Introduction

Bilateral, symmetric accumulation of adipose tissue (fat) in the legs, and occasionally the arms and lower body, is the hallmark of lipedema, a chronic medical illness that mostly affects women. Pain, soreness, swelling, and easy bruising are all possible side effects of lipedema.¹ 

Although it is estimated that one in ten adult women may have lipedema, little is known about the condition and its underlying causes. However, several lines of evidence point to the possibility that sex hormones could contribute to the onset of the illness and affect how it develops. For instance, lipedema mostly affects women, and many of them say that their symptoms started around a time of hormonal transition, such as adolescence or pregnancy. Investigating these connections between sex hormones and lipedema is a fascinating chance to learn more about the condition. Men also experienced rare cases of lipedema, which may indicate sex hormone involvement. Gynecomastia, or breast development, is an indication of aberrant sex hormone levels, and many of these guys had either excessive or low amounts of estrogen or testosterone.² Although the precise cause of lipedema is unknown, it frequently begins at times of hormonal change, such as adolescence, pregnancy, or menopause. The way that estrogen controls the distribution and metabolism of fat may shed light on this relationship. Excess estrogen may attach to fat cells and cause fat cell malfunction, which is a defining feature of lipedema, according to research.³ 

Hormonal mechanisms in lipedema 

Recent research suggests that the pathogenesis of lipedema is influenced by hormones, specifically the distribution of estradiol/oestrogen receptors in adipose tissue. Vascular, immunological, and lymphatic dysfunction, as well as adipocyte hypertrophy and inflammation, are all caused by an imbalance between receptors in adipose tissue. Additionally, gynaecological conditions like endometriosis, adenomyosis, and uterine fibroids share pathophysiological pathways with lipedema, especially when it comes to progesterone resistance, which causes localised buildup of estradiol without adequate metabolism.⁴ 

Estrogen levels 

Oestrogen is a hormone that influences the metabolism of adipose tissue by regulating food intake, energy expenditure, and body distribution. Estrone (E1), estradiol (E2), and estriol (E3) are the three forms of these. Since it is essential to the functioning of the reproductive phase and a wide range of chronic illnesses, estradiol has been investigated the most. In patients with lipedema, subcutaneous adipose tissue (SAT) accumulates due to changes in estrogen activity or the absence of estrogen receptors (ER). Additionally, it regulates hunger and weight gain, which may help to explain why people with lipedema gain weight and struggle to lose it with diet and exercise.⁵

Other hormonal interactions 

Cyclical increases in progesterone and estradiol, which control fat distribution, mark the start of reproductive activity. Studies supporting the idea that lipedema might develop or worsen during pregnancy emphasise the influence of reproductive hormones. Hormonal changes during pregnancy are even more pronounced than throughout adolescence due to the considerable increase in progesterone levels. Increased fat accumulation and resistance to lipolysis intensify the fat's favoured storage pattern.

Additionally, fat deposition is encouraged and lipolysis is inhibited by the physiological decline in insulin sensitivity that occurs during pregnancy, especially from the second trimester forward.

During the menopausal transition and menopause, FSH and LH levels increase as estrogen and progesterone production steadily decrease.

This hormonal change affects the activity of adipose tissues as well as the distribution of body fat. Adipose tissues adapt to take up steroidogenesis once the ovaries cease to do so, which could have an impact on the onset of lipedema. About 20% of instances of lipedema are discovered at menopause, even though it is most commonly diagnosed in women of reproductive age.⁶

Puberty as a critical trigger 

During puberty, lipid levels undergo significant changes, with racial and gender-specific patterns. The prevalence of dyslipidemia, or abnormal lipid levels, rises with each of the three pubertal stages in teenagers. In particular, lipid profile levels are different in females who experience precocious puberty (early onset of puberty) than in healthy controls. According to the National Institutes of Health (NIH) (.gov), triglyceride (TG) levels rise during this period, particularly in males, whereas total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels often fall. Males experience these alterations more than females do. Because the pubertal stage can vary greatly within a particular age range, chronological age is not a good indicator of it. Therefore, when evaluating lipid results, it is important to consider pubertal stage.⁷ 

Diagnosis

How is lipedema diagnosed?

By performing a physical examination and gathering your medical history, a healthcare professional can make a diagnosis. Unlike normal body fat, which is painless, lipedema is caused by painful fat accumulation. Additionally, there is a noticeable size difference between the affected legs and the unaffected feet of persons with lipedema.

What tests will be done to diagnose lipedema?

To diagnose lipedema, providers do not have a standard diagnostic test. However, they can use imaging and blood testing to rule out other problems or identify other disorders that might be causing your lipedema.

They could order the following tests:

• Ultrasound: sound waves are used in ultrasound
• DEXA scan: a bone density test using X-rays
• Magnetic resonance imaging (MRI): a scan that uses radio waves, a large magnet, and a computer
• Computed tomography (CT): a computer-aided X-ray scan
• Nuclear medicine: a scan that creates images from an injected radioactive material

Stages of lipedema

For many people, lipedema tends to worsen gradually over time. Stages of lipedema include:

• Stage 1: Although your skin appears normal, you feel as though there are pebbles beneath it. At this point, pain and bruises are possible
• Stage 2: The surface of your skin is uneven and may have dimpling that resembles cottage cheese, a walnut shell, or quilted stitching
• Stage 3: You have big folds of skin and fat, and your legs may resemble inflated rectangular balloons. Walking may be difficult if you have protruding fat on your legs
• Stage 4: You simultaneously have lymphedema and lipedema⁸

Management strategies 

Conservative measures:

• Compression therapy: applying bandages or compression clothing helps support the afflicted areas, encourages lymph flow, and lessens swelling

A specific type of massage, known as manual lymphatic drainage (MLD), can help promote lymphatic flow and reduce swelling. A qualified therapist is the ideal person to perform it.

• Exercise: By enhancing muscular tone, lymphatic drainage, and overall mobility, low-impact activities like swimming can help alleviate the symptoms of lipedema
• Skin care: In regions where fatty deposits on the skin become thin or strained, regular skin care can help prevent problems like infections
• Weight management: Although dieting may not be able to reduce the amount of fat associated with lipedema, maintaining a healthy weight can help prevent subsequent obesity and alleviate the burden on limbs that are already affected

Surgical interventions:

• Lipedema fat can be removed via liposuction. Lipedema sufferers can benefit from a variety of treatments, including water-assisted liposuction and tumescent liposuction
• Lymphatic-Sparing Procedures: These operations treat fatty deposits without endangering lymphatic vessels

Medications:

• Pain management: Non-steroidal anti-inflammatory medications (NSAIDs) and over-the-counter pain relievers can help control pain and discomfort
• Supplements: Although there is little proof, some patients have mentioned benefits from taking supplements like selenium⁹

Summary

A persistent, excruciating condition that mainly affects women, lipedema is characterised by an excessive buildup of subcutaneous fat, especially in the lower limbs. There is growing evidence that the pathophysiology of lipedema is significantly influenced by hormonal variables, particularly estrogen deficiency. During times of significant hormonal changes, such as adolescence, pregnancy, and menopause, the problem frequently arises or gets worse. Adipogenesis, lipogenesis, and fat distribution are all regulated by estrogen, and the aberrant fat deposition seen in lipedema has been connected to changes in the expression and function of the estrogen receptor. Furthermore, inflammation plays a significant role in the illness; persistent low-grade inflammation may interfere with local estrogen metabolism and prolong the cycle of abnormal fat storage. Although further study is required to determine the optimal dietary options, nutritional techniques such as the Mediterranean and ketogenic diets have shown promise in controlling lipedema symptoms by reducing inflammation and promoting healthy weight maintenance.¹⁰

FAQs

What role do hormones have in lipedema?

Because they affect fat storage, vascular function, and inflammation in subcutaneous tissues, hormones, particularly estrogen and progesterone, are considered significant contributors to lipedema.

Why does puberty tend to be the onset of lipedema?

Significant hormonal changes brought on by puberty, especially an increase in estrogen, may cause lipedema to develop in people who are genetically prone to it.

Can other stages of hormonal changes exacerbate lipedema?

Indeed. During the hormonally fluctuating stages of pregnancy, perimenopause, and menopause, lipedema symptoms frequently get worse.

Is there a hormonal remedy or cure for lipedema?

No known remedy exists. Symptom control is the primary goal of current therapy. Hormonal treatments are being studied in research settings, but have not yet been confirmed.

Can early diagnosis help?

Absolutely. Recognising lipedema during puberty allows for early intervention, potentially slowing progression and improving long-term outcomes.