Effectiveness of progestin-based therapy for morbidly obese women with complex atypical hyperplasia

  • Marcia A. Ciccone
  • Stephanie A. Whitman
  • Charlotte L. Conturie
  • Niquelle Brown
  • Christina E. Dancz
  • Begum Özel
  • Koji MatsuoEmail author
General Gynecology



While progestins can effectively treat women with complex atypical hyperplasia (CAH), the impact of body habitus on treatment outcome is not well studied. We examine the association between body mass index (BMI) and progestin treatment outcomes.


We conducted a retrospective cohort study of patients diagnosed with hyperplasia between 2003 and 2011. Demographics, past medical history, BMI, hormonal therapy, and histologic treatment response were abstracted. Patients with CAH who received progestin therapy were examined, and rates of regression were assessed.


Of 623 patients identified, 117 had CAH and satisfied the inclusion criteria. Median age was 34, and nearly, two-thirds (64%) were nulliparous. Mean BMI was 40.2, and 81% were obese (BMI 30–39.9: 36%, BMI ≥ 40: 45%). 103 patients (88%) received systemic progestin therapy and 14 patients (12%) received levonorgestrel-releasing intrauterine devices (LNG-IUS). 47 patients (40%) had a complete response to progestin-based therapy. BMI had no effect on the rate of complete response. The proportions of CAH patients with complete regression after hormonal therapy were BMI < 30: 39%, 30–39.9: 40%, and ≥ 40: 36% (P = 0.73). Women treated with LNG-IUS displayed higher rates of complete regression than those receiving systemic therapy (62% versus 38%, P = 0.096), and those with class III obesity were more likely than non-obese patients to receive LNG-IUS although neither reached statistical significance (< 40: 6.7% versus ≥ 40: 17%, P = 0.09).


In this morbidly obese population, response to progestin therapy was generally low; body habitus did not impact treatment outcome for CAH, but local therapy may be more effective than systemic therapy.


Endometrial hyperplasia Progestins Obesity Intrauterine device 


Author contributions

MAC: conceptualization, data curation, funding acquisition, investigation, methodology, project administration, visualization, and writing (original draft). CLC: data curation and writing (review/edits). SAW: data curation and writing (review/edits). NB: formal analysis, software, visualization, and writing (review/edits). CED: conceptualization, supervision, and writing (review/edits). BO: conceptualization, supervision, and writing (review/edits). KM: funding acquisition, investigation, methodology, project administration, supervision, validation, and writing (review/edits).


Ensign Endowment for Gynecologic Cancer Research (K.M.). ARCS Foundation, Inc., Los Angeles founder chapter-Margaret Kersten Ponty Postdoctoral Fellowship (M.A.C.).

Compliance with ethical standards

Conflict of interest

Honorarium, Chugai (K.M.) not related to this study; none for others.

Ethical approval

The study involving human participants performed by authors is approved by Institutional Review Board, University of Southern California. This retrospective study of archived medical records waived to obtain informed consents from study participants.


  1. 1.
    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA. 68:7–30Google Scholar
  2. 2.
    Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia A long-term study of “untreated” hyperplasia in 170 patients. Cancer 56:403–412CrossRefGoogle Scholar
  3. 3.
    Trimble CL, Kauderer J, Zaino R et al (2006) Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 106:812–819CrossRefGoogle Scholar
  4. 4.
    Matsuo K, Ramzan AA, Gualtieri MR et al (2015) Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia. Gynecol Oncol 139:261–267CrossRefGoogle Scholar
  5. 5.
    Kim JJ, Chapman-Davis E (2010) Role of progesterone in endometrial cancer. Semin Reprod Med. 28:81–90CrossRefGoogle Scholar
  6. 6.
    Parkash VFO, Tornos C, McCluggage WG (2015) Committee opinion no. 631: endometrial intraepithelial neoplasia. Obstet Gynecol. 126:897CrossRefGoogle Scholar
  7. 7.
    Trimble CL, Method M, Leitao M, Lu K, Society of Gynecologic Oncology Clinical Practice Committee et al (2012) Management of endometrial precancers. Obstet Gynecol 120:1160–1175Google Scholar
  8. 8.
    Epplein M, Reed SD, Voigt LF et al (2008) Risk of complex and atypical endometrial hyperplasia in relation to anthropometric measures and reproductive history. Am J Epidemiol. 168:563–570 (discussion 71–6) CrossRefGoogle Scholar
  9. 9.
    Flegal KM, Carroll MD, Ogden CL et al (2010) PRevalence and trends in obesity among us adults, 1999–2008. JAMA 303:235–241CrossRefGoogle Scholar
  10. 10.
    Westhoff CL, Torgal AH, Mayeda ER et al (2010) Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception. 81:474–480CrossRefGoogle Scholar
  11. 11.
    Cheymol G (2012) Effects of obesity on pharmacokinetics. Clin Pharmacokinet 39:215–231CrossRefGoogle Scholar
  12. 12.
    Huber J (1998) Pharmacokinetics of Implanon. Contraception. 58:85S–90SCrossRefGoogle Scholar
  13. 13.
    Sivin I, Wan L, Ranta S et al (2001) Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants. Contraception. 64:43–49CrossRefGoogle Scholar
  14. 14.
    Rahimy MH, Cromie MA, Hopkins NK, Tong DM (1999) Lunelle(TM) monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): effects of body weight and injection sites on pharmacokinetics. Contraception. 60:201–208CrossRefGoogle Scholar
  15. 15.
    Cholakian D, Hacker K, Fader AN et al (2016) Effect of oral versus intrauterine progestins on weight in women undergoing fertility preserving therapy for complex atypical hyperplasia or endometrial cancer. Gynecol Oncol 140:234–238CrossRefGoogle Scholar
  16. 16.
    Gallos ID, Ganesan R, Gupta JK (2013) Prediction of regression and relapse of endometrial hyperplasia with conservative therapy. Obstet Gynecol 121:1165–1171CrossRefGoogle Scholar
  17. 17.
    Rodriguez GCYN, King ME (1993) A comparison of the Pipelle device and the Vabra aspirator as measured by endometrial denudation in hysterectomy specimens: the Pipelle device samples significantly less of the endometrial service than the Vabra aspirator. Am J Obstet Gynecol 168:55–59CrossRefGoogle Scholar
  18. 18.
    Kurman RCM, Herrington C et al (eds) (2014) World Health Organisation classification of tumors of female reproductive organs, 4th edn. International Agency for Research on Cancer (IARC), LyonGoogle Scholar
  19. 19.
    Gonthier C, Walker F, Luton D et al (2014) Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer. Gynecol Oncol 133:33–37CrossRefGoogle Scholar
  20. 20.
    Edelman AB, Cherala G, Munar MY et al (2013) Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users. Contraception. 87:220–226CrossRefGoogle Scholar
  21. 21.
    Huizinga MM, Bleich SN, Beach MC et al (2010) Disparity in physician perception of patients’ adherence to medications by obesity status. Obesity. 18:1932–1937CrossRefGoogle Scholar
  22. 22.
    Modesto W, Correia VM, Borges L et al (2015) Weight variation in users of depot-medroxyprogesterone acetate, the levonorgestrel-releasing intrauterine system and a copper intrauterine device for up to ten years of use. Eur J Contracept Reprod Health Care. 20:57–63CrossRefGoogle Scholar
  23. 23.
    Pal N, Broaddus RR, Urbauer DL et al (2018) Treatment of low-risk endometrial cancer and complex atypical hyperplasia with the levonorgestrel-releasing intrauterine device. Obstet Gynecol 131:109–116Google Scholar
  24. 24.
    Nielsen SF, Nordestgaard BG, Bojesen SE (2012) Statin use and reduced cancer-related mortality. N Engl J Med 367:1792–1802CrossRefGoogle Scholar
  25. 25.
    Takiuchi T, Blake EA, Matsuo K et al (2018) Aspirin use and endometrial cancer risk and survival. Gynecol Oncol 148:222–232CrossRefGoogle Scholar
  26. 26.
    Meireles CG, Pereira SA, Valadares LP et al (2017) Effects of metformin on endometrial cancer: systematic review and meta-analysis. Gynecol Oncol 147:167–180CrossRefGoogle Scholar
  27. 27.
    Watkins JL, Thacker PH, Nick AM et al (2015) Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer. Cancer 121:3444–3451CrossRefGoogle Scholar
  28. 28.
    Gallos ID, Shehmar M, Thangaratinam S et al (2010) Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstetr Gynecol. 203:547.e1–547.e10CrossRefGoogle Scholar
  29. 29.
    Gallos ID, Yap J, Rajkhowa M et al (2012) 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 Obstetr Gynecol. 207:266.e1–266.e12CrossRefGoogle Scholar
  30. 30.
    Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R (2016) Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol 27:e8CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of Obstetrics and GynecologyUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  4. 4.Norris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations