- Primary ovarian insufficiency (POI) is linked with lower levels of 17-Beta-Estradiol and is associated with poorer health outcomes.
- 17-Beta-Estradiol is a hormone that plays a crucial role in women’s health. However, there is a lack of scientific research in this area.
- Lawrence M Nelson, President of the Mary Elizabeth Conover Foundation in the USA, explains that the development of a digital women’s health initiative would optimise global evaluation and management of POI and 17-Beta-Estradiol deficiency.
Primary ovarian insufficiency (POI) occurs when a woman’s ovaries stop working normally before the age of 40. POI is characterised by amenorrhoea (lack of a menstrual period) and changes in hormone levels, such as follicle-stimulating hormone. It has similar symptoms to other conditions, including early menopause, making an accurate diagnosis difficult.
Ovarian follicles are small sacs in the ovaries that are filled with fluid and secrete reproductive hormones. Usually, women have around 200,000-300,000 follicles at puberty. Each of these follicles has the potential to release an egg cell for ovulation. The number and size of follicles are often used for assessing fertility status, including investigations for POI.
Mechanisms behind POI
Two major mechanisms have been identified for POI so far: ovarian follicle depletion or dysfunction. It is estimated that 70% of women with POI have some detectable follicles remaining, suggesting that follicle dysfunction is more common than depletion. Currently, clinical testing methods can only identify a cause for POI in around 10% of cases; more advanced genetic testing in a research setting may find new mechanisms behind POI in approximately 25–30% of cases. In most cases, the exact cause of follicle depletion or dysfunction in POI is unknown, but it may be linked to chromosome abnormalities, dysfunctional immune responses, or specific gene mechanisms.
Due to the decrease in reproductive hormones, women are at greater risk of certain conditions as they age, such as osteoporosis and cardiovascular disease. A diagnosis of POI impacts emotional as well as physical health as it can result in unexpected infertility and may feel isolating for those newly diagnosed with the condition. Therefore, an integrated, long-term team approach to care is needed.
17-Beta-Estradiol is a hormone produced within ovarian follicles, with small amounts also made by the adrenal glands and testes. In women, 17-Beta-Estradiol plays several roles in reproductive health throughout their lifespan; for example, it mediates pubertal development, ovulation, and fertility and contributes to skin, bone, heart, and brain health. There is a natural decrease in 17-Beta-Estradiol levels towards menopause, but 17-Beta-Estradiol deficiency is also seen in POI.
Unfortunately, women’s health is widely under-researched, and this becomes obvious when considering POI and 17-Beta-Estradiol deficiency.
Dr Lawrence M Nelson is the President of the Mary Elizabeth Conover Foundation and Director of a digital women’s health initiative called My28Days.org. Nelson explains that more input is needed from global health leaders to address the knowledge gap of women’s hormone health, as well as to create a bridge between scientific research and clinical practice.
Digital women’s health community
Through their Intramural Research Program, the National Institutes of Health (NIH-IRP) have already invested over three decades of research into POI, including published research offering insight into the mechanisms and clinical management of the condition. However, there is a gap when translating this into real-world situations.
Nelson highlights the need for a global digital women’s hormonal health community, supported by a cloud-based digital hub. He explains that this central hub, approved by an ethics board, would be used to collate information about hormones’ roles within the body, stimulate research, and improve access to care.
Unfortunately, women’s health is widely under-researched, and this becomes obvious when POI and 17-Beta-Estradiol deficiency are considered.
This network has the potential to improve the evaluation and management of 17-Beta-Estradiol deficiency not only through collecting and reporting information, but also by linking to international research programmes to expand knowledge of hormonal health in women. In addition, it can give women with POI access to a global community to support them, empowering them to manage their own health.
Nelson reports the case study of a woman who experienced a 10-year delay in getting a diagnosis of secondary amenorrhoea (the absence of periods in someone who has previously had a normal menstrual cycle). Fortunately, she was able to access the Facebook page managed by the Mary Elizabeth Conover Foundation. Through this platform, she learned about available treatment options, such as physiologic hormone replacement therapy, and was able to advocate for her health. She was also able to contact healthcare professionals via the organisation, who provided further education and a letter to share with her doctor. This example provides proof of concept as to how a digital hub to share knowledge could reduce similar episodes of mismanagement and delays in care.
Similar interventions have also been shown to be effective. For example, an early menopause digital resource improved health-related empowerment, illness perception, symptoms, and knowledge.
An urgent call to women’s health leaders
There is a profound lack of knowledge of the causes of POI and the management of women’s hormones more broadly. Nelson reiterates that it is crucial to prioritise women’s hormonal health and ensure that it is a central focus within women’s overall healthcare and research.
Additionally, Nelson suggests that removing the FDA box warnings from 17-Beta-Estradiol replacement therapies would allow clinicians to provide women with accurate information about available treatment options. He feels that due to the very low dose of hormones within these treatments and their mechanisms of use, these warnings are not required. It may discourage women from taking appropriate medications and increase the likelihood that unregulated therapies are administered as an alternative option. The FDA box warnings may also mean clinicians are hesitant to prescribe replacement therapies, although they may be the best option for the patient.
Advancements in technology and the worldwide use of internet and mobile communications should be harnessed for innovative approaches to women’s health.
Nelson also highlights that most women with POI have follicles remaining in the ovary; therefore, strategies are needed to improve understanding of how fertility can be optimised in these cases. One example of how this could be achieved is through a combination of physiological hormone replacement therapy to lower elevated serum luteinising hormone levels and avoid follicle luteinisation (the proven major cause of follicle dysfunction in POI), monitoring of ovarian follicles, and timely intrauterine insemination.
Advancements in technology and the worldwide use of the internet and mobile communications should be harnessed for innovative approaches to women’s health. A central, digital hub can support patients, their families, and healthcare providers by providing a convenient, up-to-date, cost-effective and integrated solution for rare health conditions in women, such as POI.
What inspired you to conduct this research?
My true calling as an investigator was revealed after a life-changing experience with a patient. During my time as a medical student at the University of Pittsburgh, I was intrigued by Professor Ernst Knobil’s research on the neuroendocrinology of the menstrual cycle. Following my residency at Women’s Hospital, University of Southern California, I spent eight years in private practice in Lynchburg, Virginia, USA. It was during this time that I encountered my first case of Primary Ovarian Insufficiency. Through this experience, I learned how little was known about this disorder. The case ignited my curiosity and motivated me to pursue special training in research and reproductive endocrinology. Eventually, I fulfilled my passion by leading a clinical and basic science research programme on the disorder for 30 years at the National Institutes of Health Intramural Research Program in Bethesda, Maryland, USA.
How can women use a digital health platform to advocate for their own hormonal health?
Women can use a digital health platform to advocate for their hormonal health by using menstrual cycle tracking apps. These apps allow women to monitor their menstrual cycles, track symptoms, and identify patterns in their cycles. This information can be invaluable when discussing any menstrual irregularities or concerns with a healthcare provider. Another way women can use digital health platforms to advocate for their hormonal health is through telemedicine services. These services allow women to connect with healthcare providers remotely, providing access to medical advice, prescriptions, and other resources from their homes. Finally, women can also use digital health platforms to access educational resources and connect with other women who are facing similar challenges. Online forums and support groups can provide valuable insights and emotional support, helping women feel empowered to take control of their hormonal health and advocate for themselves.
What are the first steps needed by health leaders to progress a digital hub for women’s hormone health?
The first step that health leaders can take to progress a digital hub for women’s hormone health is to conduct a needs assessment to identify the most pressing concerns and challenges women face in this area. This can be done through surveys, focus groups, or other research methods. Once the needs assessment is complete, health leaders can work on identifying existing digital health platforms that can be leveraged to address these concerns. This may involve partnering with technology companies or other healthcare organisations to develop new tools or services tailored to women’s needs. Another key step is ensuring the digital hub is accessible and user-friendly for women of all ages and backgrounds. This may involve incorporating features such as multilingual support, text-to-speech functionality, or other accessibility features. Finally, health leaders should work to promote the digital hub and raise awareness among women about the resources and services that are available to them. This can be done through targeted marketing campaigns, partnerships with community organisations, or other outreach efforts.
What are the barriers to implementing digital health hubs/communities?
Several barriers exist to implementing digital health hubs/communities. One of the main barriers is the lack of digital literacy among certain populations, particularly those from low-income backgrounds. This can make it difficult for them to access and use digital health platforms effectively. Another barrier is the cost of developing and maintaining digital health platforms, which may be prohibitively expensive for some healthcare organisations. Lastly, concerns around data privacy and security may also act as a barrier to the adoption of digital health platforms. To bridge these barriers, healthcare organisations can take several steps. For instance, they can offer training and support to help individuals develop their digital literacy skills. Additionally, healthcare organisations can explore partnerships with technology companies or other healthcare organisations to share the costs of developing and maintaining digital health platforms. Lastly, healthcare organisations can work to build trust with patients by ensuring that their data is kept safe and secure. This can be done using secure data storage and encryption, as well as through transparent communication about data privacy policies and practices.
