Hypergonadism is defined by the overactivity of the gonads (testes in males and ovaries in females). This hyperfunction results in an abnormally high production and secretion of sex hormones, such as testosterone, estrogen, and progesterone. The resulting hormonal imbalance disrupts the body’s normal regulatory systems and leads to various physiological changes. Depending on the age of onset, the condition can accelerate sexual development or cause significant hormonal symptoms in adults.
Understanding the Causes
The underlying reasons for hypergonadism are categorized based on where the hormonal overproduction originates. The two main categories are primary hypergonadism and secondary hypergonadism, which affect different parts of the endocrine system.
Primary hypergonadism arises from a problem within the gonads themselves, causing them to produce sex hormones autonomously, regardless of signals from the brain. In males, causes often include Leydig cell tumors, which secrete large amounts of testosterone. Primary causes in females may involve ovarian tumors, such as granulosa cell tumors, or specific genetic conditions that make ovarian cells hyperactive. Familial male-limited precocious puberty (FMPP), where a genetic mutation overstimulates testosterone-producing cells, is another example.
Secondary hypergonadism is caused by excessive stimulation of the gonads from the pituitary gland or the hypothalamus. The hypothalamus releases gonadotropin-releasing hormone (GnRH), prompting the pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Overproduction of LH and FSH over-stimulates the testes or ovaries, leading to excessive sex hormone production. Conditions triggering this stimulation include central nervous system tumors or lesions, such as hypothalamic hamartomas, which act as an ectopic source of GnRH.
How Hypergonadism Affects the Body
The excess of sex hormones drives physical changes that vary based on whether the condition manifests before or after puberty. In children, hypergonadism frequently causes precocious puberty, marked by the early development of secondary sexual characteristics. Children experience an early growth spurt, making them initially taller than peers. However, accelerated bone maturation can ultimately lead to a shorter adult height.
In males, excess testosterone causes early testicular enlargement and the appearance of pubic, axillary, and facial hair before age nine. Other symptoms include a deepening voice, increased muscle mass, acne, and heightened libido. If the condition is ovarian hyperandrogenism in females, it leads to physical changes associated with excess androgens (male hormones).
Adult males may experience increased body hair growth, excessive muscle development, and acne due to high testosterone levels. They may also note early baldness and an elevated sex drive. Chronic high hormone levels disrupt the hormonal feedback loop, potentially leading to testicular atrophy as the body attempts to self-regulate.
For adult females, the effects relate to an excess of estrogen or androgens. Symptoms include irregular menstrual cycles, which may become infrequent or absent. Physical manifestations of androgen excess include hirsutism (the growth of coarse, dark hair in a male-like pattern on the face and body). Other signs are a deepening voice and changes in body fat distribution.
Diagnosis and Testing
Diagnosis begins with a physical examination and a review of the patient’s medical history. The initial step involves blood tests to measure key reproductive hormones, including sex steroids (testosterone and estrogen) and pituitary hormones (LH and FSH).
Analyzing the ratio of LH and FSH to the sex hormones determines the source of the problem. If sex hormones are high but LH and FSH levels are low, it suggests primary hypergonadism (gonads overproducing hormones independently). Conversely, high levels of both sex hormones and gonadotropins point toward secondary hypergonadism, where the pituitary or hypothalamus drives the overproduction.
Imaging studies are used to locate structural abnormalities or tumors causing the imbalance. Ultrasound or CT scans check the ovaries, testes, or adrenal glands for growths. An MRI scan of the brain may be necessary to check the pituitary gland and hypothalamus for tumors or lesions. Genetic testing is also employed in specific cases, particularly in children with precocious puberty, to identify underlying syndromes like McCune-Albright syndrome.
Treatment Options
Management focuses on addressing the underlying cause of hormonal excess while mitigating the effects of elevated sex hormones. When a tumor is identified as the source, the primary treatment is surgical removal of the growth. Depending on the tumor’s nature, surgery may be followed by chemotherapy or radiation therapy to ensure complete eradication.
If the cause is not a tumor or is not surgically treatable, hormonal suppression is the main strategy, especially for children with precocious puberty. Gonadotropin-releasing hormone (GnRH) agonists are a common medical intervention. These medications initially stimulate the pituitary gland, but continuous use desensitizes the GnRH receptors. This suppression reduces LH and FSH release, ultimately slowing or stopping the progression of precocious puberty by reducing sex hormone production.
Other medications, such as anti-androgens, may be used to block the effects of excess testosterone in both males and females. Symptom management focuses on issues like acne, hirsutism, and menstrual irregularities resulting from the hormonal imbalance. Treatment plans depend on the patient’s age, sex, the location of the problem, and the severity of the symptoms.