• The few studies of HPV persistence showed a possible protective effect of fruits, vegetables, vitamins C and E, beta- and alpha-carotene, lycopene, luterin/zeaxanthin and cryptoxanthin.¹ Evidence for a protective effect of cervical neoplasia was probable for folate, retinol and vitamin E, and possibly for vegetables, vitamins C and B₁₂, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin and cryptoxanthin. Evidence for an increased risk of cervical neoplasia associated with high blood homocysteine was probable, although the evidence is still inconclusive. Patients with an abnormal Pap smear should be advised to eat a diet rich in beta-carotene, vitamin C and folate (vitamin B₉) from fruits and vegetables.

• Exercise regularly.

• Reduce avoidable stress. Higher levels of perceived stress have been associated with impaired HPV-specific immune response in women with cervical dysplasia.²

ABNORMAL UTERINE BLEEDING

A normal menstrual cycle occurs every 21–35 days, with bleeding for 2–7 days. Normal blood loss is 20–60 mL per period, with > 80 mL described as heavy.

The process of normal regular menstruation requires:

• sufficient oestrogen to induce ‘follicular phase’ endometrium

• ovulation with formation of a corpus luteum, production of progesterone and induction of ‘secretory phase’ in the endometrium

• withdrawal of progesterone as the corpus luteum declines. Declining progesterone is the trigger for menstruation

• synchronous breakdown and repair of the endometrium at menses

• breakdown factors including prostaglandins, interleukin-1, matrix metalloproteinase (MMP)-1 and MMP-7

• endometrial repair factors including epidermal growth factor-alpha, endothelins and vascular endothelial growth factor (VEGF).³

FIGURE 52.5 The menstrual cycle and hormonal levels

TERMINOLOGY

Terms such as menorrhagia, metrorrhagia, polymenorrhoea, oligomenorrhoea and metropathia haemorrhagica should be replaced by descriptions of the frequency, heaviness and length of bleeding.

Abnormal uterine bleeding (AUB) covers all vaginal bleeding apart from regular ovulatory normal menses.

AETIOLOGY

Abnormal uterine bleeding is most common soon after menarche or in the years before menopause. It may be:

• anovulatory—without ovulation, a corpus luteum does not form. The resulting lack of progestogen and unopposed oestrogen stimulates the endometrium. Bleeding occurs when oestrogen levels fall or the endometrium becomes unstable:

• post-menarche—oestrogen levels rise but the immature hypothalamic-pituitary axis is unable to trigger ovulation. Menses may be infrequent but very heavy, often resulting in anaemia

• perimenopausal—ovarian follicle quality declines, resulting in variable oestrogen levels and variable menstrual flow. A dyssynchronous endometrium with irregular menstrual shedding results in prolonged menses with eventual amenorrhoea

• chronic anovulation—e.g. polycystic ovarian syndrome or hypothalamic dysfunction associated with low body weight, excessive exercise or stress. Oestrogen levels are variable. The corpus luteum does not form or is inadequate to maintain endometrial stability. Unopposed oestrogen stimulates the endometrium, which ultimately becomes unstable and bleeds irregularly

• ovulatory—periods are heavy but regular, due to:

• uterine pathology, e.g. fibroids

• abnormal endometrial function ⁴ or

• systemic causes, e.g. obesity (endogenous oestrogen), clotting disorders (including von Willebrand’s disease), hypothyroidism

• iatrogenic—an imbalance between oestrogen and progestogen associated with the oral contraceptive pill (OCP), hormone replacement therapy (HRT) or progestins results in abnormal bleeding:

• light or absent periods, often with irregular bleeding due to excess progestogen effect

• premenstrual bleeding with inadequate progestogen

• intermenstrual bleeding with triphasic contraceptives

• heavier periods with excess oestrogen effect

• midcycle bleeding with inadequate oestrogen.

Medications associated with bleeding include anticoagulants, selective serotonin reuptake inhibitors, antipsychotics, corticosteroids, tamoxifen.

Medications that interact with the OCP/HRT, including liver enzyme inducers, antibiotics, anti-tuberculous drugs and antifungals, may also cause bleeding.

Herbal substances associated with bleeding include ginseng, ginkgo and soy supplements.

Causes of abnormal uterine bleeding are listed in Box 52.1.

BOX 52.1 Causes of abnormal uterine bleeding

Endocrine:

• immature hypothalamic–pituitary axis

• menopause

• obesity

• polycystic ovarian syndrome

• premature ovarian failure

• Cushing’s disease

• hyperprolactinaemia

• endometrial or cervical polyps

• endometrial or cervical malignancy

• leiomyomas

Pregnancy:

• ectopic pregnancy

• incomplete abortion

Medications:

• oral contraceptive pill (especially low dose, missed pills or drug interactions)

• progestogen-only contraceptives

• intrauterine devices

• tamoxifen

• warfarin

Other conditions:

• bleeding disorders (including thrombocytopenia, von Willebrand’s disease)

HISTORY

The history should include:

• menstrual history—last menstrual period (LMP), flow, ‘accidents’, ‘flooding’, length of cycle, number of days of bleeding, frequency of pad/tampon changes (more than 2-hourly is heavy), limitations on daily activities, use of double pads, changing at night

• features of polycystic ovarian syndrome

• reproductive history—contraceptive use, pregnancies, fertility plans

• lifestyle factors—change in exercise, stress, weight

• symptoms of anaemia—tiredness, palpitations

• medical history—thyroid function, bleeding disorders

• drug history—anticoagulants, hormone use, aspirin, anticonvulsants, SSRIs, antibiotics, alternative and complementary therapies.

EXAMINATION

Examination may be normal but should include:

• signs of anaemia, thyroid disease, bleeding disorder, hyperprolactinaemia

FIGURE 52.6 Main causes of uterine bleeding: A Anovulatory endometrium with stromal breakdown; B Chronic endometriosis with numerous plasma cells (arrow); C Endometrial polyp; D Submucosal leiomyoma with attenuation of the endometrial lining (arrow)

• signs of polycystic ovarian syndrome (i.e. hyperandrogenism, hirsutism, acne, obesity and palpable enlarged ovaries; see Fig 7.7)

• speculum examination to exclude cervical and vaginal causes, especially if bleeding is post-coital

• bimanual examination to exclude fibroids and adnexal masses.

INVESTIGATIONS

Investigations include:

• pregnancy test

• Pap smear, STD screen

• haematology where loss is heavy:

• complete blood picture

• iron studies

• prothrombin time, activated partial thromboplastin time, von Willebrand screen—if bleeding heavy since menarche or suggestive history

• follicle-stimulating hormone, prolactin, thyroid-stimulating hormone

• transvaginal ultrasound—uterine lesions, polycystic ovarian syndrome (PCOS), retained products of conception, ovarian tumours. An endometrial thickness ≤ 4 mm virtually excludes endometrial cancer ⁵

• endometrial biopsy—does not allow visual inspection of cavity and will not allow removal of polyps, resection of fibroids or endometrial ablation

• hysteroscopy and curettage, if required—exclusion of malignancy, removal of endometrial polyp, resection of submucosal fibroid.

MANAGEMENT

Management depends on the cause of bleeding, the woman’s plans for fertility and the impact that periods have on her life. In addition to bleeding, periods may involve dysmenorrhoea, sore breasts, mood disorder, migraines or an aggravation of pelvic symptoms.

Some women may request minimal treatment. Others may wish to avoid periods entirely. Different women may choose very different treatment options.

Teenagers presenting acutely with prolonged heavy bleeding (anovulatory cycles):

• Exclude anaemia, iron deficiency, pregnancy, bleeding disorders (including von Willebrand’s disease).

• Consider options including:

• Vitex agnus castus (chaste tree) 1000 mg daily.⁶ Although few randomised controlled trials (RCTs) exist, Vitex is commonly prescribed for menstrual irregularities, based on data collected by the German Commission E.⁷ Menstrual cycle irregularities due to hyperprolactinaemia, corpus luteum insufficiency, oligomenorrhoea and secondary amenorrhoea have been effectively treated with Vitex extract in open-label, uncontrolled studies

• combined 30–35 μg OCP q.d. with antiemetic until bleeding stops (within 72 hours). Follow with 1 tablet daily without placebo for 3–6 weeks, then withdrawal bleed for 5 days, then OCP ⁸

• norethisterone 5–15 mg daily until bleeding stops, then 5–10 mg daily for 3–6 weeks

• IV conjugated oestrogen (Premarin®) 25 mg. Repeat 4-hourly until bleeding stops, usually within three doses. Follow with a combined OCP or progestin for 3–6 weeks ⁹

FIGURE 52.7 Polycystic ovaries: A Operative findings of classical enlarged polycystic ovaries. The uterus is located adjacent to the two enlarged ovaries. B Sectioned polycystic ovary with numerous follicles. C Histological section of a polycystic ovary with multiple subcapsular follicular cysts and stromal hypertrophy (low power, left). At higher power (×100, right), islands of luteinized theca cells are visible in the stroma.

FIGURE 52.8 Pathology of polycystic ovarian syndrome

FIGURE 52.9 Cervical polyp

• intracavity tamponade with 30–50 mL Foley catheter for 2–48 hours ¹⁰

• Iron therapy until ferritin level is in normal range and for 3 months after bleeding becomes normal.

Ovulatory, regular, heavy periods:

• Exclude anaemia, hypothyroidism, iatrogenic causes, uterine disease (ultrasound).

• Where dysmenorrhoea is present, consider endometriosis or adenomyosis.

Perimenopausal women with frequent irregular periods and variable flow:

• Exclude anaemia, hypothyroidism, hyperprolactinaemia, iatrogenic causes.

• Exclude uterine and cervical disease—ultrasound and cervical smear.

• Consider the woman’s general wellbeing—oestrogen/testosterone deficiency symptoms, increased exercise, dietary review, weight loss assistance, psychological support.

• Consider options:

• Vitex agnus castus 1000 mg daily

• low-dose OCP—if low risk, non-smoker < 50 years

• cyclical progestins, e.g. norethisterone 5 mg day 1–12 each calendar month until menses cease

• sequential HRT—especially with menopausal symptoms

• levonorgestrel IUD—will reduce volume but not change timing of periods

• hysterectomy.

DYSMENORRHOEA

Dysmenorrhoea can be considered ‘normal’ if:

• it is only present on day 1–2 of the cycle

• it resolves with the OCP, or anti-inflammatory medications, and

• the woman is nulliparous.

MANAGEMENT

Management options for ‘normal period pain’ include:

• acupuncture and acupressure

• vitamin B₁, 100 mg daily ¹¹

• magnesium supplement

• strenuous physical exercise.

ENDOMETRIOSIS

DEFINITION

Endometriosis is the presence of endometrial glands and stroma outside the uterus.

AETIOLOGY

The aetiology of endometriosis is unknown. It is increasing in prevalence. A tendency to develop endometriosis is inherited as a complex genetic trait influenced by environmental factors.¹³ Established lesions include inflammatory cells, fibrosis, neovascularisation and aberrant innervation. It has been associated with environmental toxins including organochlorines (polychlorinated biphenyls and dioxin-like compounds).¹⁴

Risk is increased with nulliparity and early menarche.¹⁵

SYMPTOMS

In the past, endometriosis was considered an uncommon condition of women in their thirties and forties. We now know it to be a common condition (5–10%) of women in their teens and twenties.

While some women are asymptomatic, common symptoms include:

• period pain resistant to OCP or anti-inflammatories

• period pain present for more than 1–2 days

• period pain felt on one side or in the lower back

• period-like pain during the month

• ovulation pain always felt on one side

• deep dyspareunia

• progression to chronic pelvic pain

• infertility—this is variable; many women become pregnant easily, so contraception is required

• fatigue.

Dysmenorrhoea is usually a combination of pain from the endometriosis and pain from the uterus. The endometrium of women with endometriosis has nerve fibres (pain receptors) not present in women without endometriosis.¹⁶ Optimal outcome requires management of both endometriotic lesions and the uterine component of pain.

HISTORY

Typical histories include:

• a teenager in whom periods have always been painful. Initial improvement on the OCP is followed by worsening pain resistant to NSAIDs

• a young woman with period pain on more than 1–2 days of a period, pain leading up to a period or pain that feels like period pain at other times of the cycle

• a woman who has had period pain for some time, but now has pain on most days (chronic pain), often with several different pain symptoms

• a woman whose severe period pain as a young woman did not resolve after pregnancy.

INVESTIGATIONS

CA 125

• Rarely used. Not useful for screening.

• Mildly elevated in some cases.

Ultrasound

• Usually normal unless endometriomas are present.

• Transvaginal ultrasound is preferred, except in virgins or where the vaginal probe would cause pain or distress.

• An endometrioma has a grey, homogeneous, ‘ground glass’ appearance.

• The differential diagnosis of an endometrioma is a haemorrhagic corpus luteum. Repeat scan in 2–3 months will show persistence of an endometrioma or resolution of a corpus luteum.

• 99% of women with an endometrioma on ultrasound will have additional peritoneal deposits found at laparoscopy.¹⁷

• An endometrioma may be a marker for severe peritoneal or rectosigmoid disease.

MRI

Rarely required. May be used to investigate rectosigmoid disease or diagnose coexistent adenomyosis.

Laparoscopy

• Required for definitive diagnosis and treatment.

• Lesions may be clear, pink, yellow, brown, white, red or bluish black. May show only as increased vascularity, white scarring or adhesions. Frequently under-diagnosed.

• Histological confirmation of lesions is required.

• Areas of inflammatory tissue are common, but rare in women without pain.

TREATMENT OPTIONS

The treatments chosen will depend on the woman’s individual symptoms, preference, desire for fertility and coexistent conditions.

Explanation and support

• Ensure she knows you believe in her pain. Many women have been told that their pain is exaggerated, it is all in their head or their pain is normal.

• Provide education regarding endometriosis, her specific situation and the treatment options.

• Provide a management plan for when pain is severe, to allow her to control her pain. Anticipation of severe uncontrolled pain causes distress and anxiety as the period approaches.

• Involve a psychologist/counsellor where possible. The psychological, educational, financial, employment and relationship sequelae of pain, low self-esteem and self-doubt are common.

Laparoscopy

Once the diagnosis has been made, options include:

• excision of the endometriosis lesions if an experienced laparoscopic surgeon is present. Conservation of the uterus and ovaries is usual unless the woman is older and removal of these organs has been discussed

• documentation of the lesions and referral to a laparoscopic surgeon for repeat laparoscopy with excision

• diathermy to the endometriosis lesions—this is suitable for superficial ovarian lesions and some superficial peritoneal lesions. It is less effective than excision as deep lesions are incompletely removed and lesions close to the bowel or ureter cannot be safely diathermied

• no surgical treatment, with consideration of medical therapies.

Dietary and complementary therapies

These aim to:

• reduce oestrogen dominance

• reduce inflammation

• block aromatase activity in the endometriosis lesion.

Management includes:

• reducing dietary saturated fats

• avoiding trans fats (found in many processed foods)¹⁸

• maintaining healthy weight range

• reducing caffeine and alcohol intake

• engaging in regular strenuous exercise.

Herbs and supplements:¹⁹

• Vitex agnus castus 1000 mg daily

• anti-inflammatory—Boswellia, cat’s claw, turmeric, bromelain

• magnesium

• vitamin C 500 mg daily, vitamin E 400 IU daily ²⁰

• fish oil 1–2 g daily

• traditional Chinese medicine ²¹—herbs often prescribed include corydalis, cnidium, bupleurum, dong quai and perilla, sometimes accompanied by acupuncture.

Medical treatments

Medical treatments do not improve fertility, will not divide adhesions or remove scar tissue, will not resolve an endometrioma and will not resolve deep endometriotic lesions. They may improve symptoms in the short term. Medical treatments are not required where excision of endometriotic lesions is complete. However, endometriosis surgery is challenging and requires advanced laparoscopic surgical skills and equipment. Medical treatments include:

• gonadotrophin-releasing hormone (GnRH) analogues—by daily nasal spray or monthly depot injection, for 3–6 months. Hypo-oestrogenic side effects include hot flushes, poor sleep, tiredness, dry vagina and loss of bone density. May be used with combined HRT to minimise side effects without decreased efficacy

• progestins (e.g. norethisterone 5–10 mg daily)—can be used in the long term if effective

• danazol or dimetriose—used less now due to androgenic side effects

• aromatase inhibitors.

Consider treatment of coexistent causes of pelvic pain at the laparoscopic procedure. For example:

• insertion of levonorgestrel IUCD to manage uterine aspect of dysmenorrhoea

• cystoscopy with hydrodistension to diagnose interstitial cystitis

• starting a medication for neuropathic pain

• providing photographs to allay fears and increase understanding.

A full discussion of the management of endometriosis is available in textbooks on this topic.²²

MANAGEMENT OF OVARIAN ENDOMETRIOMAS / SEVERE ENDOMETRIOSIS

Effective treatment of endometriomas requires removal of the cyst wall from inside the ovary, by either ‘stripping’ cystectomy or diathermy (less effective). Drainage alone is rapidly followed by recurrence. Where endometriosis is severe, the pouch of Douglas may be obliterated, and endometrosis may invade the muscularis of the rectum.

Where laparoscopy does not help her pain

Either the endometriosis was incompletely removed, or the pain is due to another condition (e.g. uterine pain, pelvic muscle pain, interstitial cystitis or neuropathic pain). Even when present, the endometriosis may not be the main cause of pain.

Recurrent pain after previously successful surgery

Where the current pain is the same as the pain that resolved with surgery, review laparoscopy is reasonable. Where the pain is different, consider other causes of pain (e.g. uterine pain, interstitial cystitis, neuropathic pain).

ADENOMYOSIS

Adenomyosis is the presence of endometrial glands and stroma in the myometrium with adjacent smooth muscle hyperplasia. It is generally diffuse but may form an adenomyoma locally. The aetiology is unknown, but it is more common in women with endometriosis.

SYMPTOMS

Symptoms where present include:

• dysmenorrhoea, often with back pain

• heavy periods

• dyspareunia.

Suggestive histories include:

• dysmenorrhoea due to endometriosis as a young woman, few problems during childbearing years, then increasing dysmenorrhoea due to adenomyosis once childbearing complete

• trouble-free periods when young, with worsening dysmenorrhoea after the birth of a child.

TREATMENT

If asymptomatic, no treatment is required. Treatment options include:

• levonorgestrel-releasing IUCD

• NSAIDs with back-up narcotic-based analgesia for dysmenorrhoea

• progestogens, e.g. norethisterone 5 mg daily continuously or progestogenic OCP

• treatment of coexisting menorrhagia, to minimise the contribution from ‘clot colic’. Endometrial ablation may worsen adenomyosis

• treatment of coexisting menstrual symptoms, to minimise the number of symptoms the woman must cope with during menses (e.g. premenstrual mood disorder, menstrual migraine, bloating, lethargy)

FIGURE 52.12 Pathology of adenomyosis: Sagittal (A) and axial (B) MR images through the pelvis show focal junctional zone widening and characteristic thickened areas (*); Sagittal (C) and axial (D) MR images in a different patient show widening of the entire junctional zone (*) which contains endometrial rests

• hysterectomy.

• A danazol-loaded IUCD has been investigated in Japan.²³

CHRONIC PELVIC PAIN

While some women with endometriosis improve over time and others persist with dysmenorrhoea over the long term, a proportion progress to chronic pelvic pain. Pain becomes a mixture of pelvic symptoms and central sensitisation with neuropathic pain. Symptoms include some or all of:

• dysmenorrhoea present before the chronic pain began, that now affects more days per month

• urinary symptoms of frequency, urgency, nocturia and bladder pain

• variable bowel symptoms, often with food intolerance and bloating

• sharp, stabbing, burning or aching pains that occur spontaneously, often at night

• painful pelvic muscles with dyspareunia

• other pain conditions, including migraine, muscle trigger points, generalised muscle aches or vulvodynia

• hypersensitivity of the abdomen or pelvis

• poor sleep, fatigue, anxiety and diminished quality of life.

These symptoms may develop even when all her endometriosis has been removed and after hysterectomy. In women with pain on most days, a central chronic pain process is likely, and management usually includes neuropathic pain medications, cognitive behavioural lifestyle changes, and management of the local pelvic symptoms.²⁴

MANAGEMENT

Pain is now complex. No single treatment and no surgery will resolve all the woman’s pain. While complete cure is unlikely, substantial improvement can be achieved by managing local pain symptoms, treating central sensitisation and rehabilitation of the sequelae of her chronic pain condition.

• Make a list of each pain she has, what it feels like, where it is and when it happens. Ask specifically about sharp pains, bladder function, bowel function, dyspareunia and pain in other areas of the body.

• Diagnose pain from pelvic muscles with a one-finger examination of the muscles just inside the vagina posteriorly and laterally. Diagnose a painful bladder by pressure with one finger anteriorly with suggestive symptoms.

• Plan treatment for each pain.

• At each follow-up visit, return to the initial list of pains and ask about each one, to assess the benefit of the treatments used. Many women forget a particular pain once it resolves and may feel that they have made little progress because another pain remains.

• Treat coexisting health problems, to allow her more energy to cope with any remaining problems.

SPECIFIC PAIN SYMPTOMS AND THEIR MANAGEMENT

Urgency, frequency and nocturia

These are commonly due to interstitial cystitis (IC) or painful bladder syndrome (PBS). IC commonly coexists with endometriosis.²⁵ There is often a history of ‘frequent UTI’ managed with antibiotics, but with negative urine culture. Urine may show WBC or RBC. Pelvic floor dysfunction secondary to IC, with painful intercourse, cervical smear tests and tampon use is common.

General measures:

• Explain that the bladder is inflamed rather than infected.

• Explain that the woman should drink enough that urine is not concentrated—approximately 2 litres daily.

• Consider dietary triggers. May require exclusion diet with dietician. Where triggers can be identified and avoided, medication may not be necessary. Common triggers include:

• foods high in acid, such as citrus fruit, cranberry juice, vitamins B and C, teas including green teas and some herbal teas, coffee including decaffeinated coffee, tomatoes

• foods that stimulate nerves, such as caffeine, cola drinks

• foods high in histamine, such as chocolate

• artificial sweeteners, carbonated drinks, spicy foods, alcohol and cigarettes

• Urine culture to exclude UTI.

Herbal:

• A TCM combination of Rosa laevigata (Cherokee rose), Smilax china (China root) and Lygodium japonicum (Japanse climbing fern) can have a urinary analgesic and anti-inflammatory effect.

Medications:²⁶

• amitriptyline 5–50 mg taken early evening. Also helps sharp pains, sleep and some migraines

• hydrozine 10–50 mg at night, especially if the woman has allergies

• oxybutinin 5 mg 1–3 times daily, solifenacin 5 mg (or half a 10 mg tablet) daily, or tolterodine 1–2 mg daily, which cause less sedation. Consider long-acting formulations.

Other treatments:

• cystoscopy with hydrodistension under anaesthesia. Plain cystoscopy is normal in most cases. View after hydrodistension shows typical bleeding glomerulations. Excludes other pathology

• pelvic floor physiotherapy for pelvic floor dysfunction. Bladder retraining is only useful where pain has already been managed

• sodium pentosan polysulfate 100 mg t.d.s.

• self-management plan for exacerbations (Box 52.2)

• intravesical heparin and lignocaine for acute exacerbations

• intravesical dimethyl sulfoxide (DMSO).

BOX 52.2 Self-management plan for acute bladder symptoms

• Drink 500 mL water mixed with 1 tsp of bicarbonate soda or 2 sachets urinary alkaliniser with paracetamol 500 mg and an anti-inflammatory.

• Follow with 250 mL water every 20 minutes, up to 500 mL.

• If no better, then urine culture (provide her with urine culture request form in case of symptoms).

• Antibiotics only if culture confirms infection.

Sharp, stabbing, burning or aching pain (neuropathic pain)

This pain is commonly neuropathic in origin. Frequently there is a history of endometriosis, although current laparoscopy may be normal. Surgery is rarely effective and may induce de novo symptoms.

Typical symptoms include:

• hyperalgesia—sensations that would normally be painful become more painful

• allodynia—sensations that would not normally be painful become painful

• wind-up pain—pain felt over a larger area when severe

• unusual sensations—sharp, stabbing, burning pains

• worse pain when tired, stressed, exercise decreases or over-exercised.

On examination, there may be reduced cold sensation or other sensory changes in the area of maximal pain.

Management options include:

• explaining that pain is due to a change in pain processing by nerves, rather than weakness on her part. Nerves may generate pain impulses spontaneously. Pain is not curable and cannot be treated with surgery, but can be managed effectively

• acupuncture ²⁷

• amitriptyline 5–25 mg taken early evening; 10 mg is often effective. Start with 5 mg nocte (half a 10 mg tablet) and increase slowly, to avoid sedation

• pregabalin 75–600 mg daily. Initially 37.5 mg dose, dissolve contents of 75 mg capsule in water and drink half (100% soluble)

• regular sleep—tired nerves are irritable

• regular gentle exercise—start slowly

• stress management—stress exacerbates but does not cause the pain

• pain clinic referral if symptoms persist.

Where effective medication has ceased, pain may not recur immediately. When pain recurs, re-commence medication. Increase or reduce doses slowly. The woman may decide to use the medication for episodes of weeks/months, then cease it until pain recurs. An exacerbation of pain may be due to increased stress, overwork, tiredness or a decrease in regular exercise.

SSRI medications and narcotics are usually ineffective. Stabbing pains may also be due to pelvic muscle spasm.

Bowel dysfunction

(See Ch 30, Gastroenterology.)

Women with chronic pelvic pain have more to gain from a good diet, and more to lose from a bad diet, than other women. Sensitisation of the bowel means that any dietary indiscretion may result in pain. Food intolerance of certain carbohydrates is common.

General measures:

• Consider lifestyle factors such as alcohol, stress, hurried meals, irregular sleep and cigarettes.

• Review her medications and herbal supplements.

• Antibiotics, antacids, laxatives, thyroid medicines, magnesium, some blood pressure tablets and several herbal therapies can worsen diarrhoea.

• Amitriptyline, iron tablets, pain killers, sedatives and other blood pressure tablets can worsen constipation.

• Consider bloods for ESR, CRP (inflammatory bowel disease), iron studies, coeliac screen.

• Consider comprehensive stool pathogen analysis by a specialised laboratory (organisms such as Blastocystis hominis, Giardia lamblia and Dientamoeba fragilis can cause persistent bowel dysfunction).

• Breath test for lactose intolerance or other food intolerances.

• Gastroenterology review for colonoscopy/endoscopy where constipation is unmanageable, there is bleeding from the bowel, inflammatory bowel disease is possible or the presence or absence of coeliac disease is uncertain.

Treat constipation:

• Increase exercise and water intake.

• Dietary fibre—consider sterculia (a low-flatus fibre supplement).

• Magnesia S. Pellegrino daily.²⁸

Treat bowel spasms and indigestion:

• peppermint oil capsules t.d.s./q.i.d. half an hour before meals for bloating and pain (may aggravate indigestion)

• anti-spasm medications such as mebeverine

• anti-diarrhoeal medications such as loperamide.

Bloating

Dietary bloating is frequently due to slow absorption of certain carbohydrates in the small intestine. If these substances reach the large intestine, they are fermented by large intestine bacteria and result in flatus, bloating, distension of the bowel and sometimes pain. Common foods of this type include:

• fructose (fructose malabsorption)—fruits with more fructose than glucose (such as apples, pears, dried fruit, fruit juice, coconut, honey) cause problems for people who absorb fructose slowly. Fruits with more glucose than fructose (such as citrus fruit, berry fruit, pineapples, kiwifruit, bananas and stone fruit) do not cause problems because the glucose facilitates fructose absorption across the bowel wall

• fructans—these are foods that release fructose when digested in the bowel. They include onions, artichokes, corn syrup, inulin (in ‘fibre-enriched’ foods) and all wheat products such as bread, biscuits, pastas, breakfast cereals and pizzas. This is another form of ‘fructose malabsorption’ and explains why some people without coeliac disease feel well on a low-gluten (i.e. low-fructan) diet

• lactose (lactose intolerance)—cottage cheese or yoghurt causes fewer problems. Alternatively, use lactose-free products or oral lactase when milk products are consumed

• raffinose and galactans—these sugars are found in brussel sprouts, cabbage, beans, cauliflower, broccoli, beans and some whole grains. Most people absorb these foods slowly, so flatus with these foods is normal

• polyols—these are artificial sweeteners such as sorbitol in chewing gum or diabetic food

Exclude coeliac disease.

Premenstrual bloating is common before a period and should resolve post menses.

A bloated feeling, associated with hypersensitivity, and sharp pains may be a feature of neuropathic pain.

For all bloating, exclude an ovarian tumour with vaginal examination or ultrasonography.

Dyspareunia

Possible causes include:

• vulvovaginal infections—vaginal swab, STD screen

• dermatological causes—lichen sclerosis, lichen planus, dermatitis, allergy, vulvar vestibulitis (tender to touch with cotton swab at posterior fourchette); consider biopsy, vulval dermatologist

• interstitial cystitis—urinary symptoms, tender anterior vagina

• pelvic floor dysfunction /vaginismus—tender, tight pelvic floor muscles. Examine with one finger pushing posteriorly on pelvic floor before speculum examination. Often secondary to another cause of pain or bladder dysfunction. Treat primary cause of pain, continence physio review to teach pelvic floor muscle relaxation, vaginal dilators, sexual counsellor, botox injection

• neuropathic pain with sensitisation of the vagina

• endometriosis in pouch of Douglas—deep dyspareunia; requires laparoscopic excision by experienced laparoscopic surgeon

• psychological causes and relationship difficulties

• other pelvic pathology.

Pelvic muscle pain

Painful pelvic muscles may mimic pelvic pathology. It is common but often misdiagnosed. Typical symptoms include:

• a chronic pain deep in the pelvis, with stabbing exacerbations, often after movement, intercourse, use of tampons or cervical smear tests. May wake her at night

• painful intercourse and a feeling that the vagina is ‘too tight’. Pain often persists next day

• pain on moving, lying flat in bed, prolonged sitting, or sometimes getting up out of a chair

• inability to pass urine at times, despite a strong urge, due to tight periurethral muscles

• pain as a bowel action is passed through the anus, due to tight perianal muscles

• possible urinary incontinence, due to urge and pelvic floor dysfunction.

On examination:

• narrowed vaginal introitus due to muscle tightness

• pain reproduced with pressure backwards on pelvic floor muscle at vaginal introitus, or laterally along pubococcygeus

• limited range of muscle movement on voluntary contraction or relaxation (short, tight muscles)

• pain on palpation laterally out to pelvic side wall (obturator internus).

Treatment options include:

• treating the precipitating causes (e.g. bladder or neuropathic)

• hot pack or hot bath for acute pain

• encouraging regular gentle exercise, starting slowly

• improving general health and posture

• pelvic floor physiotherapist for pelvic muscle relaxation training, possibly with the use of vaginal dilators

• relaxation techniques

• amitriptyline 5–25 mg in the early evening (mildly effective)

• botox injection to affected muscles.

Other musculoskeletal conditions may also cause pelvic pain. These may include trochanteric bursitis, gluteus tendinopathy, labral hip tears, iliopsoas tendinopathy. Consider physiotherapy review and MRI of hip.

WHEN TO REFER FOR LAPAROSCOPY

Many women with pelvic pain undergo multiple laparoscopies, frequently without long-term benefit. Laparoscopy is useful to:

• diagnose the presence of endometriosis

• excise endometriosis where present. This is usually beneficial for:

• dysmenorrhoea lasting longer than 2–3 days per month

• dysmenorrhoea-like pain during the month

• pain on opening bowels with periods

• deep dyspareunia where other causes of dyspareunia have been excluded

• back pain with periods (uterosacral ligament endometriosis or adenomyosis)

• provide a review of the pelvis at a later date, to manage recurrence if pain consistent with endometriosis persists and other causes of pain have been excluded.

Repeated laparoscopy with diathermy only or incomplete excision should be avoided. Endometriosis excision, particularly in the pouch of Douglas, requires advanced laparoscopic skills and equipment. Laparoscopy rarely improves:

• day 1 period pain (uterine pain)

• pelvic muscle pain

• urinary symptoms of frequency, urgency, nocturia (IC)

• superficial dyspareunia (vulvar vestibulitis, dermatological conditions, vaginal infections or neuropathic pain)

• bowel symptoms such as irritable bowel syndrome, constipation or food intolerance

• sharp, stabbing, burning pain (neuropathic pain).

PSYCHOLOGICAL SUPPORT / PSYCHOLOGIST

• Encourage the woman to become involved in her own care and take ownership of her pain. This avoids dependency and a feeling of helplessness.

• Discuss her fears, and how they apply to her situation, including:

• fear of infertility and letting her partner down

• fear of cancer; photographs taken at laparoscopy may be reassuring

• fear that she will have uncontrollable pain with no assistance

• fear that her condition will worsen and she will become dependent.

• Treat depression where present.

• Encourage her to remain involved or re-start activities she enjoys and can do, rather than concentrate on what she cannot do.

• Ensure that her family understand her condition and will support her.

• Encourage regular exercise, but start modestly to avoid pain exacerbation.

• Anticipate that even where pain is completely resolved, full recovery of confidence, optimism and independence will take some time. Regular ‘health review’ is beneficial.

MENSTRUAL MIGRAINE

Migraines are more common in women, in families and in women with endometriosis.²⁹ Menstrual migraines are migraines occurring with periods. Commonly there is a chronic low-grade headache at other times of the month too (chronic migraine), which may not be recognised as a migraine process. Headaches at the back of the head, associated with nausea, one-sided pain when severe, tender areas near the temples, pain behind the eyes, headaches on waking or pain worse with movement are all suggestive of a migraine-like process. Migraines in young children are common, and in girls they become even more common after menarche.

AETIOLOGY

There are two known causes of menstrual migraine:

• the fall in oestrogen levels at the beginning of a menses—a smaller fall in oestrogen at ovulation may trigger similar headaches in women not using the OCP. These headaches do not usually respond to NSAIDs

• high levels of prostaglandins at menses—these headaches respond to NSAID medications.

INVESTIGATIONS

A typical history of migraine at menses does not require further investigation, unless:

• the headaches have changed or started recently

• there are new sensory changes (e.g. double vision, loss of hearing, loss of feeling, weakness or abnormal movements in part of the body)

• the headache starts suddenly, is unusually painful or lasts more than 72 hours

• the headaches start after a head injury

• the woman has a stiff neck or a fever

• no one in the woman’s family has migraine headaches.

TREATMENT

Treatment involves:

• avoiding migraine triggers

• specific treatments for menstrual migraine

• preventive medications for women with chronic headache

• management of an acute migraine if it occurs.

Avoiding migraine triggers

Common triggers include:

• becoming overtired or oversleeping

• dehydration

• low blood sugar (suggest small frequent meals)

• alcohol

• hormone changes—migraines may become more frequent or severe at perimenopause, with improvement post-menopausally

• stress, or relaxation after stress (weekend migraines)

• a ‘head forward’ position of the neck

• foods containing vasoactive substances—these include:

• monosodium glutamate (MSG) (in processed and take-away food)

• nitrites (preservatives in salami/bacon/ham and some aged cheese)

• amines (many fruits and vegetables including avocados, bananas, chocolate.

• alcohol

• caffeine (may be used to treat a migraine in some cases).

An elimination–rechallenge diet may help identify triggers.

A migraine diary that records the time of the menstrual cycle, foods and drinks consumed, activities when the headache started, unusual stress and treatments used will help identify triggers.

Specific treatments for menstrual migraine

For women whose menstrual migraines are due to high prostaglandin levels (i.e. they respond to NSAIDs):

• an anti-inflammatory medication started 2–3 days before the period is due, and continued regularly for the first 2–3 days of the period, or a diclofenac 100 mg suppository early in the headache process

• a levonorgestrel-releasing IUCD (Mirena®)—will also treat painful or heavy periods and provide contraception, but will not help women with migraines triggered by a fall in oestrogen

• norethisterone 5 mg or desogestrel 75 μg every day, aiming at amenorrhoea.

For women whose menstrual migraines are due to a fall in oestrogen levels at menses:

• a 100 μg oestrogen patch at period time to stop oestrogen levels from falling at period time. Suitable for women with regular periods or who use the OCP. Use a 100 μg oestrogen patch from 5 days before menses until day 5 of the period. For the last 3 days of treatment, cut the patch in half (50 μg equivalent) so the dose decreases slowly. Where a migraine occurs at the end of the cycle, continue the patch until day 7 of the period ³⁰

• oral contraceptive pill taken continuously to avoid periods

• continuous hormone replacement therapy for women close to menopause

• a GNRHa medication with ‘add-back therapy’—usually 6 months therapy only.

The oral contraceptive pill (OCP) is relatively contraindicated in:

• women with migraine and aura

• women with migraine without aura but with one additional risk factor: age 35 years or over, diabetes, a close family member who has had a stroke, heart attack or similar ‘vascular’ disease before they were 45 years old, a high lipid (cholesterol) level, hypertension, obesity, smoking.

There are several medications used for headache prophylaxis. As none help all women, it may be necessary to try a few different medications to find one that is effective. These medications work best for chronic migraine, rather than menstrual migraine.

Common medications useful in young women include:

• amitriptyline (5–25 mg daily)—taken early in the evening to avoid morning sedation. Start with 5 mg and increase slowly. Especially suitable for women with chronic pelvic pain, bladder overactivity or poor sleep

• cyproheptadine—start with 2 mg nocte, then increase to 4 mg nocte, then 4 mg b.i.d. if needed. Useful if the woman also has allergies. Sleepiness wears off within a few days

• topiramate—start with 25 mg at night, then b.i.d. and increase if necessary. Reduces appetite, so may cause weight loss

• venlafaxine—start with 37.5 mg nocte, which may be sufficient. May cause sexual dysfunction

• pizotifen (0.5 mg daily)—weight gain and sleepiness are common

• beta-blockers—help hypertension or tachycardia, but cause reduced exercise tolerance and fatigue, and may cause sexual dysfunction.

Management of acute migraine

General measures:

• Relax in a dark, quiet room. Sleep if possible.

• Use a hot or cold pack on the head/neck or a warm shower/bath to relax tense muscles.

• Massage painful areas in the scalp, temples or shoulders.

• Relax jaw and facial muscles.

• Eat starchy food such as biscuits, rice or bread.

• Drink some water if dehydrated.

Simple medications to try:

• a single caffeinated drink—this is often helpful. Excess caffeine may cause rebound headache later, or trigger headaches in some people

• three soluble aspirin, 400 mg ibuprofen, 500 mg naproxen or diclofenac 100 mg rectal suppository (often most effective)—many women find three soluble aspirin and a cola drink taken early in a migraine very effective

• paracetamol 1 g

• metoclopramide 10 mg or prochlorperazine 5 mg for nausea.

Stronger medications:

• triptans—these are the most effective treatments available and can stop a migraine within 30 minutes if taken early. They affect the serotonin molecule in the brain and can be taken as a nasal spray, tablet or injection. The nasal spray is convenient, especially if there is nausea

• narcotic medications, often with paracetamol, an NSAID or a sedative such as doxylamine to promote sleep

• cafergot (an ergotamine compound).

While triptan medications may manage the severe headache, background ‘unwell feelings’ or milder headache may remain. Combining a triptan with one of the simpler medications or non-medication options may give the best effect.

Advise the woman to keep a dose of her medication, some food and a drink with her in case of migraine, to allow prompt treatment of a migraine if it occurs.

LEIOMYOMAS (FIBROIDS)

Leiomyomas are benign tumours of smooth muscle, commonly found in the uterus.

AETIOLOGY

The aetiology is unknown. Myomas are monoclonal. Chromosomal abnormalities are common (e.g. 12, 14 translocations, 7 deletions and trisomy 12), especially in cellular, atypical or large myomas.³⁸

FIGURE 52.13 Pathology of fibroids; locations of leiomyomas

Myoma initiation may involve intrinsic abnormalities of the myometrium, congenitally elevated myometrial oestrogen receptors, hormonal changes or a response to ischaemic injury at the time of menstruation.³⁹

Myoma growth is promoted by smooth muscle proliferation growth factors, oestrogen and progesterone. Intracellular aromatase converts androgens to oestrogens to increase intracellular oestrogen further.

Myoma size decreases with GnRH analogues or mifepristone (progesterone receptor modulator), but the myoma returns to its original size after treatment ceases.

There is no definite relationship between myoma initiation/growth and the OCP. Growth with HRT is uncommon, and where present may be due to progestin.

MYOMA CLASSIFICATION

• Submucosal—lie beneath the endometrium and bulge into the endometrial cavity. Can be seen hysteroscopically.

• Intramural—lie within the uterine wall.

• Subserous—lie on the outer (serosal) surface of the uterus. Easily seen laparoscopically.

• Pedunculated—a serosal myoma attached to the uterus by a thin pedicle. Submucosal myomas may also become pedunculated.

• Myomas of the ovaries, round ligament and cervix are less common.

SYMPTOMS

Most uterine myomas are asymptomatic.

Symptoms include:

• menorrhagia—the relationship to menorrhagia is variable; many women with fibroids have normal periods. Where menorrhagia is present, it may be due to vasoactive growth factors or to mechanical compression of veins

• pelvic pressure symptoms—e.g. heaviness in lower abdomen, urinary frequency and urgency, constipation

• dyspareunia—especially where myomas are low and posterior

• pelvic pain—uncommon; it is more common where the myoma extends laterally towards the pelvic side wall

• bleeding between periods—uncommon

• low back pain—especially after prolonged standing.

EXAMINATION

A firm, irregular, non-tender mass arising from the pelvis. May be palpable abdominally where uterine size exceeds approximately 12 weeks pregnancy size and myomas are anterior.

INVESTIGATIONS

Investigations include:

• vaginal ultrasound scan—combined abdominovaginal ultrasound for large myomas. Myomas are rounded, hypoechoic, heterogeneous, well-defined masses on ultrasound. Hyperechoic where calcification or haemorrhage is present. Anechoic in cystic areas

• saline infusion sonogram or hysteroscopy to delineate submucous myomas and assess uterine cavity

• MRI—accurate assessment of submucous myomas. Differentiates adenomyomas and presence of adenomyosis.⁴⁰

TREATMENT

Treatment options include:

• No treatment. Asymptomatic myomas where malignancy has been excluded do not require treatment.

• Exclude other causes of symptoms, e.g. other causes of menorrhagia, endometriosis, adenomyosis, ovarian mass.

• Surgical options:

• hysteroscopic resection of submucous myoma—requires > 50% myoma into endometrial cavity

• myomectomy—laparoscopic or abdominal. Allows subsequent pregnancy, but with small risk of uterine rupture and increased likelihood of caesarean section ⁴¹

• myolysis—uncommon. Cautery, laser or cryotherapy laparoscopically to decrease myoma size

• hysterectomy.

• Medical options do not improve fertility. They include:

• levonorgestrel-releasing IUCD. Decreased menorrhagia. No decrease in myoma size

• GnRH analogues. Decreased myoma size while on treatment

• progesterone receptor modulators, e.g. mifepristone (RU 486) and asoprisnil

• androgenic steroid hormones, e.g. danazol for menorrhagia

• raloxifene—postmenopausal women only.

• Uterine artery embolisation (experimental radiological procedure):

• Beads of polyvinyl alcohol are injected via radiological catheter to block both uterine arteries. Risks include infected necrotic myomas, premature ovarian failure from ovarian artery obstruction and uterine rupture with subsequent pregnancy.

MYOMAS, FERTILITY AND PREGNANCY

Growth during pregnancy or obstetric complications are uncommon. However:

• Submucous or intramural myomas with an intracavity component are associated with reduced fertility and increased miscarriage. Hysteroscopic removal of the submucous myoma returns fertility to normal.

• The relationship between intramural or subserous myomas and fertility is controversial.⁴²

• Incidence of caesarean section, malpresentation, preterm delivery, placenta praevia and postpartum haemorrhage are all slightly elevated.⁴³

• Myoma degeneration occurs in 5% of myomas during pregnancy, often with severe abdominal pain.

OVARIAN CYSTS (EXCLUDING POLYCYSTIC OVARIAN SYNDROME)

The ovary may contain a wide variety of cysts or tumours. Commonly, they include:

• functional cysts

• benign tumours—including cystadenomas derived from epithelial cell lines, germ cell tumours such as teratomas (dermoids) derived from germ cells and stromal tumours derived from ovarian stromal cells

• endometriomas

• para-ovarian (e.g. fimbrial) cysts

• malignant tumours

• tumours of low malignant potential.

PRIMARY PREVENTION

Functional cysts are common in premenopausal women. Pregnancy, breastfeeding and the OCP suppress ovulation and reduce their incidence.

SYMPTOMS

Many functional cysts are asymptomatic. Hormonal effects including menstrual irregularity, nausea, vomiting or breast tenderness are common and mimic early pregnancy. Ovarian cyst rupture may occur, with sudden acute pain spontaneously or after intercourse. The pain improves over a few hours but may be followed by an ache for a few days.

Ovarian cysts of any kind may cause:

• pressure symptoms, e.g. urinary frequency, constipation, fullness in abdomen, tighter clothing

• menstrual irregularities

• dyspareunia

• pelvic pain

• ovarian torsion—sudden acute pain with vomiting, raised pulse rate and sometimes fever. Commonly involves a benign cyst of moderate size on a long ovarian pedicle. Torsion is an acute medical emergency similar to torsion of the testis. It requires urgent laparoscopy to untwist the ovarian pedicle and avoid loss of the ovary.

Women with endometriomas may describe typical symptoms of endometriosis or be asymptomatic.

Women with ovarian cancer present with non-specific symptoms that include abdominal pain, bloating, difficulty eating/feeling full, urinary frequency or abdominal distension. There may be changes in bowel habit frequently misdiagnosed as irritable bowel syndrome. Ovarian cancer should always be considered in women with recent-onset non-specific abdominal symptoms.

Hormone-producing tumours are uncommon. Symptoms depend on the hormone produced, e.g. oestrogen from granulose cell tumours, testosterone from an androblastoma.

• Haemorrhage in a functional cyst may result in a larger cyst with bizarre intracystic echoes that may mimic an endometrioma but resolve within 3 months.

• Endometriomas have a grey, homogenous ‘ground glass’ appearance.

• Teratomas (dermoids) contain highly echogenic sebaceous or calcium-containing tissue.

• Serous cystadenomas are typically unilocular.

• Mucinous cystadenomas are typically multilocular.

• Complex cysts (unilateral or bilateral) or the presence of increased abdominal fluid/ascites must have malignancy excluded.

• The ovarian crescent sign (OCS) has been proposed, to differentiate benign and malignant disease. The OCS is defined as a rim of visible healthy ovarian tissue in the ipsilateral ovary. Where absent, invasive cancer is more likely.⁴⁵

Vaginal ultrasound provides a clearer view of the ovaries than abdominal ultrasound in most women. Abdominal ultrasound scans are appropriate for children, virgins, very large ovarian cysts or where vaginal ultrasound would cause pain or distress.

It is normal to see a 2–3 cm fluid-filled ovulation cyst/corpus luteum from ovulation until menses. To minimise false positive results, request ultrasound scans in the early follicular phase.

CT scans assess the extent of metastatic disease.

MRI may be used to assess bowel or bladder infiltration in the presence of endometriomata.

Abdominal X-ray is rarely indicated but will show the teeth or bone frequently present in a teratoma (dermoid). Radiation to the ovaries of young women should be minimised.

• serous, clear cell and endometrioid cystadenocarcinoma, but not mucinous cystadenocarcinoma

• endometriosis—mild elevation

• other benign conditions including fibroids, adenomyosis, diverticulitis, pelvic inflammatory disease, normal menstruation and liver disease

• other malignant conditions including cancer of the pancreas, breast, lung and colon.

As CA 125 is raised in a wide variety of benign conditions, it should not be used for screening, or for cysts with benign features. It is of most use in:

• postmenopausal women with an ovarian cyst, where malignancy is possible. CA 125 levels are raised in 80% of advanced ovarian cancers, but only 50% of stage 1 disease ⁴⁶

• follow-up of known ovarian malignancy to assess treatment response.

Other tumour markers used to distinguish benign from malignant disease are discussed below.

Risk of malignancy index

The risk of malignancy index (RMI, Table 52.1) combines menopausal status, CA 125 level and ultrasound features to predict the risk of ovarian malignancy in a known cyst. Two scores have been used: RMI 1 and RMI 2.

TABLE 52.1 Risk of malignancy index