservation, symptom severity and tumour characteristics.

Medical treatment

The oral contraceptive pill, progestogens and non-steroidal anti-inflammatory drugs (NSAIDs) have no effect on the size of fibroids but may be of value in controlling menstrual loss. A reduction of up to 45% in size can be achieved using gonadotrophin-releasing hormone (GnRH) analogues. However, the long-term use of these drugs is limited by their effect on bone density, and the fibroids return to their original size when treatment is stopped. The progesterone receptor modulator mifepristone has been found to be effective in reducing blood loss and fibroid size over a 6-month period, but there is still a lack of long-term data to support its use. Other selective progesterone receptor modulators, such as ulipristal, may also have a role, but their utility awaits the outcome of clinical trials, formal marketing and the clarification of potential side effects and rare hepatotoxicity.

Uterine artery embolization

Uterine artery embolization (UAE) involves the catheterization of the uterine arteries via the femoral artery and the injection of polyvinyl particles to reduce the blood supply to the uterus and to the fibroids. The fibroid shrinks because of ischaemia. The advantages of this technique are that it avoids the risks of major surgery and allows the preservation of fertility, although there is evidence that fertility can be impaired and that in those women who do conceive, there may be an increased chance of an adverse pregnancy outcome. Impairment of fertility may be associated with a small risk of ovarian damage from the embolization. The side effects of UAE include pain from uterine ischaemia and risk of sepsis in the degenerating fibroid. At present its use is recommended only in selected cases.

Surgical treatment

Where the preservation of reproductive function is not important, the surgical treatment of choice is hysterectomy. Indeed, fibroids account for about a third of all hysterectomies in the UK. In younger women or where the preservation of reproductive function is important, the removal of fibroids by surgical excision or myomectomy is indicated. This procedure involves incision of the pseudocapsule of the fibroid, enucleation of the bulk of the tumour and closure of the cavity by interrupted absorbable sutures. Myomectomy is associated with similar morbidity to hysterectomy. There may be haematoma formation in the cavity of the excised fibroid if care is not taken with surgical haemostasis. It is also impossible to be certain that all fibroids are removed without causing excessive uterine damage; there is always a possibility that residual seedling fibroids may regrow.

Recurrence of fibroids occurs within 5 years in up to 60% of cases after myomectomy.

Endoscopic resection of many submucous fibroids can be performed using the hysteroresectoscope, and resection of subserous and intramural myomas can often be accomplished using laparoscopic techniques. In skilled hands, these procedures tend to be associated with lower morbidity and recurrence rate compared to open procedures. If the fibroid is more than 3cm in diameter, pre- or perioperative measures such as the use of GnRH analogues can used to reduce the size of the fibroid prior to surgery.

Treatments in development

Clinical trials have shown that magnetic resonance imaging (MRI)–guided, focused ultrasound (that is only available in a few centres), which utilizes directed energy to heat and destroy the fibroid, is a potentially less invasive treatment option. The method requires treatment of one fibroid at a time and cannot be used for the management of pedunculated fibroids. Pregnancy is not recommended after the procedure, and long-term data are lacking.

Adenomyosis

Adenomyosis is a condition characterized by the invasion of endometrial glands and stroma into myometrium with surrounding smooth muscle hyperplasia. It probably affects around 5–10% of women and until recently the diagnosis was most commonly made only after histological assessment of tissue removed at hysterectomy. Diagnosis is now being made increasingly frequently with modern ultrasound equipment, increasing skills of the operators in recognizing the features or using MRI.

Symptoms and signs

This condition, unlike endometriosis, typically occurs in parous women and is usually diagnosed in the fourth decade. It is associated with HMB and dysmenorrhoea of increasing severity. On clinical examination, the uterus is symmetrically enlarged and tender. The condition regresses after menopause.

Pathology

The macroscopic appearances of the uterus are those of diffuse enlargement. Adenomyosis and myomas often co-exist, although the uterus is rarely enlarged to the size seen in the presence of myomas. The posterior wall of the uterus is usually thicker than the anterior wall. The cut surface of the uterus presents a characteristic, whorl-like, trabeculated appearance, but occasionally circumscribed nodules with dark haemorrhagic spots can be seen in the myometrium.

Both transvaginal ultrasound and MRI show high levels of accuracy for the non-invasive diagnosis of moderate to severe adenomyosis, but MRI is the most sensitive technique ( Fig. 16.8 ). The microscopic diagnosis is based on the presence of a poorly circumscribed area of endometrial glands and stroma invading the smooth muscle layers of the myometrium. The International Federation of Gynecology and Obstetrics (FIGO) and others are developing improved classifications of different degrees and characteristics for improved management.

Fig. 16.8, Sagittal view using magnetic resonance imaging of a uterus enlarged by adenomyosis.

Treatment

Adenomyosis can be managed conservatively with medical treatment, with UAE or surgically. Both medical and surgical approaches to treatment are controversial. Medical therapy, as for endometriosis, is effective in some cases, and symptomatic relief of dysmenorrhoea and heavy bleeding can best be obtained with insertion of a levonorgestrel-releasing intrauterine system. Prostaglandin synthetase inhibitors may sometimes help. UAE is often an effective alternative. Hysterectomy is the surgical procedure of choice, although less invasive techniques whereby the area of adenomyosis is specifically excised can sometimes be undertaken in specialized units with experienced endoscopic surgeons. Other new techniques that may gain credence include high-intensity focused ultrasound to thermally ablate the adenomyotic foci.

Lesions of the ovary

Ovarian enlargement is commonly asymptomatic, and the silent nature of malignant ovarian tumours is the major reason for the advanced stage of presentation of this cancer. Ovarian tumours may be cystic or solid, functional, benign or malignant. There are common factors in the presentation and complications of ovarian tumours, and it is often difficult to establish the nature of a tumour without direct pathological examination. The diagnosis and management of ovarian neoplasms are discussed in more detail in Chapter 20 .

Symptoms

Tumours of the ovary that are less than 10cm in diameter rarely produce symptoms. The common presenting symptoms include:

Abdominal enlargement: in the presence of malignant change, this may also be associated with ascites.
Symptoms from pressure on surrounding structures such as the bladder and rectum.
Symptoms relating to complications of the tumour ( Fig. 16.9 ); these include:
- Torsion: acute torsion of the ovarian pedicle results in necrosis of the tumour; there is acute pain and vomiting followed by remission of the pain when the tumour has become necrotic.
- Rupture: the contents of the cyst spill into the peritoneal cavity and result in generalized abdominal pain.
- Haemorrhage into the tumour is an unusual complication but may result in abdominal pain and shock if the blood loss is severe.
- Hormone-secreting tumours may present with disturbances in the menstrual cycle. In androgen-secreting tumours, the patient may present with signs of virilization. Although a greater proportion of the sex-cord stromal type of tumour (see later) are hormonally active, the commonest type of secreting tumour found in clinical practice is the epithelial type.

Signs

On examination, the abdomen may be visibly enlarged. Percussion over the swelling will demonstrate central dullness and resonance in the flanks. These signs may be obscured by gross ascites. Small tumours can be detected on pelvic examination and will be found by palpation in one or both fornices. However, as the tumour enlarges, it assumes a more central position and, in the case of dermoid cysts, is often anterior to the uterus. Most ovarian tumours are not tender to palpation; if they are painful, the presence of infection or torsion should be suspected. Benign ovarian tumours are palpable separately from the uterine body and are usually freely mobile.

Endometriosis

Endometriosis is a disease characterized by the presence of extrauterine endometrial-like tissue consisting of glands and stroma, often infiltrated by an inflammatory response. This is clearly an inflammatory condition. It affects between 5% and 15% of reproductive-age women. In women presenting with pelvic pain or infertility, or in adolescents with severe dysmenorrhoea or chronic pelvic pain, the prevalence is significantly higher. Women suffering from endometriosis very often present with a complex of debilitating symptoms, including pelvic pain, dyspareunia, dysuria, dyschezia and dysmenorrhoea. Although benign, endometriosis causes a substantial burden to the woman’s health, partly because of an average delay of 8–10 years between the onset of the symptoms and diagnosis. If undiagnosed, the condition can progress in severity and result in many years of untreated or ineffectively treated pelvic pain.

Pathophysiology

Aberrant endometriotic deposits occur in many different sites ( Fig. 16.10 ). Endometriosis commonly occurs in the ovaries ( Fig. 16.11 ), the uterosacral ligaments and the rectovaginal septum. It may also occur in the pelvic peritoneum covering the uterus, tubes, rectum, sigmoid colon and bladder. Remote ectopic deposits of endometriotic tissue may occasionally be found in the umbilicus, laparotomy scars ( Fig. 16.12 ), hernial scars, the appendix, vagina, vulva, cervix, lymph nodes and, on rare occasions, the pleural cavity.

Fig. 16.10, Common sites of endometriotic deposits.

Fig. 16.11, Endometriotic patches on the surface of the ovary.

Fig. 16.12, Endometriosis in a caesarean section scar. The dark tender mass at the left of the wound becomes tender and enlarged during menstruation.

Nowadays, endometriosis is usually recognized to present in one or more of three phenotypes, peritoneal surface lesions (superficial or deep), ovarian surface or deep cystic endometriomas, or as deep pelvic lesions, especially in the rectovaginal septum.

Ovarian endometriosis occurs in the form of small superficial deposits on the surface of the ovary or as larger cysts known as endometriomas ( Fig. 16.13 ), which may grow up to 10cm in size. These cysts have a thick, whitish capsular layer and contain altered blood, which has a chocolate-like appearance. For this reason, they are known as chocolate cysts. Endometriomas are often densely adherent both to the ovarian tissue and to other surrounding structures.

Fig. 16.13, Bilateral endometriomas removed at hysterectomy.

These cysts may leak or occasionally rupture, and in 8% of cases, patients with endometriosis present with symptoms of acute peritoneal irritation.

The microscopic features of the lesions may be of endometrium ( Fig. 16.14 ) that cannot be distinguished from the normal tissue lining the uterine cavity, but there is wide variation, and in many long-standing cases, desquamation and repeated menstrual bleeding may result in the loss of all characteristic features of endometrium. Underneath the lining of the cyst, there is often a broad zone containing phagocytic cells with haemosiderin. There is also a broad zone of hyalinized fibrous tissue. One of the characteristics of endometriotic lesions is the intense fibrotic reaction that surrounds them, and this may also contain muscle fibres. The intensity of this reaction often leads to great difficulty in dissection at the time of any operative procedure. The pathogenesis of endometriosis remains obscure, although a genetic component is frequently recognized. There is a great deal of ongoing research geared to improve the accuracy of diagnosis and assessment of this disease.

Fig. 16.14, High-powered magnification showing active epithelial lining of the cavity of an endometriotic deposit in scar tissue.

Sampson (1921) originally suggested that the condition was associated with retrograde spill of endometrial cells during menstruation and that some of these cells would implant under appropriate conditions in the peritoneal cavity and on the ovaries. This hypothesis does not account for endometriotic deposits outside the peritoneal cavity. An alternative theory suggests that endometrial lesions may arise from metaplastic changes in epithelium surfaces throughout the body.

Diagnosis

The initial assessment involves taking a detailed history of the duration and nature of pelvic pain with attention to the relationship to the menstrual cycle, the presence of bowel and bladder symptoms, the presence of dyspareunia and the impact of posture and movement on pain. Initial investigations may include urinalysis, screening for sexually transmitted infections and a transvaginal ultrasound scan. The ultrasound, if performed in expert hands, has a high degree of sensitivity and specificity for diagnosing ovarian endometriotic cysts and deep infiltrating bowel endometriosis but is of little use in identifying the commoner types of peritoneal disease. As there is no consistently reliable non-invasive test, diagnostic laparoscopy by an experienced gynaecological endoscopist remains the best way of confirming or excluding most types of endometriosis.

Management

Endometriosis is a chronic disease that often requires lifelong management. Medical treatment involves suppression of ovulation (and ovarian oestrogen secretion) and creating a steady hormone environment. Commonly used medication includes oral progestogens, progestogen subdermal implants and/or the levonorgestrel intrauterine system. Combined oral contraceptive pills are widely used, but it does not make logical sense to use an oestrogen-containing preparation in a woman with an oestrogen-sensitive disease. However, modern pills have a high progestogen balance and may work well. These medications are all generally well tolerated and are initially preferable to alternatives such as danazol, GnRH agonists and aromatase inhibitors. Medical therapy needs to be integrated with use of surgical therapies.

Surgical management of endometriosis usually involves complete excision of visible lesions. This is preferable to attempted diathermy ablation of the lesions and reduces pain and improves quality of life in 67–80% of operated patients. To prevent recurrences, preventive medical therapy after surgery should always be considered, unless pregnancy is immediately desired. Deep infiltrating pelvic endometriosis that involves the sigmoid colon or rectum requires a multidisciplinary approach with a colorectal surgeon. Laparoscopic resection of the rectovaginal endometritic nodule by a ‘shaving technique’ with reconstruction by expert laparoscopic gynaecologists is increasingly practised instead of bowel resection and anastomosis.

There is usually amelioration of endometriosis symptoms during pregnancy, and there may sometimes be long-term improvement in pain after pregnancy. However, many women with endometriosis will experience recurrence of symptoms as soon as pregnancy and breast-feeding have been completed.

Abnormal uterine bleeding

AUB is any bleeding disturbance that occurs during or between menstrual periods, or that is excessive, frequent or prolonged. This is the overarching term to describe any significant disturbance of menstruation or the menstrual cycle. FIGO has recently designed a classification system and precise terminologies for underlying causes of AUB – The FIGO AUB Systems. These recommend that causes can be grouped under categories using the acronym PALM COEIN ( Table 16.1 ). The most common menstrual abnormalities are intermenstrual (often associated with PCB) and heavy or irregular menstrual bleeding.

Table 16.1

FIGO recommendations on classification of causes underlying symptoms of abnormal uterine bleeding

Reproduced from Munro MG, Critchley HO, Fraser IS, et al. (2011) The FIGO classification system (PALM-COEIN) of causes of abnormal uterine bleeding in non-gravid women of reproductive age. Int J Gynecol Obstet 113:3–13.

	Examples
Structural lesions (‘PALM’)
	P olyps (endometrial, endocervical) A denomyosis L eiomyoma (uterine fibroids) M alignancy and hyperplasia
Non-structural causes (‘COEIN’)
C oagulopathies	Von Willebrand disease Platelet dysfunctions Rare clotting factor deficiencies Thrombocytopenia (low platelets)
O vulatory dysfunction	Anovulatory or disturbed ovulatory cycles (disturbance of oestrogen positive feedback or other ovarian mechanisms) Polycystic ovary syndrome Thyroid disease
E ndometrial primary causes	Errors of endometrial molecular pathways affecting local vascular function
I atrogenic	A category including all causes from therapeutic or human interference. This includes AUB side effects of medicinal therapies, drugs or use of devices, e.g. IUCDs.
N ot yet classified	Rare or novel causes which do not immediately or obviously fit into any of the other categories at this time. These may change with new research. Two examples of such conditions are uterine arteriovenous malformations, which can cause very heavy menstrual bleeding, or the novel diagnosis of ‘isthmocoele’ (the lower segment ‘niche’ frequently found following caesarean section).

AUB , Abnormal uterine bleeding; FIGO, The International Federation of Gynecology and Obstetrics; IUCD , intrauterine contraceptive device.

The FIGO classification is a very useful and flexible system, which can easily be used both for initial training in understanding underlying causes and for application to more complex specialized or research classifications.

Intermenstrual bleeding

IMB generally occurs between clearly defined, cyclical, regular menses.

The bleeding may occur at the same time in each cycle or may be random. This symptom is typically associated with surface lesions of the genital tract, and these women may also experience PCB. Undiagnosed pregnancy-related bleeding, including ectopic pregnancy and hydatidiform molar disease, may result in irregular bleeding mimicking IMB. In 1–2% of women, IMB may be physiological, with spotting occurring around the time of ovulation.

IMB is commonly associated with the use of hormonal contraception (when it is known as unscheduled or breakthrough bleeding ), particularly the combined oral contraceptive pill, intrauterine systems and use of progestogen-only methods, including the pills and implants.

In women with new onset of IMB, sexually transmitted infection of the cervix or vagina should be considered as a possible cause, especially Chlamydia . Less common causes are vaginitis (non-sexually transmitted), cervical ectropion, endometrial or cervical polyps, endometritis, adenomyosis, submucous myomas and sometimes cervical or endometrial cancers.

After a careful examination of the lower genital tract, the investigation of IMB should always exclude pregnancy and infection as a cause. Ensure that cervical screening is up to date, and if all these are negative, pelvic ultrasound or hysteroscopy may reveal an intrauterine cause.

Postcoital bleeding

PCB is non-menstrual bleeding that occurs during or after sexual intercourse. The symptom is reported by around 6% of women per year. Causes of PCB include surface lesions of the genital tract, typically infection; cervical or EPs; cervical, endometrial or (rarely) vaginal cancer; and trauma. PCB occurs in 1–39% of women with cervical cancer, and if there is a history of recurrent PCB, with or without IMB, colposcopy examination of the cervix is recommended even if the Pap smear is normal.

Postmenopausal bleeding

Vaginal bleeding that occurs more than 1 year after the last natural menstrual period is known as postmenopausal bleeding . Although it is not the commonest cause of this symptom, the possibility of carcinoma of the body of the uterus should be considered, and an assessment of the endometrium is advised for all women, whether with diagnostic hysteroscopy and endometrial biopsy or with a high-quality transvaginal ultrasound measurement of the endometrial thickness and appearance. When the endometrium is measured at less than 3mm, significant endometrial pathology is very unlikely.

Other causes of postmenopausal bleeding include other benign and malignant tumours of the genital tract, stimulation of the endometrium by exogenous (or endogenous) oestrogen (e.g. hormone replacement therapy [HRT] and oestrogens from ovarian tumours), infection and postmenopausal atrophic vaginitis.

Heavy menstrual bleeding

HMB, defined in research studies as more than 80mL per month of loss, affects approximately 10% of women. The recommended ‘clinical’ definition of HMB (for use in the clinic) is ‘excessive menstrual loss leading to interference with the physical, emotional, social and material quality of life of a woman, and which occurs alone or in combination with other symptoms’. HMB should be recognized as having a major impact on a woman’s quality of life. Although HMB is usually caused by benign conditions, it commonly leads to iron deficiency or iron-deficiency anaemia, which can be part of the serious impact on a woman’s social, family and working life (through the burden of managing the practical difficulties of excessive blood loss and having to curb normal activities). HMB can commonly arise from an imbalance in the clotting and other regulatory molecular factors at a local endometrial level, without the presence of obvious structural pathology. However, it also can be associated with a number of benign gynaecological conditions, including leiomyomata, EPs, adenomyosis, endometrial hyperplasia and sometimes endometrial cancer. The causes of HMB include most of the overall causes of AUB.

Causes

Structural lesions (PALM component of the FIGO classification of causes)

Leiomyomata (discussed later) are the commonest structural lesions to cause heavy regular bleeding, although most women with fibroids do not experience abnormal loss. Endometrial carcinoma is rare under the age of 40 years and is more likely initially to cause irregular bleeding. Adenomyosis is usually associated with a uniformly enlarged tender uterus, HMB and dysmenorrhoea. EPs are a common cause of HMB but usually also cause IMB. Endometrial hyperplasia is a common structural lesion causing HMB and may be associated with irregular, anovulatory cycles. It may be a premalignant condition. It may overlap with the disturbed ovulation discussed in the next section.

Non-structural conditions (COEIN component of the FIGO classification)

Disturbed ovulation or anovulation can result in very irregular, especially infrequent, cycles with prolonged, heavy and irregular bleeding of such severity that it may occasionally be life threatening. In this situation, unopposed oestrogen often leads to the endometrium becoming greatly thickened and hyperplastic. This unstable endometrium eventually breaks down in a patchy and erratic fashion. Most ovulatory disorders occur in the menopause transition and in adolescence or can be traced to endocrinopathies, e.g. PCOS and hypothyroidism.

When there is regular heavy bleeding with no underlying structural lesion, HMB is usually the result of a primary endometrial disorder where the mechanisms regulating local endometrial ‘haemostasis’ are disturbed. There may be excessive local production of fibrinolytic factors (especially tissue plasminogen activator), deficiencies in local production of vasoconstrictors and increased local production of substances that promote vasodilation. The commonest iatrogenic cause of heavy bleeding is the presence of a copper-bearing intrauterine contraceptive device (IUCD).

History and examination

An accurate history is essential to establish the pattern of bleeding and the duration of symptoms. Clinical estimation of the degree of blood loss is very subjective, although the presence of clots, the need to change sanitary protection at night and ‘flooding’ (the soiling of bedclothes or underwear during menstruation) are more likely to indicate significant bleeding. A recent change in the pattern of menstruation and associated pain are more likely to be associated with the development of structural pelvic pathology. Pain is typically associated with adenomyosis and chronic pelvic inflammatory disease (PID). Women are more likely to complain of HMB if the bleeding is accompanied by pain. Endometriosis sometimes causes HMB (as well as pain). Structural surface lesions of the uterus and cervix more typically cause IMB and PCB. Endometrial malignancy is rare under the age of 40 years, but women with a history of diabetes, hypertension, PCOS and obesity are at increased risk of endometrial hyperplasia and carcinoma.

Women with heavy periods should have a general examination for signs of anaemia and thyroid disease and a pelvic examination, including cervical screening test, if indicated. The finding of a pelvic mass on pelvic examination is most likely to indicate the presence of uterine leiomyomata (fibroids) but may indicate a uterine malignancy, adenomyosis or ovarian tumour.

Investigations

A full blood count with platelets (and sometimes serum ferritin and serum transferrin receptor saturation to assess iron status) is the only investigation needed before starting treatment, provided that clinical examination is normal. It should be remembered that iron deficiency is the commonest deficiency disease worldwide. Patients should be referred for further investigation if:

There is a history of repeated or persistent irregular or IMB or of risk factors for endometrial carcinoma.
The cervical screening test is abnormal.
Pelvic examination is abnormal.
There is significant pelvic pain unresponsive to simple analgesia.
They do not respond to first-line treatment after 6 months.

Additional investigation is mainly to confirm or exclude the presence of pelvic pathology and in particular of endometrial malignancy. The main methods of investigation are ultrasound, endometrial biopsy, hysteroscopy and transvaginal ultrasound (with or without saline sonohysterography). Investigations for systemic causes of abnormal menstruation, such as a partial coagulation screen for the disorders of haemostasis – a coagulopathy – (of which mild von Willebrand disease is the commonest of these causes associated with HMB), are only indicated if a screening history for coagulopathies is suggestive or in young women. Thyroid disease is a rare cause of HMB, and investigation is only indicated if there are other features on examination or a previous history. Endometrial biopsy can be performed as an outpatient procedure either alone or in conjunction with hysteroscopy.

Hysteroscopy allows visualization of the uterine cavity using a 3-mm endoscope introduced through the cervix. It can be performed under general anaesthetic or as an outpatient investigation using local anaesthesia. Hysteroscopy with endometrial biopsy has largely replaced the traditional and unreliable blind D&C. Transvaginal ultrasound is of value in distinguishing the structural lesions of the genital tract. In premenopausal women, ultrasound-measured endometrial thickness will vary at different times of the menstrual cycle, but it is usually possible to visualize structural lesions such as polyps in the endometrial cavity.

Management

Medical treatment

In the absence of malignancy, the treatment chosen will depend on whether contraception is required, whether irregularity of the cycle is a problem and the presence of contraindications to certain treatments. Where a copper IUD is in place, mefenamic or tranexamic acid can be used, or the device may be replaced by a levonorgestrel intrauterine system (Mirena).

Non-hormonal treatments

NSAIDs, such as mefenamic acid or ibuprofen, inhibit prostaglandin synthetase enzymes. They reduce blood loss by around 30%, and their analgesic properties may be an advantage if there is associated dysmenorrhoea. The principal side effect is mild gastrointestinal irritation. Tranexamic acid is an anti-fibrinolytic agent that reduces blood loss by about 50%. It is safe and available over the counter without prescription in many countries. It does not cause venous thrombosis, but it is wise to avoid its use in patients with a previous history of thromboembolic disease. Both groups of drugs have the advantage of only needing to be taken during menstruation.

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