What is hypogonadotropinism?
Summary of this article
Hypogonadotropic hypogonadism is a disorder in which the gonads (ovaries and testes) do not function properly due to insufficient secretion of gonadotropins (LH and FSH) caused by pituitary or hypothalamus abnormalities. This results in a deficiency of sex hormones (estrogen and testosterone) and abnormalities in sexual maturation and reproductive function. Hypogonadotropism is also called “central hypogonadism” because it is caused by a disorder of the hypothalamus-pituitary-gonadal axis.
1. Characteristics of hypogonadotropism
The main symptoms of hypogonadotropinism are related to low sex hormones (estrogen and testosterone) and include gonadal dysfunction, delayed puberty, amenorrhea, and infertility.
男性の症状
- Hypogonadism: testes do not develop and testosterone production is reduced.
- Delayed puberty: delayed secondary sexual characteristics such as voice change, muscle development, and pubic hair development.
- Insufficient spermatogenesis: Insufficient spermatogenesis may result in infertility.
- Decreased libido and muscle weakness: A deficiency of testosterone results in decreased libido and muscle strength.
Women's Symptoms
- Hypogonadism: the ovaries do not develop and produce insufficient estrogen.
- Delayed puberty: secondary sexual characteristics such as breast development and pubic hair development are delayed.
- Amenorrhea: menstruation does not begin (primary amenorrhea) or stops (secondary amenorrhea).
- Infertility: Ovulation does not occur, making natural conception difficult.
Causes2. Causes
Hypogonadotropism is caused by abnormalities in the hypothalamus-pituitary-gonadal axis.It is caused by a lack of gonadotropin-releasing hormone (GnRH) from the hypothalamus or by the pituitary gland not secreting enough gonadotropins (FSH and LH).This can be caused by genetic or acquired factors, and can be based on genetic mutations or involve damage to the pituitary gland.
2.1 Genetic factors
- Kallmann syndrome
- Kaliman syndrome is the most common hereditary form of hypogonadotropinism and is characterized by inadequate gonadotropin secretion due to lack of GnRH secretion from the hypothalamus.It is also characterized by an abnormal sense of smell (loss of olfaction).It is mainly associated with abnormalities in the KAL1 andFGFR1 genes.
- KAL1 gene: Mutations in the KAL1 gene interfere with GnRH and olfactory nerve development, causing hypogonadotropism and olfactory abnormalities.
- FGFR1 gene: Mutations in the FGFR1 gene also affect GnRH secretion and cause similar symptoms.
- GnRH receptor gene (GNRHR) mutation
- Mutations in the GnRH receptor (GNRHR) cause the pituitary gland to fail to properly secrete gonadotropins even when GnRH is normally secreted. This results in a deficiency of LH and FSH and impaired gonadal function.
- PROKR2 and PROK2 genes
- Mutations in the PROKR2 and PROK2 genes can affect GnRH nerve development and cause hypogonadotropism. These genes are often associated with Kalliman syndrome.
- CHD7 gene (CHARGE syndrome)
- Mutations in the CHD7 gene can affect the formation of the hypothalamic-pituitary axis and cause hypogonadotropism. This mutation is associated with CHARGE syndrome and may also cause other physical abnormalities.
- LEP and LEPR genes
- Genetic abnormalities in LEP (leptin) andLEPR (leptin receptor) can suppress GnRH release from the hypothalamus and cause hypogonadism.These genes are also involved in energy metabolism and appetite regulation and may be associated with severe obesity.
2.2 Acquired factors
- Head trauma and brain tumors:
- Head trauma or tumors affecting the pituitary gland (e.g., prolactinomas) can impair the function of the hypothalamic-pituitary axis, which results in decreased gonadotropin secretion.
- Chronic disease and malnutrition:
- Chronic diseases (e.g., chronic kidney disease, diabetes), excessive stress, and extreme malnutrition (e.g., restricted diet, eating disorders) can also contribute to decreased GnRH and gonadotropin secretion.
- Drugs:
- Prolonged steroid use and certain medications (e.g., antiepileptic drugs, antipsychotics) may suppress gonadotropin secretion.
3. Diagnosis
Diagnosis of hypogonadotropinism is made through hormone level measurements, imaging, and genetic testing.
- Hormone test
- Gonadotropins (FSH, LH): In hypogonadotropia, low levels of FSH and LH in the blood are observed, as are low levels of estrogen (female) and testosterone (male).
- Genetic testing
- When Kaliman syndrome or GnRH receptor abnormalities are suspected, genetic tests such asKAL1 andFGFR1 are performed. GnRH receptor (GNRHR), PROKR2, CHD7, and other genetic abnormalities may also be identified.
- Image diagnosis
- MRI or CT scan is used to check for tumors or abnormalities in the hypothalamus or pituitary gland.
4. Treatment
Treatment of hypogonadotropinism is primarily aimed at replacing deficient sex hormones and restoring reproductive function.
4.1 Hormone Replacement Therapy (HRT)
- Estrogen and progesterone replacement therapy is used to restore the menstrual cycle, relieve menopausal symptoms, and maintain bone density.
4.2 Assisted Reproductive Therapy
- Gonadotropin Therapy: Gonadotropin (FSH and LH) injections are used to stimulate the gonads, spermatogenesis, and follicle development.Used specifically as a treatment for infertility, it aims to restore ovulation and spermatogenesis.
4.3 Other treatments
- Tumor treatment: If the cause is a pituitary tumor, tumor surgery or radiation therapy may be used.
- Psychological support: psychological support and counseling are recommended for the psychological effects of loss of reproductive function and delayed puberty.
Summary
Hypogonadotropic hypogonadism is a disorder in which the hypothalamus and pituitary gland do not secrete enough gonadotropins (FSH and LH), causing a deficiency of sex hormones. The main genetic causes are Kalliman syndrome (KAL1 and FGFR1 gene abnormalities) and GnRH receptor abnormalities, while acquired tumors, chronic diseases, and malnutrition can also cause the disease. Treatment centers on hormone replacement therapy and gonadotropin therapy to alleviate symptoms and restore reproductive function.