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Amenorrhoea

Amenorrhoea is the absence or abnormal cessation of the menses. Primary and secondary amenorrhoea describe the occurrence of amenorrhoea before and after menarche. Amenorrhoea is not a diagnosis in itself but rather a sign of a disorder.

Primary amenorrhoea –absence of menses by 14 yrs of age in the absence of 2ary sexual characteristics OR absence of menses by 16 yrs of age regardless of the presence of normal growth and development including secondary sexual characteristics

Other definitions of Primary amenorrhoea include 
 Failure to establish menstruation by 15 yrs of age in those with normal secondary sexual characteristics such as breast development OR Failure to establish menses by 13 yrs of age in those with no secondary sexual characteristics.

Secondary amenorrhoea –Secondary is described as cessation of menstruation in a woman
 who has experienced menstrual bleeding previously for 3 normal cycles or for 6 months in women with previous oligomenorrhoea. Other definitions include
 the cessation of menses for 3 months in women with previously normal menstruation ,or for 9 months in women with previous oligomenorrhoea the cessation of menstruation for atleast 6 months in women wit previously normal and regular menses , or for 12 months in women with previous oligomenorrhoea

Oligomenorrhoea is menses happening less frequently than every 35 days



How common ? The most common cause of amenorrhoea in a women of child bearing age is pregnancy and lactation The majority of causes of primary and secondary amenorrhoea are similar Prevalence of amenorrhoea not due to pregnancy , lactation or menopause is thought to be between 3-4 % Primary amenorrhoea – prevalence is 0.3 % Although the list of causes which can cause amenorrhoea is extensive -majority 
of causes of secondary amenorrhoea are caused by 4 conditions
1 polycystic ovarian syndrome
2 hypothalamic amenorrhoea
3 hyperprolcatinemia
4 ovarian failure A focused history and examination to evaluate for these 4 conditions can identify these four conditions.

Causes -A full list of causes is beyond the scope of this review and is rarely needed in primary care -only required in highly specialized referral centers. If primary amenorrhoea is suspected patient should be referred promptly to secondary care.

 It is important to remember that amenorrhoea indicates failure of the hypothalamus-pituitary-gonadal axis to induce cyclical change in the endometrium that normally results in menses and may also result from the absence of end organs or from obstruction of the outflow tract.

History-Menstrual history Development of secondary sexual characteristics Any symptoms in history suggestive of hypothalamic amenorrhoea Cyclical abdominal pain Family history Sexual and contraceptive history Obstetric and fertility history Past medical history e.g
diabetes
immunodeficieicny
malignancy
haematological disorders
CKD Drug use ( e.g antiepileptic medications ) Eating and exercise patterns Changes in weight / psychological stress / dysfunction Alcohol – malnutrition and cirrhosis associated with alcoholism.

Examination tests –Check BMI Blood pressure Pelvic exam – in women who have never been sexually been active -omit External genitalia inspection may be appropriate Tanner staging for breast development Look for 
○ galactorrhoea ( if appropriate suggesting ↑ prolactin )
○ androgen excess → hirsuitism or acne
 • virilization → hirsuitism , acne , deep voice , temporal balding 
 ↑ in muscle bulk , breast atrophy , clitoromegaly
○ signs of thyroid disease
○ signs of Cushing’s syndrome
 • striae
 • buffalo hump
 • sig central obesity
 • easy bruising
 • hypertension
 • proximal muscle weakness
○ visual fields if pituitary tumour suspected Acne , virilization or hirsuitism may suggest hyperandrogenism Physical features of Tuner’s syndrome ( for eg dysmorphic features as a webbed neck or low hairline )

Tests –Pregnancy test FBC – chronic disease LH and FSH
○ ovarian failure
○ hypothalamic cause
○ PCOS Prolactin level
Thyroid function test


Total testosterone and DHEAS if clinical signs of hyperandrogenism is suspected
SHBG ( in secondary amenorrhoea only ) Pelvic Ultrasound- used to confirm presence or absence of uterus /structural abnormalities of the reproductive tract
○ PCOS
○ endometrial thickness- thin endometrium in premature ovarian failure Karyotyping if a chromosomal disorder is suspected ( specialist clinics )

Primary amenorrhoea-Genital examination is abnormal in approximately 15 % of women with primary amenorrhoea A blind or absent vagina with breast development usually indicates Mulllerian agenesis , transverse vaginal septum or androgen insensitivity syndrome Presence of breast development means there has been previous estrogen action Appearance of pubic hair depends on adrenal androgen production and normally precedes the menarche by only a few months Prevalence of primary amenorrhoea is very low ( 0.3 % )

Primary amenorrhoea- our role is recognition and referral – all suspected primary amenorrhoea cases should be referred It would be reasonable to offer baseline blood tests and an US Refer girls who have no secondary sexual characteristic who have not started to menstruating by 13 yrs of age Normal 2ary sexual characteristics who have not started menstruating by 15 yrs of age Also refer if parents are concerned or an abnormality is suspected for e.g those with
growth retardation
androgen excess ( e.g hirsuitism )
thyroid disease
galactorrhoea
genital tract malformation is suspected
suspected Turners syndrome or androgen insensitivity
eating disorder as anorexia nervosa Puberty for 5 yrs without menarche Serious underlying cause suspected as an intracranial tumour 



Secondary amenorrhoea-the most common cause of 2ary amenorrhoea in reproductive age is pregnancy PCOS accounts for 90 % of cases of oligimenorrhoea Hypothalamic dysfunction account for about 30-35 % of 2ary amenorrhoea- usually due to stress , intense exercise , weight loss and eating disorders Pituitary failure – often acquired type as the result of trauma , treatment of pituitary tumour or infarction after massive blood loss ( Sheehans syndrome ) Pituitary tumour- due to hyperprolactinemia which results in amenorrhoea Hyperprolactinemia is responsible for 20 % of cases of amenorrhoea.

Manage conditions as PCOS , hypothyroidism , menopause and pregnancy in primary care Refer if premature ovarian failure is suspected 
( persistently elevated FSH and LH ) in a women less than 40 yrs of age H/O recent surgery or infection for e.g
endometrial curettage
caesarian section
myomectomy
severe pelvic infection ( endometritis ) Infertility Hyperprolactinemia including drug induced if levels -on two occasions
greater than 1000
between 500-1000 Hypothalamo-pituitary tumour is suspected for eg low FSH and LH levels Other hormonal disturbances e.g
raised testosterone level not likely due to PCOS
suspected Cushing’s syndrome


References

  1. Amenorrhoea : An Approach to Diagnosis and Management David A.Klein et al AAFP 2013
  2. Current evaluation of amenorrhoea The Practice Committee of the American Society for Reproductive Medicine Fertil Steril. 2008 ; 90( 5 suppl) S219-S225
  3. Laboratory endocrine testing guidelines: amenorrhoea and menopause accessed via http://topalbertadoctors.org/download/541/amenorrhea_
hirsutism-summary.pdf
  4. Initial investigations of amenorrhoea BMJ 2009 ; 339 :b2184
  5. CKS NHS Amenorrhoea https://cks.nice.org.uk/amenorrhoea
  6. Amenorrhoea E Medicine accessed via http://emedicine.medscape.com/article/252928-overview#a4

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