Endometrial cancer is one of the most frequent tumors affecting the
female genital tract with the highest incidence rate in women aged
between 53 and 60 years .
Increased exposure of the endometrium to unopposed estrogen stimulation
is widely accepted as a major etiological factor. This hypothesis is
supported by increased risk associated with estrogen replacement therapy
but not with combined progestagens-estrogen therapy [2, 3]. Protective
effect of combined estrogen-progestagens oral contraceptives is ascribed
to the progestagens component .
Infertility and irregular uterine bleeding are associated with increased
risk and are likely to be related to increased frequency of anovulation
. Hypertension, obesity and diabetes are important risks factors in
peri and postmenopausal women . Family history of endometrial
carcinoma is an independent risk factor for the disease .
Although endometrial carcinoma is predominantly a disease that affects
postmenopausal women, 3-5% of the tumors develop in women under 40 years
of age . Endometrial carcinoma is extremely rarely diagnosed in women
under 25 years of age. In the very young it is often associated with
polycystic ovarian disease, obesity, infertility, risk factors that are
also associated with increased levels of estrogens . In most cases it
is diagnosed at an early stage, tumor is well differentiated with a
favorable prognosis .
The use of progestins is mostly reported as the first option of medical
treatment. Other drugs, such as gonadotropinreleasing hormone agonists,
antiestrogens, and aromatase inhibitors have been rarely used .
A 21-year-old woman was evaluated for metrorrhagia in February 2000 in
the Outpatient Clinic in the University Hospital of Obstetrics and
Gynecology "Narodni Front" in Belgrade where the author of this paper
works. A year before she was for the first time hospitalized at the
Department for Conservative Gynecology in the same hospital and treated
for metrorrhagia and adnexitis billateralis. The patient was virgo
intact nulligravida. Menarche was at the age of 14, followed by
irregular cycles. She had negative medical and family history and was
not on medication. Her physical examination and bimanual gynecological
exam was unremarkable, except that she had acyclic uterine bleeding.
There was evidence of oligoovulation so clinical diagnosis of polycystic
ovarian disease was made. The patient was not obese. Ultrasonography
revealed slightly enlarged uterus, thickened endometrii of 13 mm,
ovaries appeared polycystic. The bleeding episode was decreased on high
estrogen-progestagens dose in few days. The patient didn’t follow up
medical instructions and didn’t come for follow up visit, but continued
the therapy with lower hormone dose on her own and consequently started
to bleed again. After 11 days of bleeding she came in the Outpatient
Clinic in bad physical condition and was hospitalized again at the
Department for Conservative Gynecology, where she was treated with
intramuscular estrogen therapy without progesterone. The patient left
hospital without any advice for progesterone therapy. That is why
bleeding started again after a few days. The patient decided to start
contraceptive therapy on her own without any medical advice and bleeding
stopped. In a few days, at the end of February, she came again to the
Outpatient Department in good condition without any bleeding while on
contraceptives. On this occasion, contraceptive therapy that she had
already started on her own, was approved as a reasonable choice for her
problem. After 15 days, in March 2000, she comes to the Outpatient
Department because of another bleeding episode during contraceptive
Ultrasonography revealed endometrial thickness of 14 mm. Defloration and
dilatation and curettage was suggested. The patient decided to have
natural defloration. In April 2000 the patient underwent dilatation and
curettage which showed adenocarcinoma endometrii in situ G1N1 with
hyperplasia complex atypica and proliferative endometrium. Endometrial
sample was reviewed by two independent pathologists.
The patient was extensively counseled and given the options of medical
therapy vs. total abdominal hysterectomy. She desired to preserve her
fertility potential and consented to progestagens therapy. The
Consillium for Oncology Patients asked patient for results of hormonal
tests and in generally agreed with suggested conservative therapy. All
hormonal tests were within the normal range including prolactin and
The patient understood the importance of frequent evaluation of
endometrial sampling and the chance of progression or recurrence of the
Initial conservative hormonal therapy was gestonoroncapronat 200mg
weakly started in April 2000 for 3 months until the first follow up
dilatation and curettage was preformed. At the first follow up visit
endometrii were 8 mm and endometrial samples after dilatation and
curettage showed adenocarcinoma endometrii, hyperplasia complex atypica
but also an atrophic endometrii. The therapy was changed.
Gestonoroncapronat was cancelled and oral therapy-medroxyprogesteron
acetate 500mg daily was introduced. On the second follow up visit (at
the end of October 2000) endometrial thickness was 2.9-5.2mm with
hyperechogen focus 2.6mm long and 2mm high. After dilatation and
curettage endometrial atrophy was found in 50% of endometrial sampling.
In other parts of endometrii adenocarcinoma endometrii and hyperplasia
complex was found. Dosage of oral medroxyprogesteron was increased to
1000mg daily until next dilatation and curettage. From the end of
December 2000, the patient was followed up at the Gynaecology and
Obstetric Outpatient Clinic "Mošković" where the author was employed. In
January 2001 hysteroscopy followed with dilatation and curettage was
preformed in the University Hospital of Obstetrics and Gynecology "Narodni
Front". Hysteroscopy showed atrophic endometrii with 3 mm isthmicus
polypus. There were no signs of adenocarcinoma or hyperplasia in
endometrial samples after dilatation and curettage. Thereafter the
dosage of medroxyprogesteron acetate was decreased to 100mg daily. No
related toxicity to hormonal therapy was observed. Finally hormonal
therapy was discontinuited in March 2001. The patient didn not want
pregnancy yet and was advised to be on carefully follow up monitoring
including dilatation and curettage and cycle regulation until she
decided to become pregnant. The patient did not follow medical advice
strictly, after ten years of discontinuited therapy she had not major
gynecological problems, had one pregnancy with pure outcome, and still
is healthy young 30-year-old woman.
Between 3-5% of endometrial adenocarcinoma develop in women under 40
years . These patients, especially younger and nulligravida are
strongly motivated to preserve their fertility. The standard therapy for
early endometrial carcinoma is total abdominal hysterectomy and
bilateral salpingo-oophorectomy and when indicated, adjuvant radiation
therapy is added. Surgical treatment results in the loss of fertility.
A conservative approach can offer reasonable oncological security and
the opportunity of fulfilling their maternal desires in selected cases.
However, consideration should be taken regarding the potential adverse
outcomes. When a patient desires to retain her future fertility in the
light of this diagnosis, choices of surgical vs. conservative medical
therapy may present a dilemma for both the physician and the patient.
The first criterion for conservative treatment is an accurate diagnosis
of a well-differentiated endometrial carcinoma by an expert pathologist.
Taking advantage of this tumor's hormonal sensitivity, most authors have
used hormone-based treatments as a conservative approach .
Fortunately, in patients under 40 years of age, most tumors are at the
early stage and well-differentiated as it was in our case. But there are
dilemmas about clinical tumor staging. Transvaginal sonography may help
in the evaluation of myometrial invasion. Laparoscopy may be helpful in
staging at the adnexal level. Recent publications warn us about the
possibility of having ovarian metastasis or synchronic tumors in this
group of young patients with endometrial cancer. 
Worldwide experience and data about conservative therapy of early
endometrial cancer in young patients are lacking [11,14]. That is why it
is difficult to acquire the necessary experience to offer
recommendations regarding the conservative approach.
Progestin therapy for endometrial cancer has been used since the 60s. At
first, this treatment was only confined to patients with hyperplasia
with atypia, but nowadays patients with early endometrial carcinoma are
also treated with this therapy. In literature it can be found out that
seventy six percent of patients treated with hormonal therapy had a
complete response and the other 24% never responded to treatment .
Medroxyprogesteron Acetate is the most frequently used progestin. The
mayority of patients received progestin as the first treatment. A half
of them were treated with 200 to 600 mg daily doses of
Medroxiprogesterone Acetate . We decided to start with
gestonoroncapronat 200 mg weakly for 3 months, followed by
Medroxiprogesterone Acetate of 500mg/a day. After 3 months and an
incomplete respond, the dosage was increased to 1000 mg/a day. It is on
average a higher dosage than in the mentioned studies.
Other reported cases were treated with 17 α hydroxyprogesteron caproate,
megestrol and clomiphene. However, there is no consensus in the
literature on the most appropriate progestin, the dose and length of
According to literature, three out of four threated patients had an
initial complete response, with an average response time of 12 weeks.
The average duration of hormonal therapy was approximately 6 months
. In our case complete respond was 11 months what is, again, longer
than average. The duration of therapy was also longer than average.
The follow up performed after regression of the disease should be very
strict and should include periodic evaluation of cytology, sonographies,
hysteroscopies and histopathologic examination of endometrial samples.
Unfortunately, our patient didn not strictly followed our
Many questions about the choice of appropriate therapy and follow up
remain actual and unsolved. There is a dilemma about the treatment of
irregular bleeding and stimulation of ovulation if necessary until the
patient decides to have pregnancy. There is no consensus in literature
for stimulation protocols. The patient must be informed that there is
about 33% chance of progression or recurrence of the disease and a
possible definitive surgical therapy .
This case illustrates that with close observation and follow up by
endometrial sampling for histological diagnosis, conservative hormonal
therapy may be a successful option for treating endometrial carcinoma in
young women to allow future fertility.
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