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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.

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) and 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.
  • 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 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 opiate medicines
  • 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 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

The 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, 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
  • 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

Call 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.

References

Styne DM, Grumbach MM. Physiology and disorders of puberty. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 13th ed. Philadelphia, PA: Elsevier; 2016:chap 25.

White PC. Disorders of sexual development. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 233.

    • Endocrine glands

      Endocrine glands - illustration

      Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary to secrete hormones which determine the rate of metabolism in the body (the more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity).

      Endocrine glands

      illustration

    • The pituitary gland

      The pituitary gland - illustration

      The pituitary is a gland attached to the base of the brain which secretes hormones that govern the onset of puberty, sexual development and reproductive function.

      The pituitary gland

      illustration

    • Pituitary hormones

      Pituitary hormones - illustration

      The pituitary gland controls the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone), which govern the onset of puberty, sexual development and reproductive function.

      Pituitary hormones

      illustration

      • Endocrine glands

        Endocrine glands - illustration

        Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary to secrete hormones which determine the rate of metabolism in the body (the more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity).

        Endocrine glands

        illustration

      • The pituitary gland

        The pituitary gland - illustration

        The pituitary is a gland attached to the base of the brain which secretes hormones that govern the onset of puberty, sexual development and reproductive function.

        The pituitary gland

        illustration

      • Pituitary hormones

        Pituitary hormones - illustration

        The pituitary gland controls the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone), which govern the onset of puberty, sexual development and reproductive function.

        Pituitary hormones

        illustration

      Review Date: 8/25/2017

      Reviewed By: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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