Menopausal hormone therapy and new-onset diabetes in the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l’Education Nationale (E3N) cohort
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Aims/hypothesis Two US randomised trials found a lower incidence of type 2 diabetes in women treated by menopausal hormone therapy (MHT) with oral conjugated equine oestrogen combined with medroxyprogesterone acetate. The purpose of this study was to evaluate the influence of various MHTs, according to their formulation and route of administration, on new-onset diabetes in a cohort of postmenopausal French women.Methods The association between MHT use and new-onset diabetes was investigated by Cox regression analysis in 63,624 postmenopausal women in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N). Cases of diabetes were identified through self-reporting or drug-reimbursement record linkage, and further validated.Results 1,220 new-onset diabetes cases were validated. We observed a lower risk of new-onset diabetes among women who had ever used MHT (HR 0.82 [95% CI 0.72-0.93]), compared with those who had never used MHT. Adjustment for BMI during follow-up (rather than according to baseline BMI) did not substantially modify this association. An oral route of oestrogen administration was associated with a greater decrease in diabetes risk than a cutaneous route (HR 0.68 [95% CI 0.55-0.85] vs 0.87 [95% CI 0.75-1.00], p for homogeneity = 0.028). We were not able to show significant differences between the progestagens used in combined MHT.Conclusions/interpretation Use of MHT appeared to be associated with a lower risk of new-onset diabetes. This relationship was not mediated by changes in BMI. Further studies are needed to confirm the stronger effect of oral administration of oestrogen compared with cutaneous administration.
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Both transdermal and oral MHT delivery methods reduce diabetes risk, but oral MHT led to a greater risk reduction.
“while both transdermal and oral MHT delivery methods have been shown to reduce diabetes risk, oral MHT led to a greater risk reduction (213).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [213]
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- Authors
- de Lauzon-Guillain, B., Fournier, A., Fabre, A., Simon, N., Mesrine, S., Boutron-Ruault, M.-C., Balkau, B., & Clavel-Chapelon, F.
- Affiliations
- Inserm (FR)
- Université Paris-Sud (FR)
- Venue
- Diabetologia
- Published
- 2009-07-23
- Volume
- 52
- Issue
- 10
- Pages
- 2092-2100
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC3240590
- OpenAlex
- W2002247513
- Cited by
- 86
- References
- 40
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 1 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 2 · 2013: 12 · 2012: 6
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- 3M
- European Commission (LSHM_CT_2006_037197)
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Institut Gustave-Roussy
- Mutuelle Générale de l'Education Nationale
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- hormone replacement therapy, type 2 diabetes, new-onset diabetes, postmenopausal women, oral estrogen, transdermal estrogen, conjugated equine estrogens, medroxyprogesterone acetate, progestogens, route of administration, body mass index, E3N cohort
- MeSH terms
- Adult, Aged, Diabetes Mellitus, Estrogens, Conjugated (USP), Female, Humans, Middle Aged, Surveys and Questionnaires, Proportional Hazards Models, Randomized Controlled Trials as Topic, Medroxyprogesterone Acetate, Postmenopause, Hormone Replacement Therapy
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