Conditions Causing Amenorrhoea

Imperforate hymen

Transverse vaginal septum

Mullerian agenesis

Asherman's syndrome

Polycystic ovarian syndrome (PCOS)

Chromosome abnormalities

Premature menopause

Prolactinoma

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IMPERFORATE HYMEN

Diagnosis

• Primary amenorrhoea with cyclic abdominal pain, then continuous
• Pelvic mass (haematocolpos), +/- abdominal mass (haematometra)
• Hymen appears as a bulging bluish membrane at the introitus
• Sonar findings are immediately diagnostic. Longitudinal view

Management

1. Incision and drainage on the next emergency list
2. The hymen is easily incised (under anaesthesia)
3. A large amount of viscous dark fluid (old menstrual blood) will be released
4. Warn the patient and her caregiver that the old blood will continue to drain for several days, and to wear protection

TRANSVERSE VAGINAL SEPTUM

Diagnosis

• Primary amenorrhoea, with cyclical abdominal pain, then continuous
• Pelvic mass (haematocolpos), +/- abdominal mass (haematometra)
• The septum is paler, more pink and more solid than an imperforate hymen
• The septum may be hidden in the vagina, or present at the introitus
• Look for associated urinary tract abnormalities (IVP & sonar)

Management

1. Incision is not as simple as with imperforate hymen, and may need to be repeated
2. Do the operation on a routine elective list, supervised by a consultant
3. Though awkward in a teenager, the patient, once immediate healing has occurred, MUST use a vaginal dilator(syringe barrel without tip) for 5 mins daily until intercourse is started. IF NOT a ring of fibrosis will form, & prevent later intercourse completely. This is difficult to explain but very important

MULLERIAN AGENESIS (‘Mayer-Rokitansky-Kuster-Hauser Syndrome’)

Diagnosis

• In this condition, there is no uterus or cervix (1 in 4000)
• The patient appears as a normal XX female
• The vagina ends as a blind pouch, with no uterus seen on ultrasound scan
• There is normal pubic/axillary hair
• Differential diagnosis includes Androgen Insensitivity (pubic/axillary hair absent), 5-alpha reductase deficiency and other androgen synthesis or receptor errors
• Hormone profiles & karyotype are entirely normal
• Urinary tract abnormalities may co-exist

Management – should be strictly consultant driven

Do MRI to confirm diagnosis

There is no need for hormone replacement therapy

Counselling on infertility, sexual function & coping is essential (refer to Psychologist and communicate with that person)

Investigate for associated urinary tract abnormalities (MRI, IVP, sonar [at presentation])

Vaginal lengthening can be by pressure (intercourse, dilator [Frank technique]) or by a highly complex neo-vagina operation often using sigmoid.

ASHERMAN’S SYNDROME (INTRAUTERINE ADHESIONS or ‘synechiae’)

Diagnosis

• There is a history of previous curettage, almost always after a pregnancy
• Physical examination is normal
• The progestogen challenge test is negative
• Hormone profiles are normal
• Hysteroscopy and/or hysterosalpingogram confirm the diagnosis

Management

1. Open or hysteroscopic resection of adhesions 
2. Insertion of an IUCD after resection
3. High-oestrogen oral contraceptive pill (e.g. Ovral)
4. The possibility of pregnancy depends on the extent of the Asherman’s graded 1-3
5. After treatment: there is persistent risk of infertility, miscarriage, APH, IUGR, premature labour, & hysterectomy placenta accrete occurs 

POLYCYSTIC OVARIAN SYNDROME (PCOS) – one of the commonest causes of 2⁰ amenorrhoea

Diagnosis

• The Rotterdam Criteria: 2 out of 3 – oligo/anovulation, PCOS on sonar, clinical/serological hyperandrogenism
• Obesity & hirsutism may be present but not always
• LH to FSH ratio may be high (3:1)
• Testosterone may be raised (2-5 nmol/L, but not >6 nmol/L, that suggests a specific pathological secreting tumour)
• DHEAS may be slightly raised (not specific to PCOS). Don’t order it
• Transvaginal scan may show typical peripheral ovarian cysts, 12 or more, 2-10mm in diameter in a ‘pearl necklace’ peripheral distribution, the stroma is denser (whiter), the ovary large, the capsule may be prominent

Management

1. Reassurance is not sufficient if menstrual abnormalities, infertility and hirsutism are troublesome
2. If obese, it is essential for the patient to lose weight. This may be CAUSING the problem. Not always
3. Patients not desiring fertility can be given a combined oral contraceptive (avoid androgenic preparations e.g. those containing levonorgestrel or norethisterone). If hirsutism is present those containing ciproterone acetate or drosperinone can be used. N.B. these are expensive
4. Those desiring fertility will require Clomiphene (50-150mg po od on days 2-6 of a cycle following a withdrawal bleed after progesterone 5-10mg for 5-10 days. Ovulation occurs in 90%, pregnancy in < 50%.
5. Metformin may be of value in cases of insulin resistance* or Clomiphene failure (*fasting insulin levels to define insulin resistance are contested)
6. Low-dose oral dexamethasone may be of value
7. If hirsutism is troublesome, antiandrogens such as Cyproterone acetate or spironolactone should be used. Again weight loss if obese
8. Patients with PCOS must be managed by a consultant and referred to a specialist gynae clinic if available. ALWAYS other infertility causes should be excluded. 

CHROMOSOME ABNORMALITIES

CHROMOSOME ABNORMALITIES in amenorrhoea usually affect the ovary/gonad, occasionally the hypothalamus (Primary)

Diagnosis

• Learn to recognize the cardinal features of each condition. Syndromic ovarian dysgenesis individuals often <155cm tall – Turner’s syndrome (XO, webbed neck, short stature, multiple naevi, radio-femoral delay, diminished secondary sexual characteristics (beware Turner mosaic…)), Androgen Insensitivity (formerly testicular feminization) (XY, normal height, normal breasts, no body hair, normal vulva, introitus, blind ending vagina, gonads (testes) in pelvis or inguinal canal must be removed to prevent cancer then HRT) Ovarian dysgenesis (XX or rarely XY, varying degrees of secondary sexual characteristics) etc.
• Physical examination and hormone profile may suggest the condition
• Karyotyping is essential for correct diagnosis

Management

1. All such cases must be discussed with a consultant
2. Avoid injudicious remarks about genitalia or chromosomes. An adolescent or adult patient who appears female IS female
3. An androgen insensitivity individual is NOT male but female
4. A female patient with XY is at risk of gonadal malignancy and must have gonadectomy by laparoscopy, laparotomy (but not if gonads are in the inguinal canal – check first) 

PREMATURE MENOPAUSE

Diagnosis

• This is menopause before the age of 40 years
• NB ask for symptoms: hot flushes & night sweats
• The FSH level is >30 IU/L on two occasions 4 weeks apart
• If FSH < LH, & FSH >15 IU/L this may be a ‘surge’ value before ovulation, therefore repeat after at least a week. If FSH >15 and FSH > LH this suggests menopause. Inhibin levels & AMH (anti-mullerian hormone levels) may also fall – the latter may be used in IVF programmes to predict stimulation success

Management

1. Reassure the patient that there is a range of ages at which menopause occurs, & that this does not mean she is ‘old’
2. Consider the need for hormone replacement. Osteoporosis risk (Osteoporosis). Fertility issues (prospects are v poor) & other gland involvement should be considered 

PROLACTINOMA

Diagnosis

• Patients may present with menstrual disorder and/or galactorrhoea
• The prolactin level will be >29 ng/mL (in the non-pregnant)
• Increased prolactin levels may occur with pregnancy, hypothyroidism & with use of certain drugs (HCTZ, Aldomet), hypothyroidism - take blood for TSH level, & after chest trauma
• In female patients, only 10% of prolactinomas are macroadenomas (>1 cm diameter and cause headache, tunnel vision), in males it is 50%
• Ask about pressure symptoms – headache & visual problems (less common in females)
• Arrange a CT scan of the brain, or consider an MRI scan
• Arrange for visual field testing (ophthalmology consult if macroadenoma; you can test also). Bitemporal hemianopia is almost always not noticed by the patient

Management

1. Explain the condition to the patient
2. Refer to the Endocrine clinic or discuss with an experienced consultant
3. Management may depend on the patient’s needs – fertility, menstrual cycle control, or control of galactorrhoea
4. Surgery or radiotherapy are very rarely used
5. Oral bromocriptine (Parlodel) is an effective first-line drug:
   • Start with 1.25 mg at night (to avoid postural hypotension) for 3 days, then 2.5 mg nocte for 3 days, then 2.5 mg twice daily, with meals.
   • Follow up monthly; the prolactin level should reduce
   • The dosage may be slowly increased (rarely up to 30 mg daily)
   • Side-effects include nausea, postural hypotension and dizziness
6. Oral cabergoline (Dostinex) is a second-line agent:
   • Start with 0.5 mg weekly, increase if necessary up to 1 mg twice weekly, rarely to 4 mg per week
   • Side-effects and follow-up are as for bromocriptine

Pregnancy & prolactinoma

1. Patients not desiring fertility should use contraception (combined pill, injectable)
2. If patients on treatment for prolactinoma report amenorrhoea, consider pregnancy as a cause
3. Pregnancy is not a reason to stop bromocriptine or cabergoline

OTHER CAUSES OF AMENORRHOEA

These include delayed puberty, anorexia nervosa, cachexia, psychological stress, athletic training, Sheehan’s syndrome, previous meningitis, head trauma, intracranial space occupying lesions, Cushing’s syndrome & hypothyroidism.

Diagnosis

• Take a careful history & do a full clinical examination
• If the cause is not obvious, refer to a consultant or the Endocrine clinic
• Physiological delay may be confirmed by delayed ossification in wrist X ray

Management

• Anorexia nervosa should be referred to a psychiatrist
• Unexplained weight loss, Cushing’s syndrome & thyroid disorders require referral to specialist physicians
• Sheehan’s syndrome requires referral to the Endocrine clinic
• Neurological disorders affecting pituitary function should be referred to physicians & neurologists