A Study Comparing Mirena and Systemic Progestin for Endometrial Hyperplasia
Condition: Endometrial Hyperplasia
MeSH terms: Endometrial Hyperplasia; Hyperplasia
Study type: Interventional
Phase: Phase 4

Summary: 
      Randomized controlled multi-center study with three arms including 200 patients with low risk
      endometrial hyperplasia. After confirmed diagnosis the patients will receive one of the
      following treatments:

        1. Provera (Medroxyprogesterone (MPA)/progestin) 10 mg per oral treatment for 6 months 10
           day each cycle,

        2. MPA 10 mg continuously for 6 months,

        3. Mirena (Levonorgestrel) impregnated IUD for 6 months.
    

Detailed description: 
      Background:

      Endometrial cancer is the most common gynecologic cancer in the Western world and the
      incidence is still increasing. Endometrial cancer is principally developing through
      preliminary stages called endometrial hyperplasia and 10-30 per cent will develop into
      carcinoma when left untreated. The incidence of endometrial cancer in Norway is presently
      about 650 cases per year and about 3000 cases of endometrial hyperplasia are estimated.
      Thus,correct and optimal treatment of endometrial hyperplasia will contribute to prevent
      endometrial cancer development and also in the long term, to reduce the incidence of
      endometrial cancer. Correct treatment of endometrial hyperplasia includes operative treatment
      with hysterectomy of the high risk cases and conservative treatment and follow up for
      patients with lower risk. As diagnostics of endometrial hyperplasia has been a challenge to
      pathologists, overtreatment of patients with low risk of cancer development is unfortunately
      still a problem. In the present study an objective scoring system, D-score, is used to
      classify the patients into low and high risk hyperplasia. D-score in an objective
      morphometric analysis and the scoring system has proved reliable to predict the prognosis of
      each single case as to cancer development or not. By tradition low risk endometrial
      hyperplasia is treated conservatively with progestin hormones, however, no national routines
      really exist according to dose, type of progestin, treatment time or distribution route,
      however, varying doses of per oral treatment is mostly used.

      Progestins hormones are known to have a growth regulatory effect on the uterine mucosa.
      However, treatment success after per oral therapy has shown that up to 50% are non-responders
      after per oral treatment. On the other hand a few recent studies have reported successful
      results after using the LNG-IUD as treatment for endometrial hyperplasia with 100 per cent
      treatment response.

      The levonorgestrel impregnated impregnated intrauterine originally constructed for
      menorrhagia and contraceptive use, is delivering more than hundred times increased
      concentration of progesterone to the uterine mucosa compared to per oral therapy. Thus , the
      favourable treatment is attributable to the increased concentration of progestins obtained in
      the uterine mucosa. Another advantage is that treatment can last for years and that
      side-effects seen for per oral treatment after progestin therapy can be avoided.

      Inclusion:

      Most of the patients in the present study are seeing their gynecologist due to irregular
      bleedings.Biopsy is routinely taken by the gynecologist to exclude malignancy or verify
      hyperplasia. The biopsy is investigated routinely by a the local pathologist. If the
      diagnosis of hyperplasia is verified and the patient fulfils the inclusion criteria, the
      histological specimen is sent to the laboratory in Tromsø for D-score. When D-score is >0,
      the patient may be included in the study.

      D-score:

      The D-score system is dividing the patients into three risk groups:

        1. Patients having a D-score <0 are shown to have a high risk of cancer development are
           recommended hysterectomy.

        2. Patients having D-score >1 have very low risk of cancer development and are recommended
           progestin treatment.

        3. Patients having D-score 0-1 have an uncertain risk of cancer development and may be
           treated conservatively. Only patients with D-score > 0 may be included in the study.

      Randomization:

      When the gynecologist receive the diagnosis and the D-score results and the D-score is in
      accordance with the inclusion criteria, the patients is asked by her gynecologist to be
      included in the study.

      If consent is given, the randomization is performed by telephone contact with the
      randomization office , UNN, Tromsø, after written informed consent. The patient is free to
      leave the study any time without argument.

      Treatment:

      After randomization the treatment according to assigned treatment arm can be started. During
      the therapy period the patient will be controlled with repeat biopsy after 3 months and at
      the end of treatment after 6 months. D-score is repeated if hyperplasia persists. If a
      negative D-score is performed, the patient will have to leave the study. If D-score is still
      positive the patient will also leave the study, new therapy is then decided by the local
      gynecologist.

      Control:

      All patients will be controlled with repeat biopsy every six month for two years after end of
      therapy. If recurrence of hyperplasia occurs the patient will leave the study and receive
      other therapy decided by her own gynecologist after repeated D-score.

      Side effects:

      All side effects which can be related to treatment during treatment and/or follow-up will be
      reported.
    

Intervention name(s): Provera (medroxyprogesterone/progestin); Provera (medroxyprogesterone); Mirena (levonorgestrel)
Intervention type(s): Drug; Drug; Device
Intervention description(s): 10 mg tablet, 1 tablet per day taken 10 days per month Duration is 6 months; 10 mg per oral tablet. One tablet per day for 6 months; Inserted in the uterine cavity and kept in situ for 6 months
Other intervention name(s): Provera; Provera; Mirena
Intervention MeSH terms: Medroxyprogesterone Acetate; Levonorgestrel; Medroxyprogesterone; Progestins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: endometrial hyperplasia treatment MPA per os LNG-IUD