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Hypogonadotropic hypogonadism

Gonadotropin deficiency; Secondary hypogonadism

Hypogonadism is a condition in which the male testes or the female ovaries produce little or no sex hormones.

Hypogonadotropic hypogonadism (HH) is a form of hypogonadism that is due to a problem with the pituitary gland or hypothalamus.

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Causes

HH is caused by a lack of hormones that normally stimulate the ovaries or testes. These hormones include:

• Gonadotropin-releasing hormone (GnRH)
• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)

Normally:

• The hypothalamus in the brain releases GnRH.
• This hormone stimulates the pituitary gland to release FSH and LH.
• These hormones tell the female ovaries or the male testes to release hormones that lead to normal sexual development in puberty, normal menstrual cycles, estrogen levels and fertility in adult women, and normal testosterone production and sperm production in adult men.
• Any change in this hormone release chain causes a lack of sex hormones. This prevents normal sexual maturity in children and normal function of the testicles or ovaries in adults.

There are several causes of HH:

• Damage to the pituitary gland or hypothalamus from surgery, injury, tumor, infection, or radiation
• Genetic defects
• High doses or long-term use of opioid or steroid (glucocorticoid) medicines
• High prolactin level (a different hormone released by the pituitary)
• Severe stress
• Nutritional problems (both rapid weight gain or weight loss)
• Long-term (chronic) medical diseases, including chronic inflammation or infections
• Drug use, such as heroin or use or abuse of prescription opioid medicines
• Certain medical conditions, such as iron overload

Kallmann syndrome is an inherited form of HH. Some people with this condition also lose their sense of smell (anosmia).

Symptoms

Children:

• Lack of growth and sexual development at the standard age for puberty (development may be very late or incomplete)
  
• In girls, a lack of breast development and menstrual periods
• In boys, no development of sex characteristics, such as enlargement of the testes and penis, deepening of the voice, and facial hair
• Inability to smell (in some cases)
• Short stature (in some cases)

Adults:

• Loss of interest in sex (libido) in men
• Loss of menstrual periods (amenorrhea) in women
• Decreased energy and interest in activities
• Loss of muscle mass in men
• Weight gain
• Mood changes
• Infertility
  

Exams and Tests

Your health care provider will perform a physical exam and ask about your symptoms.

Tests that may be done include:

• Blood tests to measure hormone levels such as FSH, LH, TSH, prolactin, testosterone and estradiol
• LH response to GnRH
• MRI of the pituitary gland/hypothalamus (to look for a tumor or other growth)
• Genetic testing
• Blood tests to check for iron saturation level

Treatment

Treatment depends on the source of the problem, but may involve:

• Injections of testosterone (in males)
• Slow-release testosterone skin patch (in males)
• Testosterone gels (in males)
• Estrogen and progesterone pills or skin patches (in females)
• GnRH injections
• HCG injections

Outlook (Prognosis)

The right hormone treatment will cause puberty to start in children and may restore fertility in adults. If the condition begins after puberty or in adulthood, symptoms will often improve with treatment.

Possible Complications

Health problems that may result from HH include:

• Delayed puberty
• Early menopause (in females)
• Infertility
• Low bone density and fractures later in life
• Low self-esteem due to late start of puberty (emotional support may be helpful)
• Sexual problems, such as low libido

When to Contact a Medical Professional

Contact your provider if:

• Your child does not start puberty at the appropriate time.
• You are a woman under age 40 and your menstrual cycles stop.
• You have lost armpit or pubic hair.
• You are a man and you have decreased interest in sex.

Related Information

References

Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. PMID: 29562364 pubmed.ncbi.nlm.nih.gov/29562364/.

Styne DM. Physiology and disorders of puberty. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, eds. Williams Textbook of Endocrinology. 14th ed. Philadelphia, PA: Elsevier; 2020:chap 26.

White PC. Sexual development. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024:chap 220.

Review Date: 7/30/2023  

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