At the Intersection of Menopause and Rare Disease
Although menopause is increasingly studied as a stage of life, women living with rare diseases are still often left out of scientific research. This is an issue, as the symptoms of menopause and those of the underlying disease can overlap and influence each other in ways that have important clinical consequences.
A new review shows that certain common themes appear regardless of the type of rare disease.
“More than 30 million people in the United States, 36 million people in the European Union, and approximately 350 million worldwide live with a rare disease. Despite menopause “having its moment,” research on menopause in females with rare diseases is especially limited.” Sufian, 2026
The review author is Professor Sandy Sufian from the UIC Department of Medical Education and the UIC Department of Disability and Human Development at the University of Illinois at Chicago, USA. The review, titled “Menopause in rare diseases: Shared research concerns and the case for a dedicated subfield,” examines the intersection of menopause and rare diseases and highlights the need for more focused research in this area.
“This narrative review synthesizes the literature on menopause across eight rare diseases: Ehlers-Danlos syndrome (EDS), cystic fibrosis (CF), Huntington’s disease (HD), lymphangioleiomyomatosis (LAM), myasthenia gravis (MG), systemic scleroderma (SSc), sickle cell disease (SCD), and Turner syndrome (TS), to identify shared research priorities and propose a coordinated agenda for future investigation. Eight cross-cutting themes emerge: (1) hormonal modulation of disease pathophysiology; (2) sex disparities in populations with rare diseases; (3) earlier onset of menopause; (4) overlapping disease and menopausal symptoms that complicate diagnosis and care; (5) disease-specific symptom profiles and menopause outcomes; (6) menopause hormone therapy; (7) quality-of-life issues; and (8) unmet educational needs among rare-disease specialists and gynecologists….
We performed searches in PubMed, Web of Science, and CINAHL for articles published between 2018 and 2026 using “menopause” combined with “rare disease,” and with 8 disease-specific terms, including “Ehlers-Danlos syndrome,” “cystic fibrosis,” “Huntington’s disease,” “lymphangioleiomyomatosis,” “myasthenia gravis,” “systemic scleroderma,” “sickle cell disease,” and “Turner Syndrome… We began in 2018 because the year marked a modest uptick in publications.”Sufian, 2026
A turning point in health
One of the most important is the role of hormones in shaping the course of the disease. Hormonal changes during menopause, especially the decline in estrogen and progesterone levels, can alter the intensity of symptoms or even accelerate disease progression. This suggests that menopause is not just a natural life stage, but also a potential trigger for changes in the health status of women with rare diseases.
Another important aspect is the presence of sex-based differences, which are often more pronounced in rare diseases. In some conditions, women experience more severe forms of the disease or develop symptoms more frequently than men. These differences may become even more noticeable during menopause, yet there is still a lack of systematic research to fully explain these changes. Women with rare diseases also tend to enter menopause earlier than the general population. An earlier onset of menopause brings additional health risks, including issues related to bone health, the cardiovascular system, and cognitive function. This makes it especially important to recognize these changes early and adjust medical care accordingly.
“LAM offers a particularly striking example of hormone-induced modulation of disease: LAM cells express estrogen and progesterone receptors, and disease progression worsens with estrogen supplementation. Earlier work in LAM suggested that progesterone may attenuate lung function decline. Researchers have found that postmenopausal status is independently associated with better survival, leading them to conclude that “menopause is a milestone that segregates patients with LAM into two different subgroups with markedly different outcomes.”….Women with SSc face an elevated risk of premature menopause before age 40, and early menopause is associated with more severe disease and affects vascular and fibrotic aspects of SSc…Across all eight diseases reviewed, disease-specific symptoms substantially overlap with menopausal symptoms, complicating attribution and delaying appropriate care. EDS shares with menopause a constellation of sleep disturbance, cognitive complaints, chronic pain, fatigue, mood disorders, urogenital issues, and joint problems….
Menopause hormone therapy (MHT) is known to alleviate menopause symptoms and help preserve bone health in healthy women. For women with TS, it has also been shown to decrease stroke, endocrine issues, and hypertension. Yet some women with rare diseases may have contraindications to standard MHT routes and doses. Heightened risks and a history of thrombosis or liver or vascular disease may exclude some females with cystic fibrosis from the same formulations as healthy women. Extreme care must also be taken when considering exogenous estrogen for women with LAM, as it may cause disease deterioration.” Sufian, 2026
One of the biggest challenges in practice is the overlap of symptoms. For example, fatigue, pain, sleep disturbances, and mood changes can be linked to both menopause and the underlying condition. As a result, doctors may sometimes attribute symptoms to only one cause, which can lead to inadequate treatment or delays in appropriate care. Quality of life is another major concern. For women with rare diseases, menopause often adds an extra layer of difficulty on top of existing health challenges. In addition to physical symptoms, psychological strain is common, as well as the complexity of managing multiple medications. All of this calls for a more individualized approach and better coordination between different medical specialists.
A clear need for better education among healthcare providers
There is also a clear need for better education among healthcare providers. “Gynecologists and menopause practitioners are rarely familiar with disease-specific risks that shape hormone therapy decisions,” the author wrote. Because of this gap, patients may not receive the care they need.
Taking all of this into account, there is a strong need to develop a dedicated area of research focused specifically on menopause in the context of rare diseases. “We propose establishing a dedicated subfield within menopause research focused on rare-disease populations…Establishing a dedicated rare-disease subfield within menopause research would provide the coordinated infrastructure needed to address these challenges systematically, through cross-disease collaboration, methodological innovation, and the generation of evidence for disease-specific clinical guidelines. The aging of rare-disease populations, combined with therapeutic advances that have extended survival into midlife and beyond, makes this work both timely and urgent,” concluded Professor Sufian.
Image: Endocrine Society
