menorrhagia can pose a significant challenge to the gynaecologist when
associated with serious systemic complications like anaemia and hypoproteinaemia.
The present ongoing study analyses 35 cases at a multidisciplinary tertiary
institute of severe puberty menorrhagia which needed medical management.
There were 35 indoor admissions in the gynaecology ward at LTMG Hospital
(2001-2002) for critical puberty menorrhagia over a span of two years.
The leading cause was anovulatory dysfunctional uterine bleeding. Other
systemic associations included hypothyroidism, idiopathic thrombocytopenic
purpura, genital tuberculosis, and PCOD. Each case was analyzed for
demographic profile, duration of menorrhagia, severity of symptoms,
degree of anaemia, final diagnosis, requirement of blood and component
therapy and response to conservative management. Early diagnosis and
treatment with individualization of each and every case is the keystone
in the management of puberty menorrhagia. Exclusion of pregnancy is
mandatory in every case, irrespective of the history, reassurance, counselling,
regular follow-up along with a balanced nutritional diet and long term
iron therapy go a long way in successful management of such cases.
Menarche is a hallmark event in the life of most adolescent girls. It
marks the transition from childhood to puberty. Although mechanisms
triggering puberty and menarche remain uncertain, they are dependent
on genetics, nutrition, body weight and maturation of the hypothalamic
pituitary- ovarian axis. The complete maturation of the axis may take
up to 2 years. During this time, it is common for adolescents to present
with complaints of menstrual irregularities.
Abnormal bleeding accounts for approximately 50% of gynaecological visits
in adolescent girls.1 These complaints encompass disorders
ranging from minimal spotting to profuse bleeding. Puberty menorrhagia
is defined as excessive bleeding occurring between menarche and 19 years.
In 80% of cases puberty menorrhagia is caused by anovulatory cycles.2
There is an immaturity of the hypothalamus and inadequate positive feedback
resulting in sustained high levels of oestrogen. An organic disease
or malignancy in particular is very rare.
In all cases of puberty menorrhagia it is mandatory to exclude pregnancy,
especially an incomplete abortion or ectopic pregnancy. In persistent
abnormal bleeding coagulation disorders and leukaemia should be ruled
out. Occasionally menorrhagia is the only presenting symptom in a patient
of coagulation disorders. In general the prognosis is better when dysfunctional
uterine bleeding starts after a period of regular menstruation than
when it starts at menarche.4
Material and Methods
The present ongoing study evaluates 35 cases of critical puberty menorrhagia
managed by domiciliary care at a multidisciplinary tertiary care institute,
over a span of 2 years. Data was collected from medical case records
in each of these cases.
Each case was evaluated for the demographic profile, severity of symptoms,
degree of anaemia, final diagnosis, requirement of blood and component
therapy and response to conservative management. The baseline investigations
in all the cases included exclusion of pregnancy by urine testing, complete
blood count, peripheral smear for RBC and WBC morphology, coagulation
profile, blood grouping and Rh typing and transabdominal USG. In selected
cases thyroid function test (T3, T4, TSH) and hormonal assays including
(LH, FSH, Prolactin) and chest X-ray were done.
Analysis of data (Table 1) showed that 50% of patients were in the age
group of 13-15 years.
Majority of the patients belonged to the lower socioeconomic status.
As shown in Table 2 almost 62% of patients had onset of menorrhagia
since less than 6 months. Of these 33% of patients had haemoglobin less
than 6 gms%.
As shown in Table 3 anovulatory dysfunctional uterine bleeding occurred
in 27 cases (80%). Two patients of secondary DUB had a final diagnosis
of idiopathic thrombocytopenic purpura, 2 patients were diagnosed to
have hypothyroidism. Genital tuberculosis was detected in another 2
cases. One patient was found to have a rare cause - Glanzmanns thromboasthenia
that is discussed later.
Analysis of data showed that 37% of patients received fresh blood transfusion,
8% required component therapy in the form of fresh frozen plasma, platelets
and cryoprecipitates. Majority of patients received a combination medical
therapy as shown in the following Table:
Combination medical therapy regimes
Majority of patients received OCPills + ethamsylate (20%).
Six patients received i.v. oestrogens plus progesterone while ethamsylate
along with progestogens was used in 5 patients. Tranexamic acid was
used with Biphasic OCPills in 17.1% of cases and with progestogens in
Puberty menorrhagia is excessive bleeding occurring between menarche
and 19 years of age. It severely affects the quality of life.5
The main causes of abnormal uterine bleeding adolescent are shown in
In the present study
series in 80% of cases of puberty menorrhagia the cause was found to
be anovulatory dysfunctional uterine bleeding. A review of literature
shows that during puberty, maturation of the hypothalamic pituitary
- ovarian axis is characterised by an increase in the frequency and
amplitude of pulsatile GnRH, which initiates and regulates secretion
of pituitary gonadotropins.9 During the prepubertal years,
LH is secreted primarily at night in an episodic fashion. With the progression
to puberty, LH peaks increase in a pattern similar to that seen at night.
The timing of these LH pulses is crucial in establishing normal ovulatory
cycles. Increases in basal LH as well as immature timing of pulses result
in anovulatory cycles. These cycles are characterized by levels of LH
and FSH secretion that are sufficient to induce follicular development
and oestrogen production but inadequate to induce follicular maturation
and ovulation. Thus unopposed oestrogen stimulates endometrial growth.
This ultimately outgrows its blood supply and architectural support,
resulting in partial breakdown and shedding in an irregular manner.
In the proliferative phase the endometrium synthesizes equal amounts
and weak platelet aggregator) and PGE2 (Vasodilator with
weak platelet antiaggregatory effect). However in the luteal phase the
levels of progressively
increase under the influence of estradiol and progesterone. In normal
menstruation the ratio of
so that it is the vasoconstrictor and platelet aggregator action that
predominates. In anovulatory DUB the lack of progesterone results in
decrease in the :
PGE2 ratio and relative increase in the vasodilator and antiplatelet
aggregatory PGE2 which would account for the increased mean
menstrual blood loss. It could also account for the absence of uterine
contractions and painless periods characteristics of anovulatory menstruation.
In the present series of patients, majority were administered a combination
medical regime, to control the acute phase of bleeding. The primary
management of anovulatory bleeding should be directed at controlling
symptoms and prevention of anaemia. In adolescents with mild bleeding,
reassurance and prophylactic iron treatment are suitable. However in
patients who are sexually active or symptomatic for 3 to 6 months with
anaemia (Hb 9-12 mg/dl) require cyclical medroxy progesterone acetate
or a monophasic oral contraceptive pill in addition to iron. If the
patient is actively bleeding, but haemodynamically stable, the acute
phase is managed with one oral contraceptive pill three times daily
for 3 days followed by two oral contraceptive pills twice daily for
2 days; this is followed by one oral contraceptive pills until completion
of the packet. The cycles are further stabilized by a course of oral
contraceptive for 3 to 6 months. If the patient continues to bleed heavily
after the first 3 days, treatment is extended to three times daily for
7 days, twice daily for 7 day and then daily as mentioned previously.
In patient with severe bleeding associated with haemodynamic changes,
blood transfusions are indicated with administration of intravenous
conjugated oestrogens (e.g. Premarin) in a dose of 25 mg every 4 to
6 hours until bleeding stops for 24 hours.13 Once bleeding
is controlled, the patient is started on a regimen of strong androgenic
progestogen or oral contraceptive pills.
The occurrence of excessively heavy irregular menses should prompt an
evaluation of haematological status to rule out blood dyscrasias. In
the present study group 3 patients (8.5%) had blood dyscrasias manifesting
as DUB. Claessens and Cowell reported 19% of adolescents with menorrhagia
requiring hospitalization had an underlying coagulation disorder in
their study.6 A more recent retrospective study by Falcone
et al in 1994 found that 4.9% of admissions over a 10 year period were
secondary to a coagulopathy.9
The most common coagulation disorders were idiopathic thrombocytopenic
purpura, Von Willebrands disease, leukaemia and platelet dysfunction
like Glanzmanns thromboasthenia. Young girls with blood coagulopathies
are at a high risk for abnormal bleeding with the onset of menarche,9
and must be treated appropriately at the time of puberty. Laboratory
evaluation, including a complete blood count, platelets, prothrombin
time, partial thromboplastin time and bleeding time provides an adequate
screen for coagulation disorders.
In our study there were 2 patients diagnosed to have idiopathic thrombocytopenic
purpura. 80% patients of idiopathic thrombocytopenic purpura have menorrhagia.4
Acute Idiopathic thrombocytopenic purpura is most commonly seen in young
and is immunological thrombocytopenia, caused by immuno complexes containing
viral antigens that bind to the platelet, Fc receptors, or, by antibodies
produced against viral antigens that cross react with platelets. It
can be associated with infectious mononucleosis, acute toxoplasmosis,
CMV infections, viral hepatitis and HIV.11
In the present study group there was one rare case of Glanzmanns thromboasthenia.
This is a disorder in which the IIb-IIIa complex glycoprotein on the
platelet surface is defective and platelets cannot form aggregates.
Our case required multiple platelet transfusions. All haematological
disorders underlying dysfunctional uterine bleeding cases are best treated
in liaison with the haematologist. They require adequate blood transfusion,
component therapy and platelet transfusion.
Hypothyroidism can be associated with pubertal DUB. The reported incidence
of subjective menorrhagia in myxoedema varies from 32-80% and menorrhagia
may not infrequently be the presenting complaint (Scoot and Massey 1964).
The menorrhagia associated with hypothyroidism responds promptly to
the thyroid replacements, often in doses insufficient to correct the
other manifestations of the condition. This suggests that thyroxine
does have a direct effect on the spiral arterioles and on haemostasis
In our study there were two cases of genital TB which were treated with
Anti-Kochs therapy along with OCPs. Of these one case presented initially
with idiopathic thrombocytopenic purpura and was detected to have genital
tuberculosis on further evaluation. The incidence of genital TB is about
1% amongst the gynaecological patients attending the ODP in developing
countries.10 Menorrhagia or irregular bleeding in genital
TB is probably due to ovarian involvement, pelvic congestion or endometrial
Polycystic ovarian disease can be infrequently associated with irregular
heavy bleeding in 30% of cases, as reported by Goldzeiher et al.
Chronic anovulation may result from an increased pulsatility of GnRH.
This results in elevated LH levels and increased ovarian androgen production.
These hormone increases result in menstrual irregularity and oily skin.
Ovaries typically have multiple follicular cysts less than 10 mm in
size and increased stroma. This condition may be temporary in adolescent
or may eventually progress to advanced polycystic ovarian disease with
hirsuitism. Peripheral conversion of androstenedione to oestrone causes
a hyperoestrogenic effect that perpetuates menstrual irregularity.
The goals of treatment in adolescents are to regulate menstruation and
decrease hirsuitism and acne. The best treatment modality is an oral
contraceptive pill because of the inhibition of LH and decrease in circulating
testosterone levels. Sex hormone -binding globulin is increased and
available to bind and inactivate testosterone in the circulation.7
Oral contraceptive pills do not seem to aggravate the underlying insulin
resistance significantly and may attenuate some of the lipid derangement’s
induced by sustained excess androgen exposure.8 Another treatment
option to control abnormal bleeding is cyclic medroxyprogesterone acetate
10 mg orally for 10 days of each month. However this regimen does not
alleviate the associated androgenic effects of polycystic ovaries.9
To summarize, Blood and component therapy along with hormones constitute
the main medical therapy in the treatment of critical puberty menorrhagia.
In the present study 6 patients required intravenous conjugated oestrogen.
Various studies suggest that these are of value in arresting profuse
haemorrhage4 and are usually given with antiemetics. Oral contraceptive
pills were administered to 19 patients in our study group. These form
an effective hormonal therapy to restore the balance between prostaglandins
and thromboxane A2 and reduce the mean menstrual blood loss with additional
cycle stabilization. 45.7% patients in our study series had received
progestogens for medical curettage. Androgenic progestogens alone may
be used to arrest uterine haemorrhage or administered cyclically throughout
the menstrual cycle (5th to 25th day) Norethisterone acetate (primolut
N) 20-30 mg daily is given to arrest haemorrhage and not more than 3
days. The progestogen may then be continued at a lower dose for upto
21 days. The patient should be warned that a withdrawal bleeding will
occur on stopping treatment that will cease in 4-5 days. Norethisterone
acetate can also be given from 5th to 25th day in a dose of 5 mg once
Androgens like Danazol are less favoured because of their masculinizing
side effects in adolescent girls.
Antifibrinolytic like tranexamic acid are a newer form of treatment
in puberty menorrhagia. Plasminogen activator are a group of enzymes
that cause fibrinolysis. An increase in the levels of plasminogen activators
has been found in the endometrium of patients with heavy menstrual bleeding
compared to those with normal menstrual loss. Plasminogen activators
have been therefore been prompted as a treatment in heavy menstrual
There has been reluctance to prescribe tranexamic acid due to possible
side effects of the drugs such as thrombogenic disease (DVT). Long term
studies in Sweden, however have shown that the rate of incidence of
thrombosis in women treated with tranexamic acid is comparable with
the spontaneous frequency of thrombosis in women.3
Ethamsylate was used in 8 of our patients. It reduces capillary bleeding
when the platelets are adquate; probably it corrects abnormal platelet
function. It is not an antifibrinolytic. It does not stabilize fibrin.
Majority of patients in the study group received a combination therapy
with OCPs with androgens or with progesterone or with antifibrinolytic
In conclusion, most abnormal bleeding in adolescents is caused by immaturity
of the hypothalamic - pituitary ovarian axis resulting in anovulation.
Approximately 20% of adolescents have an underlying endocrine or haematological
disorder requiring targeted diagnostic testing.
Individualizing every case, excluding pregnancy, timely hospitalization,
a thorough history, physical examination and base line workup are crucial
in the management of every case. Reassurance, counselling of adolescent
girls about reproductive physiology, regular follow-up, balanced diet
and long term iron therapy go a long way in treatment of puberty menorrhagia.
We thank the Dean, LTMG Hospital, Dr. ME Yeolekar for permitting
us to use hospital data.
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bleeding. The Cochrane Library, Issue 1, 2003.
4. Davey DA. Dewhurst’s textbook of Obstetrics and Gynaecology
for postgraduates. 5th edition, pages 591-607.
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Principles of internal medicine 15th edition 745-750.
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Pediatr Adolesc Gynaecol 1996; 9 : 16.
OF BREAST CANCER MAY BE HIGHER THAN PREVIOUSLY THOUGHT
National programmes of mammographic screening can lead to one
in three breast cancers being overdiagnosed. Zahl and colleagues
report that the incidence of breast cancer among women 50-69
years of age increased by 50% when Norway and Sweden introduced
mammographic screening. They also found no compensating fall
in incidence over age 69, when women are no longer invited for
screening. In the absence of screening, the authors say, one
of three women in the 50-69 age group who were diagnosed with
invasive breast cancer would not have been diagnosed as having
breast cancer in her lifetime. The authors conclude that women
cannot make an informed choice on screening unless the level
of overdiagnosis is properly explained to them.
BMJ, 2004; 328 : 921.
Obstetrics and Gynaecology, LT Medical College, Sion, Mumbai - 22.