Early Menopause/Premature Ovarian Insufficiency

Amanda J. Vincent, MBBS, BMedSci, PhD, FRACP

Joop S. Laven, MD, PhD

Although often considered “too young for menopause,” this issue of Seminars in Reproductive Medicine concerns the loss of ovarian function in women younger than 45 years (early menopause, EM) or 40 years (premature ovarian insufficiency, POI). Article 1 indicates that the prevalence of EM/POI is higher than was originally perceived, affecting up to 12% of women. International collaborations resulting in the ability to investigate large observational datasets have yielded new data regarding the potential risk factors for EM/POI and in particular the impact of early life, reproductive, and socioeconomic factors. Increasing cancer survivorship means that more women are living with the sequelae of medically induced EM/POI. The experiences of women navigating the often complex processes of diagnosis and treatment are explored in article 2. Most women are diagnosed with idiopathic spontaneous POI, and in article 3, Prof. Laven summarizes the latest evidence regarding the genetic underpinnings of spontaneous POI. He challenges us with the proposal that premature aging of the soma associated with POI drives the loss of ovarian function rather than the reverse. A reliable method to accurately predict and diagnose POI is sorely needed. Prof. Anderson, in article 4, outlines the role of anti-mullerian hormone in fulfilling this need. Cardiovascular disease is the most common cause of death in women. Article 5 highlights that early menopause is a female-specific risk factor for cardiovascular disease and describes the potential underlying mechanisms. Osteoporosis is one of the long-term sequelae of POI/EM and musculoskeletal health is explored in Articles 6 and 7. POI guidelines advocate the use of hormone replacement therapy in women with POI/EM until the usual age of menopause; however, the optimal regimen is unknown. In article 8, Prof. Santoro discusses hormone replacement therapy in the management of POI/EM. Women with EM/POI and a diagnosis of breast cancer are advised to avoid hormone therapy. The options for managing menopausal symptoms and bone and cardiovascular health in the setting of breast cancer are discussed in article 9. Dissatisfaction with information provided, unreliable sources, lack of evidence-based information and care variation prompted the codesign and development of an EM digital resource for women and health professionals. This knowledge translation project is described in article 10. The multiple causes, symptomatology, and comorbidities associated with EM/POI have led to the recommendation for multidisciplinary care, but what constitutes a model of care? This subject is explored in the final article of this issue and the key elements comprising a model of care identified.

This issue of Seminars in Reproductive Medicine provides a comprehensive update regarding important topics relevant to POI/EM. Yet it also highlights the numerous knowledge gaps that exist. Critically important next steps include further research to:

• Further identify and define candidate genes which may contribute to new biomarkers.

• Further explore the natural history of POI/EM and whether changes in modifiable risk factors impact incidence and sequelae.

• Refine POI/EM prediction and diagnostic criteria with identification of potential new biomarkers.

• Further explore the bone–muscle interface and novel diagnostic strategies for assessing bone health.

• Identify the optimal hormone replacement therapy including the role of testosterone therapy.

• Identify novel effective nonhormonal agents to manage menopausal symptoms for those women unable to use hormone therapy.

• Using new knowledge and best practice methodology to update POI guidelines.

• Expand POI/EM information provision incorporating mobile health options.

• Develop and evaluate a model of care for women with POI/EM incorporating codesign, integrated multidisciplinary care, and updated evidence-based guidelines.

Publication History

Article published online:
25 January 2021