What is Hypogonadotropic Hypogonadism?

Hypogonadotropic Hypogonadism (HH) (often called secondary hypogonadism) is a condition in which the gonads (ovaries and testes), produce little or no sex hormones, as a result of anatomical or functional lesions in the hypothalamus or the pituitary. The latter causes disruption in the secretion of gonadotropins that signal to the testes or to the ovaries to produce sex hormones. These lesions may be congenital or acquired.


What are the clinical features of Hypogonadotropic Hypogonadism?

The clinical features of HH depend upon the time of the onset of this condition. Possible manifestations in men include:

  • Ambiguous genitalia at birth in a boy indicates onset of the problem during the first trimester of pregnancy
  • Microphallia (or micropenis) and/or cryptorchidism indicates onset of the condition during the third trimester
  • Failure to undergo or complete puberty indicates onset of the condition at any time after birth during the first decade.
  • Decreased libido, erectile dysfunction and infertility, if the condition develops in adulthood

In women, respectively, it can manifest as:

  • failure to initiate sexual maturation (eg, lack of secondary sexual characteristics)
  • primary or secondary amenorrhea
  • infertility

What causes Hypogonadotropic Hypogonadism?

Congenital (Genetic) causes of Hypogonadotropic Hypogonadism include several genetic syndromes, such as:

  • Kallmann syndrome, characterized by hypogonadism, anosmia (little or no sense of smell) and various craniofacial (skeletal) abnormalities
  • Prader-Willi and Laurence-Moon-Bield syndromes, characterized by obesity, hypogonadism and cognitive impairment
  • a rare hypogonadotropic hypogonadism syndrome, accompanied by adrenal hypoplasia and therefore adrenal insufficiency

Acquired causes include various anatomical and functional lesions, usually accompanied by additional hormonal disorders:

Some of the most common anatomical lesions include:

  • Tumors of the hypothalamus-pituitary area, such as craniopharyngioma and pituitary adenomas
  • Infiltrative diseases of the same area, such as sarcoidosis and histiocytosis
  • Head injuries
  • Exposure to external radiation

On the other hand, functional forms of acquired HH are relatively common and are caused by:

  • severe stress
  • significant weight loss
  • strenuous exercise
  • obesity
  • diabetes mellitus
  • sleep apnea
  • chronic systemic disease
  • medicines

How is Hypogonadotropic Hypogonadism diagnosed?

The diagnosis of Hypogonadotropic Hypogonadism includes physical examination, measurement of gonadotropins and sex hormones in the blood, and depending on the cause, various imaging tests, such as magnetic resonance imaging of the hypothalamic-pituitary area, olfactory tests, and DNA analysis are also needed.


What is the treatment of Hypogonadotropic Hypogonadism?;

The treatment of HH depends upon the time of the onset of the disease, the severity and the symptoms. In young adolescents the goals of therapy are induction of puberty and maintenance of sexual maturation and for this purpose, increasing doses of testosterone (or human chorionic gonadotropin injections (hCG) are given to boys, or estrogen and progesterone in girl.

In adults, on the other hand, the goal of treatment is to relieve the symptoms of hypogonadism, restore sexual function, and the maintenance of bone and muscle mass and good physical condition. For this purpose, sex hormones are administered: testosterone in men and estrogen/progesterone in women.

If there is a desire for childbearing, spermatogenesis and ovulation induction in men and women respectively should take place. In a small percentage (10%), in which infertility persists, in vitro fertilization (IVF) is recommended.

Regular monitoring of patients is important for their successful treatment, while in the cases of genetic syndromes and anatomical lesions, genetic counseling and treatment of the comorbidities are required.