Amenorrhea/Oligomenorrhea
last authored: April 2012, David LaPierre
last reviewed:
Introduction
Amenorrhea describes a lack of menstrual flow, while oligomenorrhea is defined by menstrual cycles that are longer than normal - over 35 days. Both may be related to hormone function or the reproductive system.
Amenorrhea is classified as either primary or secondary. Primary amenorrhea describes:
- no menses by age 16 with the presence of secondary pubertal changes
- no menses by age 14, with no secondary pubertal changes
- no menses 4 years after thelarche
Secondary amenorrhea occurs after the beginning of menarche, followed by 6 months, or three missed cycles, of menses.
The Case of Alice W.
Alice is a 34 year-old woman who is trying to become pregnant. Her cycles have been irregular for the past three years, after the birth of her son. She has not had a period in 2 months now, but a pregnancy test she took last week was negative.
- What questions do you ask Alice?
- What investigations do you organize?
Causes and Risk Factors
Normal physiologic events such as pregnancy, breastfeeding, and menopause are by far the most common cause of secondary amenorrhea.
Other causes and may be broken down according to the location of concern.
- central
- peripheral
- outflow tract
central - hypothalamic or pituitary failure
Primary causes are normally genetic. In these conditions, FSH is normally decreased, resulting in hypogonadotrophism.
- idiopathic (most common cause)
- Kallmans's syndrome:
- X-linked, autosomal dominant
- GnRH neuron deficiency
- anosmia (no sense of smell)
- congenital hypopituitarism
- Prader-Willi syndrome
- Lawrence-Moon-Beidi
Secondary causes related to the hypothalamus or pituitary are more likely environmental and reversible. FSH may be normal.
- pregnancy, breastfeeding
- hypothyroidism
- hyperthyroidism
- hypothalamic dysfunction (very common)
- drugs (ie marijuana)
- stress
- malnutrition, including anorexia
- extreme exercise
- chronic disease (eg inflammatory bowel disease, sickle cell anemia, cystic fibrosis)
- hypothalamic tumour
- hyperprolactinemia
- pituitary lesion
- medications: antipsychotics, TCAs alpha methy-dopa
- hypothyroidism
- renal failure
- Sheehan syndrome (pituatary necrosis secondary to postpartum hemorrhage)
- polycystic ovarian syndrome
- testosterone administration
- adrenal hyperplasia
- Cushing's syndrome
peripheral - ovaries
Primary causes - hypergonadrotrophic - FSH is increased
- ovarian agenesis
- ovarian dysgenesis (eg Turner's syndrome (XO))
- enzymatic deficiency
Secondary amenorrhea (or primary)
- menopause
- premature ovarian failure (1-3% of women under 40)
- idiopathic
- genetic: Turner's mosaic, enzyme deficiencies
- autoimmune (associated with autimmune thyroiditis, SLE, type 1 diabetes)
- ovarian damage (chemotherapy, radiation, surgery)
- mumps infections
- smoking (smokers reach menopause on avg 1-2 years earlier)
- polycystic ovarian syndrome: LH/FSH ratio >2
- ovarian tumour
outflow tract - (uterus, cervix, vagina)
eugonadotrophic: LH/FSH is normal
- imperforate hymen
- transverse septum in the vagina
- agenesis/dysgenesis of cervix leading to stenosis
agenesis of vagina and uterus
- Mullerian agenesis (Mayer-Rokitansky)
- mullerian duct agenesis
- 1/4,000= 1/10,000
- renal and skeletal anomalies
- normal ovaries
- treat with vaginal dilatation or vaginoplasty
- AIS: androgen insensitivity syndrome (formerly testicular feminization)
- X-linked recessive
- 1/13,000 births
- no ovaries
- undescended testes: can become malignant
- treat with gonadectomy, estrogen replacement, vaginal dilatation
secondary amenorrhea
- uterus: synechiae (Asherman's syndrome: adhesions from repeated D and C)
History and Physical Exam
- history
- physical exam
History
Questions will depend on possible cause:
- pregnancy: nausea, breast fullness
- menopause: hot flashes, night sweats, mood changes
- hypothalamic or pituitary: galactorrhea, headache, visual changes
- endocrine: weight change, signs of virilization, hypothyroid/hyperthyroid symptoms
- hypothyroidism (cold intolerance, dry hair, constipation, weight gain, fatigue, etc)
- cyclical abdominal pain
puberty
- age of breast development
- pubertal growth spurt
- adrenarche
medical history
- chronic disease
- operations
- chemotherapy, radiation
family history
- delayed puberty
social history
- exercise and diet patterns
- drugs
- sexual activity
medications
- metoclopramide
- systemic steroids
- oral contraceptive pills
- depo-provera
- neuroleptics
- danazol
Physical Exam
overall appearance
- height, weight, plot BMI (anorexia)
- vital signs
head and neck exam
- evidence of tooth erosions, palate damage (bulemia)
- webbed neck (Turner syndrome)
thyroid exam
neurological exam
- visual fields testing
- fundoscopic changes
- olfaction (pituitary dysfunction)
skin exam
- acne (androgenization)
- hirsuitism (androgenization)
- acanthosis nigracans
breast exam
- breast development
- galactorrhea
Tanner staging
abdominal exam
- masses
- tenderness
external genitalia
- clitoromegaly (androgen excess)
- sparse pubic hair (androgen insensitivity or deficiency)
- imperforate hymen
- vaginal septum
- vaginal agenesis
pelvic exam : tough if they are not sexually active. ultrasound instead?
- ovarian enlargement (tumour, PCOS)
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
low or normal FSH, LH
- hypothalamic
high FSH, LH
- ovarian
Labs will should be based on history and physical findings.
- beta-hCG (rule out pregnancy)
- CBC (overall health)
- prolactin (increased in prolactinoma, hypothyroidism, medications)
- FSH and LH (see box at right)
- TSH
- estrogen, testosterone, DHEA
- bone age (for primary)
- karyotype (primary, or for women <30 with ovarian failure)
- progesterone challenge to assess for withdrawal bleeding (suggests problem with ovulation)
With secondary amenorrhea, always begin with beta-hCG to rule our pregnancy.
Diagnostic Imaging
Ultrasound can be done to assess pelvic anatomy and if PCOS is suspected.
CT or MRI of the head may be done if FSH/LH are low without good cause, or if a prolactinoma is suspected.
Hysterosalpingogram may be done if Asherman syndrome, cervical stenosis, or infection may be present.
Management
For hypothalamic dysfunction, remove offending medications, decrease stress, increase nutrition.
For hyperprolactinemia, bromocriptine or carbergoline may be used.
A progesterone challenge test can be done, resulting in a withdrawal bleed if the HPG axis is intact.
In cases of premature ovarian failure, or primary amenorrhea, hormone replacement may be helpful for maintaining secondary sexual characteristics, preventing osteoporosis, and reducing menopausal symptoms.
If PCOS is the cause, weight loss may be helpful.
Pathophysiology
Resources and References
Topic Development
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