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.

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 an 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 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 the unicornuate uterus or in uterus bicornis bicollis

• premature labour

• malpresentation (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.

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 of the surface 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.

Signs

EPs are usually detected during the investigation for abnormal uterine bleeding 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 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.

Benign tumours of the myometrium

Uterine fibroids (myomas) 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 30–40 kg. Fibroids may be single or multiple and may occur in the cervix or in the body of the uterus. There are three types of fibroids according to their anatomical location. The most common are within the myometrium (intramural fibroids). Those located on the serosal 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 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.

The size and site of the tumour has 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. Cervical fibroids have symptoms similar to other cervical polyps and, in addition, during attempted extrusion pain can occur as well as when there is degeneration of a fibroid or torsion of a pedunculated myoma.

The aetiology of fibroids is not known. They are more common in women who are Afro-Caribbean ethnicity, overweight, nulliparous, have polycystic ovary syndrome (PCOS), diabetes, hypertension and those with a family history of fibroids. Pregnancy causes enlargement and the menopause is associated with involution.

Adenomyosis

Adenomyosis is a condition characterized by the invasion of endometrial glands and stroma into myometrium with surrounding smooth muscle hyperplasia. It affects around 1% of women and until recently the diagnosis was most commonly made only after histological assessment of tissue removed at hysterectomy.

Pathology

The macroscopic appearances of the uterus are those of diffuse enlargement. Adenomyosis and myomas often coexist, 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.

Symptoms

Tumours of the ovary that are less than 10 cm 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 below) 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.

Pathophysiology

Aberrant endometrial 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 endometrium may 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.

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 10 cm 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.

These cysts are likely to 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. 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 life-long 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, gonadotrophin-releasing hormone 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 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.

Leiomyomata (discussed below) 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. Endometrial polyps 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.

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. 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 smear, 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 to assess iron status) is the only investigation needed before starting treatment, provided that clinical examination is normal. Patients should be referred for further investigation if:

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 hemostasis – 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 anesthetic or as an outpatient investigation using local anesthesia. 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.

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®).

Hormonal treatments

Use of the combined oral contraceptive pill or the levonorgestrel intrauterine system is associated with around 30% and 90% reduction in average monthly blood loss, respectively (Fig. 16.15). The levonorgestrel-releasing intrauterine system is widely recommended as the first choice for medical therapy of HMB in those women who do not have contraindications to its use. Synthetic oral progestogens, such as norethisterone or medroxyprogesterone acetate, can be given for 21 days out of 28 over prolonged periods to effectively control irregular, heavy bleeding, but do tend to be associated with a higher incidence of nuisance-value side effects. They can also be used in higher doses in an acute situation to control severe heavy menstrual bleeding (oral norethisterone 5 mg, or medroxyprogesterone acetate 10 mg, three times daily for 21 days). Danazol is a synthetic mild impeded androgen derivative that acts on the hypothalamic–pituitary axis and endometrium, and is uncommonly used nowadays. Given at high doses it will normally cause amenorrhoea but is associated with significant side effects in 10% of patients. The efficacy of various medical therapies in reducing HMB is documented in Figure 16.15.

Surgical treatment

Endometrial resection or ablation

The endometrium can be removed or destroyed using an operating hysteroscope or with a number of modern third-generation intrauterine heating or cooling devices that ablate the endometrium. The first and second generation techniques involve using laser or diathermy resection with a wire loop or coagulation with a rollerball or a combination of the two (Fig. 16.16). The endometrium can be thinned prior to treatment with danazol or GnRH analogues for 4–8 weeks before surgery, allowing more effective ablation. The uterine cavity is distended with an irrigation fluid such as glycine or normal saline. There is a rare risk of intraoperative uterine perforation and, possibly, damage to other organs requiring laparotomy and repair. The other potential complication is fluid overload from excessive absorption of the irrigation fluid. Hysteroscopic procedures have now been largely replaced by newer semi-automatic techniques that do not require the same hysteroscopic skills. Balloon ablation involves inserting a fluid filled balloon into the endometrial cavity, which is then very precisely heated so that it destroys the entire endometrium. There are now a range of other devices, which are all based on the principle of excessively heating or cooling the endometrium using different energy sources, so that it is very precisely destroyed without damaging adjacent structures. Around 30–70% of patients will become amenorrhoeic, with a further 20–30% achieving major reduction in HMB. A minority of patients will eventually need further surgery and hysterectomy.

Hysterectomy

This remains the definitive treatment, and is more likely to be appropriate for those women with pelvic pathology such as adenomyosis and fibroids, than medical treatment or endoscopic surgery. Hysterectomy is associated with a mortality of around 1 in 2000, although the mortality for women with benign gynaecological diseases should be less. Significant complications occur in 25–40% of patients, and tend to be more common in patients undergoing abdominal hysterectomy. Intraoperative bleeding is the major concern, and intraoperative precautions should always be taken to minimize postoperative venous thromboembolism. The commonest postoperative complications are infections (urinary, respiratory or at the operation sites), but any postoperative complication may occasionally occur in individual cases. Hysterectomy can be undertaken abdominally, vaginally or laparoscopically.

Abdominal hysterectomy is carried out through a transverse lower abdominal or midline incision. The round ligaments, Fallopian tubes and ovarian vessels are cut and ligated on each side, either medial or distal to the ovaries, depending on whether these are to be conserved (see below). The uterovesical peritoneum is opened and the bladder is reflected off the lower part of the uterus and cervix so as to displace the ureters away from the uterine vessels, which are then cut and ligated. Finally, the transverse cervical ligaments are cut and the vagina opened around the cervix, allowing removal of the uterus. If there has been no history of cervical disease the cervix can be conserved by removing the uterine corpus just below the internal os after the uterine vessels have been ligated (subtotal hysterectomy). This may be indicated if other pelvic disease makes dissection of the cervix difficult, in order to reduce the risk of ureteric damage, or because of patient preference. Radical abdominal hysterectomy involves removing the uterus, cervix, the upper vagina and supporting tissues and is performed when there is known uterine or cervical cancer.

In vaginal hysterectomy (with approach through the vaginal introitus) the vaginal skin is opened around the cervix and the bladder and reflected up into the pelvis. The peritoneum over the uterovesical and rectovaginal space is opened, and the cervical ligaments are clamped, cut and ligated. The uterine and ovarian vessels are clamped, ligated, the uterus is removed and the peritoneum and vaginal skin are closed. Removal of the ovaries is possible but is less commonly carried out by this route. The absence of an abdominal wound substantially reduces postoperative morbidity, making this the method of choice for most cases of hysterectomy. It is contraindicated where malignancy is suspected. Other relative contraindications include a uterine size of over 14 weeks, the presence of endometriosis, and in women who require concurrent removal of the diseased ovaries.

Laparoscopic hysterectomy involves dividing and occluding or fixing the attachments of the uterus under direct visualization through the laparoscope, and then removing the uterus either vaginally or through the abdominal ports after reducing it to strips (morcellation). Laparoscopic hysterectomy by a skilled endoscopist is the best approach to hysterectomy when a vaginal hysterectomy cannot be performed because of the presence of diseases such as endometriosis, adhesions or when the ovaries need be removed.

Conservation of the ovaries, if normal, is usually recommended for women under the age of 50 years undergoing hysterectomy for HMB, to avoid the onset of a surgically induced early menopause. For women near the menopause this advantage has to be offset against the small possible risk of later ovarian malignancy, and the option of oophorectomy should be discussed. Family history of ovarian cancer is usually considered in this decision.

Physiological causes, including pregnancy and lactation account for most cases of amenorrhoea in the reproductive years. Breastfeeding causes a rise in prolactin which inhibits GnRH release and prevents normal ovarian stimulation. The duration of amenorrhoea depends on the extent, frequency and length of time of breastfeeding.

Pathological

Pathological causes can be divided into disorders of the hypothalamus, anterior pituitary, ovary and genital tract (Fig. 16.17).

Ovarian disorders

Ovarian failure

Premature ovarian failure (POF) is usually defined as the cessation of ovarian function before the age of 40 and is characterized by amenorrhoea and raised gonadotrophin levels. It affects 1% of women and is most often non-reversible. Genetic factors play an important role and 20–30% of women with POF have an affected relative. There are a range of genetic syndromes that lead to POF, of which Turner’s syndrome is the most obvious. Autoimmune oophoritis is found in around 4% of women who present with spontaneous POF. This condition is most often associated with autoantibodies to multiple endocrine and other organs, but has also been seen in women with systemic lupus erythematosus and myasthenia gravis.

Surgical removal of the ovaries or destruction by radiation or infection inevitably results in secondary amenorrhoea. All these conditions are characterized by high levels of gonadotrophins and hypo-oestrogenism (hypergonadotropic hypogonadism). Rare ovarian neoplasms, particularly those associated with excessive, abnormal production of oestrogen or testosterone, may cause amenorrhoea, but constitute only a very small percentage of known causes.

Polycystic ovary syndrome

PCOS affects 5–10% of reproductive age women and is associated with 75% of all anovulatory disorders causing infertility and with 90% of women with oligomenorrhoea (Box 16.2). PCOS is found in women with symptoms of androgen excess: in 90% of women with hirsutism and 80% of women with acne. Approximately 50% of women with the condition are overweight or obese. PCOS was first described by American gynaecologists Irving Stein and Michael Leventhal in 1935 who noticed the association between polycystic ovaries, amenorrhoea and hirsutism. The ovaries in PCOS appear enlarged and contain multiple (more than 10–12), small (less than 10 mm) fluid-filled structures just under the ovarian capsule. These are small, normal antral and atretic follicles, and are not true ‘cysts’. They are present in much greater numbers than are present in the normal ovary, but they have the same functions as normal (Fig. 16.18). The PCO ovary also has a greatly increased ovarian stroma, which may have abnormal endocrine properties.

Box 16.2   Features of polycystic ovarian syndrome

The presence of polycystic ovaries on ultrasound is very common, and around 25% of women in the population may have such appearances. Only a small proportion of these women will have the polycystic ovary syndrome (which comprises PCO appearances on ultrasound, associated with at least one of the androgenic or ovulation symptoms).

Biochemical investigations (Fig. 16.19) indicate abnormally raised LH levels and absence of the LH surge. Oestrogen and FSH levels are normal, and as a result there is an increase in the LH: FSH ratio. There may be increased ovarian secretion of testosterone, androstenedione and dehydroepiandrosterone. Prolactin levels are increased in 15% of cases.

Pathogenesis

The exact aetiology of PCOS is unknown but there is a strong genetic component. The primary disorder may be abnormalities in androgen biosynthesis and insulin resistance. As a result of insulin resistance and hyperlipidemia, women with PCOS are prone to developing non-insulin-dependent diabetes and are at greater risk of the metabolic syndrome. Many women with PCOS have substantial obesity. Inappropriate exposure of antral follicles to excessive concentrations of androgens results in inhibition of FSH release and may result in the ‘polycystic’ changes in the ovaries. The primary source of androgens may be both the ovary and/or the adrenals. The excretion of dehydroepiandrosterone sulphate – an exclusively adrenal steroid – is elevated in up to 50% of all women with PCOS. The principal androgens raised in PCOS and produced by the ovary include testosterone and androstenedione. Their production is significantly increased by insulin and insulin-like growth factors. They will not be suppressed by adrenal steroids but can be suppressed by GnRH agonists. About 10% of women with PCOS have type 2 diabetes and 30% have impaired glucose tolerance.

Diagnosis

Diagnosis (and criteria for the definition) is controversial. An international consensus meeting in Rotterdam proposed the following definition of PCOS, which has been widely adopted.

Any two of the following three are sufficient to confirm the diagnosis:

1. oligo- or anovulation

2. hyperandrogenism (biochemical or clinical) and

3. polycystic ovaries on ultrasound examination.

Investigations in women with amenorrhoea or oligomenorrhoea

The possibility of pregnancy should always be considered and if necessary excluded by pregnancy test. The history should include details of recent emotional stress, changes in weight, menopausal symptoms and current medication. In the majority of cases nothing abnormal is found on clinical examination, although a body mass index of less than 19 kg/m² is likely to be associated with weight-related amenorrhoea. In the absence of clinical evidence of thyroid or adrenal diseases it is unusual to find biochemical evidence. The differential diagnosis is established by the measurement of FSH and LH, prolactin, oestradiol and thyroid function tests (TFTs). A pelvic ultrasound can provide additional evidence of polycystic ovary syndrome, ovarian tumours and abnormalities of the lower genital tract. Nowadays, it is not usual to do routine imaging of the pituitary fossa, unless there is an elevated prolactin or some unusual features in the history suggesting other intracranial pathology. If such imaging is needed, MRI is now usually recommended.

The progesterone challenge test in which the administration of medroxyprogesterone acetate 10 mg daily for 5 days should produce withdrawal bleeding 2–7 days after completing the course (progestogen challenge test) is sometimes used as a diagnostic tool. This is really an in vivo bioassay of oestrogen presence. A positive test indicates a functional uterus with an intact endometrium and a patent outflow tract where circulating levels of oestrogen are adequate. Modern measurement of serum estradiol levels is now usually sufficient to provide this evidence.

Management

The treatment depends on the cause. Outside the ‘physiological’ group, the majority of cases are hypothalamic or PCOS in origin. Most of these will eventually resolve spontaneously and, where weight loss is the main underlying factor, the emphasis should be on restoring normal body mass. However, oestradiol levels are low and in some cases it is useful to administer cyclical oestrogen–progestogen therapy. Hyperprolactinaemia will usually respond to stopping any dopamine-inhibiting drugs or to treatment with dopamine agonists such as cabergoline, bromocriptine or quinagolide. Treatment for PCOS depends on which of the presenting symptoms predominate. Lifestyle changes including weight loss and exercise are the cornerstone and a loss of as little as 5% in weight can improve the menstrual pattern, endocrine profile and fertility.

Hirsutism can be treated by the local use of depilatory aids and electrolysis but the presence of hirsutism, acne and alopecia may also respond to antiandrogens such as cyproterone acetate combined with an oestrogen such as ethinylestradiol given on a cyclical basis. If the problem is primarily one of subfertility, then clomiphene citrate or carefully monitored human menopausal gonadotrophin can be used to stimulate ovulation. Approximately 15–40% of women with PCOS have clomiphene resistance, which may result from its antioestrogenic effects on the endometrium and cervical mucus. Second-line treatment has previously involved laparoscopic ovarian drilling, whereby the ovarian surface is punctured multiple times, but early evidence suggests the use of aromatase inhibitors may be more effective than surgical intervention. Medical management with the oral hypoglycaemic, insulin-sensitizing agent, metformin also appears to be effective in some cases. The long-term sequelae of PCOS need to be considered. Prolonged unopposed oestrogen action may result in the development of endometrial hyperplasia, which may rarely undergo malignant change. Hyperplasia will often regress following the administration of a progestational agent, such as norethisterone or medroxyprogesterone acetate. PCOS is associated with metabolic disturbances, and regular testing for the development of late onset (type II) diabetes and lipid abnormalities should occur.

Investigations

A careful history is important with attention to the timing of the onset and characteristics of pain and associated symptoms, e.g. such as dyspareunia, dysuria. Pelvic examination is to be avoided in those women with primary dysmenorrhoea who have never been sexually active. The decision to perform a vaginal examination should be individually assessed, taking into account sexual activity and the need for a Pap smear. In women with primary dysmenorrhoea there is usually no pelvic tenderness or any abnormality on vaginal examination.

In secondary dysmenorrhoea a pelvic examination is essential to assess uterine and adnexal tenderness, masses and uterine mobility, as well as the posterior fornix and cervical movement pain. Swabs should be taken for pelvic infection and a pelvic ultrasound organized. Although transvaginal ultrasound is a good investigation for fibroids, it is less reliable for adenomyosis and will not commonly detect endometriosis, unless there is an endometrioma or deep lesion present. Laparoscopy is required for women with persistent or progressive pain symptoms that are unresponsive to medical therapies.

Management

An explanation of the causes of menstrual pain is helpful and, where appropriate, reassurance that there is no underlying pathology. Clinicians should adopt a holistic approach with attention to diet and lifestyle factors as well as to medical therapies. There is good evidence that smoking increases dysmenorrhoea and some evidence that exercise can be beneficial. Using a heat pack on the lower abdomen anecdotally provides relief and several dietary supplements have been investigated, with Vitamin B₁ indicated to be a helpful treatment.

Symptoms and signs

The symptoms associated with PMS and PMDD are listed in Table 16.2.

Pharmacological

The first line medications for severe PMS and PMDD are the selective serotonin reuptake inhibitors (SSRIs) or the serotonin–norepinephrine reuptake inhibitors (SNRIs). These medications, such as sertraline, citalopram and fluoxetine, taken either daily or during the luteal phase of the cycle, have been found to significantly reduce the physical and psychological symptoms of PMS compared to placebo. The positive impact on PMS is often seen within a few weeks of taking the medication but improvement in mood, if there is associated depression, may take up to a month to improve.

The combined oral contraceptive pill has been commonly used to treat PMS, but there are no data to support its effectiveness with the exception of some studies of pills containing progestogens with antidiuretic properties. Several studies suggest that pills containing drospirenone, a spironolactone derivative, in a 24 day pack are better than placebo in reducing the symptoms of PMS. Further, taking the pills in a continuous manner (hormone tablets every day without a break) is beneficial compared with taking a conventional 28 day pill with 7 day break.

Gonadotrophin-releasing hormone agonists suppress ovarian function and relieve symptoms during treatment. However, these recur when treatment is stopped. They are unsuitable for long-term use because of their cost and adverse side effects including menopausal symptoms and osteoporosis.

Precocious puberty

In girls precocious puberty is defined as the development of the physical signs of puberty before the age of 8 years. It usually progresses from premature thelarche to menarche because breast tissue responds faster to oestrogen than the endometrium. It is useful to categorize possible causes as central, i.e. dependent on GnRH secretion, and peripheral, i.e. GnRH independent. The majority of cases do not have a pathological basis. In girls older than 4-years-old specific causes are less likely to be found with the majority being idiopathic (80%). Below this age CNS causes predominate.

Central (GnRH dependent) in order of frequency:

Patients with central precocious puberty have unregulated GnRH release. FSH and LH levels fluctuate so multiple samples may be required, remembering a propensity to nocturnal secretion. A GnRH stimulation test will show a pubertal, threefold response in LH levels. FSH also rises but to a lesser degree. In central precocious puberty the progression follows the usual pattern, albeit earlier.

Peripheral or GnRH independent causes:

Evaluation

The first step in evaluating a girl with precocious puberty is to obtain a complete family history including the age of onset of puberty in parents and siblings. The heights of both parents should be recorded and the projected height of the child calculated (Fig. 16.22). The history of pubertal development needs to be documented and along with other symptoms such as headache or visual disturbance. A history of illness, trauma, surgery and medications is also pertinent. Physical examination should include documentation of the Tanner stage and examination for other signs to indicate a peripheral cause such as skin lesions or ovarian masses. Signs of virilization must be looked for including, acne, hirsutism and clitoromegaly.

Variations on normal puberty

Delayed puberty

Delayed puberty is defined by the absence of breast development in girls beyond 13 years. The diagnosis is also made in the absence of menarche by age 16 or within 5 years after the onset of puberty. Mostly delayed puberty is constitutional, arising from inadequate GnRH from the hypothalamus. It may also be secondary to chronic illness such as anorexia nervosa, asthma, chronic renal disease and inflammatory bowel disease. Anatomic considerations such as outflow obstruction in haematocolpos need exclusion. The hypogonadism that characterizes this state may occur with both elevated and lowered levels of gonadotrophins. As with precocious puberty it is essential to establish the status of the gonadotrophins to determine causation (Table 16.3).

Menopause transition

The menopausal transition or ‘perimenopause’ is defined by the WHO as ‘that period of time immediately before menopause when the endocrinological, biological and clinical features of approaching menopause commence.’ The menstrual cycle shortens in women over the age of 40 years, and the change in the cycle length is related to shortening of the follicular phase. FSH levels are higher at all stages of the cycle than levels seen in younger women, whilst oestradiol levels maybe lower with erratic elevations. In the early part of the menopause transition, associated with rising FSH and LH levels, menstrual cycle irregularity often occurs with a predominance of short and normal-length cycles. In the later stages where there are further elevations in FSH and LH, cycle irregularity occurs with a predominance of elongated menstrual cycles. Although AUB is common in the perimenopause, persistent irregular bleeding should never be considered normal because it may be associated with uterine neoplasms.

Hormone changes after the menopause

There is a marked reduction in ovarian production of oestrogen and, in particular, of oestradiol. Some oestrogen production occurs in the adrenal gland but the major source of oestradiol arises from peripheral conversion of both oestrone and testosterone in fat tissue. Thus, women with a high BMI have higher circulating oestrogen levels than slender women. There is considerable variation in the circulating levels of oestradiol in the menopause, and this may account for the variation in severity of menopausal symptoms. The absence of any significant oestrogen production results in excessive release of FSH and LH, with the major increases occurring in FSH. The levels of gonadotrophins continue to show pulsatile release similar to the pattern seen in the premenopausal phase. Androgens produced in the ovary and adrenal glands are mainly androstenedione and testosterone and these levels fall in menopausal women. There is also a reduction in adrenal androgen secretion, including that of dehydroepiandrosterone (DHEA) and DHEA sulphate. Oestrogen production by the ovary is reduced but the production of testosterone persists.

Symptoms and signs of menopause

Numerous symptoms are described in relation to the menopause, but the two that are the most significant are hot flushes (often associated with insomnia) and vaginal dryness. These symptoms are experienced by 70% of women and result from reduced oestrogen levels. A range of other symptoms, both physical and psychological, are associated with the menopause, including palpitations, headaches, bone and joint pain, asthenia, tiredness and breast tenderness. Most women will have little or only mild symptoms. Around 20% of women seek help for management of their symptoms.

Physical symptoms

Vascular disturbances

The commonest symptom, occurring in around 75% of women is the development of hot flushes.

These episodes usually last for 4–5 minutes and consist of flushes and perspiration affecting the face, neck and chest. Hot flushes are typically experienced maximally in the first year after the menopause and last up to 5 years. Although the exact pathophysiology remains elusive, the flushes co-inside with pulsatile release of LH, an acute rise in the skin temperature of several degrees centigrade, a transient increase in heart rate, and fluctuations in the electrocardiographic baseline. The administration of oestrogens relieves these symptoms, but the mechanism is unknown. Night sweats and insomnia also occur.

Urogenital tract

The urogenital tissues of the uterus, vaginal and bladder contain oestrogen and progesterone receptors. Loss of oestrogen results in epithelial thinning, reduced vascularity, decreased muscle bulk and increased fat deposition. Up to half of women experience urogenital symptoms after the menopause including uterovaginal prolapse, dry vagina and urinary symptoms.

The vaginal walls lose their rugosity and become smooth and atrophic. In severe cases, this may also be associated with chronic infection and atrophic vaginitis. The complaint of vaginal and vulval dryness can manifest as discomfort or pain during intercourse as well as bleeding or spotting after sex. The cervix diminishes in size, and there is a reduction in cervical mucus production. The uterus also shrinks in size, and the endometrium becomes atrophic. The bladder epithelium may also become atrophic with the development of frequency, dysuria and urge incontinence. It is important to recognize these symptoms because they can be relieved by oestrogen replacement therapy.

Other physical symptoms

The skin over the body becomes thinner and drier and body and facial hair become coarser. The reduction in ovarian oestrogen production results in involution and regression of target organs, including breasts that become less dense and reduce in size (Fig. 16.23).

Consequences of menopause

Treatment of the menopause

Many women pass through the menopause without any symptoms, and there is considerable variation in serum oestradiol levels between individuals after the menopause. Oestrogen therapy is the most effective treatment for symptomatic relief, but maybe associated with significant adverse effects in a small minority of women. The decision to use HRT is made on an individual basis taking into account each woman’s history, risk factors and personal preferences (Table 16.4). This should be done in a way that can be understood so that each woman can make an informed choice.

Vulval neoplasia

Skin cancers will occur on the vulva and present with itchiness and need to be differentiated from the benign dermatoses. Suspicion should be increased in any persistently eroded or scaly and hypervascular lesions with a very low threshold for biopsy (see Chapter 20).

Vaginal discharge

Vaginal discharge describes any fluid loss through the vagina. While most discharge is normal and can reflect physiological changes throughout the menstrual cycle, some discharge can occur because of infection or trauma. White discharge usually occurs in response to hormonal changes at the beginning and the end of the cycle whilst midcycle, with high oestrogen levels, the discharge is clear. The common causes and management of vaginal discharge are summarized in Table 16.6. Further details on the common infections of the genital tract and their treatment can be found in in Chapter 19.

Cervical polyps

Benign polyps arise from the endocervix and are pedunculated, with a covering of endocervical epithelium and a central fibrous tissue core. The polyps present as bright red, vascular growths that may be identified on routine examination. The presenting symptoms may include irregular vaginal blood loss or postcoital bleeding.

Less frequently, the polyps arise from the squamous epithelium, when the appearance will resemble the surface of the vaginal epithelium.

Small polyps can be avulsed in the outpatient clinic by grasping them with polyp forceps and rotating through 360°. Larger polyps may need ligation of the pedicle and excision of the polyp under general anaesthesia.

Benign tumours of the vulva and vagina

Benign cysts of the vulva include sebaceous, epithelial inclusion and wolffian duct cysts (Fig. 16.24), which arise from the labia minora and the per-urethral region, and Bartholin’s cysts, see below. A rare cyst may arise from a peritoneal extension along the round ligament, forming a hydrocele in the labium major. Benign solid tumours include fibromas, lipomas and hidradenomas. True squamous papillomas appear as warty growths and rarely become malignant. All these lesions are treated by simple biopsy excision.

Cysts arise in the vagina from embryological remnants; the commonest varieties are those arising from Gartner’s duct (wolffian duct remnants). These are not rare and occur in the anterolateral wall of the vagina. They are usually asymptomatic and are found on routine examination.

Histologically, the cysts are lined by cuboidal epithelium but sometimes a flattened layer of stratified squamous epithelium is seen.

The cysts are treated by simple surgical excision and rarely give rise to any difficulties.

Endometriosis

Endometriotic lesions may appear anywhere in the vagina, but occur most commonly in the posterior fornix. The lesions may appear as dark brown spots or reddened ulcerated lesions. The diagnosis is established by excision biopsy. If the lesions are multiple, then medical therapy should be instituted as for lesions in other sites.

Solid benign tumours

These lesions are rare but may represent any of the tissues that are found in the vagina. Thus, polypoid tumours may include fibromyomas, myomas, fibromas, papillomas and adenomyomas. These tumours are treated by simple surgical excision.

Vaginal adenosis

This is the presence of columnar epithelium in the vaginal epithelium and has been found in adult females whose mothers received treatment with diethylstilboestrol during pregnancy. The condition commonly reverts to normal squamous epithelium but in about 4% of cases the lesion progresses to vaginal adenocarcinoma. It is therefore important to follow these women carefully with serial cytology.

Bartholin’s abscess/cyst

The Bartholin’s glands lie in the posterior vaginal wall at the introitus and secrete mucous like fluid via a short duct into the vagina. They are normally the size of a pea but when the duct becomes blocked a cyst can form. These cysts may present acutely as an oval shaped lump, in the posterior labia sometimes growing to the size of a golf ball or larger. They are unusually unilateral and cause discomfort with walking, sitting and sexual intercourse. When the gland is infected, most commonly with skin or genitourinary bacteria, e.g. Staphylococcus, Escherichia coli, an abscess can develop. These arise more acutely than the Bartholin’s cysts and are particularly painful.

Small asymptomatic cysts may not require treatment and abscesses can sometimes resolve with antibiotics. However, treatment of large cysts and abscesses require surgery. The procedure, called marsupialization, involves making a pouch like opening to the gland by incising into the cyst wall and then suturing it to the overlying skin to ensure the new opening continues to drain the fluid from the glands (see Chapter 19, Fig. 19.13).

Vulval and vaginal trauma

Injuries to the vulva and vagina may result in severe haemorrhage and haematoma formation. Vulval bruising may be particularly severe because of the rich venous plexus in the labia, and commonly results from falling astride. Lacerations of the vagina are often associated with coitus. Vulval haematomas often subside with conservative management but sometimes need drainage. It is important to suture vaginal lacerations and to be certain that the injury does not penetrate into the peritoneal cavity.

Acute abdominal pain of uncertain origin

In a woman of reproductive age presenting with acute abdominal pain it is firstly important to take a good history about the nature of the pain, and the presence of associated symptoms. A thorough examination will identify the site of maximal tenderness, rebound tenderness and guarding. It is vital to always exclude pregnancy and particularly ectopic pregnancy. Gynaecological disorders in women with a negative pregnancy test and acute pelvic pain include PID, functional ovarian cysts, ovarian or peritoneal endometriosis and adnexal torsion. The most common gastrointestinal causes that can present with acute pelvic pain include appendicitis, acute sigmoid diverticulitis, and Crohn’s disease.

It is important in the assessment of a woman with acute pelvic pain to exclude those diagnoses that require urgent intervention: PID, ovarian torsion and appendicitis. The investigation and diagnosis of PID has been discussed above. Ovarian torsion usually occurs in the presence of an enlarged ovary (see ovarian cysts in Chapter 20). Women with torsion present with sudden onset of sharp unilateral pelvic pain that is often accompanied by nausea and vomiting. The sonographic findings in ovarian torsion are variable. The ovary is enlarged and can be seen in an abnormal location above or behind the uterus. The absence of blood flow is an important sign and a lack of venous waveform on Doppler ultrasound has a high positive predictive value. However the presence of arterial and venous flow does not exclude torsion and any cases where it is suspected clinically require laparoscopy to visualize the adnexae. If the torsion is reversed early in the process the ovary may be saved.

Acute and excessively heavy unscheduled vaginal bleeding

The entity of acute HMB has recently been defined by FIGO as heavy uterine bleeding not associated with pregnancy that is of sufficient volume to require urgent or emergent medical intervention. Women presenting with acute bleeding most often have ovulatory dysfunction but may also have an underlying coagulopathy. The management of acute AUB/HMB can require dilatation and curettage but can be usually managed non-surgically with the administration of gonadal hormones, and/or intrauterine tamponade. Previously, parenteral conjugated oestrogens were used and more recently oral progestogens and sometimes double-doses of the combined oral contraceptive pill have been shown to be successful. The safer option is high doses of progestogens, sometimes in combination with the antifibrinolytic agent, tranexamic acid. A regimen of norethisterone 5 mg tds can be used to settle the bleeding. Follow up is required to establish the cause of the bleeding. For really severe cases, the insertion of a small inflated Foley catheter balloon into the uterine cavity can be useful to achieve endometrial tamponade.