Causes of lipedema: hormones, genetics and inflammation — what science knows

“Why are my legs like this if I don’t overeat?” — most consultations begin with this question. Lipedema was long considered a “mysterious disease”, but in recent years researchers have found many answers. Here is what science knows for certain, what is still a hypothesis and what you can take from it in practice.

What lipedema is from a scientific point of view

In 2026, Lipedema World Alliance experts from 19 countries agreed on 59 statements on the definition and management of lipedema [1]. On the causes of the disease, the consensus says:

• lipedema is a chronic disease affecting subcutaneous fat tissue;
• numerous findings suggest that inflammation and hormonal factors may contribute to it;
• hormonal changes may trigger or worsen symptoms;
• lipedema is hereditary in some cases;
• lipedema is not an obesity-related comorbidity.

In other words, lipedema is not a “wrong body shape” or the result of lifestyle, but a distinct condition of fat tissue. At the same time, no single mechanism that explains all cases has been found. A review in Deutsches Ärzteblatt names three main hypotheses: altered fat cell formation, damage to small blood vessels and impaired lymphatic microcirculation [2].

Hormones: why lipedema is a “women’s” disease

Lipedema occurs almost exclusively in women and often appears at times of hormonal change. The US consensus guidelines name three such periods: puberty, pregnancy and menopause [10].

The largest survey to date — 707 women with lipedema in the United States — showed when symptoms first appeared [3]:

Why female sex hormones? As early as 2010, British geneticists analysing the pedigrees of families with lipedema suggested that oestrogen is required for the disease to appear, since it usually develops at puberty [4]. The exact way hormones affect fat tissue in lipedema is still being studied: in the 2026 consensus, more than half of the experts said that this statement needs further evidence [1].

Heredity and genes

Lipedema often runs in families: 60–80% of patients have female relatives with similar changes [5]. An analysis of British pedigrees showed an inheritance pattern consistent with autosomal dominant transmission with sex limitation: men can pass on the gene, but the disease appears mainly in women [4].

However, “the” gene has not yet been found:

• The largest family study (2024). Scientists sequenced the DNA of 31 people from 9 families. They found no variant shared by all families that would cause the disease. The authors concluded that lipedema probably has different genetic causes in different families [5].
• The UK Biobank genome-wide study (2023). An analysis of women in the UK Biobank identified 18 regions of the genome linked to the characteristic fat distribution. Two of them — near the VEGFA gene (which regulates blood vessel growth) and GRB14-COBLL1 — were confirmed in a separate group of patients with clinically diagnosed lipedema [6].

The practical takeaway: if your mother, sister or grandmother had “heavy” legs that did not slim down, this is a good reason to take your own symptoms seriously. There is not yet a genetic test that could be used to diagnose lipedema [1].

Inflammation, blood vessels and fluid in the tissue

The 2026 consensus acknowledges that inflammation may contribute to lipedema and that the affected tissue probably contains more extracellular fluid than in women of the same weight without lipedema [1].

An MRI study published in 2026 offered interesting support: the skin of women with lipedema contained more sodium than that of healthy women (17.7 vs 12.3 mmol/L). The higher the sodium, the higher the stage of lipedema and the stronger the pain [7]. Tissue sodium is associated with swelling and inflammation, so researchers suggest that some of the pain in lipedema relates to the fluid in the tissue rather than only to the amount of fat.

Associated conditions

Women with lipedema have certain other conditions more often. The largest comparison involved 1,001 patients in Spain compared with national health survey data for women [8]:

Note the bottom of the chart: high blood pressure and diabetes were less common in women with lipedema than in the general population. This is another argument that lipedema is not the same as obesity, in which these conditions are more common. The most frequent “associated” finding in this survey was vitamin D deficiency, reported by 63.4% of patients [8].

Lipedema and weight: cause and effect

Lipedema and obesity often occur together, but they are different conditions [1]. Lipedema tissue responds poorly to dieting: in the same US survey, 52% of women saw no improvement from diet and exercise [3].

Weight still matters, though. Spanish researchers followed 100 patients for 4.6 years and measured the volume of their legs [9]. Lipedema remained stable in 62% of women, progressed in 28% and improved in 10%. Progression was linked to increases in body mass index and waist-to-height ratio — in other words, to fat gain around the waist. Age did not affect progression.

So obesity does not cause lipedema, but it may speed up its progression. That is why doctors advise watching your waist measurement, not just your weight.

Can lipedema be prevented?

There is no proven way to prevent lipedema — we cannot control heredity or hormonal changes. But some things are in our hands:

1. Early diagnosis. The earlier the diagnosis, the earlier you can start compression, exercise and weight management. The international consensus stresses that a missed or delayed diagnosis worsens symptoms, mental well-being and quality of life [1].
2. Keeping an eye on your waist. In the Spanish follow-up, it was fat gain around the waist that was linked to progression of lipedema [9].
3. Attention at times of hormonal change. If your legs changed noticeably during pregnancy or after childbirth and the tissue hurts when pressed, see a doctor rather than waiting for it to “go away by itself”.

If you recognise yourself in this description, start with our short screening questionnaire. To learn how a doctor tells lipedema apart from obesity and lymphedema, read “Diagnosing lipedema”.