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Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review

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An Author Correction to this article was published on 28 December 2017

This article has been updated

Abstract

Purpose

Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI.

Methods

A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study.

Results

The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and eight cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with three out of eight studies showing HT associated increase benefits. Only one study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent.

Conclusions

Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes, and heterogeneity of trials regarding the formulation, dose, route of administration, and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke, and cardiovascular mortality are crucial to optimize benefits of this therapy.

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Change history

  • 28 December 2017

    In the original publication, the given and family name of the author Mohammad Hassan Murad was incorrect. This has been corrected with this erratum.

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Funding

DC and GSB were supported by the CTSA Grant Number TL1 TR000137 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). GSB was also supported by grant number 3R01HL131535-01S1 from the National Heart Lung and Blood Institute (NHLBI). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH.

Author information

Author notes

    Authors and Affiliations

    1. Internal Medicine Department, VA Caribbean Health Care System, San Juan, PR, 00921, USA

      Nydia Burgos

    2. Mayo Graduate School, Mayo Clinic, Rochester, MN, 55905, USA

      Dahima Cintron & Gabriela Spencer-Bonilla

    3. University of Puerto Rico-Medical Sciences Campus, San Juan, PR, 00921, USA

      Dahima Cintron & Paula Latortue-Albino

    4. Department of Medicine, Knowledge and Evaluation Research Unit in Endocrinology, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, 55905, USA

      Valentina Serrano, Rene Rodriguez Gutierrez & Gabriela Spencer-Bonilla

    5. Department of Nutrition, Diabetes and Metabolism, Escuela de Medicina, Pontifica Universidad Católica de Chile, Santiago, Chile

      Valentina Serrano

    6. Department of Medicine, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, 55905, USA

      Rene Rodriguez Gutierrez

    7. Department of Internal Medicine, Division of Endocrinology, University Hospital “Dr. Jose E. Gonzalez”, Autonomous University of Nuevo Leon, Monterrey, 64460, Mexico

      Rene Rodriguez Gutierrez

    8. Laboratorio Nacional para el Estudio y Aplicación de la Medicina Basada en Evidencia, Análisis Crítico de la Información Científica y Farmacoeconomía, Universidad Autónoma de Nuevo León, Monterrey, 66460, Mexico

      Rene Rodriguez Gutierrez

    9. Women’s Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA

      Stephanie Faubion

    10. Mayo Clinic Libraries, Rochester, MN, 55905, USA

      Patricia J. Erwin

    11. Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, 55905, USA

      Mohammad Hassan Murad

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    1. Nydia Burgos
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    Corresponding author

    Correspondence to Dahima Cintron.

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    Conflict of interest

    S.F. is currently a consultant for Mithra Pharmaceuticals. The remaining authors declare that they have no competing interests.

    Ethical approval

    This article does not contain any studies with human participants performed by any of the authors.

    Additional information

    Nydia Burgos and Dahima Cintron contributed equally to this work.

    A correction to this article is available online at https://doi.org/10.1007/s12020-017-1491-2.

    Appendix

    Appendix

    Table 4

    Table 4 Search strategy January 2016
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    Table 5

    Table 5 Clinicaltrials.gov search results
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    Burgos, N., Cintron, D., Latortue-Albino, P. et al. Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review. Endocrine 58, 413–425 (2017). https://doi.org/10.1007/s12020-017-1435-x

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