leuprolide and Endometrial-Hyperplasia

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75 mg gonadotropin-releasing hormone agonist (GnRHa)--leuproreline acetate depot every 4 weeks. After the third injection of 3.75 mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52 mg levonorgestrel (Mirena®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75 mg of GnRHa every 4 weeks. After the third injection of 3.75 mg of GnRHa, we also inserted a GnRH-IUS (Mirena®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.

Topics: Adenocarcinoma; Administration, Intravaginal; Adult; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Delivery Systems; Drug Therapy, Combination; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Leuprolide; Levonorgestrel; Neoplasm Staging; Organ Sparing Treatments; Pilot Projects; Progestins; Young Adult

To investigate the response of the various hyperplastic disorders of the endometrium to a prolonged treatment with leuprolide acetate, a gonadotropin-releasing hormone agonist (GnRH-a), plus tibolone, as add-back therapy, and further to study if the tibolone addition reduces the hypoestrogenic actions of the GnRH-analogue.. We treated 26 women with histologically confirmed simple (n = 9), complex (n = 15) or atypical (n = 2) endometrial hyperplasia (EH) for 12 months with monthly injections of 1Ampulle/3.75 mg of leuprolide acetate, followed by tibolone, 2.5mg per day per os. Every woman underwent a hysteroscopic evaluation and biopsy of the endometrium after 3 (in cases with atypical EH), 6 and 12 months of treatment, as well as after 12 and 24 months of follow-up. The clinical, paraclinical and laboratory course of the disease was followed-up by using of a climacteric scoring system and by testing of various parameters.. The histopathologic evaluation of the endometria revealed regression of EH in all women after 12 months of treatment, however, during the first 2 years of follow-up EH reappeared in four women (4/21, 19%). Bone mineral density and serum parameters did not show significant changes during treatment, whereas only a mild suffering from hypoestrogenic side-effects was noted.. It seems that the combined GnRH-a/tibolone treatment in women with EH is a potent alternative, so far as the endometrial status and the clinical course of the disease are concerned, whereas tibolone appears to act sufficiently as add-back therapy to prolonged GnRH-a treatment. The probability of relapse of the disease during the follow-up period makes the close monitoring of the endometrium after cessation of the treatment absolutely necessary.

Topics: Adult; Drug Therapy, Combination; Endometrial Hyperplasia; Estrogen Receptor Modulators; Female; Gonadotropin-Releasing Hormone; Humans; Injections; Leuprolide; Middle Aged; Norpregnenes; Treatment Outcome

On the basis of the recently reported observation that gonadotropin-releasing hormone agonists (GnRH-a) can affect endometrial cell proliferation, both indirectly, through the hormonal axis, and directly, by acting on the GnRH-a receptors, we investigated how far GnRH-a can be used as a new treatment mode for endometrial hyperplasias. Forty-two women, aged 28-60 years, with histologically confirmed simple (n = 30) or complex (n = 12, 2 with atypias) hyperplasia of the endometrium were involved in the study. According to the protocol they were treated for 6 months with GnRH-a (leuprolide acetate or triptorelin), and each patient underwent uterine curettage in the third and the sixth month of treatment, and 6 and at least 12 months after cessation of the treatment, for histological examination and morphometric and DNA-cytometric evaluation of the endometrium (mean pathological follow-up, 19.2 months; mean clinical follow-up, 30.7 months). During treatment, most of the women first revealed endometrial atrophy, and, after cessation of the treatment, again an atrophic or mainly functional endometrium; in 7 women, all with initial diagnosis of simple hyperplasia, the endometrial hyperplasia reappeared, which led in all 7 cases to hysterectomy. The mean values of almost all morphometric and DNA-cytometric parameters during and after treatment showed statistically significant changes in relation to pretreatment values, indicating a decrease in the proliferative activity of the endometrial cells; the GnRH-a antiproliferative effect was still active for a long time after cessation of the therapy. Our results, based for the first time not only on histological but also on serial nuclear morphometric and DNA-cytometric examinations of the endometrial cells and on the longest follow-up time, support the view that in cases of endometrial hyperplasia, especially of complex type, the use of GnRH agonists, which decrease the proliferative tendency of endometrial cells, could represent an alternative conservative therapeutic approach, which, however, requires close monitoring of the endometrium.

Topics: Adult; Cell Division; Cell Nucleus; DNA; Dose-Response Relationship, Drug; Endometrial Hyperplasia; Endometrium; Female; Flow Cytometry; Gonadotropin-Releasing Hormone; Humans; Image Processing, Computer-Assisted; Leuprolide; Middle Aged; Time Factors; Triptorelin Pamoate

The natural history and the factors that lead to the acquisition of atypia in endometrial hyperplasias in young aged women, especially under the age of 20, have not been fully elucidated. In such cases, although there exists a considerable risk of progression to carcinoma, a conservative antiestrogenic treatment is primarily indicated, in attempt to preserve the reproductive ability of the young woman. We report of a 18-year-old girl with atypical hyperplasia of the endometrium, a diagnosis confirmed by reviewing of the histologic material by specialized gynecopathologists. The patient has been treated with gonadotropin releasing hormone agonist (leuprolide acetate) and tibolone for 1 year, which led to endometrial atrophy and amenorrhea, without hypoestrogenic side effects. Six months after cessation of the therapy the endometrial hyperplasia relapsed (this time without atypia), but in about 2 years of follow-up and after short courses of treatment with clomiphene citrate and progestins the biopsy of the endometrium revealed a functional endometrium and the patient presents with an almost regular menstrual cycle.

Topics: Adolescent; Clomiphene; Diagnosis, Differential; Endometrial Hyperplasia; Female; Humans; Leuprolide; Neoplasm Recurrence, Local; Norpregnenes; Precancerous Conditions; Progestins; Ultrasonography

In order to assess the efficacy and tolerability of leuprorelin acetate depot in pre-operative flattening of the endometrium prior to hysteroscopic endometrial ablation, 94 patients from eight centres were included in the per protocol analysis.. The patients included were pre- or peri-menopausal, had completed their family planning and had intractable uterine bleeding. The primary target criterion was the reduction in maximum endometrial thickness after two injections of leuprorelin acetate depot with an interval of four weeks between injections. Surgery took place two weeks after the second injection.. Sufficient pre-treatment was achieved in 91.5% of the patients with > 50% decrease and/or a type 1 endometrium according to sonographic and/or endometrial atrophy (Score 11) according to the central histological evaluation. The endometrium was flattened by a mean of 4.0 +/- 4.1 mm. In terms of clinical response, amenorrhoea, hypomenorrhoea or normal menstruation were achieved after endometrial ablation. Hence 91.5% of patients benefited from the overall treatment after six weeks and still 83% after six months. The trial medication was well tolerated overall. The most common side-effect described was hot flushes which could be attributed to the deliberate oestrogen withdrawal.. In view of the good study results, hormone-suppressive pretreatment of the endometrium can be recommended prior to elective ablation. Surgery should take place during the oestrogen-suppressed phase.

Topics: Adult; Biopsy; Delayed-Action Preparations; Drug Administration Schedule; Endometrial Hyperplasia; Endometrium; Female; Humans; Hysteroscopy; Leuprolide; Menorrhagia; Metrorrhagia; Middle Aged; Preoperative Care