Male Hypogonadotropic Hypogonadism: Causes, Symptoms & Fertility Treatment

In short: Male hypogonadism is weak or absent production of male hormones by the testicles. It may result from a disorder of the pituitary gland or hypothalamus, such as Kallmann syndrome, or from tumours, infections, certain medicines or obesity. Symptoms include erection problems, infertility and reduced body hair and muscle. Testosterone alone does not restore fertility; treatment with FSH and hCG together is needed.

Hypogonadism is a condition in which the male testes produce little or no sex hormones. If you or a loved one has been told testosterone levels are low, understanding the underlying cause can help you feel more confident about the next steps in treatment.

Hypogonadotropic hypogonadism is a form of hypogonadism that is due to a problem with the pituitary gland or hypothalamus. It is caused by a lack of hormones that normally stimulate the testes. These hormones include gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Causes of hypogonadotropic hypogonadism

Kallmann syndrome. Abnormal development of the hypothalamus — the area of the brain that controls the secretion of pituitary hormones — can cause hypogonadism. This abnormality is also associated with impaired development of the ability to smell (anosmia) and red-green color blindness.

• Pituitary disorders. An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or brain tumors located near the pituitary gland may cause testosterone problems. In addition, the treatment for a brain tumor, such as surgery or radiation therapy, may impair pituitary function and cause hypogonadism.
• Inflammatory disease. Certain inflammatory diseases, such as sarcoidosis, histiocytosis and tuberculosis, involve the hypothalamus and pituitary gland and can affect testosterone production, causing hypogonadism.
• HIV/AIDS. HIV/AIDS can cause low levels of testosterone by affecting the hypothalamus, the pituitary and the testes.
• Medications. The use of certain drugs, such as opiates or some hormones, can affect testosterone production.
• Obesity. Being significantly overweight may be linked to hypogonadism.
• Normal aging. Older men generally have lower testosterone levels than younger men. As men age, there is a decrease in testosterone production.
• Concurrent illness. The reproductive system can shut down due to the physical stress of an illness or surgery, as well as emotional stress. This is a result of diminished signals from the hypothalamus and usually resolves with successful treatment of the underlying condition.

In adult males, hypogonadism can alter masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include:

• Erectile dysfunction
• Infertility
• Decrease in body hair growth
• Decrease in muscle mass
• Enlargement in breast (gynecomastia)
• Loss of bone mass (osteoporosis)

Hypogonadism can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include:

• Fatigue
• Decreased sex drive
• Difficulty concentrating
• Hot flashes

Treatment Options

The good news is that hypogonadotropic hypogonadism can often be managed with the right medical approach, and fertility may still be possible for many men who wish to have children.

• Testosterone therapy for males is used to improve genital development, develop secondary sexual characteristics, allow for the growth and closure of the epiphyseal plate, and improve sexual function. This therapy does not restore fertility and actually suppresses sperm production further, so it should not be used by men who are trying to conceive. If fertility is desired, testosterone is stopped and pulsatile GnRH therapy or gonadotropin therapy (hCG with or without FSH) is used instead.
• Gonadotropin therapy involves the use of human chorionic gonadotropin (hCG) and FSH. HCG stimulates Leydig cells to produce testosterone. With the increased levels of testosterone, sexual activity, libido and overall wellbeing should improve.
• Some men produce sperm with hCG alone, particularly if the condition started after puberty; FSH, which acts on Sertoli cells, is added when sperm do not appear after about 3–6 months or when the testes are small. It can take 6 to 24 months of treatment before sperm appear in the semen, and sperm can be frozen once they do.
• FSH is required for maintaining the production of high numbers of good quality sperm.
• Gonadotropin therapy in men with hypogonadotropic hypogonadism is usually able to generate enough sperm for fertility to occur, but sperm count is still lower than normal.
• For hyperprolactinemia, dopamine agonists such as cabergoline are used to lower prolactin levels. Once prolactin falls, the suppression of GnRH is removed and the production of LH, FSH and testosterone usually recovers.
• In up to 10-20% of cases, patients can exhibit sustained fertility and steroid production after therapy, resulting in reversal of hypogonadotropic hypogonadism. The mechanism for this reversal is unknown, but there is believed to be some neuronal plasticity within GnRH-releasing cells.

If you have concerns about low testosterone, fertility, or symptoms mentioned above, our team at Dr. Najeeb Layyous clinic can help guide you through diagnosis and personalized treatment options.

Dr Najeeb Layyous F.R.C.O.G

Consultant Obstetrician, Gynecologist and Infertility Specialist