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Premature ovarian insufficiency has life-altering impacts on women’s psychological and physical health and can be challenging for clinicians. New guidelines have been developed to help clinicians apply best practice care for women experiencing this condition.
Premature ovarian insufficiency (POI), defined as loss of ovarian function prior to the age of 40 years, presents a significant challenge to women’s health. More common than previously thought, POI affects around 4% of women. POI may occur spontaneously or as a result of medical treatment but often no cause is identified and the term “idiopathic POI” is applied. It is likely that many cases of idiopathic POI are caused by an as yet unidentified genetic mutation. POI is associated with significant adverse psychological and physical impacts including menopausal symptoms, infertility and increased risk of chronic disease including osteoporosis and cardiovascular disease. However, our and others’ research has shown consumer and clinician knowledge gaps, delayed diagnosis, patient dissatisfaction, suboptimal care and care variation. Recognising this, the recent Senate commission addressing menopause called for greater research into the impact of early menopause.
An international collaboration
An international partnership involving the NHMRC Centre for Research Excellence – Women’s Health in Reproductive Life (CRE-WHiRL), Monash University, European Society for Human Reproduction (ESHRE), American Society for Reproductive Medicine, and International Menopause Society was formed to update the 2016 ESHRE POI guideline. The guideline development group, co-chaired by A/Prof Amanda Vincent and Prof Nick Panay (UK), comprised international experts and women with POI.
This guideline aims to help clinicians apply best practice care for women with POI. Using established ESHRE methodology, informed by a scoping survey, lived experience and integrity review, 40 clinical questions were developed with 145 subsequent recommendations (92 evidence-based and 53 good practice points) on symptoms, diagnosis, causation, sequelae and treatment of POI. Stakeholder review of the draft guideline was sought and the final version was approved by the guideline development group and the ESHRE Executive Committee. In December 2024 , a summary of the guideline was published in the three journals of the partnering organisations, Human Reproduction Open, Fertility and Sterility and Climacteric.
A significant change from the previous guideline is the recommendation that only one elevated follicle stimulating hormone level (FSH) > 25 IU is required for diagnosis of POI; repeat FSH measurement and/or anti-mullerian hormone testing is only needed where there is diagnostic uncertainty. It is hoped that this will facilitate faster diagnosis.
New information is provided regarding genetic causes of POI, fertility preservation and muscle health. The updated guideline reiterates the importance of personalised hormone therapy (HT), unless contraindicated, for symptom relief and chronic disease prevention; with the need for prompt institution and continuation until the usual age of menopause. Additional information is provided regarding oestrogen doses and regimens with special considerations for hormone treatment in iatrogenic POI. Although data specific to POI is limited, recommendations regarding the use of testosterone therapy, non-hormonal therapies for menopausal symptoms, lifestyle interventions and complementary therapies are included. Importantly, informed by women with lived experience of POI, guidance regarding provision of care and implications for relatives is provided, emphasising the need for providing information, referral to support groups, shared decision making and continuity of care. A separate list of research recommendations is provided to stimulate further studies in POI.
The updated guideline was presented at the POI symposium at the World Congress of Menopause, Melbourne, October 2024.
Looking ahead
Uptake of previous guidelines and recommendations has been suboptimal. To address this, MCHRI and CRE-WHiRL, with expertise in guideline translation, lead the guideline resource translation and dissemination. A co-designed health professional toolkit, consumer summary of the guideline, consumer ASK Early Menopause mobile phone application and fact sheets have been developed and are freely available. Activities directed at increasing awareness of POI through social media, including consumer and health professional presentations and learning modules, are being undertaken.
International and national research into POI is ongoing, especially regarding genetic causes of POI, treatments, fertility preservation and POI prediction. The low certainty of evidence for many of the recommendations in the updated guideline highlights this need for more research. Although multidisciplinary care is recommended for women with POI, this can be difficult to implement in reality. We are currently conducting research into the best models of care for POI with integration of digital health tools. The recent Australian Government decision to increase funding for menopause consultations and Pharmaceutical Benefits Scheme reimbursement for HT is welcome, especially as a woman with POI diagnosed at age 25 will conceivably require HT for 25 years. This updated POI guideline is welcome but transformation to a “living” guideline needs consideration as knowledge evolves.
Looking ahead, we hope the future will bring: access to POI gene panel testing, which will result in fewer idiopathic POI diagnoses and facilitate prediction/identification of those at risk of POI; prompt POI diagnosis conveyed in a sensitive manner, and optimisation and accessibility of treatment to improve outcomes. Ultimately, with greater understanding of ovarian biology and genetics, the ability to prevent POI or restore ovarian function will lead to a reduction in the prevalence of POI.
Conclusion
POI has life-altering impacts on women’s psychological and physical health and can be challenging for clinicians. An international partnership of organisations, expert representatives and women with lived experience of POI, has led to the updated ESHRE POI guideline and co-designed accompanying resources. These aim to provide clinicians with clear advice on best practice in POI care, based on the best evidence currently available, and increase consumer awareness and knowledge regarding POI. The overall aim being to enhance quality of life and outcomes for women. However, ongoing research is needed to facilitate optimal management of POI and hopefully prevention of POI in the future.
A/Prof Amanda Vincent MBBS (Hons), B Med Sci (Hons), PhD, FRACP is an endocrinologist, Menopause clinic, Monash Health and leads early menopause research at Monash Centre for Health Research and Implementation (MCHRI), Monash University. She was co-lead of the POI guideline development group with Prof Nick Panay (UK). She is a current board member of the International Menopause Society.
A/ Prof Carolyn Ee MBBS, PhD, FRACGP, is an academic GP at Western Sydney University and was a POI guideline development group member.
Prof Helena Teede AM, PhD, MBBS, FRACP, FRANZCOG, FRCOG, FAAHMS is an endocrinologist at Monash Health, Prof Women’s Health, Equity & Impact, and Director, Monash Centre for Health Research and Implementation (MCHRI), Monash University. She is the lead researcher for the NHMRC Centre for Research Excellence – Women’s Health in Reproductive life (CRE-WHiRL) and a member of the POI guideline development group. She is President of the International Society of Endocrinology.
The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
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