| Hypogonadism |
| Classification and external resources |
| ICD-10 |
E28.3,E29.1,E23.0 |
| ICD-9 |
257.2 |
| OMIM |
146110 |
| DiseasesDB |
21057 |
| MedlinePlus |
001195 |
| MeSH |
D007006 |
Hypogonadism is a medical term which describes a diminished functional activity of the gonads, the testes and ovaries in males and females, respectively, that may result in diminished sex hormone biosynthesis and impaired gamete production and/or regulation. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen (e.g., estradiol) as hypoestrogenism, and may occur as symptoms of hypogonadism in both sexes, but are generally only diagnosed in males, respectively. Other hormones produced by the gonads which may be decreased by hypogonadism include progesterone, DHEA, anti-Müllerian hormone, activin, and inhibin. Spermatogenesis and ovulation in males and females, respectively, may be impaired by hypogonadism, which, depending on the degree of severity, may result in partial or complete infertility.
|
Contents
- 1 Classification
- 1.1 Affected system
- 1.2 Primary or secondary
- 1.3 Congenital vs. acquired
- 1.4 Hormones vs. fertility
- 2 Symptoms
- 2.1 In both sexes
- 2.2 Exclusively in men
- 2.3 Exclusively in women
- 3 Diagnosis
- 4 Treatment
- 5 Testosterone and longevity
- 6 See also
- 7 References
- 8 External links
|
Classification
Main article: Hypergonadotropic hypogonadism
Main article: Hypogonadotropic hypogonadism
Main article: Isolated hypogonadotropic hypogonadism
Deficiency of sex hormones can result in defective primary or secondary sexual development, or withdrawal effects (e.g., premature menopause) in adults. Defective egg or sperm development results in infertility. The term hypogonadism is usually applied to permanent rather than transient or reversible defects, and usually implies deficiency of reproductive hormones, with or without fertility defects. The term is less commonly used for infertility without hormone deficiency. There are many possible types of hypogonadism and several ways to categorize them. Hypogonadism is also categorized by endocrinologists by the level of the reproductive system that is defective. Physicians measure gonadotropins (LH and FSH) to distinguish primary from secondary hypogonadism. In primary hypogonadism the LH and/or FSH are usually elevated, meaning the problem is in the testicles, whereas in secondary hypogonadism, both are normal or low, suggesting the problem is in the brain.
Affected system
- Hypogonadism resulting from defects of the gonads is traditionally referred to as primary hypogonadism. Examples include Klinefelter syndrome and Turner syndrome. Mumps is known to cause testicular failure, and in recent years has been immunized against in the US. A varicocele can reduce hormonal production as well.
- Hypogonadism resulting from hypothalamic or pituitary defects are termed secondary hypogonadism or central hypogonadism (referring to the central nervous system).
- Examples of Hypothalamic defects include Kallmann syndrome.
- Examples of Pituitary defects include hypopituitarism.
- An example of a hypogonadism resulting from the lack of hormone response is androgen insensitivity syndrome, where there are inadequate receptors to bind the testosterone, resulting in a female appearance despite XY chromosomes.
Primary or secondary
- Primary - defect is inherent within the gonad: e.g. Noonan syndrome, Turner syndrome (45X,0), Klinefelter syndrome (47XXY), XY females with SRY gene-immunity
- Secondary - defect lies outside of the gonad: e.g. Polycystic ovary syndrome, and Kallmann syndrome, also called hypogonadotropic hypogonadism.[1] Hemochromatosis and diabetes mellitus can be causes of this as well.
Congenital vs. acquired
- Examples of congenital causes of hypogonadism, that is, causes that are present at birth:
- Turner syndrome in females, and Klinefelter syndrome in males. It is also one of the signs of CHARGE syndrome.
- Examples of acquired causes of hypogonadism:
- Opioid Induced Androgen Deficiency (resulting from the prolonged use of opioid class drugs, e.g. morphine, oxycodone, methadone, fentanyl, hydromorphone)
- Anabolic steroid-induced hypogonadism (ASIH)
- Childhood mumps
- Children born to mothers who had ingested the endocrine disruptor diethylstilbestrol for potential miscarriage
- Traumatic brain injury, even in childhood
- In males, normal aging causes a decrease in androgens, which is sometimes called "male menopause" (also known by the coinage "manopause"), late-onset hypogonadism (LOH), and andropause or androgen decline in the aging male (ADAM), among other names.
Hormones vs. fertility
Hypogonadism can involve just hormone production or just fertility, but most commonly involves both.
- Examples of hypogonadism that affect hormone production more than fertility are hypopituitarism and Kallmann syndrome; in both cases, fertility is reduced until hormones are replaced but can be achieved solely with hormone replacement.
- Examples of hypogonadism that affect fertility more than hormone production are Klinefelter syndrome and Kartagener syndrome.
Symptoms
|
This section needs additional citations for verification. (January 2012) |
In both sexes
Symptoms of hypogonadism in both sexes may include:[2][3]
- Delayed, reduced, or absent puberty (which may result in sexual infantilism if left untreated)
- Low or complete lack of libido (sexual desire/interest)
- Infertility
- Depression
- Anxiety
- Irritability
- Fatigue
- Poor sleep or sleep disturbances
- Cognitive problems such as difficulty concentrating and memory loss
- Reduced quality of life[4]
- Hot flashes and night sweats
- Diarrhea
- Aches and pains (such as in muscles)
- Dry skin and/or cracking nails
- Diminished or lacking pubic, underarm, and leg hair growth
- Loss of or nonexistent sense of smell (in cases due to Kallmann syndrome)
- Loss of bone mass (osteoporosis)[5]
- Increased abdominal fat
- Glucose intolerance (early-onset diabetes)
- High cholesterol/lipids
Exclusively in men
Symptoms of hypogonadism exclusive to men may include:
- Muscle loss/atrophy
- Diminished or lacking facial and body hair growth
- Small or shrunken testicles, penis, and/or prostate
- Decreased firmness of the testicles
- Erectile dysfunction
- Frequent urination (polyuria) without infection; waking at night to urinate (nocturia)
- Gynecomastia and feminization in general
Exclusively in women
Effects of hypogonadism exclusive to women may include:[2][1]
- Menstrual irregularity or loss of menstruation
- Small or shrunken ovaries, uterus, and/or breasts
- Urinary bladder discomfort like frequency, urgency, frequent infections, lack of lubrication, discharge
- Symptoms of masculinization, such as acne, hirsutism, and alopecia
Diagnosis
In men
Low testosterone can be identified through a simple blood test performed by a laboratory, ordered by a physician. This test is typically ordered in the morning hours, when levels are highest, as levels can drop by as much as 13% during the day.[6]
Normal total testosterone levels range from 300 - 1000 ng/dL[7]
Treatment is often prescribed for total testosterone levels below 350 ng/dL.[8] If the serum total testosterone level is between 230 and 350 ng/dL, repeating the measurement of total testosterone with sex hormone-binding globulin (SHBG) to calculate free testosterone or free testosterone by equilibrium dialysis may be helpful.
Treatment may be necessary even if the patient's total testosterone level is within the "normal" range. The standard range given is based off widely varying ages and, given that testosterone levels naturally decrease as humans age, age-group specific averages should be taken into consideration when discussing treatment between doctor and patient.[9] A twenty-seven year old male with a testosterone level of 380 ng/dL would be in the "normal" range, but would likely have low testosterone to blame if he experiences some or many of the above symptoms. This score would put him in the bottom 5% of his age-group, but would be a more common score for a man who is 80+ years old.[9]
- Blood testing
A position statement by The Endocrine Society has expressed dissatisfaction with the manner in which most assays for TT (Total Testosterone) and FT (Free Testosterone) are currently performed.[10] In particular, research has questioned the validity of commonly administered assays of FT by RIA.[10] The FAI (Free Androgen Index) has been found to be the worst predictor of Free Testosterone.[11]
In women
Similar to men, the LH and FSH will be used, particularly in women who believe they are in menopause. These levels change during a woman's normal menstrual cycle, so the history of having ceased menstruation coupled with high levels aids the diagnosis of being menopausal. Commonly, the post-menopausal woman is not called hypogonadal if she is of typical menopausal age. Contrast with a young woman or teen, who would have hypogonadism rather than menopause. This is because hypogonadism is an abnormality, whereas menopause is a normal change in hormone levels.
Hypogonadism is often discovered during evaluation of delayed puberty, but ordinary delay, which eventually results in normal pubertal development, wherein reproductive function is termed constitutional delay. It may be discovered during an infertility evaluation in either men or women.
Treatment
Male hypogonadism is most often treated with testosterone replacement therapy (TRT) in patients who are not trying to conceive. Commonly-used testosterone replacement therapies include transdermal (through the skin) using a patch or gel, injections, or pellets. Oral testosterone is no longer used in the U.S. because it is broken down in the liver and rendered inactive; it also can cause severe liver damage. Like many hormonal therapies, changes take place over time. It may take as long as 2–3 months at optimum level to reduce the symptoms, particularly the wordfinding and cognitive dysfunction. Testosterone levels in the blood should be evaluated to ensure the increase is adequate. Levels between 500 and 700 ng/dL are considered adequate for young, healthy men from 20 to 40 years of age, but the lower edge of the normal range is poorly defined and single testosterone levels alone cannot be used to make the diagnosis. Modern treatment may start with 200 mg intramuscular testosterone, repeated every 10–14 days. Getting a blood level of testosterone on the 13th day will give a "trough" level, assisting the physician in deciding whether the correct dose is being given.[citation needed]
Recently some have reported using anastrozole (Arimidex), an aromatase inhibitor used in women for breast cancer, to decrease conversion of testosterone to estrogen in men, and increase serum testosterone levels.[citation needed]
While historically men with prostate cancer risk were warned against testosterone therapy, that has shown to be a myth.[12]
Other side effects can include an elevation of the hematocrit to levels that require blood to be withdrawn (phlebotomy) to prevent complications from it being "too thick". Another is that a man may have some growth in the size of the breasts (gynecomastia), though this is relatively rare. Finally, some physicians worry that Obstructive Sleep Apnea may worsen with testosterone therapy, and should be monitored.[citation needed]
Another feasible treatment alternative is human chorionic gonadotropin (hCG).[13]
For both men and women, an alternative to testosterone replacement is Clomifene treatment which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects as a consequence of direct hormone replacement therapy.[14]
For women, estradiol and progesterone are replaced. Some types of fertility defects can be treated, others cannot. Some physicians will also give testosterone to women, mainly to increase libido.[citation needed]
Testosterone and longevity
A longitudinal (18 year) study published by The Endocrine Society and funded by the National Institute on Aging and the American Heart Association stated: Men over 50 may not live as long if they have low testosterone. The study looked at death from any cause in nearly 800 men ages 50 to 91 years who were living in a southern California community and who participated in the Rancho Bernardo Study in the 1980s. At the beginning of the study, almost one-third of these men had suboptimal blood testosterone levels for men their age. The men with low testosterone levels had a 33 percent greater risk of death during the next 18 years than the men with higher testosterone. This difference was not explained by smoking, alcohol intake, level of physical activity, or by pre-existing diseases such as diabetes or heart disease.[15]
The new study is the second report linking the deficiency of this sex hormone with increased death from all causes over time, said study author Gail Laughlin, PhD.
See also
- Hypergonadotropic hypogonadism
- Hypogonadotropic hypogonadism
- Isolated hypogonadotropic hypogonadism
- Hypoandrogenism and hypoestrogenism
- Delayed puberty and infertility
- Hypothalamus, pituitary gland, and HPG axis
- Gonads (testicles and ovaries)
- GnRH and gonadotropins (FSH and LH)
- Sex hormones (androgens and estrogens)
- Hypergonadism (hyperandrogenism and hyperestrogenism)
References
- ^ a b MedlinePlus Medical Encyclopedia - Hypogonadotropic hypogonadism, accessed on July 3, 2009.
- ^ a b MedlinePlus Medical Encyclopedia - Hypogonadism, accessed on July 3, 2009.
- ^ "Low Testosterone Symptoms". Low Testosterone Supplements. http://www.howtousetestosterone.com/lowtestosteronesymptoms.html. Retrieved 7 January 2012.
- ^ Brooke JC et al. "Severity of Erectile Dysfunction and Testosterone Deficiency Are Associated with Reduced Quality of Life (HRQoL) in Men with Type 2 Diabetes Mellitus". http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P1-332?sid=755cf241-e421-42c3-a8de-bdd1015fa100.
- ^ NIH Osteoporosis and Related Bone Diseases - National Research Center http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/men.asp#b
- ^ Crawford, E. David; Barqawi, Al Baha; O'Donnell, Colin; Morgentaler, Abraham (2007). "The association of time of day and serum testosterone concentration in a large screening population". BJU International 100 (3): 509–13. doi:10.1111/j.1464-410X.2007.07022.x. PMID 17555474. Lay summary – UroToday (12 July 2007).
- ^ Cooper, Robert (January 21, 2010). "Testosterone". MedlinePlus. United States National Library of Medicine. http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/003707.htm.
- ^ Nieschlag E, Swerdloff R, Behre HM, et al. (2006). "Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations". Journal of Andrology 27 (2): 135–7. doi:10.2164/jandrol.05047. PMID 16474020.
- ^ a b http://www.mens-hormonal-health.com/normal-testosterone-levels.html
- ^ a b Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H (February 2007). "Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement". The Journal of Clinical Endocrinology and Metabolism 92 (2): 405–13. doi:10.1210/jc.2006-1864. PMID 17090633.
- ^ Morris PD, Malkin CJ, Channer KS, Jones TH (August 2004). "A mathematical comparison of techniques to predict biologically available testosterone in a cohort of 1072 men". European Journal of Endocrinology 151 (2): 241–9. doi:10.1530/eje.0.1510241. PMID 15296480.
- ^ Morgentaler (2006). "Testosterone and prostate cancer: an historical perspective on a modern myth". European Urology 50 (5): 935–9. doi:10.1016/j.eururo.2006.06.034. PMID 16875775.
- ^ Chudnovsky, A.; Niederberger, C. S. (2007). "Gonadotropin Therapy for Infertile Men with Hypogonadotropic Hypogonadism". Journal of Andrology 28 (5): 644–6. doi:10.2164/jandrol.107.003400. PMID 17522414.
- ^ Whitten, S; Nangia, A; Kolettis, P (2006). "Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate". Fertility and Sterility 86 (6): 1664–8. doi:10.1016/j.fertnstert.2006.05.042. PMID 17007848.
- ^ Laughlin, G. A.; Barrett-Connor, E.; Bergstrom, J. (2007). "Low Serum Testosterone and Mortality in Older Men". Journal of Clinical Endocrinology & Metabolism 93 (1): 68–75. doi:10.1210/jc.2007-1792. PMC 2190742. PMID 17911176. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2190742. Lay summary – The Endocrine Society (5 June 2008).
External links
- GeneReview/NIH/UW entry on Hypogonadotropic Hypogonadism Overview
- NIH
- eMedicine.com
- The Pituitary Foundation
|
Endocrine pathology: endocrine diseases (E00–E35, 240–259)
|
|
Pancreas/
glucose
metabolism |
|
Hypofunction
|
Diabetes mellitus
types: (type 1, type 2, MODY 1 2 3 4 5 6) · complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy)
insulin receptor (Rabson–Mendenhall syndrome) · Insulin resistance
|
|
|
Hyperfunction
|
Hypoglycemia · beta cell (Hyperinsulinism) · G cell (Zollinger–Ellison syndrome)
|
|
|
Hypothalamic/
pituitary axes |
|
Hypothalamus
|
gonadotropin (Kallmann syndrome, Adiposogenital dystrophy) · CRH (Tertiary adrenal insufficiency) · vasopressin (Neurogenic diabetes insipidus) · general (Hypothalamic hamartoma)
|
|
|
Pituitary
|
|
Hyperpituitarism
|
anterior (Acromegaly, Hyperprolactinaemia, Pituitary ACTH hypersecretion) · posterior (SIADH) · general (Nelson's syndrome)
|
|
|
Hypopituitarism
|
anterior (Kallmann syndrome, Growth hormone deficiency, ACTH deficiency/Secondary adrenal insufficiency, GnRH insensitivity, FSH insensitivity, LH/hCG insensitivity) · posterior (Neurogenic diabetes insipidus) · general (Empty sella syndrome, Pituitary apoplexy, Sheehan's syndrome, Lymphocytic hypophysitis)
|
|
|
|
Thyroid
|
|
Hypothyroidism
|
Iodine deficiency · Cretinism (Congenital hypothyroidism) · Myxedema · Euthyroid sick syndrome
|
|
|
Hyperthyroidism
|
Hyperthyroxinemia (Thyroid hormone resistance, Familial dysalbuminemic hyperthyroxinemia) · Hashitoxicosis · Thyrotoxicosis factitia · Graves' disease
|
|
|
Thyroiditis
|
Acute infectious · Subacute (De Quervain's, Subacute lymphocytic) · Autoimmune/chronic (Hashimoto's, Postpartum, Riedel's)
|
|
|
Goitre
|
Endemic goitre · Toxic nodular goitre · Toxic multinodular goiter
Thyroid nodule
|
|
|
|
Parathyroid
|
|
Hypoparathyroidism
|
Hypoparathyroidism · Pseudohypoparathyroidism · Pseudopseudohypoparathyroidism
|
|
|
Hyperparathyroidism
|
Primary · Secondary · Tertiary · Osteitis fibrosa cystica
|
|
|
|
Adrenal
|
|
Hyperfunction
|
aldosterone: Hyperaldosteronism/Primary aldosteronism (Conn syndrome, Bartter syndrome, Glucocorticoid remediable aldosteronism) · AME · Liddle's syndrome · 17α CAH
cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome)
sex hormones: 21α CAH · 11β CAH
|
|
Hypofunction/
Adrenal insufficiency
(Addison's, WF) |
aldosterone: Hypoaldosteronism (21α CAH, 11β CAH)
cortisol: CAH (Lipoid, 3β, 11β, 17α, 21α)
sex hormones: 17α CAH
|
|
|
|
Gonads
|
ovarian: Polycystic ovary syndrome · Premature ovarian failure
testicular: enzymatic (5α-reductase deficiency, 17β-hydroxysteroid dehydrogenase deficiency, aromatase excess syndrome) · Androgen receptor (Androgen insensitivity syndrome)
general: Hypogonadism (Delayed puberty) · Hypergonadism (Precocious puberty) · Hypoandrogenism · Hypoestrogenism · Hyperandrogenism · Hyperestrogenism
|
|
|
| Height |
Gigantism · Dwarfism/Short stature (Laron syndrome, Psychosocial)
|
|
| Multiple |
Autoimmune polyendocrine syndrome (APS1, APS2) · Carcinoid syndrome · Multiple endocrine neoplasia (1, 2A, 2B) · Progeria (Werner syndrome, Acrogeria, Metageria) · Woodhouse-Sakati syndrome
|
|
|
|
|
noco(d)/cong/tumr, sysi/epon
|
proc, drug (A10/H1/H2/H3/H5)
|
|
|
|
