Oncologic and Reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 Adenocarcinoma: A systematic review

doi:10.1016/j.ygyno.2012.01.003

Gynecologic Oncology

Volume 125, Issue 2, May 2012, Pages 477-482

https://doi.org/10.1016/j.ygyno.2012.01.003 Get rights and content

Abstract

Objective

The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical management with progestin therapy.

Methods

A systematic review of oncologic and pregnancy outcomes in women with complex atypical hyperplasia or grade 1 adenocarcinoma was performed using a comprehensive search of the MEDLINE literature. English language studies published from 2004 to 2011 which utilized hormonal therapy were identified using key words endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Fisher's exact test was used to calculate statistical differences.

Results

Forty-five studies with 391 study subjects were identified. The median age was 31.7 years. Therapies included medroxyprogesterone (49%), megestrol acetate (25%), levonorgestrel intrauterine device (19%), hydroxyprogesterone caproate (0.8%), and unspecified/miscellaneous progestins (13.5%). Overall, 344 women (77.7%) demonstrated a response to hormonal therapy. After a median follow up period of 39 months, a durable complete response was noted in 53.2%. The complete response rate was significantly higher for those with hyperplasia than for women with carcinoma (65.8% vs. 48.2%, p = .002). The median time to complete response was 6 months (range, 1–18 months). Recurrence after an initial response was noted in 23.2% with hyperplasia and 35.4% with carcinoma during the study periods (p = .03). Persistent disease was observed in 14.4% of women with hyperplasia and 25.4% of women with carcinoma (p = .02). During the respective study periods, 41.2% of those with hyperplasia and 34.8% with a history of carcinoma became pregnant (p = .39), with 117 live births reported.

Conclusion

Based on this systematic review of the contemporary literature, endometrial hyperplasia has a significantly higher likelihood of response (66%) to hormonal therapy than grade 1 endometrial carcinoma (48%). Disease persistence is more common in women with carcinoma (25%) compared to hyperplasia (14%). Reproductive outcomes do not seem to differ between the cohorts.

Highlights

► Endometrial hyperplasia is more responsive to hormonal therapy than is carcinoma. ► Disease persistence is more common with endometrial carcinoma than hyperplasia. ► Reproductive outcomes are similar with grade 1 endometrial carcinoma and hyperplasia.

Introduction

Endometrial carcinoma is the most frequently occurring gynecologic malignancy in the United States with approximately 44,000 new cases in 2011 [1]. It is predominantly a disease of postmenopausal women; however, greater than 25% of cases occur in premenopausal women. An even larger proportion of premenopausal women is diagnosed with complex atypical hyperplasia, a known precursor of endometrial carcinoma [2].

The standard treatment for endometrial carcinoma is a total extrafascial hysterectomy, bilateral salpingo-oophorectomy (BSO), and pelvic and para-aortic lymph node assessment [3]. However, in spite of oncologic risk, this definitive approach may be undesirable in select women who wish to maintain their fertility. Prior studies have described the feasibility and safety of treating women with endometrial hyperplasia or early-stage, low grade carcinoma with high-dose progestin therapy to allow for future fertility [4], [5], [6], [7], [8], [9]. Reversal of endometrial hyperplasia or cancer by progestin therapies is believed to occur through activation of progesterone receptors, resulting in stromal decidualization and subsequent thinning of the endometrial lining.

In 2004, Ramirez et al. published a review of 81 women with grade 1 endometrial carcinoma who were managed with hormonal treatment [6]. Seventy-six percent responded to therapy, and 58% had no evidence of recurrence at the time of publication. This review highlighted the efficacy and safety of continuous progestin therapy in the treatment of low grade endometrial carcinoma but was limited by relatively short follow-up periods, a small number of subjects, and exclusion of women with endometrial hyperplasia. Therefore, the objective of this manuscript is to analyze the contemporary oncologic and reproductive outcomes in conservatively treated women with either endometrial hyperplasia or carcinoma and to determine if there are differences in hormonal response and fertility rates and between these cohorts.

Section snippets

Methods

An electronic literature search via the MEDLINE database was performed to identify published English language articles addressing hormonal treatment of women with a histologic diagnosis of complex atypical hyperplasia or grade 1 adenocarcinoma of the endometrium. Key words searched include endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Previous reviews by other authors have adequately characterized the data prior to 2004; thus, we limited the

Results

Forty-five studies with 391 study subjects were identified. Five studies were prospective, and the remainder were retrospective series (n = 20) or case reports (n = 20). (Table 2, Table 3) One hundred eleven women had a histologic diagnosis of complex atypical hyperplasia, and 280 women had grade 1 adenocarcinoma of the endometrium. The median age for the overall cohort was 31.7 years (range 19–80 years); however, in nine studies, individual ages were not reported [11], [12], [13], [14], [15], [16],

Discussion

Hysterectomy may not be an acceptable option for young women diagnosed with complex atypical hyperplasia or endometrial carcinoma if they wish to maintain their fertility. Although hormonal management of complex atypical hyperplasia and low-grade, apparent early-stage endometrial carcinoma has been utilized for fifty years, high quality data regarding the efficacy and safety of this approach is nevertheless lacking [56]. To our knowledge, the current study is the most comprehensive systematic

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgment

Grant support: Kathryn A. Carson's work on this manuscript was supported by Johns Hopkins Institute for Clinical and Translational Research grant number UL1RR025005 from the National Institutes of Health/National Center for Research Resources. Dr. Robert E. Bristow was supported by a grant from the Queen of Hearts Foundation.

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To evaluate satisfaction with information, treatment, and decision regret during management to preserve fertility for atypical hyperplasia (AH) or endometrial cancer (EC).
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Trial registration ClinicalTrials.gov NCT03241888. https://www.clinicaltrials.gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1

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ReviewOncologic and Reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 Adenocarcinoma: A systematic review

Abstract

Objective

Methods

Results

Conclusion

Highlights

Introduction

Section snippets

Methods

Results

Discussion

Conflict of interest statement

Acknowledgment

Int J Gynaecol Obstet

Obstet Gynecol

Gynecol Oncol

Cancer Lett

Obstet Gynecol

Fertil Steril

Eur J Obstet Gynecol Reprod Biol

Maturitas

Gynecol Oncol

Gynecol Oncol

Reprod Biomed Online

Reprod Biomed Online

Gynecol Oncol

Cancer Lett

Reprod Biomed Online

Fertil Steril

Reprod Biomed Online

Int J Gynaecol Obstet

Minim Invasive Gynecol

Gynecol Oncol

Gynecol Oncol

Fertil Steril

Fertil Steril

Am J Obstet Gynecol

Cancer statistics, 2009

CA Cancer J Clin

Adenocarcinoma of the endometrium in women 40 years of age or younger

Obstet Gynecol

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases

Eur J Gynaecol Oncol

Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature

Cancer

The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses

Prolonged conservative treatment of endometrial cancer patients: more than 1 pregnancy can be achieved

Ann Oncol

Conservative treatment with progestin and pregnancy outcomes in endometrial cancer

Int J Gynecol Cancer

Review
Oncologic and Reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 Adenocarcinoma: A systematic review