Obstet Gynecol Sci.  2016 Jan;59(1):24-31. 10.5468/ogs.2016.59.1.24.

Fertility-preserving treatment in complex atypical hyperplasia and early endometrial cancer in young women with oral progestin: Is it effective?

• Baek JS
• Lee WH
• Kang WD
• Kim SM

• KMID: 2152640
• DOI: http://doi.org/10.5468/ogs.2016.59.1.24

Abstract

OBJECTIVE
The aim of this study is to assess the effectiveness of oral progestin treatment in women diagnosed with complex atypical hyperplasia (CAH) or grade 1 endometrial cancer (G1EC), who desire to preserve their fertility, as alternative treatment to a hysterectomy.
METHODS
We reviewed the medical records of women younger than 45 years old that had been diagnosed with CAH or G1EC, who expressed a desire to preserve their fertility using alternative treatment at our institution. Women without evidence of myometrial invasion on pelvic magnetic resonance imaging scans were included. The study period was between 2004 and 2014. Endometrial biopsies were taken at follow-up appointments.
RESULTS
We identified 31 young women with CAH or G1EC. The median age was 33 years old (range, 20 to 41), and the median period of time undertaking the treatment was 5 months (range, 1 to 12). Twenty-three patients (74.2%) achieved complete remission (CR; median time to CR was 3 months; range, 1 to 22), 16 patients (88.9%) with CAH and 7 (53.8%) with G1EC achieved CR. 6 patients (26.1%) who had achieved CR, had recurrence of the disease (median time from CR to recurrence was 12.5 months; range, 4 to 18). Eight patients (25.8%) finally underwent a hysterectomy.
CONCLUSION
Oral progestin therapy is an alternative treatment for women with CAH or G1EC who desire fertility preservation. However, more prospective studies are needed for standard progestin regimen. Also, there still remains a risk of disease progression and recurrence. Therefore, close follow-up is important during treatment and after CR. In addition, a hysterectomy is recommended as a definitive treatment after completion of childbearing.

Keyword

Endometrial hyperplasia; Endometrial cancer; Fertility; Progestins

MeSH Terms

Appointments and Schedules
Biopsy
Disease Progression
Endometrial Hyperplasia
Endometrial Neoplasms*
Female
Fertility
Fertility Preservation
Follow-Up Studies
Humans
Hyperplasia*
Hysterectomy
Magnetic Resonance Imaging
Medical Records
Mortuary Practice
Progestins
Prospective Studies
Recurrence
Progestins

Figure

• 

  Fig. 1 The distribution of evaluated patients.

Reference

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61:69–90.

2. Gallup DG, Stock RJ. Adenocarcinoma of the endometrium in women 40 years of age or younger. Obstet Gynecol. 1984; 64:417–420.

3. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64:9–29.

4. Creasman WT, Odicino F, Maisonneuve P, Beller U, Benedet JL, Heintz AP, et al. Carcinoma of the corpus uteri. J Epidemiol Biostat. 2001; 6:47–86.

5. Barakat RR, Bundy BN, Spirtos NM, Bell J, Mannel RS. Gynecologic Oncology Group Study. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2006; 24:587–592.

6. Duska LR, Garrett A, Rueda BR, Haas J, Chang Y, Fuller AF. Endometrial cancer in women 40 years old or younger. Gynecol Oncol. 2001; 83:388–393.

7. Gitsch G, Hanzal E, Jensen D, Hacker NF. Endometrial cancer in premenopausal women 45 years and younger. Obstet Gynecol. 1995; 85:504–508.

8. Lee NK, Cheung MK, Shin JY, Husain A, Teng NN, Berek JS, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol. 2007; 109:655–662.

9. Tran BN, Connell PP, Waggoner S, Rotmensch J, Mundt AJ. Characteristics and outcome of endometrial carcinoma patients age 45 years and younger. Am J Clin Oncol. 2000; 23:476–480.

10. Soliman PT, Oh JC, Schmeler KM, Sun CC, Slomovitz BM, Gershenson DM, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol. 2005; 105:575–580.

11. Simpson AN, Feigenberg T, Clarke BA, Gien LT, Ismiil N, Laframboise S, et al. Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin. Gynecol Oncol. 2014; 133:229–233.

12. Crissman JD, Azoury RS, Barnes AE, Schellhas HF. Endometrial carcinoma in women 40 years of age or younger. Obstet Gynecol. 1981; 57:699–704.

13. Lajer H, Elnegaard S, Christensen RD, Ortoft G, Schledermann DE, Mogensen O. Survival after stage IA endometrial cancer: can follow-up be altered? A prospective nationwide Danish survey. Acta Obstet Gynecol Scand. 2012; 91:976–982.

14. Silverberg SG, Makowski EL, Roche WD. Endometrial carcinoma in women under 40 years of age: comparison of cases in oral contraceptive users and non-users. Cancer. 1977; 39:592–598.

15. Dorais J, Dodson M, Calvert J, Mize B, Travarelli JM, Jasperson K, et al. Fertility-sparing management of endometrial adenocarcinoma. Obstet Gynecol Surv. 2011; 66:443–451.

16. Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol. 2004; 95:133–138.

17. Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol. 1997; 90:434–440.

18. Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012; 125:477–482.

19. Koskas M, Azria E, Walker F, Luton D, Madelenat P, Yazbeck C. Progestin treatment of atypical hyperplasia and well-differentiated adenocarcinoma of the endometrium to preserve fertility. Anticancer Res. 2012; 32:1037–1043.

20. Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women: report of seven cases and review of the literature. Cancer. 1997; 79:320–327.

21. Shirali E, Yarandi F, Eftekhar Z, Shojaei H, Khazaeipour Z. Pregnancy outcome in patients with stage 1a endometrial adenocarcinoma, who conservatively treated with megestrol acetate. Arch Gynecol Obstet. 2012; 285:791–795.

22. Cade TJ, Quinn MA, Rome RM, Neesham D. Progestogen treatment options for early endometrial cancer. BJOG. 2010; 117:879–884.

23. Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013; 49:868–874.

24. Penner KR, Dorigo O, Aoyama C, Ostrzega N, Balzer BL, Rao J, et al. Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy. Gynecol Oncol. 2012; 124:542–548.

25. Eftekhar Z, Izadi-Mood N, Yarandi F, Shojaei H, Rezaei Z, Mohagheghi S. Efficacy of megestrol acetate (megace) in the treatment of patients with early endometrial adenocarcinoma: our experiences with 21 patients. Int J Gynecol Cancer. 2009; 19:249–252.

26. Vereide AB, Kaino T, Sager G, Arnes M, Orbo A. Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-alpha and ER-beta) in human endometrial hyperplasia. Gynecol Oncol. 2006; 101:214–223.

27. Gunderson CC, Dutta S, Fader AN, Maniar KP, Nasseri-Nik N, Bristow RE, et al. Pathologic features associated with resolution of complex atypical hyperplasia and grade 1 endometrial adenocarcinoma after progestin therapy. Gynecol Oncol. 2014; 132:33–37.

28. Gallos ID, Yap J, Rajkhowa M, Luesley DM, Coomarasamy A, Gupta JK. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012; 207:266.e1–266.e12.