Hypogonadism is a medical term which describes a diminished functional activity of the gonads – the testes and ovaries.

Hypogonadism is divided into two main categories - hypogonadotropic hypogonadism and hypergonadotropic hypogonadism.

1.    Hypogonadotropic hypogonadism (HH) 

Also known as secondary or central hypogonadism, as well as gonadotropin-releasing hormone deficiency or gonadotropin deficiency (GD), is a condition which is characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.

The type of HH, based on its cause, may be classified as either primary or secondary. 

Primary HH, also called isolated hypogonadotropic hypogonadism (IHH), is a condition that results in a small subset of cases of hypogonadotropic hypogonadism due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH) where the function and anatomy of the anterior pituitary is otherwise normal and secondary causes of HH are not present. 

It presents as hypogonadism (e.g., reduced or absent puberty, low libido, infertility, etc.) due to an impaired release of the gonadotropins, follicle-stimulating hormone and luteinizing hormone, and a resultant lack of sex steroid and peptides production by the gonads. 

In addition, anosmia (loss of the sense of smell) occurs in instances of IHH that are the result of Kallmann syndrome, which is responsible for approximately 50% of all cases of the condition. Other causes of IHH include GnRH insensitivity, which is the second most common cause of IHH and is thought to be responsible for up to 20% of cases, and a minority (less than 5-10%) due to inactivating mutations in a variety of other genes which positively regulate GnRH secretion.

Secondary HH, also known as acquired or syndromic HH, is far more common than primary HH, and is responsible for most cases of the condition. It has a multitude of different causes, including brain or pituitary tumors, pituitary apoplexy (bleeding into or impaired blood supply of the pituitary gland), head trauma, ingestion of certain drugs, and certain systemic diseases and syndromes. 

Primary and secondary HH can also be attributed to a genetic trait inherited from the biologic parents. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. 

2.    Hypergonadotropic hypogonadism (HH)

Also known as primary or peripheral/gonadal hypogonadism, is a condition which is characterized by hypogonadism due to an impaired response of the gonads to the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and in turn a lack of sex steroid production and elevated gonadotropin levels (as an attempt of compensation by the body). HH may present as either congenital or acquired, but the majority of cases are of the former nature.

There are a multitude of different etiologies of HH. Congenital causes include the following: 

  • Chromosomal abnormalities (resulting in gonadal dysgenesis) - Klinefelter's syndrome, Turner syndrome, and 45 X/46/XY mosaicism.
  • Defects in the enzymes involved in the gonadal biosynthesis of the sex hormones.
  • Gonadotropin resistance (e.g., due to inactivating mutations in the gonadotropin receptors). 

Acquired causes (due to damage to or dysfunction of the gonads) include gonadal torsion, vanishing/anorchia, orchitis,trauma, surgery, autoimmunity, chemotherapy, radiation, infections (e.g., sexually-transmitted diseases), toxins (e.g., endocrine disruptors), and drugs (e.g., antiandrogens,opioids, alcohol). 

Associated disease 

  • gonadal torsion
  • anorexia nervosa
  • vanishing/anorchia
  • autoimmunity diseases
  • Klinefelter syndrome
  • Turner syndrome
  • 45x/46xy mosaicism
  • brain, pitutary tumors
  • pituitary apoplexy
  • systemic diseases and syndromes
  • 17-α hydroxylase deficiency (a rare genetic disorder of steroid synthesis)
  • 17,20 lyase deficiency (a condition that affects the function of the gonads)
  • 17-β hydroxysteroid dehydrogenase 3 deficiency (a condition that affects male sexual development)
  • lipoid congenital adrenal hypoplazia (a rare disorder of steroid synthesis)
  • Leydig cell hypoplasia (a condition that affects male sexual development which is characterized by underdevelopment of Leydig cells in the testes)

Risk factors 

  • chronic alcoholism
  • medications (e.g., opioids, anabolic steroids, and glucocorticosteroid, opioid analgesics, antidepressants cimetidine, spironolactone, and antifungal drugs)
  • head or testicular trauma
  • head or testicular surgery
  • orchitis
  • radiation
  • infection
  • toxins

When plasma testosterone levels are below a minimum level, many aging men experience symptoms of low libido, changes in erectile function, and possibly changes in morning erection frequency. 

Low testosterone levels can lead to reduced sperm production (oligospermia) sometimes even azoospermie (absence of sperms in ejaculate), which leads to lower possibility of natural conception, due to less sperms capable of reaching the egg.

Female menstruation and ovulation is triggered by hormones such as estrogens, lutenizing hormone, progesterones and follicle stimulating hormone. All of them are controlled by gonadotropins. If the levels of gonadotropins drop, the menstruation and ovulation will not occure. All these processes are neccessary for natural conceptions, because without egg produced during ovulation, it is not possible to concieve a child.

Hypogonadism cannot be prevented, but it is possible to reduce risk factors by avoiding alcohol, avoiding drugs and maintaining healthy lifestyle.

  • impaired muscle
  • increased body fat
  • decreased energy
  • increased sleepiness
  • sleep disturbance
  • poor concentration and memory
  • visceral obesity (body fat that's stored within the abdominal cavity around a number of important internal organs such as the liver, pancreas and intestines)
  • osteopenia
  • depression
  • beard development
  • reduced height
  • reduced body hair
  • enlarged breasts
  • sexual difficulties
  • late, incomplete or lack of development at puberty
  • sometimes short stature or the inability to smell
  • penis and testes enlargement
  • deepening voice
  • low libido
  • infertility
  • oligospermia
  • azoospermia
  • lack of menstruation
  • anovulation
  • slow or absent breast growth
  • hot flashes
  • milky discharge from your breasts

Get a good night’s sleep, because lack of sleep can greatly reduce a healthy young man’s testosterone levels. 

Overweight men with prediabetes are also likely to have lower testosterone. Men with a normal weight have a lower risk of developing diabetes as well as hypogonadism. 

No self therapy is known for women.

Hypogonadism is a condition, which can be treated with hormonal replacement therapy, but it will not suit for every case. 

Surgical therapy is the option for brain tumors.

Pharmacotherapy 

There must be a definitive diagnosis of hypogonadism before the treatment is initiated. Borderline testosterone levels alone are not necessarily an indication to begin testosterone replacement therapy. If testosterone level drops under borderline level, it must be replaced with hormonal replacement therapy. 

The goal of testosterone therapy is to raise serum testosterone level into the midnormal range (400–700 ng/dL) and resolution or reduction in symptoms of hypogonadism. However, the ultimate goals of therapy are to reduce disease and disability, maintain or improve quality of life, and hopefully add vitality to the years.

There are several types of testosterone preparations that are available including testosterone injections, scrotal and nonscrotal transdermal patches, oral testosterone, buccal testosterone, and testosterone gel preparations. Medications that stimulate the production of endogenous testosterone (i.e., hCG, clomiphene) may be used in the treatment of older men when fertility is an issue.

Aging males who are started on testosterone replacement therapy should be followed periodically. After the initiation of testosterone replacement therapy, subjects should have a clinic visit, within 3 months, to make needed dosage and formulation adjustments. Subjects should have regular visits (3 to 6 months after treatment initiation and then annually) for assessment of symptom improvement. 

Hormonal replacement pills or skin patch are the option for girls and women suffering from hypogonadism. This hormonal replacement can be sufficient to induce ovulation again. Some of these female can have a low sex drive, which can be managed wih low-dose of testosterone. 

Surgical therapy 

Surgical therapy can be an option in cases of brain tumor.

If conservative medical treatments fail to achieve a full term pregnancy, the physician may suggest the patient the methods of assisted reproduction techniques (ART). 

Assisted reproduction techniques generally start with stimulating the ovaries to increase egg production. Most fertility medications are agents that stimulate the development of follicles in the ovary. Examples are gonadotropins and gonadotropin releasing hormone.

After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Hypogonadotrophic hypogonadism is characterized by oligospermia or azoospermia and low testosterone. Microscopic epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE) is the method of choice for recovering sperms for in vitro fertilization (IVF).

Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.

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Sources

Hypogonadotropic hypogonadism ―sourced from Wikipedia licensed under CC BY- SA 3.0
Hypergonadotropic hypogonadism ―sourced from Wikipedia licensed under CC BY-SA 3.0
Assisted reproductive technology ―sourced from Fertilitypedia licensed under CC BY-SA 4.0
Isolated hypogonadotropic hypogonadism ―sourced from Wikivisually licensed under CC BY- SA 3.0
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