by Benjamin Bunting BA(Hons) PGCert
Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.
Hypogonadotropic hypogonadism (HH) occurs when either testes or ovaries produce virtually no or only minimal levels of sexual hormones, typically as the result of problems within either the pituitary gland or hypothalamus.
Idiopathic Hypogonadism (HH) is rare, yet can be successfully managed in some men by hormone therapy with testosterone and/or pulsatile gonadotropin-releasing hormone. Reversal has been documented at an average timeframe of 7+-4 weeks after discontinuing these treatments.
What is Hypogonadism?
Hypogonadism, which is characterized by low levels of testosterone and sperm production, affects men of all ages. While its causes vary, they often include congenital or acquired conditions affecting the hypothalamus, pituitary gland, testes or both. Treatment options available to men depending on their specific form include androgen replacement therapy or GnRH or gonadotropin therapy or both combined as necessary.
Testosterone deficiency increases the risk of metabolic disorders such as obesity, insulin resistance and type-2 diabetes mellitus. Furthermore, testosterone and sperm deficiencies contribute further to these conditions by increasing visceral adipose tissue and stimulating release of pro-inflammatory factors like leptin and adiponectin.
Diagnoses of hyperplasia can be challenging and require a comprehensive history, physical exam and blood tests.
Your physician will measure levels of FSH and LH, produced by the pituitary gland; semen analysis will be performed to check sperm count; finally a pelvic ultrasound may also be ordered to evaluate any potential hyperplasia.
Primary Hypothyroxemia is the most prevalent form of the disorder and may be caused by genetic disorders like Klinefelter's syndrome or medical conditions like type-2 diabetes mellitus or obesity.
Side effects from medications like sex steroids and gonadotropin-releasing hormone analogs, infiltrative infections or any process affecting either sella or pituitary glands.
Acquired hypogonadism (HH) is the second-most-common cause, often associated with age and reduced gonadotropin secretion.
Additionally, acquired HH can result from systemic diseases like sarcoidosis or hemochromatosis; toxic exposure such as heavy metals; chemotherapy agents or radiotherapy drugs can also play a part.
Late onset hypogonadism is the third category of hypogonadism and may be caused by many different factors, including metabolic conditions or medical procedures like surgery for brain tumors or pituitary cysts or radiation treatments for cancer.
Additionally it may also be caused by chronic stress and depression. Treatment depends on its cause; therapy aims to restore androgen production among men hoping to conceive and preserve fertility.
The Journal of Clinical Endocrinology and Metabolism explaines that Hypogonadotropic hypogonadism (HH) is an endocrine condition in men and women.
This is where there is inadequate gonadal hormone production due to either failure of the hypothalamic luteinizing hormone releasing hormone (LHRH) pulse generator, or due to failure of the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
It may occur spontaneously or as the result of various diseases affecting either or both glands.
Men can experience reduced sperm production and azoospermia; for women it causes irregular menstrual cycles and abnormal vaginal bleeding.
Diagnosis depends upon primary or secondary amenorrhea as well as negative progestin challenge tests as well as low serum fSH, LH, and testosterone levels.
Medical treatments of HH may help restore normal spermatogenesis and androgen levels for both males and females, but clinical results vary widely among patients; successful pregnancy requires long-term hormonal therapy.
Recombinant human chorionic gonadotropin (rec-hCG), free from other GnRH hormones, has been demonstrated to restore sperm production in adult-onset HH patients and restore fertility.
Some cases of HH have seen sustained sperm response with normal serum testosterone levels following restarted rec-hCG therapy. This may be related to neuronal plasticity induced by secretion of sex steroid hormones.
Treatable causes of Hypogonadism Hypogonadotropic can allow men with HH to achieve normal testosterone and sperm levels after treatment, and those seeking fertility may consider harvesting, donor sperm injection or intracytoplasmic sperm injection (ICSI).
Unfortunately if treatment for the cause is left untreated for too long then lifelong treatment will be necessary in order to preserve sperm production; otherwise they risk becoming infertile.
Causes of Hypogonadotropic Hypogonadism
This condition occurs when your ovaries do not produce enough GnRH (full name gonadotropin-releasing hormone) and FSH (full name follicle stimulating hormone), both essential for producing eggs and sexual hormones in your ovaries.
Too few of these hormones can lead to infertility as well as other symptoms which depend on whether or not you're male, female, and the type of hypogonadism you suffer from.
Idiopathic Hypogonadotropic Hypogonadism
Although its causes remain enigmatic, this condition appears to result from something going amiss between the hypothalamus and pituitary gland, inhibiting their production of male hormones.
This condition may be present from birth or may develop later as a result of injury, illness or surgery.
This condition, also known as isolated GnRH deficiency or Kallmann syndrome (KS).
It can be caused by mutations to genes controlling migration of GnRH neurons from nasal placode to their final destination in hypothalamus. Additionally, congenital migration interruption may also contribute.
Other causes could be medications or conditions like polycystic ovary syndrome (PCOS). Tests may be performed to measure your levels of sex hormones, and an MRI or CT scan used to search for tumors in or near your pituitary gland.
Treatment for both genders includes shrinking or removing tumors causing hypogonadism as well as therapy that increases female sex hormone production; this may assist with breast growth, menstruation cycle length and fertility issues.
Symptoms and Treatment of Hypogonadotropic Hypogonadism
Men may also notice their muscle mass diminishing before or after puberty - all symptoms which may indicate primary or secondary hypogonadism which may either be congenital or acquired.
Your physician will likely order blood tests to look for increased levels of FSH and LH (luteinizing hormone and follicle stimulating hormone) which indicate your pituitary gland is misfunctioning.
Hypogonadism in boys and men is treated by increasing their levels of sexual hormones - estrogen and progesterone for girls; for men, testosterone. Treatment often improves symptoms associated with this condition.
Your doctor can diagnose hypogonadism with a physical exam and thorough health history review, followed by blood and urine samples to detect tumors on the pituitary gland or detect higher-than-usual estradiol levels in case of polycystic ovarian syndrome or another ovarian disorder.
Hypogonadotropic hypogonadism in males is typically the result of an imbalance of gonadotropin-releasing hormone (GnRH) between their brain and pituitary gland.
GnRH acts through this gland to control luteinizing hormone and follicle-stimulating hormone production that promote testosterone synthesis within testes, leading to decreased sperm count over time.
With Klinefelter syndrome being one of the primary culprits, followed by age-related testes thinning as well as chemotherapy or radiotherapy therapies.
Hypogonadism in young men varies depending on its source. If the issue stems from an anatomical factor like tumors on pituitary or other glands that control pituitary-gonadal axis, medication to shrink or remove these tumors might be effective.
Otherwise, hormone replacement therapy (HRT), where doctors inject testosterone or similar substances directly into muscle groups twice weekly may provide relief.
Most children and adolescents suffering from hypogonadism benefit from hormone replacement therapy to increase sex drive, muscle mass and hair growth.
However, this doesn't provide a permanent solution; its root cause must also be addressed for long-term relief of symptoms.
To maintain proper hormone levels, patients may require long-term dosage of testosterone or another similar compound, which can be both expensive and requires close monitoring.
As a result, treatment can become quite costly with ongoing support necessary.
Before beginning treatment with any medication, patients must understand its long-term implications and possible adverse side effects, including increased red blood cell count - polycythemia - which increases the risk of deep vein thrombosis (DVT).
Diagnosing and Testing Hypogonadotropic Hypogonadism
If you suspect your child has delayed puberty or is unable to produce sperm, health care providers can perform an early morning blood test. This test is vital since testosterone levels tend to peak early each day.
Male hypogonadotropic hypogonadism, more commonly referred to as central or tertiary hypogonadism, is caused by genetic disorders that impair the pituitary gland's functioning and consequently lower luteinizing hormone (LH) and follicle stimulating hormone (FSH).
This leads to decreased testosterone and sperm production as well as infertility. This disorder may occur alone or as part of Kallmann syndrome or Idiopathic Hypogonadotropic Hypogonadism (IHH).
Tests on the pituitary gland can provide insight into underlying causes of male CHH.
A tumor located near or in the pituitary gland that interferes with LH and FSH production is one common factor; other possible contributors could include infections, radiation therapy or surgery.
Genetic testing for CHH can be difficult due to its complex genes and diagnostic challenges, but new multiplex PCR technology with next generation sequencing (NGS) provides an efficient and cost effective screening tool to detect mutations that cause CHH, such as in KS/IHH cases where this has proven successful.
Hypogonadism Treatment Options
Since hypogonadism results from an inadequate supply of androgens (testosterone for men, estrogen for women), hormone replacement therapy, commonly referred to as HRT, should be utilized as the most effective form of management.
HRT treatments include transdermal patches and gels; intramuscular injections like Delatestryl (enanthate and depotestosterone); oral formulations like Aveed (testosterone undecanoate).
Your doctor may order a blood test to check your levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), two reproductive hormones produced by your pituitary gland and low levels can result in decreased testosterone and sperm production.
Hypogonadism is caused by multiple conditions:
Congenital primary hypogonadism
More commonly known by its name Klinefelter's syndrome, is one of the most prevalent forms of primary hypogonadism. This genetic condition damages seminiferous tubules and Leydig cells within the testes causing reduced production of sperm as well as low testosterone levels in males.
Acquired primary hypogonadism
This may be brought on by medication such as glucocorticoids and alkylating agents such as cyclophosphamide, chlorambucil, and busulfan; or due to chronic infections like HIV infection or tuberculosis.
Warne et al conducted a retrospective study and discovered that in males with hypogonadotropic hypogonadism, treatment with human chorionic gonadotropin (hCG) for three to six months followed by combination therapy consisting of HMG can lead to statistically significant increases in testicular size and production.
While such medications can have severe side effects, it's essential that any risks be discussed with your physician prior to beginning.
Conclusion- Hypogonadotropic Hypogonadism Explained
Hypogonadotropic Hypogonadism (HH) refers to an absence or delay in puberty combined with low levels of gonadotropins (FSH, LH).
Idiopathic cases of HH can occur when there is an isolated deficiency of GnRH secretion among individuals aged 18 years old or above; those under this age generally fall within the definition of delayed puberty.
Idiopathic hyperhidrosis (HH) can be caused by diseases of the hypothalamus and pituitary gland, or decreased GnRH production in the testis (central hypogonadism).
Furthermore, individuals presenting symptoms consistent with CHARGE syndrome could have IHH and anosmia and should be evaluated for mutations of the CHD7 gene that encodes for chromodomain helicase DNA-binding protein 7.
Male Congenital Hypogonadotropic Hypogonadism can be traced to any of a wide variety of genetic disorders that cause dysfunction to the hypothalamic-pituitary-gonadal hormone axis and lead to low testosterone levels and reduced fertility.
New genetic testing techniques have greatly increased our knowledge about CHH's causes; over 30 gene defects have now been identified as contributing to CHH; however many cases of idiopathic HH remain undetected.