Secondary amenorrhoea
Dr.ASMAA AL SANJARY
The student at the end of this lecture should be able to:
Define secondary amenorrhoea.
Classify the causes of secondary amenorrhoea.
Describe the commonest three cases of secondary amenorrhoea.
Analyze the history and examination of a case of secondary
amenorrhoea.
Diagram an outline of a case of secondary amenorrhoea.
Analyze the diagnostic role of progesterone challenge test.
Secondary amenorrhoeaIs cessation of menstruation for 6consecutive
months in a women whohas previously had regular periods
, or for 12
months in a women Withprevious oligomenorrhoea.
WOMEN WITH SECONDARY AMENORRHOEA
Must have a patent lower genital tract.
Endometrium that have responsive to hormonal stimulation.
Ovaries that have responded to pituitary gonadotrophin
-Amenorrhoea is absence of menstruation,
Which might be temporary or perminant.
-It may occur as normal physiological condition
as before puberty ,during pregnancy, lactation
or after monopause.
OR as a feature of a systemic or endocrine
disease
CLASSIFICATION OF SECONDARY AMENORRHOEA
UTERINE CAUSES
Asherman ‘s syndrome
Cervical stenosis :after cone biopsy (require dilatation)
OVARIAN CAUSES
PCOS
Premature ovarian failure : genetic, autoimmune, infective ,
radio/chemotherapy.
HYPOTHALAMIC CAUSES
(HYPOGONADOTROPHIC HYPOGONADISM)
Weight loss
Exercise
Chronic illness
Psychological distress
Ideopathic
PITUITARY CAUSES
Hyperprolactinaemia
Hypopitutarism(sheehan’s syndrome)
CAUSES OF HYPOTHALAMIC/PITUITARY
DAMAGE(HYPOGONADISM)
Tumors (craniopharyngiomas, gliomas,
germinomas, dermoid cysts)
Cranial irradiation
Head injuries
Tuberculosis
Sarcoidosis
SYSTEMIC CAUSES
Debilitating illness
Endocrine disorders(thyroid disease , cushing syndrome)..
Drugs:COCP,danazol
THE MOST COMMON CAUSES OF
SECONDARY AMENORRHOEA
POLYCYSTIC OVARY SYNDROME
PREMATURE OVARIAN FAILURE
HYPERPROLACTINAEMIA
THESE ACCOUNTS FOR
75 %
OF CASES
MANAGEMENT OF ACASE OF SECONDARY AMENORRHOEA
HISTORY AND EXAMINATION:
-Any change in weight (BMI between 20-25
kg/m2)
-unusual exercise or stress
-intrauterine instrumination (pregnancy termination)
-drug history
-family history of premature menopause
-signs of hyperandrogenism or virilism.
-signs of hyperthyroidism or hypothyroidism
-signs of cushing’s syndrome
-bitemporal hemianopia and visual disturbance
-examination of the breast for galactorrhoea
-bimanual pelvic examination.
Always exclude pregnancy in a women of any
age in case of secondary amenorrhoea
.
Endocrine Investigation:
Baseline gonadotrophin level (FSH,LH(
FSH and LH >15 IU/l indicate impending ovarian failure (unrelated to
preovulatory surge ),their level can differentiate ovarian from
hypothalamic causes LH raise alone will indicate PCOS
Serum prolactin
if >1500 mIU/l indicate pituitary microadenoma
.
>
5000 mIU/l indicate pituitary macroadenoma.
Thyroid function test
Oestrogen state of the endometrium: by
examination of the genital tract or induce
withdrawal bleeding by progesterone
administration.
Serum testosterone: if greater than 5 nmol/l
should be investigated to exclude adrenal or
ovarian tumors.
24 hour urinary cortisol: is elevated in cushing syndrome(700
nmol/24 hr)
Other investigation like:
Ultrasound : to exclude PCOS, ovarian cyst or tumor,post
menstrual endometrial thickness if >10mm then endometrial
biopsy indicated to exclude malignancy.
Hystyrosalpingography and hysteroscopy: in cases suspected to
have asherman’s syndrome.
CT scan or MRI :hypothalamic tumor, non
functioning pituitary tumor compressing
the hypothalamus or a prolactinoma.
Skull X ray
Karyotype: in patient of premature ovarian failure(<40 years) to
exclude sex chromosomes mosaisim.
Auto antibody screen: in patient with POF.
management of individual causes
Asherman’s syndrome:
Is a condition in which intauterine adhesions
prevent normal growth of the endometrium.
Aetiology:
1. .Too vigorous endometrial curettage affecting the basalis layer of
the endometrium.
2. .Episodes of endometritis.
3. .Oestrogen deficiency in breast feeding
Women
Amenorrhoea is not absolute,withdrawal
Bleeding can be induced with oestrogen
/progesterone administration.
Diagnosis: by HSG and or hysteroscopy.
Treatment: by adhesiolysis followed by 3
months of oestrogen progesterone cyclical
therapy. A foley catheter can be inserted
postoperatively for 7-10 days, or IUD
inserted for 2-3 months.
The pregnancy rate after treatment
depends on initial severity of the adhesions
93
% for mild adhesions
57
% for sever adhesions
Premature ovarian failure (POF)
Is cessation of periods accompanied by
raised gonadotrophin level prior to the age
of 40 years.
It occurs in 1-5% of female population.
POF have increased risk of:
osteoporosis
cardiovascular disease
Aetiology:
1. .Chromosomal abnormality : it occurs in
70
%
of cases of primary amenorrhoea
2
-
5
%
of cases of secondary amenorrhoea
2. .Autoimmune disease.
3. .chemo/radiotherapy.
4. .surgery.
.
Treatment
:
oestrogen deficiency : HRT preparation
Infertility: in established cases there isresistant to gondotrophin with
absence ofovarian follicle, and reports of pregnancy intreated cases only
indicate fluctuatingovarian function rather than treatmentsuccess.
Hyperprolactinaemia:
Is the commonest pituitary cause of secondary amenorrhoea.
Causes of elevation of serum prolactin:
Mild elevation: -pregnancy(10 fold)
-stress.
-venepuncture.
-postprandial.
-breast examination.
Moderate elevation:
-hypothyroidism
-PCOS (up to 2500 Iu/l)
-drugs : dopaminergic antagonist phenothiazines,
domperidone,verapamil, methyldopa,metoclopramide and oestrogen.
Sever elevation
:
-
prolactin secreting tumor : micro and macroadenoma.
-
non-functioning tumor of the hypothalamus or pituitary
Symptoms of hyperprolactinaemia:
Amenorhoea: is the bioassay of prolactin excess.
Galactorrhoea: in up to 1/3 of patients.
Symptoms of hypooestrogenism (amenorrhoea no withdrawal
bleeding after progesterone therapy)
Visual disturbances.(bitemrporal hemianopia)
Diagnosis:
Prolactin serum assay: ( tumor marker)
Skull X ray:
-
asymmetrical enlarged pituitary fossa with double contour of it’s
floor
.
-
Erosion of the clinoid processes.
Ct-scan or MRI
Treatment of galactorrhea and amenorrhea
Observation
:
periodic observation for patient with galactorrhea who have
normal prolactin or idiopathic elevation.
Patient with oligomenorrhea who not desire fertility should be
treated with periodic progesterone if not desire fertility and with
COCP,if contraception is required. failure of progestin to introduce
bleeding is suggestive ofhypooestrogenism.
Long term treatment with bromocriptine in women with normal
estrogen is not indicated.
Observation can be extended to some women with radiologic
evidence of pituitary microadenoma(<=10mm in diameter)
because the growth rate in slow,an annual measurement of serum
prolactin is appropriate in patient with normal oestrogen level.
Macroadenoma >=10mmrequire further evaluation by periodic
scanning and possible treatment.
Medical treatment
:
Patient aim to restore menstrual cyclicity or to prevent
osteoporosis COCP are given.
Patient require reduction of prolactin and restoration of cyclic
physiologic estrogen secretion require ergot compund:
Bromocriptine:dopamine antagonist: starting with small dose of
1.25 mg at bed
time increased gradually 7.5 mg in divided
Daily doses to initiate response then reduce
To a maintenance lower dose .some tolerate
the drug more if given vaginally.
Side effect :nausea,vomiting,headache,
postural hypotension
Cabergoline :longer acting ,better tolerated,more expensive
Given in 0.25 mg twice weekly,
Bromocriptine normalizes the secretion of prolactin in 82% of
cases of women with microadenoma and restore cycle and fertility
in more than 90%. It require 6-10 weeks to restore cycle and 10-
16week to establish ovulation. discontinuation of therapy result
into return of hyper-prolactinaemia leading to galactorrhea and
amenorrhea.
Patient with macroadenoma require visual field assesment,other
pituitary hormone assesment,repeat MRI after full therapeutic
dose of bromocriptine is reached.treatment is continued as long
as shrinkage of adenoma is required
During pregnancy treatment is stopped tumors unlikely to enlarge
during pregnancy,macroadenoma extending beyound the sella
tursica require debulking surgery before pregnancy (15%-30%) risk
of enlargement, bromcriptine therapy is started,patient require
repeated visual field assessment once abnormality develops
Bromocriptine is instituted or increased for the rest of
pregnancy.(there is no increase in congenital abnormality
)
Medical treatment is preferred over surgery as recurrence is high:
microadenoma recure30%and macroadenoma recurs in 90%.
Surgical : transphenoidal adenectomy
Indicated in cases of
-Resistance to treatment.
-intolerance to medical treatment.
-supracellar extention not respond to
bromocriptine and pregnancy is desired
Radiotherapy: is not desired with modern
surgery