Hypogonadism represents a multifaceted clinical condition characterized by diminished or absent gonadal function, leading to reduced secretion of sex steroids and disrupted gametogenesis. This endocrine disorder manifests through a constellation of symptoms that depend on the timing, severity, and cause of the gonadal insufficiency.
Simply put, hypogonadism occurs when your body does not produce enough sex hormones. Treatment options often depend on whether you are trying to conceive.
The condition arises when the sex glands produce little to no sex hormones. These sex glands, or gonads, primarily refer to the ovaries in people assigned female at birth (AFAB) and the testes in people assigned male at birth (AMAB). Sex hormones regulate secondary sex characteristics such as breast development in AFAB individuals, testicular growth in AMAB individuals, and pubic hair growth. They also play a crucial role in the menstrual cycle and sperm production.
Hypogonadism is also known as gonadal deficiency. When it occurs in AMAB individuals, it may be called andropause or low serum testosterone.
Etiological Dichotomy: Primary Versus Secondary Hypogonadism
Clinicians categorize hypogonadism into two main types based on the location of dysfunction within the hypothalamic-pituitary-gonadal (HPG) axis: primary (hypergonadotropic) and secondary (hypogonadotropic).
Primary hypogonadism means your gonads fail to produce enough sex hormones despite receiving proper signals from the brain. This condition, also called hypergonadotropic hypogonadism, indicates that the problem lies within the gonads themselves.
In contrast, secondary hypogonadism originates in the brain. Your hypothalamus or pituitary gland, which regulates gonadal function, may malfunction or fail to stimulate the gonads adequately. This form is also known as hypogonadotropic or central hypogonadism.
What Causes Hypogonadism?
Primary hypogonadism results from direct damage or dysfunction of the gonads. Common causes include:
- Autoimmune diseases such as Addison’s disease and hypoparathyroidism
- Genetic disorders like Turner syndrome and Klinefelter syndrome
- Inflammation or infections such as mumps affecting the testes or ovaries
- Undescended testes
- Liver and kidney diseases
- Surgical removal or injury of sexual organs
- Radiation exposure
Secondary hypogonadism arises from problems in the brain’s regulatory centers. These causes include:
- Genetic disorders like Kallmann syndrome (abnormal hypothalamic development)
- Injury or trauma to the hypothalamus or pituitary gland
- Tumors near the pituitary gland
- Pituitary gland disorders
- Infections, including HIV
- Inflammatory diseases such as sarcoidosis and tuberculosis
- Obesity
- Rapid weight loss
How Is Hypogonadism Diagnosed?
Doctors diagnose hypogonadism through a combination of physical exams, laboratory tests, and imaging studies.
During the physical exam, the doctor evaluates your sexual development to ensure it aligns with your age. They may check muscle mass, body hair, and sexual organs.
- Laboratory Tests:
Doctors measure the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) via blood tests. In AFAB individuals, testosterone levels also require assessment. Since testosterone fluctuates during the day, doctors usually test it in the morning when levels peak. In addition, they might request a semen analysis to evaluate sperm count, which hypogonadism often reduces.
To confirm the diagnosis and exclude other causes, doctors may order further blood tests:
- Prolactin: This hormone promotes breast development and milk production in AFAB individuals but is present in AMAB individuals as well.
- Thyroid function tests: Thyroid disorders can mimic hypogonadism symptoms.
- Iron tests: Excess iron can influence sex hormone levels, so doctors check iron status.
- Genetic tests: These are especially useful when chromosomal abnormalities such as Turner syndrome are suspected.
- Imaging Tests:
Ultrasounds help doctors visualize the ovaries to detect cysts or polycystic ovary syndrome (PCOS). MRI or CT scans assess tumors or abnormalities in or near the pituitary gland.
Treatment for Hypogonadism
Treatment often involves hormone replacement tailored to sex and individual needs.
For girls and women, doctors prescribe estrogen and progesterone, available as pills or skin patches. Boys and men usually receive testosterone through skin patches, gels, solutions applied to the armpit, upper gum patches, or injections.
Women who experience menopausal symptoms may benefit from estrogen alone if they do not have a uterus, or a combination of estrogen and progesterone if their a uterus remains. This approach is called combination hormone therapy.
Certain women require ovulation stimulation via injections or pills, while men might receive pituitary hormone injections to boost sperm production. In cases where tumors or hypothalamic causes contribute, surgery or radiation therapy might be necessary.
Prognostic Considerations and Future Directions
If left untreated, hypogonadism can lead to serious complications such as metabolic syndrome, cardiovascular disease, osteoporosis, and profound psychosocial distress. Early diagnosis and treatment improve quality of life and reduce long-term risks.
Current research aims to clarify the molecular mechanisms behind congenital hypogonadotropic hypogonadism and advance gene therapy and regenerative medicine. Additionally, selective androgen receptor modulators (SARMs) show promise by delivering effective androgen replacement with fewer side effects.
Conclusion
Hypogonadism constitutes a complex endocrinopathy that demands a thorough understanding of its varied causes, clinical features, and treatment options. Through attentive clinical assessment and thoughtful application of diagnostic tools and therapies, healthcare providers can significantly improve outcomes for patients facing this often under-recognized disorder. As endocrinology, genetics, and reproductive medicine continue to evolve, they offer fresh hope for restoring gonadal function and enhancing patient well-being.
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