Bioidentical hormone micronized progesterone

Clinical question

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

Evidence

Here is some of the evidence comparing MP with MPA.

• Menopausal symptoms and tolerability

  • -An RCT (N = 875): no difference in symptoms¹ or in bleeding episodes² (when both used cyclically).
  • -Survey study³ (N = 176): improvement in quality of life, but patients had already switched from MPA to MP, potentially biasing the results.
• Cardiovascular disease

  • -An RCT⁴ (N = 875, 3 years): MP had slightly greater effect on high-density lipoprotein levels (increase of < 0.1 mmol/L), but clinical outcomes not recorded.
• Venous thromboembolism

  • -Case-control study⁵: neither MP nor MPA had an effect.
• Breast cancer

  • -Cohort study^6,7 (99 000 postmenopausal women): authors suggest MP might be preferred to most synthetic progestins; validity in question (imbalance in estrogen treatment; multiple subgroup analyses, some apparently post hoc; and selective grouping of high-risk progestins).

• A number of other studies are too small (< 25 patients) to provide any meaningful information.^8–10

Context

• Reliance on observational studies, small RCTs, and surrogate end points is reminiscent of when synthetic hormones were believed to reduce coronary artery disease by 35% to 50%.^11,12 Later, a large well-designed RCT showed increased cardiovascular events.¹³

• The Endocrine Society warns claims of improved safety or effectiveness are unproven.¹⁴ The Society of Obstetricians and Gynaecologists of Canada and others¹⁵ strongly recommend against compounding of bioidentical hormones.

Bottom line

The theoretical advantages of MP are not supported by the evidence. We risk repeating errors of the past by concluding MP is more or less safe or efficacious than other hormone replacement therapy (HRT) without results of large RCTs. Compounding of bioidentical hormones only serves to “compound” the uncertainty.

Implementation

The Women’s Health Initiative¹³ found combined HRT increased breast cancer, venous thromboembolism, myocardial infarction, and stroke by 8, 18, 7, and 8 events in 10 000 patient-years, respectively; HRT decreased colorectal cancer and hip fracture by 6 and 5 less events in 10 000 patient-years, respectively. However, HRT is the most effective therapy for menopausal symptoms, particularly hot flashes.¹⁶ Patients desiring treatment should be advised that there is no convincing evidence that bioidentical hormones are safer or more effective than synthetic HRT. Overall, if 100 women take synthetic HRT for 5 years, there will be 1 more serious adverse event relative to benefit.¹³

Tools for Practice articles in Canadian Family Physician (CFP) are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in CFP are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.