Unexplained Weight Gain and Fatigue: Underlying Conditions

Weight gain and fatigue are common issues that many people experience. These symptoms are often natural consequences of dealing with everyday stressors and a lack of sleep. But unexplained weight gain and fatigue can sometimes be symptoms of an underlying condition.

However, since many diseases could produce these symptoms, it may be difficult to pinpoint the exact cause. If you are eating a healthy diet and sleeping well but experiencing weight gain and fatigue, talk to a healthcare provider to find out what may be happening.

This article explores some common causes of weight gain and fatigue.

A person's feet on a scale with the number replaced with HELP! (Common Causes of Unexplained Weight Gain and Fatigue)

Verywell / Laura Porter


The thyroid gland creates thyroid hormone that keeps the body running. An underactive thyroid, or hypothyroidism, occurs when the thyroid gland fails to produce enough of these hormones. As a result, your metabolism slows, leading to weight gain and fatigue.

Other symptoms of hypothyroidism include:

  • Numbness and tingling in the hands
  • Constipation
  • Muscle and body soreness
  • High cholesterol
  • Cold intolerance
  • Dry and coarse skin and hair
  • Low libido (sex drive)
  • Frequent and heavy periods
  • Drooping eyelids or puffiness
  • Low and hoarse voice
  • Forgetfulness

Hypothyroidism treatment consists of hormone replacement therapy. This medication replaces the hormone no longer produced by the thyroid.

Too much thyroid hormone can also lead to fatigue and greater appetite, translating to weight gain. So following your healthcare provider's instructions is extremely important while undergoing treatment.

Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome, or PCOS, occurs when there is an imbalance of reproductive hormones in people with ovaries. Weight gain and difficulty losing weight are typical in people with PCOS.

Weight gain with PCOS is often the result of insulin resistance, which commonly co-occurs with PCOS. Insulin resistance happens when the body has difficulty pulling glucose (sugar) from the bloodstream and converting it into energy.

When the body doesn't have enough glucose to work with, it needs more insulin to maintain an adequate blood sugar level. Over time, the body begins to overproduce insulin to keep blood sugar levels stable. This overproduction can lead to weight gain and type 2 diabetes.


In addition to weight gain, people with PCOS may also experience fatigue. Other symptoms of PCOS include:

  • Chronic irregular or missed menstrual periods
  • Infertility
  • High cholesterol
  • Signs of high androgen hormones such as excessive hair growth on the face, arms, chest, and abdomen
  • Depression


Although there is no cure for PCOS, people can manage their symptoms with medications. These may include:

In addition, following a healthy diet and eating natural, unprocessed foods, fatty fish, dark leafy greens, and food rich in fiber can help curb some of the symptoms of PCOS.


PCOS commonly leads to weight gain and fatigue due to insulin resistance that sometimes occurs alongside the condition. When well-managed with diet and medications, symptoms tend to reduce.


Depression, or major depressive disorder, is a mood disorder where sadness affects a person’s ability to function. People with depression often struggle with chronic fatigue. Unfortunately, it is also often a side effect of commonly used antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs).

People with depression may also experience appetite changes and have weight loss or gain unrelated to their eating behavior.

According to the Centers for Disease Control and Prevention (CDC), roughly 43% of people with depression have obesity. Those with depression are much more likely to become obese than those who are not depressed.

Besides fatigue and weight gain, other symptoms of depression include:

  • Loss of interest in activities once enjoyed
  • Trouble sleeping or sleeping too much
  • Inability to sit still
  • Slowed movements or speech
  • Feeling worthless or guilty
  • Difficulty thinking, concentrating, or making decisions
  • Thoughts of death or suicide

Primary treatment options for depression include therapy, antidepressants, and lifestyle changes.

If you or a loved one is suffering from depression, seek help by calling the Substance Abuse and Mental Health Administration national helpline at 1-800-662-HELP (4357). They offer treatment referrals and information on local mental health resources such as support groups and community-based organizations.

If you are having suicidal thoughts, dial 988 to contact the 988 Suicide & Crisis Lifeline and connect with a trained counselor. If you or a loved one are in immediate danger, call 911.


Insomnia is a sleep disorder that makes it difficult to fall or stay asleep. It can also lead to waking up too early.

When someone doesn't get enough sleep because of insomnia, they naturally become tired and experience fatigue. In addition, this sleep disorder has also been linked to weight gain and obesity.

Increases Appetite

In a 2016 study, researchers found that sleep deprivation had effects in the body similar to activation of the endocannabinoid system (ECS). ECS is a critical player in the brain’s appetite regulation and energy levels. 

The study found that when participants were sleep-deprived, they had higher and longer-lasting ECS levels in the afternoons than when they had a full night’s rest. These levels occurred around the same time that they reported increased hunger and appetite. They also consumed more and unhealthier snacks between meals.

Linked to Depression

Insomnia is linked to other conditions that can cause unexplained weight gain and fatigue, such as depression. It is one of the diagnostic criteria of major depressive disorder. It is so common that around 90% of people with depression have insomnia or daytime sleepiness.


Menopause occurs when menstrual periods stop for a consecutive 12 month period. It typically happens after age 45. During this time, your body produces significantly less estrogen and progesterone.

Weight Gain

During perimenopause, the period leading up to menopause, estrogen levels begin their decline. This hormonal shift begins to slow down a person's metabolism. During this time, even if someone continues to eat a healthy diet, they are much more likely to gain weight.


Fatigue is common in those going through menopause. That's because estrogen and progesterone both play a role in sleep, among other things.

Estrogen metabolizes serotonin and other neurotransmitters (chemical messengers) that affect your sleep-wake cycle.

Estrogen helps keep your body temperature low at night and therefore more conducive to restful sleep. Also, night sweats, which are hot flashes that occur during sleep, cause unpleasant sensations that disrupt sleep and lead to insomnia.

Other Symptoms

Other symptoms associated with perimenopause and menopause include:

  • A change in periods (shorter or longer, lighter or heavier, with more or less time in between)
  • Hot flashes and night sweats
  • Vaginal dryness
  • Mood swings
  • Less hair on the head and more on the face

Doctors sometimes prescribe estrogen therapy or estrogen and progesterone therapy to help relieve hot flashes, night sweats, and mood changes. Non-hormonal medications can help with depression and anxiety and relieve vaginal dryness.


Menopause and perimenopause can lead to weight gain and fatigue. That's due to shifting hormones that affect metabolism and lead to symptoms that disrupt sleep. Hormone replacement therapy and other medications can help lessen sleep symptoms.

Cushing's Disease

Cushing's disease, a subset of Cushing's syndrome, is an endocrine disorder in which there is too much of the stress hormone cortisol in the body. When the body releases adrenocorticotropic hormone (ACTH) from the pituitary gland, it triggers cortisol production. This excess cortisol sometimes results from a tumor in the pituitary gland.

Weight gain is often the first sign of this condition. That's because too much cortisol can change the amount and distribution of body fat. With Cushing's, weight tends to center in the face ("moon face"), around the midsection and upper back, and between the shoulders ("buffalo hump").

People with Cushing's disease also experience severe tiredness. Other Cushing's disease symptoms include:

  • Muscle weakness
  • Progressively thin and brittle bones leading to osteoporosis
  • Weakened immune system
  • Mood disturbances
  • Trouble concentrating and memory problems
  • High blood pressure (hypertension)
  • Thinning skin causing stretch marks and easy bruising
  • Impaired blood sugar regulation, leading to diabetes
  • Excessive hair growth on the face

Cushing's disease can mimic many other conditions, so it's essential to rule them out when looking for a proper diagnosis.

If a pituitary gland tumor causes Cushing's, surgery to remove it, along with radiation or chemotherapy is necessary. A doctor might also prescribe hormone-inhibiting drugs to reduce the body's cortisol level.


Excessive cortisol causes Cushing's disease. This condition can lead to fatigue and weight gain. Surgery, chemotherapy, and radiation treat pituitary tumors that sometimes cause Cushing's disease. In addition, medication to suppress hormones may resolve some symptoms.


Several types of medications can also cause weight gain, including:

Antidepressants, blood pressure medications, some seizure medications, and antihistamines can also cause fatigue.

Congestive Heart Failure

Congestive heart failure (CHF) is a condition where the heart isn't pumping enough blood to the rest of your body. Because the heart isn't pumping as it should, fluids can build up, leading to congestion in the lungs and other tissues. However, not everyone with this condition will have fluid build-up.

Sudden weight gain (such as two to three pounds in 24 hours or five pounds over a couple of weeks) is a symptom of fluid retention. This type of weight gain may be a sign of congestive heart failure.

CHF can also cause fatigue. That's because when the heart doesn't pump blood effectively throughout the body, not as much oxygen and blood can get to the brain.

Other symptoms of CHF include:

  • Shortness of breath
  • Leg weakness
  • Fatigue
  • Weight gain and swelling
  • Dizziness, confusion, fainting, or difficulties with concentration
  • Irregular or quick heartbeat

Treatment for CHF focuses on alleviating symptoms and slowing further heart damage. Typically, it involves lifestyle changes and medications to reduce fluid retention and improve heart function.


CHF can cause weight gain due to fluid retention. It can also cause fatigue from reduced oxygen and blood to the brain. Therefore, weight gain that occurs rapidly can be an indicator of CHF.


Many things can cause weight gain and fatigue, including conditions involving hormones, sleep, mental health, and more. Since weight gain and fatigue are common symptoms of numerous health issues, receiving an accurate diagnosis is vital. Only then can you treat the cause of your symptoms.

A Word From Verywell

Dealing with unexplained weight loss and fatigue can be difficult, especially if you are unsure if a health issue may be causing it. Not knowing what is going on with your own body is scary, but it’s important not to lose hope. Being in control of your health is the best way to address new or worsening symptoms.

When you experience unexplained weight gain and fatigue, it’s crucial to deal with the issue as quickly as possible so that you can treat any health problems accordingly. Enjoying life with an illness is possible with the proper diagnosis, treatment, and attitude.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Angelica Bottaro
Angelica Bottaro is a professional freelance writer with over 5 years of experience. She has been educated in both psychology and journalism, and her dual education has given her the research and writing skills needed to deliver sound and engaging content in the health space.