HRT for women with premature ovarian insufficiency: a comprehensive review
Open accessAbstract
BACKGROUND: Premature ovarian insufficiency (POI), often and misleadingly referred to as 'premature menopause', is defined as a loss of ovarian activity before the age of 40 years and is characterized by irregular or absent periods and reduced fertility. Symptoms include those associated with the natural menopause (night sweats and vaginal dryness), and with the long-term adverse effects of estrogen deficiency (osteoporosis and cardiovascular disease): the latter is believed to explain the shorter life expectancy associated with POI. OBJECTIVE AND RATIONALE: The objective of the current review was to collect all relevant studies supporting recommendations on the indications, treatment options, and risks of hormone replacement therapy (HRT) (estrogen, progestogens and androgens) for women with POI. SEARCH METHODS: The current review was written based on the best available evidence on the topic collected for the recently published ESHRE guideline on the management of women with POI. PUBMED/MEDLINE and the Cochrane library were searched in a stepwise approach. Relevant references were summarized in evidence tables, with assessment of the quality. OUTCOMES: HRT is strongly recommended for women with POI, mainly for vasomotor and genito-urinary symptom relief. In addition, HRT has been shown to have a role in bone protection and probably also in primary prevention of cardiovascular disease. There is little evidence on the optimal type, regimen and dose of HRT; patient preference for route and method of administration of each component of HRT must be considered when prescribing, as should contraceptive needs. In women with POI, physiological replacement of estrogen (and progesterone) is essential for their health, and the controversies that surround the use of HRT in postmenopausal women do not apply. LIMITATIONS REASONS FOR CAUTION: N/A. WIDER IMPLICATIONS: New areas of study on HRT for women with POI should focus on life expectancy, quality of life and neurological function. Furthermore, randomized controlled trials comparing transdermal estradiol with oral estrogens with regard to efficacy, patient satisfaction and side effects are urgently needed. STUDY FUNDING/COMPETING INTERESTS: The authors received no funding for the review. The costs for the development of the ESHRE guideline were covered by ESHRE. The authors have no conflicts of interest to disclose.
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Conjugated equine estrogens are a non-standardized mixture of many different estrogens and metabolites.
“they are a non-standardized mixture of many different estrogens and metabolites”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [283]
Conjugated equine estrogens increase the risk of venous thromboembolism.
“Conjugated equine estrogens are no longer recommended because they increase the risk of venous thromboembolism”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [283]
Vaginal E2 is not believed to carry a risk of endometrial hyperplasia based on data in older menopausal women.
“Vaginal E2 is not believed to carry a risk of endometrial hyperplasia based on data in older menopausal women.283”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [283]
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- European Society of Human Reproduction and Embryology Guideline Group on POI External review report ‘Management of women with Premature Ovarian Insufficiency’. 2015.
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- Authors
- Webber, L., Anderson, R. A., Davies, M., Janse, F., & Vermeulen, N.
- Affiliations
- University College Hospital (GB)
- MRC Centre for Reproductive Health (GB)
- University Medical Center Utrecht (NL)
- European Society of Human Reproduction and Embryology (BE)
- Corresponding author
- Webber, Lisa
- Venue
- Human Reproduction Open
- Publisher
- Oxford University Press (OUP)
- Published
- 2017
- Volume
- 2017
- Issue
- 2
- Pages
- hox007-hox007
- ISSN
- 2399-3529 (ISSN-L)
- PMC
- PMC6276684
- OpenAlex
- W2735417387
- Cited by
- 141
- References
- 138
- Citations by year
- 2026: 26 · 2025: 10 · 2024: 19 · 2023: 20 · 2022: 21 · 2021: 30 · 2020: 11 · 2019: 4
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Human Reproduction Open (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- European Society of Human Reproduction and Embryology
- 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
- premature ovarian insufficiency, hormone replacement therapy, estrogen deficiency, vasomotor symptoms, genitourinary symptoms, bone protection, cardiovascular disease prevention, progestogens, androgens, transdermal estradiol, oral estrogen, ESHRE guidelines, life expectancy, quality of life
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