Despite estimates that Lipedema may affect approximately 1 in 10 adult women [1,2,3], Lipedema is understudied, and its root causes remain unknown. Several lines of evidence, however, suggest that sex hormones may help trigger the condition and influence its progression. For example, Lipedema primarily occurs in women, and many women report that their symptoms began during a period of hormonal changes, such as puberty or pregnancy [4,5,6,7,8,9,10,11,12], Studying these links between sex hormones and Lipedema offers an exciting opportunity to deepen our understanding of the disease in ways that could facilitate diagnosis, help us characterize exactly how Lipedema affects adipose (fat) tissue, and ultimately design better treatments.
What Are Sex Hormones?
Sex hormones are sometimes called reproductive hormones, sex steroids, or gonadal steroids. As the name “gonadal steroids” implies, many sex hormones are produced by the gonads, or sex organs—the ovaries in biological females and the testes in biological males—as well as by the adrenal glands. These hormones help regulate the development of sex-related characteristics, sex drive (libido), and bone growth. They also influence immune and neurological function.
In biological females, the ovaries produce three types of sex hormones: estrogens, progestogens, and androgens. In addition to their role in the development and maintenance of female sex characteristics (e.g., breasts), these hormones play critical roles in fertility, pregnancy, and menstruation. In biological males, the testes produce androgens (e.g., testosterone), the main sex hormone in males. Biological males also produce estrogens and progestins, just at generally lower levels than in biological females.
Evidence That Sex Hormones Contribute to Lipedema
Indirect evidence suggests that sex hormones play a role in Lipedema’s initiation and possibly its progression. When providing clinical histories or answering online surveys, a majority of women with Lipedema report that their symptoms began during a period of hormonal changes [4,5,6,7,8,9,10,11,12], mainly around the time of puberty, but also during pregnancy, while breastfeeding, or when starting hormonal birth control or hormone therapy. We have seen the same link among women who shared their experiences through the Lipedema Foundation’s online registry. This link makes sense, because sex hormones, particularly estrogen, are known to help regulate fat metabolism and accumulation [13]. Genetic studies on risk for developing Lipedema have also implicated genetic factors involved in regulating sex hormone levels [14, 15] as well as genetic factors that help dictate responses to sex hormones.
Although lipedema occurs almost exclusively in women, the rare instances of Lipedema that have occurred in men also suggest [16] sex hormone involvement. Many of these men had low levels of testosterone or high levels of estrogen, [17], and some displayed breast growth (gynecomastia), a sign of abnormal sex hormone levels.
Why Lipedema Researchers Need to Study the Role of Sex Hormones
Despite the evidence that sex hormones contribute to Lipedema, studies have not directly examined the role of sex hormones in Lipedema. This topic represents a key area for future research that could improve all aspects of managing the disease. For example, longitudinal studies might follow women with a family history of Lipedema over time to see whether they develop Lipedema during hormonal transitions, and to track which hormonal changes coincide with its onset. If we can understand the role of sex hormones as an initiating factor, we could develop standardized diagnostic criteria and harness the power of providers whose expertise overlaps with periods of significant hormonal change (i.e., pediatricians and OBGYNS) to apply these criteria to improve timely diagnosis. With more standardized and field-wide approaches to diagnosis, we could indirectly improve data on Lipedema prevalence, which currently varies widely. And perhaps most importantly, research on sex hormones could also help researchers understand the biological processes that lead to Lipedema, and ultimately aid the development of new treatments and clinical care.
Advancing Scientific Research and Clinical Progress on Sex Hormones
Funding for Lipedema research is limited, so the field must focus its efforts on the best avenues for progress. The study of sex hormones is key to progress in the field, and there are several areas in which research could rapidly advance our understanding of the potential links between sex hormones and Lipedema. The Lipedema Foundation is leading the way by supporting an ongoing study that examines the role of estrogen in the development of adipose tissue in the thighs of women with and without Lipedema. Many more approaches are possible. For example, researchers could examine the relationship between Lipedema symptoms and hormonal fluctuations that occur during the menstrual cycle. Studies might also assess the occurrence of Lipedema among women who start hormonal birth control or hormone therapy. Medical record data, such as urine and blood test results, may contain information about hormone levels, metabolism, and other physiological parameters, and could provide a low-cost resource for initial studies on this link.
The Lipedema Foundation is committed to advancing research and advocating for better diagnosis and clinical care for patients, and we believe that study of the likely role of sex hormones in Lipedema can help transform our approach to these goals in a wide variety of ways. We are committed to working with you to unpack the biological mechanisms involved in this common and understudied condition. And we want to hear from you! Tell us your thoughts on how to stimulate research in this important area by reaching out to LF at info@lipedema.org.
References
1. Kruppa, P., Georgiou, I., Biermann, N., Prantl, L., Klein-Weigel, P., & Ghods, M. (2020). Lipedema-Pathogenesis, Diagnosis, and Treatment Options. Deutsches Arzteblatt International, 117(22–23), 396–403. https://doi.org/10.3238/arztebl.2020.0396
2. Ghods, M. (2021). In Reply to: Herpertz “The Prevalence was probably overestimated.” Deutsches Ärzteblatt International, 118(3), 39–40. https://doi.org/10.3238/arztebl.m2021.0060
3. Herpertz, U. (2021). The Prevalence Was Probably Overestimated (Comment on Kruppa 2020). Deutsches Ärzteblatt International, 118(3), 39. https://doi.org/10.3238/arztebl.m2021.0059
4. Bauer, A.-T., von Lukowicz, D., Lossagk, K., Aitzetmueller, M., Moog, P., Cerny, M., Erne, H., Schmauss, D., Duscher, D., & Machens, H.-G. (2019). New Insights on Lipedema: The Enigmatic Disease of the Peripheral Fat. Plastic and Reconstructive Surgery, 144(6), 1475–1484. https://doi.org/10.1097/PRS.0000000000006280
5. Dudek, J. E., Białaszek, W., & Ostaszewski, P. (2016). Quality of life in women with lipoedema: a contextual behavioral approach. Quality of Life Research : An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation, 25(2), 401–408. https://doi.org/10.1007/s11136-015-1080-x
6. Dudek, J. E., Białaszek, W., Ostaszewski, P., & Smidt, T. (2018). Depression and appearance-related distress in functioning with lipedema. Psychology, Health & Medicine, 23(7), 846–853. https://doi.org/10.1080/13548506.2018.1459750
7. Fetzer, A., & Fetzer, S. (2014). Lipoedema UK BIg Survey 2014 research report. https://www.lipoedema.co.uk/wp-content/uploads/2016/04/UK-Big-Surey-version-web.pdf
8. Herpertz, U. (2004). Entstehungszeitpunkt von Lipödemen. LymphForsch, 8, 79–81. https://scholar.google.com/scholar_lookup?title=Entstehungszeitpunkt+von+Lip%C3%B6demen&author=+&publication_year=2004&journal=LymphForsch&volume=8&pages=79-81
9. Kruppa, P., Georgiou, I., Schmidt, J., Infanger, M., & Ghods, M. (2022). A 10-Year Retrospective before-and-after Study of Lipedema Surgery: Patient-Reported Lipedema-Associated Symptom Improvement after Multistage Liposuction. Plastic and Reconstructive Surgery. https://doi.org/10.1097/PRS.0000000000008880
10. Lipedema Foundation. (2022). Learning By Listening: Early Findings from the Lipedema Foundation Registry Survey (p. 14). Lipedema Foundation. https://lipedema.org/lfr-report
11. Romeijn, J. R. M., de Rooij, M. J. M., Janssen, L., & Martens, H. (2018). Exploration of Patient Characteristics and Quality of Life in Patients with Lipoedema Using a Survey. Dermatology and Therapy, 8(2), 303–311. https://doi.org/10.1007/s13555-018-0241-6
12. Vaquero Ramiro, E., Gutiérrez Retortillo, M., Goiri Noguera, D., Morello Ostos, P., & Solera-Martínez, M. (2021). Diagnóstico y tratamiento del lipedema en España. Resultados de encuesta online. Rehabilitación. https://doi.org/10.1016/j.rh.2020.12.001
13. Katzer, K., Hill, J. L., McIver, K. B., & Foster, M. T. (2021). Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation. International Journal of Molecular Sciences, 22(21), 11720. https://doi.org/10.3390/ijms222111720
14. Michelini, S., Chiurazzi, P., Marino, V., Dell’Orco, D., Manara, E., Baglivo, M., Fiorentino, A., Maltese, P. E., Pinelli, M., Herbst, K. L., Dautaj, A., & Bertelli, M. (2020). Aldo-Keto Reductase 1C1 (AKR1C1) as the First Mutated Gene in a Family with Nonsyndromic Primary Lipedema. International Journal of Molecular Sciences, 21(17). https://doi.org/10.3390/ijms21176264
15. Grigoriadis, D., Sackey, E., Riches, K., Zanten, M. van, Brice, G., England, R., Mills, M., Dobbins, S. E., Lipoedema Consortium, G. E. R. C., Jeffery, S., Dong, L., Savage, D. B., Mortimer, P. S., Keeley, V., Pittman, A., Gordon, K., Ostergaard, P., & Lee, L. L. (2022). Investigation of clinical characteristics and genome associations in the ‘UK Lipoedema’ cohort. PLOS ONE, 17(10), e0274867. PLoS Journals. https://doi.org/10.1371/journal.pone.0274867
16. Paolacci, S., Precone, V., Acquaviva, F., Chiurazzi, P., Fulcheri, E., Pinelli, M., Buffelli, F., Michelini, S., Herbst, K. L., Unfer, V., Bertelli, M., & GeneOb Project. (2019). Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. European Review for Medical and Pharmacological Sciences, 23(13), 5581–5594. https://doi.org/10.26355/eurrev_201907_18292
17. Buso, G., Depairon, M., Tomson, D., Raffoul, W., Vettor, R., & Mazzolai, L. (2019). Lipedema: A Call to Action! Obesity (Silver Spring, Md.), 27(10), 1567–1576. https://doi.org/10.1002/oby.22597