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Hypogonadism: Causes and Risk Factors


Hypogonadism occurs when your body doesn’t produce enough sex hormones. In children, this delays onset of puberty and can cause significant developmental delays.

Symptoms in adults vary based on sex. Females with low estrogen experience hot flashes, fatigue, mood disorders, and menstruation problems, while males may develop erectile dysfunction and low libido, experience gynecomastia (breasts), among other symptoms.

There are two types of hypogonadism. Primary hypogonadism is caused by disorders of the glands that produce the sex hormones: female ovaries and male gonads (located in the testes). Additionally, secondary hypogonadism (also known as “hypogonadotropic hypogonadism”) can arise due to problems in the pituitary gland, which regulates these glands, or the surrounding hypothalamus of the brain.

Everything from your age, surgery, taking opioids or anabolic steroids, genetics, and cancer treatments can lead to hypogonadism. Further, a number of other health conditions, such as kidney and liver diseases, endocrine and autoimmune disorders, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), tumors, excessive iron intake, and obesity raise the risk of it developing.

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Common Causes

A lot of factors affect testosterone production in men and estrogen production in women. In fact, as adults age, there’s a natural reduction in levels of sex hormones produced. As such, menopause is by far the most common cause of hypogonadism in women.

Around age 50, the ovaries stop producing estrogen, which propels the menstrual cycle. Older men produce less testosterone (and other androgens, male sex hormones) as they age, too, though the drop-off is more gradual.

When the hypogonadism is primary, the female ovaries and male gonads that produce estrogen and testosterone, respectively, aren’t functioning properly. Diseases and conditions that cause this type include:

  • Endocrine disorders: Diseases affecting the adrenal, thyroid, and other glands of the endocrine system, such as diabetes and Addison disease, can impact ovary or gonad function.
  • Genetic conditions: Two inherited conditions, Turner syndrome in women and Klinefelter syndrome in men, cause developmental delays due to their impact on sex hormone production.
  • Hemochromatosis: Also known as “iron overload,” this is when you have too much iron in your blood because your intestines aren’t able to properly process it. Along with damage to the heart and liver, arthritis, and other impacts, this condition causes hypogonadism.
  • Undescended testicles: During pregnancy, male testicles develop first in the abdomen and then descend into the scrotum before birth. When this doesn’t occur, a condition called cryptorchidism may develop, and sperm and testosterone production can be affected.
  • Liver and kidney diseases: Diseases of the liver (such as cirrhosis or liver failure) and chronic kidney disease can also impact sex hormone production.

In addition, both primary and secondary hypogonadism—developing due to disorders of the pituitary gland or surrounding brain structures—can arise due to certain medical treatments or medications. These include:

  • Cancer treatments: Radiation therapy and chemotherapy for cancer can damage the ovaries and gonads, especially if these areas are affected.
  • Reproductive organ surgery: Operations, such as oophorectomy (also known as ovariectomy) and genital confirmation surgery can severely limit or completely stop sex hormone production, causing primary hypogonadism.
  • Medications: Long-term opioid use—including illicit heroin use—as well as use of corticosteroids (also known as glucocorticoids) can significantly limit pituitary gland function. Suddenly stopping the use of anabolic steroids can also bring on hypogonadism.
  • Brain surgery: Surgery at or near the pituitary gland can impact its function and is a common cause of secondary hypogonadism.

Finally, several conditions can lead to secondary hypogonadism:

  • HIV/AIDS: Among the many impacts of HIV infection and AIDS is disruption of pituitary gland function. Other infections, especially if they cause inflammation near the gland, can also cause the condition.
  • Inflammation: Conditions like sarcoidosis—in which inflammation in the lungs and/or lymph glands produce irregular lumps of cells—can interrupt pituitary gland signaling, leading to underproduction of sex hormones.
  • Anorexia nervosa: This eating disorder is characterized by an aversion to gaining weight, leading to a severe, unhealthy restrictions in diet. Alongside other potentially very serious health impacts, this impacts pituitary gland function, causing hypogonadism.
  • Rapid weight loss: Gaining or losing a great deal of weight can cause hypogonadism, with cases being linked, especially, to weight loss surgery.
  • Obesity: Among the many health impacts of clinical obesity is impaired pituitary function, causing hypogonadism.
  • Pituitary tumors: Small benign tumors, called adenomas, can form on the pituitary gland. While they usually aren’t cancerous, they can impact the gland as well as surrounding parts of the brain (especially those involving vision).
  • Trauma: Bleeding around the pituitary gland or damage due to blunt impact to the head or a piercing injury can cause hypogonadism.

Genetics

As noted, a significant portion of hypogonadism cases occur due to genetic conditions and factors. Two conditions leading to primary hypogonadism result from congenital disorders of the genes that typically aren’t inherited:

  • Turner syndrome is when assigned females at birth are born with one of their two X chromosomes partially or completely missing. In addition to hypogonadism, Turner syndrome causes shortness of stature as well as a lack of periods and breast development during puberty.
  • Klinefelter syndrome only occurs in assigned males at birth. In these cases, babies are born with an extra sex chromosome (usually an extra X chromosome). This can cause significant developmental delays, infertility, coordination difficulties, physical abnormalities (smaller penis, long legs, short trunk, etc.), and other issues.

In addition, those with two other genetic conditions develop secondary hypogonadism:

  • Prader-Willi syndrome affects brain development and childhood metabolism, leading to lifelong health issues. Infants have feeding difficulties, but then have an abnormally large appetite after age 2. Puberty is often delayed, and health issues arise due to resulting weight problems. This condition is typically not inherited, though it can be.
  • Kallmann syndrome: The absence of or a significant delay in puberty, along with impaired senses of taste and smell, are chief signs of this rare genetic disorder. Occurring in both sexes, but seen more often in males, Kallmann syndrome is caused by inherited mutations of several genes.

If any of these conditions are suspected clinically, genetic testing is the part of the panel that will help confirm diagnosis. In some cases, noninvasive prenatal genetic testing (NIPT) and genetic counseling may be recommended if there’s family history or other factors that increase risk of developing a genetic condition.

Cardiovascular

Since obesity is recognized as a cause of some hypogonadism cases, factors associated with it—high cholesterol and hypertension (high blood pressure)—can raise the risk of developing this condition. For instance, research into male obesity secondary hypogonadism (MOSH), a type arising in obese men, has shown that managing weight can improve testosterone levels.

Notably, hypogonadism is associated with poorer outcomes for those with heart disease or other cardiovascular issues, and it can increase the risk of death as a result. In men, low levels of testosterone are considered a risk factor for these kinds of problems, and women with insufficient estrogen are at higher risk.

Lifestyle Risk Factors

A couple of lifestyle and medication factors can also raise the risk of developing hypogonadism. Cases have been linked to:

  • Opioid abuse: Long-term use of opioids, or use of illegal drugs like heroin and fentanyl, has been linked to problems with the pituitary gland. This can cause insufficient production of testosterone in males and estrogen in females.
  • Anabolic steroid use: Anabolic steroids are synthetic versions of androgens (male sex hormones like testosterone) prescribed for certain conditions (including hypogonadism) and sometimes abused by athletes to enhance performance. Stopping these suddenly can severely impact sex hormone production.
  • Iron intake: Management of cases of hypogonadism caused by hemochromatosis (excess iron in the bloodstream) can include making dietary changes to help reduce iron levels. This entails steering clear of foods rich in this mineral, avoiding vitamin C and iron supplements, and stopping alcohol consumption.

A Word From Verywell

Though cases vary a great deal in severity, there’s no doubt that hypogonadism can leave a heavy toll. Hormonal changes like menopause impact life for older women, and developmental delays in pubescent children due to this condition can severely impact emotional and social life. In adults, symptoms like low sex drive, erectile dysfunction, and mood disorders further add to the burden.

That said, we now have more and more tools than ever before for taking on that toll and treating hypogonadism. Hormone replacement therapy effectively manages chronic hypogonadism, and surgeries removing pituitary gland tumors can restore levels to healthy ranges.

No doubt, as research continues and as doctors get a better understanding of this condition, therapeutic approaches will continue to evolve and improve. If you suspect you have hypogonadism or have been diagnosed, learn as much as you can about it from your doctor, and try to take a proactive role in taking on hypogonadism.



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