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Hypogonadotropic hypogonadism

  • Definition
    • 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.

  • Alternative Names
    • Gonadotropin deficiency; Secondary hypogonadism

  • Causes
    • HH is caused by a lack of hormones that normally stimulate the ovaries or testes: gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinizing hormone (LH).

      Normally:

      • The hypothalamus in the brain releases gonadotropin-releasing hormone (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.
      • Any change in this hormone release chain causes a lack of sex hormones and prevents normal sexual maturity.

      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
      • Severe stress
      • Nutritional problems (both rapid weight gain or weight loss)
      • Chronic medical diseases, including chronic inflammation or infections
      • Certain medical conditions, such as iron overload

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

  • Symptoms
    • Children:

      • Lack of development at puberty (development may be very late or incomplete)
      • In girls, a lack of breasts 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
  • Exams and Tests
    • Tests that may be done include:

      • Blood tests to measure hormone levels such as FSH, LH, and 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 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
  • Outlook (Prognosis)
    • The right hormone treatment will cause puberty to start and may restore fertility. 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
    • Call your health care provider if:

      • Your child does not start puberty at the appropriate time
      • You are a woman under 40 and your menstrual cycles stop
      • You have lost armpit or pubic hair
      • You are a man and you have decreased interest in sex
  • References
    • Haddad NG, Eugster EA. Delayed puberty. In: Jameson JL, De Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric. 7th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 122.

      Molitch ME. Anterior pituitary. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 224.

      Silveira LF, Latronico AC. Approach to the patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013;98(5):1781-1788. PMID: 23650335 www.ncbi.nlm.nih.gov/pubmed/23650335.