Amenorrhoea

 

Amenorrhoea is the absence or cessation of menses.  It may be physiological (before puberty or due to pregnancy, lactation, or menopause), pathological, or iatrogenic (for example due to contraceptives or surgery).  Amenorrhoea can be classified as primary amenorrhoea or secondary amenorrhoea.  The prevalence of amenorrhoea not due to pregnancy, lactation, or menopause is approximately 3–4% in women of reproductive age

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Primary amenorrhoea

Definition

Primary amenorrhoea can be defined as:

  • the absence of menstrual periods by age of 16yrs with normal secondary sexual characteristics or
  • the absence of menstrual periods by age 14yrs with no secondary sexual characteristics

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Causes

NOTE Causes can include physiological causes such as pregnancy and constitutional delay (the most common physiological cause), as well as pathological causes (some of which are shown below)

Causes of primary amenorrhoea include:

  • Imperforate Hymen
  • Transverse vaginal septum
  • Vaginal atresia
  • Congenital absence of uterus
  • Congenital adrenal hyperplasia
  • Chromosomal abnormality – Fragile X, Turner’s syndrome
  • Depression and emotional or physical stress
  • Malnutrition or chronic disease
  • Weight loss and eating disorders
  • Post chemo-radiation ovarian failure
  • Post-encephalitis

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Assessment to identify underlying cause

  1. Exclude pregnancy
  2. Enquire about:
    1. Cyclical lower abdominal pain (suggesting haematocolpos caused by a genital tract malformation)
    2. Stressdepressionweight loss, disturbance of perception of weight or shape, level of exercise, and chronic systemic illness (suggesting hypothalamic dysfunction)
    3. Headache, visual disturbance, or galactorrhoea (suggesting prolactinoma)
    4. Sexual history and contraception (suggesting pregnancy or a contraceptive cause of amenorrhoea)
    5. Age at menarche of mother and sisters (family history of late menarche suggests constitutional delay)
    6. Family history of genetic anomalies (for example androgen insensitivity [46XY female])
    7. Drugs (such as antipsychotics), previous chemotherapy or radiotherapy, and illicit drug use (in particular opiates and cocaine)
  3. Measure height and body weight, and calculate body mass index (BMI) (that might suggest amenorrhoea secondary to a low BMI)
  4. Examine for:
    1. Features of Turner's syndrome (short stature, web neck, shield chest with widely spaced nipples, wide carrying angle, and scoliosis)
    2. Hirsutism, acne and weight gain (suggesting polycystic ovary syndrome)
    3. Signs of thyroid and other endocrine disease
  5. If appropriate examine for:
    1. Clitoromegaly (indicating virilization due to possible androgen-secreting tumour) if hirsutism is present
    2. Galactorrhoea (suggesting raised prolactin)
    3. Haematocolpos (if there is a history of cyclical lower abdominal pain — separation of the labia reveals a bulging blue-coloured membrane and a pelvic mass may be palpable)
    4. Features of androgen insensitivity (absence of axillary and pubic hair with normal breast development; testes may be palpable in the inguinal canal or labia)
  6. Pelvic examination:
    1. This is inappropriate in young girls who are not sexually active; ultrasonography can be done to assess pelvic anatomy
    2. In older women presenting with primary amenorrhoea, it may be appropriate to do a pelvic examination, for example to look for an absent uterus

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Investigations prior to referral

The following preliminary investigations may help facilitate diagnosis and should be undertaken if the decision is taken to refer:

  • FSH/LH
  • TSH
  • Prolactin
  • Testosterone (if symptoms and signs of androgen excess)
  • Pelvic Ultrasound (if the presence of a vagina and uterus cannot be confirmed by physical examination or in young girls who are not sexually active in place of a pelvic examination)

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Management and referral

In general, refer for specialist investigation and, where appropriate, management of the cause:

  1. Girls who have no secondary sexual characteristics who have not started menstruating by 14 years of age
  2. Girls with normal secondary sexual characteristics who have not started menstruating by 16 years of age

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Refer at an earlier age if the girl, or her parents are concerned or if an abnormality is suspected — for example, in girls and women with:

  1. Growth retardation
  2. Symptoms and signs of androgen excess (such as hirsutism) or thyroid disease
  3. Galactorrhoea
  4. Suspected genital tract malformation, intracranial tumour (for example prolactinoma), chromosomal anomaly (for example Turner's syndrome or androgen insensitivity), or anorexia nervosa
  5. Puberty lasting 5 years without menarche (for example presenting at 15 years of age when pubic hair and breast development started at 10 years of age)

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Referral to a gynaecologist (preferably with a special interest in adolescent gynaecology) is appropriate for most girls and women

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Refer to an endocrinologist those girls and women with hyperprolactinaemia, thyroid disease, or signs of androgen excess

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Manage amenorrhoea caused by weight loss, excessive exercise, stress, or chronic illness after an endocrinologist has assessed and excluded a hypothalamic or pituitary tumour, for:

  1. Weight related amenorrhoea — encourage weight gain and refer to a dietician if necessary. If an eating disorder is suspected, consider referral to a psychiatrist
  2. Exercise related amenorrhoea — advise reducing exercise, increasing calorie intake, and weight gain. Consider referral to, or liaison with a sports physician, if available
  3. Stress-related amenorrhoea — consider measures to manage stress and improve coping strategies, such as cognitive behavioural therapy

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If amenorrhoea persists for more than 12 months, consider whether osteoporosis prophylaxis is required

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Information to include in referral letter

Include the following information when making a referral:

  • Secondary sexual development
  • FH of delayed menarche
  • PMH
  • Current regular medication
  • Height/weight/BMI – growth chart
  • Smoking status
  • Blood test results
  • USS report

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Secondary amenorrhoea

Definition

Primary amenorrhoea can be defined as:

  • the absence of menstruation for at least 6 months in women with previously normal and regular menstruation

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Causes

Physiological causes of secondary amenorrhoea include:

  • pregnancy
  • lactation
  • menopause

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Pathological and iatrogenic causes include:

  • polycystic ovary syndrome
  • hypothalamic dysfunction (by weight loss, excessive exercise, or chronic systemic illness)
  • premature ovarian failure
  • hyperprolactinaemia

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Assessment to identify underlying cause

  1. Exclude pregnancy and other physiological causes, such as lactation or menopause (in women 40 years of age or older)
  2. Exclude Hypothyroidism — menses may take several months to resume with treatment
  3. Enquire about:
    1. The duration of amenorrhoea
    2. Contraceptive use (combined oral contraceptive may cause amenorrhoea for up to 6 months after stopping treatment and injectable progesterone for up to 9 months)
    3. Hot flushes and vaginal dryness (suggesting premature ovarian failure)
    4. Headaches, visual disturbances, or galactorrhoea (suggesting a pituitary tumour)
    5. Acnehirsutism and weight gain (suggesting polycystic ovary disease)
    6. Weight loss (suggesting an eating disorder)
    7. Stress or depression (suggesting stress-related hypothalamic amenorrhoea)
    8. Exercise levels (suggesting exercise-associated hypothalamic amenorrhoea)
    9. Symptoms of thyroid and other endocrine disease
    10. A history of obstetric or surgical procedures (such as endometrial curettage) that may have resulted in intrauterine adhesions)
    11. A history of chemotherapy; pelvic radiotherapy (which can cause premature ovarian failure); and cranial radiotherapy, head injury, or major obstetric haemorrhage (which can cause hypopituitarism)
    12. Drugs (such as antipsychotics which can cause increased prolactin levels) and illicit drug use (in particular cocaine and opiates which can cause hypogonadism)
    13. family history of cessation of menses before 40 years of age (for premature ovarian failure)
  4. Measure height and body weight, and calculate body mass index (for weight-related causes for amenorrhoea)
  5. Examine for:
    1. Galactorrhoea, if appropriate (suggesting raised prolactin levels)
    2. Signs of excess androgens (hirsutism, acne) or virilization (hirsutism, acne, deep voice, temporal balding, increase in muscle bulk, breast atrophy, and clitoromegaly)
    3. Signs of thyroid disease
    4. Signs of Cushing's syndrome (striae, buffalo hump, significant central obesity, easy bruising, hypertension, and proximal muscle weakness)
    5. Assess visual fields if a pituitary tumour is suspected

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Investigations prior to referral

The following preliminary investigations may help facilitate diagnosis and should be undertaken if the decision is taken to refer:

  • FSH/LH
  • TSH
  • Prolactin
  • Total Testosterone
  • Pelvic Ultrasound (if polycystic ovary syndrome is suspected)

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Management and referral

Manage girls and women with the following causes for secondary amenorrhoea in primary care:

  1. Polycystic ovary syndrome when appropriate
  2. Hypothyroidism — menses may take several months to resume with treatment
  3. Menopause (women 40 years of age or older)
  4. Pregnancy

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Refer all other girls and women for specialist investigation and, where appropriate, management of the cause:

  1. Refer to a gynaecologist if she has any of the following:
    1. Persistently elevated FSH and LH levels — which suggests premature ovarian failure in women younger than 40 years of age
    2. Recent history of uterine or cervical surgery (such as endometrial curettage, Caesarean section, or myomectomy) or severe pelvic infection (endometritis) — which suggests Asherman's syndrome or cervical stenosis
    3. Infertility
    4. Suspected polycystic ovary syndrome, if diagnosis and management are not feasible in primary care
  2. .Refer to an endocrinologist if she has any of the following:
    1. Hyperprolactinaemia: serum prolactin level greater than 1000 mIU/L, or 500–1000 mIU/L on two occasions. This includes girls and women on drugs that are known to increase prolactin levels
    2. Low FSH and LH levels (to exclude hypopituitarism or a pituitary tumour, although stress, excessive exercise, or weight loss are more likely causes)
    3. An increased testosterone level that is not explained by polycystic ovary syndrome (suggesting an androgen-secreting tumour, late-onset congenital adrenal hyperplasia, or Cushing's syndrome)
    4. Other features of Cushing's syndrome or late-onset congenital adrenal hyperplasia (besides an increased testosterone level)

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Manage amenorrhoea caused by weight loss, excessive exercise, stress, or chronic illness after an endocrinologist has assessed and excluded a hypothalamic or pituitary tumour, for:

  1. Weight related amenorrhoea — encourage weight gain and refer to a dietician if necessary. If an eating disorder is suspected, consider referral to a psychiatrist
  2. Exercise related amenorrhoea — advise reducing exercise, increasing calorie intake, and weight gain. Consider referral to, or liaison with a sports physician, if available
  3. Stress-related amenorrhoea — consider measures to manage stress and improve coping strategies, such as cognitive behavioural therapy

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Offer contraceptive advice to women who do not wish to become pregnant, as a small number of women with secondary amenorrhoea will become pregnant

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If amenorrhoea persists for more than 12 months, consider whether osteoporosis prophylaxis is required

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Information to include in referral letter

Include the following information when making a referral:

  • Secondary sexual development
  • FH of delayed menarche
  • PMH
  • Current regular medication
  • Height/weight/BMI – growth chart
  • Smoking status
  • Blood test results
  • USS report

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Blood tests / Phlebotomy

If your practice does not have a practice nurse who is trained to take bloods, you can refer a patient to the Pathology Department at East Kent Hospitals for a blood test (find details here)

Alternatively, Buckland Hospital (Dover) and the Royal Victoria Hospital (Folkestone) both operate a walk-in service where no appointment is necessary, except for if the patient requires a Glucose Tolerance Test (GTT).  In the event that a GTT is required, please call 01304 222552 (for Buckland) and 01303 854484 (for Royal Victoria) to arrange a suitable appointment

Please ensure that the patient remembers to take with them their blood test form to the walk-in centres

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Ultrasound

For ultrasonography investigations you refer a patient to one of the following acute or community ultrasound providers (find details here)

Advice and Guidance is being made available for all specialties, and is being provided by consultant specialists at East Kent Hospitals.  To make a request or to check to if a query has been answered, you will need to log in via the electronic Referral System (eRS)

Click here for the "how to access" e-Referral Advice and Guidance Manual for instructions on how to make a request and check responses

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