Gonadotropin deficiency

Gonadotropin deficiency is a condition characterized by the decreased secretion of the gonadotropins – follicle-stimulating and luteinizing hormones (FSH and LH), and, respectively, impaired development and functioning of the reproductive system.


Gonadotropins, hormones which control the development and maturation of the reproductive system in both Family with children blow soap bubbles females and males are produced by the pituitary gland in a pulsatile manner in response to the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus. Any disorder of the hypothalamic-pituitary axis and insufficient secretion of FSH and LH leads to the development of the hypogonadotropic hypogonadism (secondary hypogonadism), which results in the poor stimulation of the ovaries with gonadotropins, delayed sexual development and impaired development of the ovarian follicles and disorders of the menstrual cycle in women or impaired spermatogenesis in men.


Gonadotropin deficiency may be congenital or acquired; it may be caused by the disorders which affect the hypothalamus or the pituitary gland.

Congenital hypogonadism

Congenital gonadotropin deficiency is associated with various gene mutations which affect the development of the brain structures responsible for the secretion of GnRH or gonadotropins (FSH and LH).

  • Isolated hypogonadotropic hypogonadism (IHH)
    IHH is a disorder characterized by the deficiency of gonadotropin-releasing hormone or receptors insensitivity to it, whereas the anterior part of the pituitary is not affected. Isolated hypogonadism includes two forms: Kallmann syndrome and normosmic IHH (with a normal sense of smell).

    • Kallmann syndrome
      Kallmann syndrome is a type of IHH caused by various genetic mutations (X-linked, autosomal dominant or autosomal recessive) associated with the absent sense of smell. The disorder is observed both in males and females. Individuals with Kallman syndrome are infertile. Usually, the diagnosis is made during teenage years when a child fails to develop puberty and distinct sexual characteristics. However, the disease may be suspected earlier, for example, in infant boys with undescended testicles or a small penis. If treated these persons may restore their fertility and develop normally. Individuals born with Kallmann syndrome may also present other developmental failure, such as a harelip, cleft palate, color blindness, sensorineural deafness, renal agenesis (absence of one kidney, in case of bilateral kidney absence a child dies soon after the birth), dental agenesis (missing teeth), obesity and movement disorders such as spontaneous upper limb mirror movements and abnormal eye movements.
    • Normosmic IHH
      IHH with a preserved sense of smell is associated with different gene defects and mutations of the genes responsible for the synthesis of gonadotropin-releasing hormone.
  • Prader-Willi syndrome
    Prader-Willi syndrome is a disorder caused by the deletions of the chromosome 15q11-15q13  region, characterized by obesity, mental retardation, muscular weakness and hypotonia, strabismus, short stature, small hands and feet, cryptorchidism, and hypogonadotropic hypogonadism.

Acquired hypogonadism

Acquired disorders are more common than inherited ones. Typically, gonadotropin deficiency is caused by the dysfunction of the hypothalamus or higher brain centers due to malnutrition, stress, chronic illness, depression, excessive exercise, and low body weight. Women tend to be more susceptible to functional abnormalities of the hypothalamus and pituitary. Organic causes of gonadotropin deficiency include the tumors, neoplasms (sellar masses, for example, craniopharyngioma, lymphoma or metastasis), trauma, surgical interventions or radiotherapy, infiltrative disorders (sarcoidosis, hemochromatosis, tuberculosis) affecting the hypothalamus or the pituitary gland.

  • Eating disorders
    Anorexia nervosa and bulimia may lead to amenorrhea in females. However, the return to normal weight not always helps women to regain a normal menstrual cycle.
  • Exercise
    Women whose exercise regimen is associated with the loss of big amounts of fat (ballet, gymnastics, running) are at risk of developing menstrual cycle abnormalities or secondary amenorrhea. Girls who start exercising before the onset of regular menstruations may have delayed puberty.
  • Stress
    Stressful life events may lead to amenorrhea.

A reference should be made to some medications which may lead to hypogonadism either directly or indirectly (via hyperprolactinemia) inhibiting the secretion of gonadotropins such as opiates,  glucocorticoids, sex steroids, GnRH agonists and antagonists, tranquilizers, antidepressants, and antipsychotic medications.

Acquired gonadotropin deficiency causes a gradual loss of facial,  axillary,  public, and body hair. Males experience decreased libido, erectile dysfunction, diminished muscle mass, infertility and osteopenia (low bone density). Women have amenorrhea, infertility, and osteoporosis.

Hypogonadotropic hypogonadism in males

Gonadotropic hormones (FSH and LH) are necessary for the development of the testes and spermatogenesis. Therefore, the low values of these hormones result in the development of secondary hypogonadism and low testosterone levels. All these factors influence the reproductive system development and puberty causing from puberty delays to complete or absence of puberty, sexual infantilism, hypospadias (the opening of the urethra not at the usual location) and undescended testes (cryptorchidism).

Features of hypogonadism depend on its severity due to the amount of the secreted gonadotropins and age of the onset.

  1. Onset before the puberty
    • High-pitched voice;
    • Absent terminal facial hair;
    • Decreased or absent body hair;
    • Eunuchoid habitus and tall stature;
    • Small testicles;
    • Undescended testes;
    • Small penis;
    • Hypopigmented scrotum;
    • Small prostate;
    • Decreased libido;
    • Decreased muscle and bone mass;
  2. After the puberty
    • Decreased libido;
    • Decreased spontaneous erections;
    • Slow beard growth;
    • Decreased body hair;
    • Testicular atrophy if long-standing;
    • Decreased muscle and bone mass;
    • Fine facial wrinkling;

Hypogonadotropic hypogonadism in females

  1. Onset before the puberty
    • Primary amenorrhea;
    • Absence of secondary sexual characteristics;
  2. After the puberty
    • Menstrual cycle abnormalities to oligomenorrhea and amenorrhea;
    • Decreased vaginal  secretion;
    • Dyspareunia (pain during sexual intercourse);
    • Hot flashes;
    • Decreased bone density;
    • Breast tissue atrophy;

Laboratory findings

In both men and women, serum gonadotropin levels (FSH and LH) are very low as well as testosterone and estrogens/progesterone. Rapid urine tests may be used to determine the level of FSH and LH. Spermatogenesis is impaired in males – oligospermia (reduced number of spermatocytes in the semen) or azoospermia (absence of semen in the sperm) may be observed.


  • Male hypogonadism
    Testosterone replacement therapy administered by intramuscular injections or skin patches is required to promote the development of secondary sex characteristics and promote puberty. Despite the fact that oral androgens are also available, their use is not recommended due to the high liver toxicity of these preparations. Injections of gonadotropin are recommended to restore fertility.
  • Female hypogonadism
    Treatment of female hypogonadism should include cyclical replacement therapy with estrogens and progesterone (in the form of tablets, patches, gel or implants). Estrogen replacement therapy should be maintained until a woman reaches the age of 50. Gonadotropins (human menopausal gonadotropin or recombinant FSH; human chorionic gonadotropin or human LH) are administered to induce ovulation.  

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