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#63 Bio-identical hormone micronized progesterone: The same but totally different?

Is “bioidentical” micronized progesterone (MP) instead of the “synthetic” medroxyprogesterone acetate (MPA) safer and better for menopausal symptom control?

Theoretical advantages of bioidentical hormones over synthetic hormones are not supported by reliable evidenceUntil results from large, randomized controlled trials (RCTs) are available, we risk repeating errors of the past by concluding bioidentical hormones are more or less safe or efficacious than other hormone replacement therapies. Compounding of bioidentical hormones only serves to ‘compound’ the uncertainty.

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Here is some of the evidence comparing MP with MPA: 
  • Menopausal symptoms 
    • RCT with 875 patients: No difference in symptoms1 or in bleeding episodes2 (when both used cyclically). 
    • Survey study3 (176 patients): Improvement in quality of life.  
      • However, patients included had already switched from MPA to MP, potentially biasing the results 
  • Cardiovascular disease: 
    • RCT,4 875 patients, three years: MP had slightly greater impact on HDL (increase of <0.1 mmol/L) but clinical outcomes not recorded. 
  • Venous thromboembolism: 
    • Case control study:5 Neither MP nor MPA had an effect. 
  • Breast Cancer:  
    • Cohort study,6,7 approximately 99,000 postmenopausal womenAuthors suggest MP may be preferred to most synthetic progestins.   
      • Validity in question due to imbalance in estrogen treatment; multiple subgroup analyses, some apparently post-hoc; and selective grouping of high risk progestins.    
    • Case-control study of 1,555 postmenopausal women suggested MP had less risk than MPA.8 
      • Retrospective nature, small sample size, differences in baseline risk between groups, and lack of clarity on in-situ versus invasive disease all serious limitations.   
  • A number of other studies are too small (<25 patients) to provide any meaningful information.9-11 
  • A thorough review identified three RCTs of bioidentical progesterone cream versus placebo: Only one of three RCTs found improvement in vasomotor symptoms.12  
  • Reliance on observational studies, small RCTs and surrogate endpoints are reminiscent of when synthetic hormones were believed to reduce coronary artery disease by 35-50%.13,14 Later, a large well-designed RCT showed increased cardiovascular events.15  
  • The Endocrine Society warns claims of improved safety or effectiveness are unproven.16 
    • Society of Obstetricians and Gynecologists of Canada17 and others18,19 strongly recommend against compounding of bioidentical hormones.   
updated July 2 2015 by Adrienne

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  • Christina Korownyk MD CCFP
  • James McCormack BSc (Pharm) Pharm D

1. Greendale GA, Reboussin BA, Hogan P, et al. Obstet Gynecol. 1998 Dec; 92(6):982-8.

2. Lindenfeld EA, Langer RD. Obstet Gynecol. 2002 Nov; 100(5 Pt 1):853-63.

3. Fitzpatrick LA, Pace C, Wiita B. J Womens Health Gend Based Med. 2000 May; 9(4):381-7.

4. The Writing Group for the PEPI Trial. JAMA. 1995 Jan 18; 273(3):199-208.

5. Canonico M, Oger E, Plu-Bureau G, et al. Circulation. 2007 Feb 20; 115(7):840-5.

6. Fournier A, Berrino F, Riboli E, et al. Int J Cancer. 2005 Apr 10; 114(3):448-54.

7. Fournier A, Berrino F, Clavel-Chapelon F. Breast Cancer Res Treat. 2008 Jan; 107(1):103-11.

8. Cordina-Duverger E, Truong T, Anger A, et al. PLoS One. 2013; 11:e78016.

9. Cummings JA, Brizendine L. Menopause. 2002 Jul-Aug; 9(4):253-63.

10. Hargrove JT, Maxson WS, Wentz AC, et al. Obstet Gynecol. 1989 Apr; 73(4):606-12.

11. Rosano GM, Webb CM, Chierchia S, et al. J Am Coll Cardiol. 2000 Dec; 36(7):2154-9.

12. Whelan AM, Jurgens TM, Trinacty M. Ann Pharmacother. 2013; 47:112-6.

13. Grady D, Rubin SM, Petitti DB, et al. Ann Intern Med. 1992; 117(12):1016-37.

14. Stampfer MJ, Colditz GA. Prev Med. 1991 Jan; 20(1):47-63.

15. Rossouw JE, Anderson GL, Prentice RL, et al. JAMA. 2002 Jul 17; 288(3):321-33.

16. The Endocrine Society. The Endocrine Society Re-Issues Position Statement on Bioidentical Hormones. 2009. Available at: Last accessed July 2, 2015.

17. Society of Obstetricians and Gynaecologists of Canada. Bioidentical hormone therapy. Available at: Last accessed July 2, 2015.

18. McBane SE, Borgelt LM, Barnes KN, et al. Pharmacotherapy. 2014; 34(4):410-23.

19. Committee on Gynecologic Practice and the American Society for Reproductive Medicine Practice Committee. Obstet Gynecol. 2012; 120(2 Pt 1):411-5.

Authors do not have any conflicts of interest to declare.