Patient’s characteristics
Of all 15 patients treated at our department between 2006 and 2018, one patient was excluded due to loss of follow-up. Of the 14 patients included, 1 patient had been diagnosed with endometrial cancer grading G2 (7%), 10 (71%) had been diagnosed with G1EC, 3 patients (21%) with CAH. The median age of the patients was 32.2 years (range 30.1–47.9 years) at time of diagnosis, with a mean age of 34.2 years (SD 4.8 years). The median body mass index (BMI) was 32.8 kg/m2 (range 21.6–47.9 kg/m2), the mean BMI was 33.1 kg/m2 (SD 8.5 kg/m2). Eight patients had a BMI higher than 30 kg/m2 (Table 1).
Table 1
Management according to initial diagnosis, age, BMI and treatment duration
Patient ID | Diagnosis | Age at diagnosis (years) | BMI (kg/m2) | Therapy (mg) | Treatment duration (months) | Follow-up time (months) | Outcome after first treatment | Outcome after last treatment |
1 | G2EC | 35.9 | 42.8 | Dydrogesteron 10 | 3 | 5 | SD | / |
2 | G1EC | 30.7 | 47.9 | MA 160 | 3 + 3 + 3 + 3 | 33 | PR | SD |
3 | G1EC | 37.0 | 21.6 | MPA 500 | 3 + 3 | 18 | CR | PR |
4 | G1EC | 30.4 | 38.6 | MPA 500 | 3 | 5 | SD | / |
5 | G1EC | 31.4 | 42.7 | MPA 500 | 6 + 4 | 40 | PR | CR |
6 | G1EC | 30.2 | 40.8 | MPA 500 | 3 | 10 | CR | / |
7 | G1EC | 32.9 | 26.7 | MA 160 | 3 | 5 | SD | / |
8 | G1EC | 35.6 | 32.2 | MA 320 | 3 | 6 | PR | / |
9 | G1EC | 36.6 | 26.9 | MPA 500 | 3 | 4 | CR | / |
10 | G1EC | 47.9 | 33.5 | MPA 500 | 1.5 | 6 | PR | / |
11 | G1EC | 30.6 | 28.5 | MA 160 | 2.5 | 40 | CR | / |
12 | CAH | 31.6 | 36.7 | MPA 500 | 3 | 7 | CR | / |
13 | CAH | 30.1 | 23.4 | MA 160 | 4 + 3 | 46 | CR | CR |
14 | CAH | 37.4 | 22.2 | MPA 500 | 3 | 11 | CR | / |
G2EC = Endometrial cancer grade 2 |
G1EC = Endometrial cancer grade 1 |
CAH = Complex atypical hyperplasia |
SD = stable disease |
PR = partial remission |
CR = complete remission |
Table 2
Baseline characteristics of the 14 patients diagnosed with endometrial cancer or atypical hyperplasia
Initial diagnosis n (%) - Atypical hyperplasia - Endometrial cancer, G1 - Endometrial cancer, G2 | 3 10 1 | (21%) (71%) (7%) |
Age at diagnosis (years) median (range) | 32.2 | (30.1–47.9) |
Body mass index (kg/m2) median (range) | 32.8 | (21.6–47.9) |
Body mass index (kg/m2) n (%) < 24.9 kg/m2 25–29.9 kg/m2 30–34.9 kg/m2 35–39.9 kg/m2 ≧ 40 kg/m2 | 3 3 2 2 4 | (21%) (21%) (14%) (14%) (29%) |
Other risk factors n (%) - PCOS - Diabetes mellitus type II | 2 3 | (14%) (21%) |
Reason for initial diagnosis n (%) - Primary infertility - Secondary infertility Ectopic pregnancy Caesarian section Vaginal delivery | 10 4 1 2 1 | (71%) (29%) |
Pelvic imaging n (%) Pelvic ultrasound MRI | 14 10 | (100%) (71%) |
Progestin therapy n (%) MPA 500 mg/day MA 160 mg/day MA 320 mg/day Dydrogesteron 10 mg/day | 8 4 1 1 | (57%) (29%) (7%) (7%) |
PCOS = Polycystic ovarian syndrome |
MPA = Medroxyprogesterone acetate |
MA = Megestrol acetate |
MRI = Magnetic resonance imaging |
Of all 14 patients, 10 (71%) presented with primary infertility, 4 (29%) patients demanded diagnostics due to secondary infertility. Out of the 4 patients with secondary infertility, 2 women have had a caesarian section before, 1 has had an ectopic pregnancy and 1 had previously delivered vaginally.
Treatment
The conservative management consisted of the oral application of 500 mg MPA (Medroxyprogesterone acetate), 160 mg MA (Megestrol acetate) or 10 mg Dydrogesteron on a daily basis for 3 months. 8 patients (57%) received MPA, whereas in 5 patients (35%) MA was administered. One patient (7%) was treated with 10 mg Dydrogesteron. The mean duration of treatment was 4.3 months. The majority of patients received progestin agents for at least 3 months. One patient received for MPA 500 mg for only 1.5 month. Treatment was terminated earlier due to side effects.
One patient with a BMI of 42.7 kg/m2 was treated with MPA 500 mg for 10 months in total, another patient with a BMI of 47.9 kg/m2 with MA 160 mg for 12 months in total, both belonging to those three patients with the highest BMI of the cohort. The patient diagnosed with G2EC (BMI 42.8 kg/m2) was treated with 10 mg Dydrogesteron for three months in total.
Of the 10 patients suffering from G1EC, 6 patients were treated with 500 mg MPA between 1.5 and 10 months in total. 3 patients were treated with 160 mg MA, thereof one for 2.5 months, one for three months, one patient for 12 months in total. One patient was treated with 320 mg MA for three months. Of the three patients diagnosed with complex atypical hyperplasia one (BMI 23.4 kg/m2) received 160 mg MA for 7 months in total, two were treated with MPA 500 mg for 3 months.
The histological follow-up, based on endometrial tissue samples obtained by hysteroscopy and D&C was performed shortly after treatment, only in one case the clinical control was performed 5 months after end of treatment, due to non-compliance of the patient. Control-hysteroscopies and D&C were usually performed regularly every three months after end of therapy to ensure treatment success. If no histopathological treatment success could be found, a new treatment cycle was initiated.
Outcome
Outcome after first treatment cycle
Treatment with MA
In total, four patients of the cohort were treated with MA 160 mg. Three had been diagnosed with G1EC, one patient with CAH. One patient with a G1EC was administered MA 320 mg. After the first cycle of conservative management in the group of 3 patients with low grade endometrial carcinoma, who had been treated with 160 mg MA, one patient showed a partial response with remaining CAH. One patient showed complete response.
One patient didn’t respond to treatment. In the patient treated with 320 mg MA a partial response with remaining CAH could be seen. The patient with the initial diagnosis of atypical hyperplasia and MA treatment showed a complete remission after the first cycle of treatment (see Fig. 1).
Treatment With Mpa
8 patients were treated with 500 mg MPA, thereof 6 with low grade endometrial cancer, two with atypical hyperplasia. 3 patients with endometrial carcinoma had a complete response with no remaining disease after one cycle of treatment of three months. Two patients showed partial remission with remaining atypical hyperplasia. One of those had been treated for only one month, as treatment had been finished earlier due to side effects.
One patient did not respond to MPA therapy and showed remaining cancer cells. This patient underwent surgical treatment with total hysterectomy and BSO. The two patients with initially diagnosed CAH showed a complete response after one cycle of treatment.
Treatment With Dydrogesteron
One patient diagnosed with G2EC received Dydrogesteron 10 mg for 3 months but did not respond.
Outcome After Various Treatment Cycles
4 patients were treated for more than one cycle with progestin agents. One patient with G1EC (ID 2) was treated with four cycles of MA 160 mg in total. After the first cycle partial remission with remaining complex atypical hyperplasia was obtained. The patient then was treated with a second cycle with MA. In the following D&C a complete remission was diagnosed. Yet in the following control D&C´s the patient relapsed with treatment control revealed still remaining complex atypical hyperplasia. Thus the patient received a fourth cycle of MA. After treatment complete remission was seen. In the subsequent curettage 8 months after end of the last treatment, the patient was re-diagnosed with endometrial cancer.
Another patient with G1EC (ID 3) showed complete remission after 3 months of treatment with 500 mg MPA. She then relapsed with CAH, so another treatment cycle with 500 mg MPA was administered. The control D&C performed directly after the end of the second treatment cycle revealed remaining CAH. In the control hysteroscopy and D&C after 3 months complete remission could be diagnosed again.
A third patient with G1EC (ID 5) was treated with MPA 500 mg for two cycles. During the first treatment cycle complete remission could be seen. In the control D&C the patient relapsed with complex atypical hyperplasia. Hence, a second treatment cycle was started. In the first histopathological control after the second treatment cycle no pathology was found. The following curettage again revealed complex atypical hyperplasia. The patient then had two control D&C´s, both with no pathological findings.
One patient initially diagnosed with CAH (ID 13) also received two cycles of treatment with MA 160 mg. After the first treatment cycle complete remission was diagnosed. Yet the patient relapsed with CAH and was treated with another cycle of MA. In the control D&C, complete remission was again diagnosed (see Fig. 1).
For the 9 patients with response to therapy, median duration to first progression after last successful treatment was 7.8 months.
Of all 14 patients one patient with initial endometrial cancer became pregnant but aborted in the 10th week.
Figure 1: