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Published in: Archives of Gynecology and Obstetrics 3/2019

01-03-2019 | Obesity | General Gynecology

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

Authors: Marcia A. Ciccone, Stephanie A. Whitman, Charlotte L. Conturie, Niquelle Brown, Christina E. Dancz, Begum Özel, Koji Matsuo

Published in: Archives of Gynecology and Obstetrics | Issue 3/2019

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Abstract

Objective

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.

Methods

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.

Results

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).

Conclusion

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.
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA. 68:7–30PubMed Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA. 68:7–30PubMed
2.
go back to reference Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia A long-term study of “untreated” hyperplasia in 170 patients. Cancer 56:403–412CrossRefPubMed Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia A long-term study of “untreated” hyperplasia in 170 patients. Cancer 56:403–412CrossRefPubMed
3.
go back to reference 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 106:812–819CrossRefPubMed 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 106:812–819CrossRefPubMed
4.
go back to reference Matsuo K, Ramzan AA, Gualtieri MR et al (2015) Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia. Gynecol Oncol 139:261–267CrossRefPubMed Matsuo K, Ramzan AA, Gualtieri MR et al (2015) Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia. Gynecol Oncol 139:261–267CrossRefPubMed
6.
go back to reference Parkash VFO, Tornos C, McCluggage WG (2015) Committee opinion no. 631: endometrial intraepithelial neoplasia. Obstet Gynecol. 126:897CrossRefPubMed Parkash VFO, Tornos C, McCluggage WG (2015) Committee opinion no. 631: endometrial intraepithelial neoplasia. Obstet Gynecol. 126:897CrossRefPubMed
7.
go back to reference Trimble CL, Method M, Leitao M, Lu K, Society of Gynecologic Oncology Clinical Practice Committee et al (2012) Management of endometrial precancers. Obstet Gynecol 120:1160–1175PubMedPubMedCentral Trimble CL, Method M, Leitao M, Lu K, Society of Gynecologic Oncology Clinical Practice Committee et al (2012) Management of endometrial precancers. Obstet Gynecol 120:1160–1175PubMedPubMedCentral
8.
go back to reference 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) CrossRefPubMedPubMedCentral 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) CrossRefPubMedPubMedCentral
9.
go back to reference Flegal KM, Carroll MD, Ogden CL et al (2010) PRevalence and trends in obesity among us adults, 1999–2008. JAMA 303:235–241CrossRef Flegal KM, Carroll MD, Ogden CL et al (2010) PRevalence and trends in obesity among us adults, 1999–2008. JAMA 303:235–241CrossRef
10.
go back to reference Westhoff CL, Torgal AH, Mayeda ER et al (2010) Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception. 81:474–480CrossRefPubMedPubMedCentral Westhoff CL, Torgal AH, Mayeda ER et al (2010) Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception. 81:474–480CrossRefPubMedPubMedCentral
11.
go back to reference Cheymol G (2012) Effects of obesity on pharmacokinetics. Clin Pharmacokinet 39:215–231CrossRef Cheymol G (2012) Effects of obesity on pharmacokinetics. Clin Pharmacokinet 39:215–231CrossRef
13.
go back to reference Sivin I, Wan L, Ranta S et al (2001) Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants. Contraception. 64:43–49CrossRefPubMed Sivin I, Wan L, Ranta S et al (2001) Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants. Contraception. 64:43–49CrossRefPubMed
14.
go back to reference 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. 60:201–208CrossRefPubMed 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. 60:201–208CrossRefPubMed
15.
go back to reference 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 140:234–238CrossRefPubMed 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 140:234–238CrossRefPubMed
16.
go back to reference Gallos ID, Ganesan R, Gupta JK (2013) Prediction of regression and relapse of endometrial hyperplasia with conservative therapy. Obstet Gynecol 121:1165–1171CrossRefPubMed Gallos ID, Ganesan R, Gupta JK (2013) Prediction of regression and relapse of endometrial hyperplasia with conservative therapy. Obstet Gynecol 121:1165–1171CrossRefPubMed
17.
go back to reference 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 168:55–59CrossRefPubMed 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 168:55–59CrossRefPubMed
18.
go back to reference 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), Lyon 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), Lyon
19.
go back to reference 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 133:33–37CrossRefPubMed 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 133:33–37CrossRefPubMed
20.
go back to reference 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. 87:220–226CrossRefPubMed 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. 87:220–226CrossRefPubMed
21.
go back to reference Huizinga MM, Bleich SN, Beach MC et al (2010) Disparity in physician perception of patients’ adherence to medications by obesity status. Obesity. 18:1932–1937CrossRefPubMed Huizinga MM, Bleich SN, Beach MC et al (2010) Disparity in physician perception of patients’ adherence to medications by obesity status. Obesity. 18:1932–1937CrossRefPubMed
22.
go back to reference 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. 20:57–63CrossRefPubMed 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. 20:57–63CrossRefPubMed
23.
go back to reference 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 131:109–116PubMedPubMedCentral 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 131:109–116PubMedPubMedCentral
24.
go back to reference Nielsen SF, Nordestgaard BG, Bojesen SE (2012) Statin use and reduced cancer-related mortality. N Engl J Med 367:1792–1802CrossRef Nielsen SF, Nordestgaard BG, Bojesen SE (2012) Statin use and reduced cancer-related mortality. N Engl J Med 367:1792–1802CrossRef
25.
go back to reference Takiuchi T, Blake EA, Matsuo K et al (2018) Aspirin use and endometrial cancer risk and survival. Gynecol Oncol 148:222–232CrossRefPubMed Takiuchi T, Blake EA, Matsuo K et al (2018) Aspirin use and endometrial cancer risk and survival. Gynecol Oncol 148:222–232CrossRefPubMed
26.
go back to reference Meireles CG, Pereira SA, Valadares LP et al (2017) Effects of metformin on endometrial cancer: systematic review and meta-analysis. Gynecol Oncol 147:167–180CrossRefPubMed Meireles CG, Pereira SA, Valadares LP et al (2017) Effects of metformin on endometrial cancer: systematic review and meta-analysis. Gynecol Oncol 147:167–180CrossRefPubMed
27.
go back to reference 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 121:3444–3451CrossRefPubMedPubMedCentral 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 121:3444–3451CrossRefPubMedPubMedCentral
28.
go back to reference 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.e10CrossRef 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.e10CrossRef
29.
go back to reference 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.e12CrossRef 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.e12CrossRef
30.
go back to reference Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R (2016) Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol 27:e8CrossRef Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R (2016) Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol 27:e8CrossRef
Metadata
Title
Effectiveness of progestin-based therapy for morbidly obese women with complex atypical hyperplasia
Authors
Marcia A. Ciccone
Stephanie A. Whitman
Charlotte L. Conturie
Niquelle Brown
Christina E. Dancz
Begum Özel
Koji Matsuo
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 3/2019
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-019-05059-2

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