Unexplained Weight Gain and Fatigue: Underlying Conditions

Weight gain and fatigue are common issues that almost everyone grapples with. They are 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, they are nonspecific symptoms and many diseases could manifest these symptoms, so 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 your healthcare provider to find out what may be happening.

Low Section Of Woman Standing On Electronic Weight Scale On Floor

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The thyroid gland creates thyroid hormone that keeps the body running, and when the gland fails to produce enough of these hormones, a person has an underactive thyroid, or hypothyroidism. When there are inadequate levels of thyroid hormones in the blood, metabolism slows and this leads to weight gain and fatigue.

Other symptoms of hypothyroidism include:

  • Numbness and tingling in the hands
  • Constipation
  • Muscle and body soreness
  • High cholesterol
  • An inability to tolerate cold temperatures
  • Dry and coarse skin and hair
  • Low libido
  • Frequent and heavy periods
  • Physical changes in the face such as drooping eyelids or puffiness
  • Low and hoarse voice
  • Forgetfulness

Hypothyroidism treatment consists of hormone replacement therapy. A person with this condition will take a medication designed to replace the hormone that is no longer being produced by the thyroid. Taking too much thyroid hormone can also lead to fatigue and greater appetite, which may translate into 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 women. Weight gain and difficulty losing weight are common in women with PCOS because the condition leads to insulin resistance, which happens when the body has difficulty pulling glucose from the bloodstream and converting it into energy. The body then needs to produce more insulin to maintain a normal blood sugar level. Over time, the body begins to overproduce insulin to keep blood sugar levels normal, which can lead to weight gain as well as type 2 diabetes.

People with PCOS may also experience fatigue. Other symptoms of PCOS include:

  • Chronic irregular or missed menstrual periods
  • Infertility
  • High cholesterol
  • Signs of high male 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. The diabetes medication metformin may be prescribed to lower insulin and blood sugar levels. Other treatment options for PCOS include birth control pills, hormone therapy with progesterone, and fertility treatments such as IVF.

PCOS and Diet

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


Depression, or major depressive disorder, is a mood disorder where feelings of sadness affect a person’s ability to function in daily life. People with depression often struggle with chronic fatigue. It is also often a side effect of commonly used antidepressants.

People with depression may also experience appetite changes and have weight loss or gain unrelated to dieting. According to the Centers for Disease Control and Prevention, roughly 43% of people with depression are obese, and those with depression are much more likely to become obese than those who are not depressed. Weight gain is also a highly recognized side effect of many antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs).

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

  • Loss of interest or pleasure in activities once enjoyed
  • Trouble sleeping or sleeping too much
  • Increase in purposeless physical activity, such as an inability to sit still, pacing, handwringing, or slowed movements or speech
  • Feeling worthless or guilty
  • Difficulty thinking, concentrating, or making decisions
  • Thoughts of death or suicide

Main 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 referral and information on local mental health resources such as support groups and community-based organizations. 


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. However, this sleep disorder has also been linked to weight gain and obesity.

Researchers found that sleep deprivation has effects in the body similar to activation of the endocannabinoid (eCB) system, a key player in the brain’s regulation of appetite and energy levels. When sleep-deprived, participants in the study had eCB levels in the afternoons that were higher and lasted longer than when they had a full night’s rest. This occurred around the same time that they reported increased hunger and appetite. They also consumed more and unhealthier snacks in between meals.

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


Menopause is when menstrual periods stop and the ovaries no longer produce the hormones estrogen and progesterone. It typically occurs after age 45. A person is said to have reached menopause when they haven't had a period for one year.

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

Changes and symptoms of menopause can start several years earlier, including:

  • 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

Fatigue is common in those going through menopause because estrogen and progesterone are both essential to sleep, among other things. Estrogen plays a role in the metabolism of serotonin and other neurotransmitters (chemical messengers) that affect our sleep-wake cycle. Estrogen also helps keep our 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 can disrupt sleep and lead to insomnia.

Estrogen therapy or estrogen and progesterone therapy may be used to help relieve hot flashes, night sweats, and mood changes. Nonhormonal medications can help with depression and anxiety and relieve vaginal dryness. Other treatments may also be prescribed to manage other menopause symptoms.

Cushing's Disease

Cushing's disease, a subset of Cushing's syndrome, is an endocrine disorder where there is too much of the stress hormone cortisol in the body. The production of cortisol is triggered by the release of the adrenocorticotropic hormone (ACTH) from the pituitary gland. When a tumor forms in the pituitary gland, it can cause the gland to secrete too much ACTH and increase the production of cortisol.

Weight gain is often the first sign of this condition. Too much cortisol can change the amount and distribution of body fat, making a person's face round ("moon face) and leading to weight gain around the midsection and upper back as well as accumulation of fat 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 such as anxiety or depression
  • Trouble with concentrating and memory problems
  • High blood pressure (hypertension)
  • Thinning skin causing stretch marks and easy bruising
  • Impaired regulation of blood sugar level, leading to diabetes
  • Excessive hair growth on the face in women

Surgery, radiation, or chemotherapy will need to be done to remove the tumor on the pituitary gland. Hormone-inhibiting drugs may also be prescribed to reduce the level of cortisol in the body.

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


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

  • Diabetes medications such as insulin, thiazolidinediones, and sulfonylureas
  • Antipsychotics such as clozapine, olanzapine, and lithium
  • Antidepressants such as paroxetine, escitalopram, and mirtazapine
  • Epilepsy medications such as valproate, divalproex, and gabapentin
  • Steroid hormones such as birth control pills and prednisone
  • Blood pressure-lowering medications such as propranolol and metoprolol

Antidepressants, blood pressure medications, and some seizure medications can also cause fatigue. Antihistamines is another drug with this side effect.

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 start to build up and this can cause congestion in the lungs and other tissues. However, not everyone with this condition will have fluid build-up.

Sudden or steady gain in daily weight (such as 2 to 3 pounds in 24 hours or 5 pounds over a couple of weeks) shows that the body is retaining fluid and may be a sign of congestive heart failure. Since the heart isn't pumping blood effectively throughout the body, not as much oxygen and blood are going to the brain and muscle, which causes fatigue.

Other symptoms of CHF include:

  • Shortness of breath
  • Fatigue and leg weakness
  • 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.

A Word From Verywell

Dealing with unexplained weight loss and fatigue can be difficult, especially if you are unsure of any health issue that 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 go about addressing new or worsening symptoms.

When experiencing unexplained weight gain and fatigue, it’s important to address the issue as quickly as possible so that any health problems can be treated accordingly. Enjoying life with an illness can be entirely possible with the right diagnosis, treatment, and attitude.

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