Hypergonadism is an endocrine condition defined by the excessive production of sex hormones by the gonads, which are the testes in males and the ovaries in females. This overactivity results in abnormally elevated levels of hormones such as testosterone or estrogen in the bloodstream, disrupting the body’s delicate hormonal balance. The high sex hormone levels can lead to a variety of physiological changes, with specific effects depending heavily on the patient’s age and biological sex.
The Difference Between Primary and Central Overproduction
The origin of the dysfunction determines how hypergonadism is functionally classified within the hypothalamic-pituitary-gonadal (HPG) axis. Primary hypergonadism arises from a problem located directly within the gonads, meaning the testes or ovaries are autonomously overproducing hormones. This gonadal overactivity typically suppresses the pituitary gland’s hormone release via a negative feedback loop.
In contrast, Central hypergonadism originates higher up in the regulatory system, specifically in the pituitary gland or the hypothalamus. The pituitary releases an excessive amount of gonadotropins, such as Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). These elevated pituitary hormones then overstimulate the gonads, causing them to produce excessive sex hormones.
Specific Symptoms in Males and Females
Symptoms vary significantly depending on whether the condition develops before or after puberty. If overproduction occurs in childhood, it commonly results in precocious puberty, the early development of secondary sexual characteristics. Children experience an early growth spurt, but the rapid acceleration of bone maturation can lead to a shorter final adult height because growth plates fuse prematurely.
In prepubertal boys, the first sign is often testicular enlargement, marking pubertal onset. Other signs include the early appearance of pubic and axillary hair, increased muscle mass, and acne. Prepubertal girls may exhibit early breast development (thelarche) and the onset of menstrual bleeding. The early appearance of coarse body hair and acne is also common in affected girls due to excess androgen exposure.
In adult males, elevated hormone levels can manifest as heightened libido and increased aggression. Paradoxically, excess sex hormones often suppress the pituitary’s release of LH and FSH, leading to secondary testicular atrophy and potential infertility due to suppressed sperm production. Males with estrogen excess may develop gynecomastia, the enlargement of breast tissue.
Adult females primarily experience symptoms related to elevated androgen levels, known as hyperandrogenism. Hirsutism, the growth of excessive, coarse hair in a male-like pattern on the face, chest, and back, is a frequent complaint. The hormonal imbalance can also cause menstrual irregularities, ranging from infrequent periods (oligomenorrhea) to a complete absence of menstruation (amenorrhea). Severe hyperandrogenism may lead to virilization, including a deepening of the voice and changes in body habitus.
Sources of Excessive Hormone Production
The underlying sources of excessive hormone production are broadly categorized into tumors, genetic conditions, and disorders of related endocrine organs. Tumors are a significant cause and can be located in the gonads. In males, Leydig cell tumors are the most common testosterone-secreting testicular neoplasms. In females, ovarian tumors such as granulosa cell tumors can secrete estrogen, while other ovarian tumors may secrete androgens, leading to virilization symptoms.
Tumors can also originate in the pituitary gland or the hypothalamus, leading to central hypergonadism. Pituitary adenomas may secrete excessive gonadotropins, driving the gonads to overproduce sex hormones. Excess hormones can also come from the adrenal glands, which produce sex hormone precursors. Adrenal tumors or conditions like Congenital Adrenal Hyperplasia (CAH), which is a group of genetic disorders, can result in the overproduction of androgens that mimic gonadal hyperfunction.
Genetic conditions, such as McCune-Albright syndrome, involve mutations that cause cells to be overactive, resulting in autonomous gonadal function. The use of exogenous hormones, such as anabolic steroids, is another common cause of hormone excess that disrupts the natural HPG axis.
Confirming the Diagnosis
Diagnosis begins with a detailed physical examination and assessment of the patient’s symptoms and history. Confirmation requires laboratory testing to measure hormone levels in the blood, including total and free testosterone, and various forms of estrogen.
Measuring the pituitary hormones, Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), is essential to determine the origin. High sex hormone levels accompanied by suppressed LH and FSH suggest primary hypergonadism originating in the gonad. Conversely, high levels of both sex hormones and gonadotropins point to central hypergonadism, indicating the pituitary is driving the overproduction.
Once the imbalance is confirmed and localized, medical imaging identifies the structural source. If a gonadal cause is suspected, a scrotal or pelvic ultrasound can visualize the testes or ovaries to detect a tumor. For central or adrenal causes, a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen, pelvis, or pituitary gland may be ordered to locate an adenoma or other structural abnormality.
Medical Management and Treatment
Treatment for hypergonadism depends highly on the underlying cause identified during diagnosis. If a hormone-producing tumor is discovered in the gonads, adrenal glands, or pituitary gland, surgical intervention is often the primary course of action. Removing the tumor stops the source of excessive hormone production, resolving symptoms and preventing complications.
For central hypergonadism, especially when causing precocious puberty, medical management uses gonadotropin-releasing hormone (GnRH) agonists. These medications are administered continuously to suppress the pituitary’s release of LH and FSH, halting the overstimulation of the gonads. This pharmacological suppression slows the progression of puberty and allows for normal growth plate closure.
When surgery is not an option, medication can block hormone action at the receptor level. For example, anti-androgen drugs may be prescribed to adult females to combat symptoms like hirsutism and acne. Patients require long-term monitoring with periodic hormone level checks to ensure the condition is controlled and to watch for recurrence.